The Center for Nanoscience & Nanotechnology Scientific Report 2009–2011

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The Center for Nanoscience and Nanotechnology

Scientific Report 2009-2011 Acknowledgements

All the activity and achievements described in this report would not have been possible without the support and help of numerous individuals and organizations. We are deeply grateful to them for their help and support.

The Chaoul Center for Nanoscale Materials and Systems Mr. Robert Goldberg James Russell DeLeon – The Center for Nanostructuring The Jack H. Skirball National Center for Biomedical Nanoscience Nanotechnology Research Fund in Cooperation with Clal Biotechnical Industries The Marian Gertner Institute for Medical Nanosystems The Ilona Rich Institute for Nanoscale Bioscience and Biotechnology The Dr. Teodoro Jack and Dorothea Krauthamer Laboratory for Scanning Electron Microscopy A.V.B.A. Students Laboratory for Electron Beam Lithography Infrastructure Equipment for Nanotechnology Research – Wolfson Family Charitable Trust ,UK The Raymond and Beverly Sackler Chair in Clusters and Nanoparticles The Edouard Seroussi Chair for Protein Nanobiotechnology The Herman and Kurt Lion Chair in Nanosciences and Nanotechnologies The Bernard L. Schwartz Chair and Program in Nano-scale Information Technology Support for Nanotechnology Research donated by The Gilman Foundation Walanpatrias Stiftung Peamey Tikva (Israel 2004) LTD TELEM equipment fund Mr. Shlomo Eliahu

Starting from 2007 we participate in the Israel Nanotechnology National Initiative (INNI) program, founded by TELEM, with the total budget of 30M$ spread over the five academic years 2007-2011. The monitory resources are according to the triangle model in which the university, donors and the INNI initiative are contributing 10 M$ each. Dear colleagues and friends,

I am delighted to present to you the third scientific report microscopy combined with micropatterning technology of the Tel Aviv University center for nano science and nano to probe the Notch signaling pathway from the nanoscale technology. This year we mark 12 years of nano science and to the whole organ levels. To approach these questions technology research at Tel Aviv University. The nano center, the team uses mathematical models of differentiation to the first one in Israel, was instrumental in forming a vibrant obtain quantitative understanding of the role of the Notch scientific community with many excellent recruits who signaling pathway during development and disease. joined Tel Aviv University in the past recent years. Research Dr. Tal Dvir from the Faculty of Life Sciences is interested in infrastructure was also expanded and now provides Tel the field of tissue engineering and regenerative medicine. Aviv researchers with state of the art fabrication and Tissue engineering has evolved as an interdisciplinary characterization resources. These facilities are serviced by a technology combining principles from the life, material team of outstanding researchers and engineers. and engineering sciences, with the goal for developing Our most recent recruits include 8 outstanding new functional substitutes for damaged tissues and organs. Dr. faculty members: Dvir’s lab develops and uses existing nanotechnological tools for the design of advanced nanocomposite scaffolds Dr. Iftach Nachman from the Faculty of Life Sciences that can better mimic the extracellular matrix, sense studies how cells within a population reach developmental and report the condition of the engineered tissues, and decisions at the phenotypic and mechanistic level, and eventually assemble large and complex functional tissues. how information processing done by signaling pathways A different approach investigated in Dvir’s lab is involved in affects these decisions. His team studies these questions vivo engineering of organs with nanoparticulate systems. in yeast and mammalian cells using methods from live These systems can manipulate stem cells in the body to cell fluorescent imaging, microfluidics, statistical and target diseased tissues and promote regenerative processes. computational analysis. The team designs and fabricates microfluidic devices capable of generating spatial and Dr. Roy Beck-Barkay from the School of Physics is temporal signal gradients which can be imaged for long interested in the intermolecular forces and interactions periods of time under controlled conditions. responsible for supramolecular nanometric complex assembly, as they are extremely important for the proper Dr. Avigdor Eldar from the Faculty of Life Sciences is function of many biological systems. In addition to interested in understanding symmetry breaking and its a biochemistry and molecular wet laboratory, which relation with cell signaling and differentiation on multiple includes a protein purification HPLC setup and a couple temporal and spatial scales. The main model system in his of optical microscopy units, Dr. Beck’s laboratories consist lab is the sporulation process of the bacteria Bacillus subtilis. of a new, top-of-the-line nanoscience characterization Using this model, his team plans to study differentiation tool called the Small Angle X-ray Scattering (SAXS). This decisions, symmetry breaking in cell division and signaling characterization tool is unique as it has capabilities to across a septum. Light will be extensively used to guide measure repeating nanometric structures in a non- gene expression and protein localization. Super-resolution destructive manner, without staining or other perturbation, microscopy (STORM) will be used to reconstruct the in various conditions such as aqua mediums, gel state or signaling apparatus at the 10nm resolution and analyze embedded on surfaces. their dependence on interaction and signaling. Dr. Yuval Ebenstein from the School of Chemistry is Dr. David Sprinzak from the Faculty of Life Sciences developing in his lab single molecule approaches to studies the biophysics of intercellular signaling and its genetic and epigenetic research. Fabricated nano-fluidic role during development and disease. His group focuses chips are utilized for the optical analysis of genomic DNA. mainly on the Notch signaling pathway, which is the A set of micro and nano-pillars are used to unravel the DNA canonical signaling pathway coordinating differentiation molecules which are then extended by electrophoresis between neighboring cells across metazoans. The team through an array of nano-channels with diameters of 45nm. uses state of the art live imaging and super-resolution The labeled DNA is imaged in its extended linear form to

3 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY create an optical “bar-code” of the labeled information. institutions as well as 38 research projects with industrial Super-resolution microscopy techniques are used to partners took place in the past two years. bridge the resolution gap between optical and electron Nano related research at Tel Aviv University extends microscopy and localize fluorescence signals from the beyond basic research and many researchers have DNA at nm resolution. In addition, functional quantum- activity geared towards applicative research. Twenty five dot biosensors and tags for imaging and diagnostics nano related patents have been approved during 2009- applications are developed in the lab. 2010. Five ties with industries have been signed, three of Dr. Alon Bahabad from the Faculty of Engineering is which are related to renewable energy. Several others are interested in theoretical and experimental physical optics. in final stages of negotiations. One of his major areas of research is the generation of Recruiting and training students and post-docs is a major coherent light sources at very high photon energies focus of our activity. One hundred and sixty seven PhD and (soft X-rays). For this purpose, his group employs the 141 MSc research students were involved in nano-research extreme nonlinear optical process of high-harmonic- at Tel Aviv over the course of 2009-2010. The MSc program generation (HHG). The group is interested in mediating in Materials and Nanotechnology provides a valuable optical processes by employing Plasmon-assisted field source to recruit new students and has established itself as enhancement. When the laser light interacts with a metallic a well respected program. We continued our tradition of a nanostructure, electron oscillations on the metal surface weekly seminar program on materials and nanotechnology can lead to a significant field enhancement. The geometry seminars in 2009-2010, which was attended by MSc and of the metallic nanostructure can be used to control the PhD students, as well as faculty members. We have also beam shape and polarization state of the generated high continued the exchange program of graduate students and harmonic radiation. senior scientists between Northwestern University and TAU. Dr. Amir Natan from the Faculty of Engineering is using Five exchange scholarships have been granted last year. first principles quantum calculations and other tools to Expanding our research facilities has been a primary investigate the electronic properties of materials and focus of the nano center, in particular in the past 5 years. devices. He uses commercial and public software and also The TAU Micro and Nano Central Characterization and develops software and new theoretical methods in the field. Fabrication Facility was inaugurated in October 2007. It now His interests include: Properties of novel nano materials encompasses the majority of micro and nano fabrication, (structural and electronic), interaction of light with matter as well as most of the characterization instrumentation on and electron dynamics, as well as multi-scale modeling of Tel Aviv University campus. The center is responsible for materials and devices. Amir is also interested in physical providing service, training and consultation to costumers, phenomena on surfaces and interfaces, in particular electric as well as maintaining and upgrading its facilities. The and magnetic properties on interfaces and in modeling of facility serves over 30 Tel Aviv University research groups, dynamical processes of atom adsorption on surfaces. including more than 25 external academic and industrial Iftach, Avigdor, David, Tal, Roy, Yuval, Alon and Amir join a users. We have recently recruited Dr. Nava Ariel- vibrant and active research community which habitually Sternber to lead the facility. Under Nava’s leadership, produces excellent academic output. This report reflects we aim to become the top academic facility in Israel for the recent scientific output of these researchers. Overall, micro and nano fabrication and characterization. Dr. in the last two years, 389 nano-related papers, originating Artium Khatchtouriants has recently joined our team from 71 different research groups have been published, as an AFM researcher and Dr. Yigal Lilach is our new many of them in highly ranked journals. A hundred of these electron microscopy unit manager. Yigal replaced Dr. Alex publications are the result of cooperation with researchers Tsukernik after many years of exemplary service. from other universities. One hundred and forty nine Major items that were purchased or installed recently collaborative research projects involving other academic include:

4 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Raith FIB ionLiNE. The ionLiNE is a dedicated ion beam nanometric resolution, we have purchased a biological lithography, nanofabrication and engineering workstation oriented AFM system. The system allows the investigation with direct surface modification capabilities down to of biological cells and tissues under a wide range of the sub 10 nm level. It is designed as a versatile tool for chemical environments, temperatures and atmospheres. advanced nanostructuring applying direct patterning, When combined with an inverted microscope (Olympus lithography, etching and deposition processes applying IX81), it makes a very powerful tool to correlate topography focused ion beam technology. Its design is based on the and nano scale mechanical properties with traditional concept of a fixed beam moving stage. It is unique in Israeli fluorescence spectroscopy. Academia in its ability to fabricate thin extended lines or Raman Microscopy system. This Raman spectroscopy paths with no stitch field boundaries. system is the only public Raman system at Tel Aviv University. Fixed Beam Moving Stage (FBMS) module for E-beam As such, it makes a very useful tool for the characterization lithography. The FBMS exposure mode yields excellent of nanomaterials, as well as a general tool in the service precision and flexibility in fabricating thin extended lines of chemistry and material science research. The system is or paths (limited only by the stage travel range) with no coupled to an upright microscope, but can also be coupled stitch field boundaries. This is an ideal replacement for to our new biological AFM system (mentioned above). The the standard “step and repeat” strategy for long lines latter combination provides the combined power of tip production, in which stitching error of several tens of enhanced Raman Spectroscopy, a very important analytic nanometers is always present. Typical applications of the tool in the investigation of nanostructures with spatial FBMS mode are fabrication of integrated optics structures, resolution of tens of nanometers. such as waveguides or x-ray optics. LC Ion-Trap Mass Spectrometer. LC/MS is a tool of Solid-state NMR (SSNMR) spectrometer. The 14.1 Tesla great importance in nanoscience and nanotechnology, NMR is capable of performing solid-state magic-angle which allows to identify unknown materials; to determine spinning NMR measurements and magnetic resonance the compound’s mass; to elucidate the structure of imaging (MRI). The unique capability of the SSNMR to compounds; to determine protein and peptide sequences; analyze nearest neighbor distributions will serve our to find the places of molecules’ modifications; to search for researchers in characterizing complex nanoparticles. In biomarkers; to define the length, sequence and branching addition, magnetic nano particles can be investigated of polymers; to detect and characterize metabolites, and and characterized using the imaging capability of the to perform the precise quantification of substances in the spectrometer. This system serves as a strong research tool investigated samples (including complex, “dirty” matrices). in general and specifically strongly supports our research We now look beyond the initial building phase. After 12 efforts in nano-magnetics and nano-ferroelectrics and years of constant growth, we are switching gears towards nano superconductivity. a second stage which will focus on strengthening focal MALDI Electro Spay and LC Mass Spectrometer. The areas, and strengthening ties with the industry. We new mass spectrometer (installed in the Chemistry mass will, of course, continue to promote and support excellent spectrometry lab) is an ESI/MALDI exchangeable Synapt nano related research across the campus and to foster new mass spectrometer equipped with an HPLC for LC-ESI initiatives across disciplines. Based on the achievements of methodologies (metabolomics, proteomics and chemical Tel Aviv researchers so far, we look forward to many exciting reactions optimization). The MALDI probe of the instrument years of productive scientific activity. allows the analysis of the chemical composition of chemicals, nanoparticles, biochemicals, microbial and human cell cultures, as well as MALDI-Imaging of organs and surfaces. Yours, Biological AFM. Within the framework of building a Prof. Ori Cheshnovsky general lab for the investigation of biological systems with Head of the Center for Nanoscience and Nanotechnology

5 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY

Table of Contents

Researchers 9 Progress reports 81 Publications 171 Patents 189 Collaborations 190 Scientific Groups 196 Scientific committee 199 Staff members 200

Cover picture in courtesy of Prof. Ehud Gazit and Ms. Hadar Cohen Graphic Design: Michal Semo-Kovetz and Yael Bieber, TAU Graphic Design Studio

7 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY B Tel Aviv University micro and nano central characterization and fabrication facility M issions „„To provide Tel Aviv University users with access to state of the art micro- and nanofabrication and characterization equipment. „„To consult and help users develop suitable process protocols. „„To train users to operate equipment and wet chemical stations. „„To provide services to external academic users as well as industry.

E quipment Electron microscopes Measurements „„Environmental Scanning Electron Microscope „„Profile/Step height (Tencor, Veeco) (ESEM - FEI Quanta 200 FEG) „„Spectroscopic Ellipsometer (Woollam „„Field Emission High Resolution Scanning M2000DUV) Electron Microscope (HRSEM - Jeol JSM-6700) „„Spectroscopic Reflectometer (Sentech FTP) „„Film Stress (2d and 3d) and 3d surface Particle Beam Lithography profiling (KLA P-16+) „„E-beam lithography (Raith 150) „„SEM with e-beam writing attachment (Jeol Optical microscopy 6400 + Elphy) „„Metallurgical confocal microscope (Olympus „„Focused Ion Beam Milling (Raith ionLine) LEXT) „„Measurement microscope (Hisomet II) AFM/STM „„Inspection Microscopes (Olympus MX-40, MX-50) „„AFM (Molecular Imaging PicoSPM II) „„Scanning Raman microscope (maybe coupled „„AFM (Veeco NanoScope IV MultiMode) to AFM) „„Variable Temperature Ultra-High Vacuum STM/AFM System (Omicron) Thin film deposition and etching „„AFM in a glove box (NT-MDT SMENA-A) „„E-beam deposition (VST, Edwards 306) „„Thermal evaporation (VST) Photolithography and nanoimprint „„RF sputtering (MRC) lithography „„DC sputtering (Penta Vacuum) „„Contact lithography (Suss MA6, MJB3) „„RIE etching (Nextral 860 HDP RIE, Oerlikon „„Direct laser writing & photomask preparation 790 RIE) (Heidelberg Instruments Fast Scan DWL-66fs) „„DRIE etching (Plasma Therm 770 ICP DRIE) „„Nanoimprint Lithography (S.E.T. FC-150) „„Wet etching Backend „„Wet and dry substrate cleaning „„Ion Beam Sputtering „„Dicing (Disco DAD 3350) „„PECVD (Oerlicon 790) „„Wire Bonding (K&S) C ontact „„Precision Diamond Scriber (ATV) Thermal Treatment n Mark Oksman „„Tousimis Critical Point Dryer „„RTP (Jipelec Jetfirst 100) Email: [email protected] Phone: 03-6407926

n Dr. Nava Ariel-Sternberg C ustomers Email: [email protected] Companies: Active Implants n Ayalan n Bright View n Cima Nanotech n Civan Phone: 03- 6405722 n El-Mul n Flamingo Electronics n HP-Indigo n IAI n IMH n Impel n ITH n Kadoor Microelectronics n Maradin n MEMS & Optomechanics Design n Mizur Technologies n Nanometrics n Nanoready n Nano-Retina n Orbotech n Orbotech Medical Solutions n Piercell n PlanXwell n PV NanoCell n RAFAEL n SOREQ NRC n Utilight n VislC Technologies

Academia: Bar Ilan University n HUJI n Technion n Weizmann Institute

October 2011 http://www.tau.ac.il/~nanotau/Fabrication.html

Flyer of the TAU micro and nano central characterization and fabrication facility ResearcherS (sorted by cademic unit)

Researchers

Prof. David Andelman Physics

Polymeric Nano- Templates and Nano-Structures various surface energies. This set-up is studied Producing a surface with an ultradense array of addressable by us theoretically in collaboration with several nanoscopic elements that is perfectly ordered over macroscopic experimental groups. length scales is a formidable challenge. The self-assembly of block copolymers (BCP), two chemically dissimilar polymers joined together, Electric Field Effects is emerging as a promising route to generate templates and scaffolds Electric fields can be employed to re-orient and for the fabrication of nanostructured materials, in particular in relation control morphology of BCP films. We study the to their applications in nanowires, quantum dots, magnetic storage role of added ionic impurities, as they have been media, flash memory devices, photonic crystals, and silicon capacitors. shown to have a large effect on film morphologies.

NanoImprint Lithography – NIL References NanoImprint Lithography (NIL) is a new method for macroscopic 1. X. K. Man, D. Andelman, H. Orland, Block Copolymers alignment of BCPs on molecular scale. It can be used as a tool for at Nano-Patterned Surfaces, Macromolecules, in press (2010). locally controlling the self-assembly of BCPs and determining the 2. G. G. Putzel, D. Andelman,Y. Tsori, M. Schick, Ionic precise position of the phase-separated domains. Using numerical Effects on the Electric Field Needed to Orient techniques, we investigate theoretically the role of important system Dielectric Lamellae, J. Chem. Phys. 132, 164903 parameters in producing well aligned BCP templates. (2010). 3. Y. Tsori and D. Andelman, Coarse Graining in Block Chemically Nano-Striped Surfaces Copolymer Films, J. Polym. Science – Polymer Physics 44, 2725 (2006). Another way to control the structure of BCP films is by creating chemical nano-patterns on a silicon wafer and adjusting locally the

Two steps of Nano-Imprint Lithography. A mold formed out of a grooved surface is pressed on a polymeric film (a). After temperature annealing, the mold is removed (b) and the film obtained a perfect inplane alignment.

Tel: (972)-3-6407239 Fax: (972)-3-6419529 Email: [email protected] Personal Website: http://star.tau.ac.il/~andelman/

11 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Roy Beck-Barkai Physics

Biomolecules Supramolecular Assemblies In many significant biological functions the four basic building blocks (proteins, lipids, sugars and nucleic acids) aggregate to form supramolecular structures and assemblies. The forces and interactions responsible for these assemblies are composed of a set of interactions with energy scales from the order of thermal fluctuation (few BK T) to specific covalent bonds on the order of 100’s BK T. Moreover, relevant length scales in biological systems span over many orders of macromolecules. In our laboratory we use small magnitude, from the single amino acid through polypeptide chains, angle x-ray scattering (SAXS) technique to cover protein complexes, organelles and up cells and organs. These different length scales from 0.1-100 nm. This technique is length scales present an enormous challenge both experimentally suitable to measure weak scattering from biological and theoretically. Therefore, in order to properly study biological system in their natural environment. Detailed systems and the interactions within them, it is important to have analysis and advanced computational techniques complementary techniques covering different length-scales and are regularly used to convert the reciprocal space energies, with proximity to their natural environment. In our laboratory to real-space structures and enable studies on the we purify the subunit building-blocks using various biochemical and nature of the interactions within the biological molecular procedures and reassemble them in various conditions to assemblies. SAXS, in particular, provides a ready study their supramolecular forces, dynamics and steady-state structures means of determining inter-filament spacing and as appear in healthy and diseased states. interactions. Recent advances in solid-state type Supramolecular Forces within Intermediate Filaments x-ray detectors and the high flux microfocous x-ray sources allow investigation of dynamic structural Cytoskeletal proteins are the major structural components of cells. In events and highly penetrated lens-less tomography recent years, much fruitful research has dealt with the structures and of biomolecular samples. Conveniently, these interactions of microtubules (25 nm in diameter hollow nanotube) approaches do not require staining or other and actin filaments (8 nm in diameter). However, little is known about modifications, and thus do not perturb our system, the third component of the cytoskeleton, intermediate filaments allowing more ready access to the supramolecular (IFs), which, in contrast to actin and microtubules, are cell specific. IFs forces underlying self-assembly and simplifying principal function is to mechanically support the cell and its membrane. data analysis. The common denominator to all IFs is that they form a 10 nm filament core while the difference is found mainly in the unstructured brushes. References In our laboratory we aim to understand the forces and interactions 1. R. Beck, J. Deek, J.B. Jones, C.R. Safinya, Gel Expanded responsible for the assemblies of the different IFs from the single to Gel Condensed Transition in Neurofilament filament properties to the condensed hydrogel network composed Networks revealed by Direct Force Measurements, from many interacting filaments. Nature Materials 9, 40-46 (2010). 2. R. Beck, M.C. Choi, J. Deek, T. Ikawa, O. Watanabe, Small Angle X-ray Scattering E. Frey, P. Pincus, C.R. Safinya, Unconventional Salt X-ray scattering and diffraction has been a leading tool in the past Trend from Soft to Stiff in Single Neurofilament century in characterizing material structures. Traditionally, strong Biopolymers, Langmuir, (2010). repeating scatters were needed, usually in a crystal state, in order to gain 3. H. Hesse, R. Beck, C. Ding, J.B. Jones, J. Deek, N.C. structural information. In such cases, x-ray studies can enable ångström MacDonald, Y. Li, C.R. Safinya, Direct imaging of resolution. Advances in the field introduced the possibility for non- aligned neurofilament networks assembled using invasive studies of softer and more flexible materials, such as biological in-situ dialysis in microchannels, Langmuir 24, 8397-8401 (2008). 4. Y. Li, R. Beck, T. Huang, M.C. Choi, M. Divinagracia, Tel: (972)-3-6408477 Scatterless Hybrid Metal-Single Crystal Slit for Small Fax: (972)-3-6422979 Angle X-ray Scattering and High Resolution X-ray Email: [email protected] Diffraction, Journal of Applied Crystallography 41, Personal Website: http://www2.tau.ac.il/Person/exact/physics/researcher. 1134-1139 (2008(. asp?id=aejikeflk

12 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Eshel Ben Jacob Physics

I. Engineered neural networks using nanotechnology The investigations are done in collaboration with Prof. Yael Hanein from Electrical Engineering. See her page for more details. The idea is to use island made from CNT to grow neural networks with different geometries and topology. The CNT are also used for recording the electrical activity of the networks and for electrical stimulations. In parallel to the electrical activity we also perform optical recordings of calcium dynamics. In addition for fundamental understandings of the behavior of neural networks and coupled neural networks, our studies are also aimed towards developments of neuro-memory chips (including electrical and chemical stimulations). Their chemical content is consistent with calcium In another line of research together with Prof. Ari Barzilai from carbonate (CaCO3) nanoprticles with some Neurobiology, we investigate neural networks from transgenic additional trace chemicals that vary between the animals and chimera neural networks in which the glia are taken different types of natural water. The nanoparticles from transgenic animals and the neurons are taken from wild type are homogeneously spread in the natural water animals and vice versa. solutions with about 0.5mm -1.5 mm mean distances between particles. Hence, we refer to II. The effect of nanobubbles and nanoparticles on water such water as natural, nanoparticle-doped water 1. Formation of networks of nano-bubbles in water using weak or N-NPD water. In contrast, purified drinking RF signals water (e.g., Aqua Nova) contains much lower It is known that weak RF signals can have long time effect on water. density of nanoparticles, and in ultra pure water We have shown the effect on electrochemical deposition and on the (UPW) only very few nanoparticles are observed. growth of bacterial colonies. The shape and chemical contents of most of Understanding the mechanism of this phenomenon can serve the the naoparticles in these waters are different basis for many new applications. We investigate the idea that the from the shape and chemical contents of the effects are the outcome of the formation of networks of nanobubbles nanoparticles in N-NPD water. We investigate the (networks with long-range orientation correlations). N-NPD water buffering capacity both for acids Our research also includes the effect of cellular phone and other and bases, dilution buffering effect, stabilization man-made rf pollution on biological systems and organisms. salt precipitation and broken chiral symmetry. Noteworthy, we found that the N-NPD water 2. The effect of naturally-occuring nanoparticle in natural wa- exhibit protection of DNA-polymerase activity ters on biological processess (protection of the Taq polymerase against We found that waters from natural sources, including bottled thermal stress) and have a remarkable effect spring water and tap water, contain a significant density of on bacteria growth and colony development. naturally-occurring nanoparticles – about 1011-1012 particles/ml. The The investigations are extended now to study nanoparticle have spherical shapes with typical size of 10-50nm. the effect of cell cultures. We propose that the observations indicate the existence of multi-scale (nanometers to microns) water order induced by

Tel: Office: (972)-3-6407845, Lab: (972)-3-6407837 the nanoparticles. If it exists, such induced order Fax: (972)-3-6425787 in natural water can have significant effect on a Email: [email protected], [email protected], benjacob. wide range of chemical and biological processes [email protected] with far reaching implications. Personal Website: http://star.tau.ac.il/~eshel/

13 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. David J. Bergman Physics

n Nano-plasmonics: SPASER, meta-materials, plasmonic resonances 7. K. Li, X. Li, M. I. Stockman and D. J. Bergman. Surface n Classical magneto-transport in composite media: Periodic and plasmon amplification by stimulated emission in disordered microstructures, critical points nanolenses. Phys. Rev. B 71, 115409-1–115409-5 (2005). n Physical properties in the physiology and micro-structure of the 8. K. Kim, D. Stroud, X. Li and D. J. Bergman. Method Oriemtal Hornet to calculate electrical forces acting on a sphere in an electrorheological fluid. Phys. Rev. E 71, 031503- References 1–031503-12 (2005). 1. D. J. Bergman and Y. M. Strelniker. Exact asymptotics for the strong-field 9. X. Li, D. J. Bergman and D. Stroud. Electric Forces macroscopic magnetotransport of a composite medium. Phys. Rev. B 82, between Nanospheres in a Dielelctric Host, 174422 (16 Nov. 2010) (19 pp.). Europhys. Lett. 69, 1010–1016 (2005). 2. Y. M. Strelniker, D. J. Bergman, Y. Fleger, M. Rosenbluh, D. Stroud and A. 10. D. J. Bergman and M. I. Stockman. Surface plasmon O. Voznesenskaya. Manipulating the optical transparency of anisotropic amplification by stimulated emission ofradiation: meta-materials with magnetic field and liquid crystals: Influence of Quantum generation of coherent surface plasmons the nano-structures shape. In Proc. of the SPIE Conference entitled in Nanosystems. Phys. Rev. Letters 90, 027402-1– Plasmonics: Nanoimaging, Nanofabrication and their Applications, in 027402-4 (2003). the SPIE Meeting on Optics and Photonics, The San Diego Convention 11. J. S. Ishay, V. Pertsis, E. Rave, A. Goren and D. J. Center, San Diego, CA, 2–6 August 2009. Bergman. Natural thermoelectric heat pump in 3. M. I. Stockman and D. J. Bergman. Surface plasmon amplification by social wasps. Phys. Rev. Letters 90, 0218102-1– stimulated emission of radiation (SPASER), United States Patent No. 0218102-4 (2003). 7,569,188 (filed January 5, 2004; approved August 4, 2009); assigned to 12. K. Li, M. I. Stockman and D. J. Bergman. Self- Ramot at Tel Aviv University and The Georgia State University Research similar chain of metal nanospheres as an efficient Foundation. nanolens. Phys. Rev. Letters 91, 227402-1–227402-4 4. Y. M. Strelniker and D. J. Bergman. Transmittance and transparency (2003). of subwavelength-perforated conducting films in the presence of a 13. M. I. Stockman, S. V. Faleev and D. J. Bergman. magnetic field. Phys. Rev. B 77, 205113 (2008) (5 pages). Coherent control of femtosecond energy 5. D. J. Bergman, U. Evra and X. Li. Radiative lifetimes of nano-plasmonic localization on Nanoscale. Phys. Rev. Letters 88, states. Proc. SPIE 5927(18), 59270I, Plasmonics: Metallic Nanostructures 067402-1–067402-4 (2002). and Their Optical Properties III; Mark I. Stockman; Ed. (12 pp.) (Aug 2005). 14. M. I. Stockman, S. V. Faleev and D. J. Bergman. 6. J. S. Ishay, Z. Joseph, D. V. Galushko and D. J. Bergman. The Nanostructure Localization versus Delocalization of Surface of the Oriental Hornet (Hymenoptera, Vespinae) Cuticle and Silk and Plasmons in Nanosystems: Can One State Have Some of their Biophysical Properties. Current Nanoscience 1, 125–156 Both Characteristics? Phys. Rev. Letters 87, 167401- (2005). 1–167401-4 (2001).

Tel: (972)-3-640-8543 Fax: (972)-3-640-9306 Email: [email protected] Personal Website: http://www.tau.ac.il/~bergman/BergmanHomePg.asp. html

14 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Yoram Dagan Physics

1. Superconductivity in the nanoscale Superconductivity is a macroscopic quantum phenomenon. However, when the superconducting specimen is constituted of weakly connected nano-grains many interesting physical phenomena occur. In our laboratory we are able to probe superconducting fluctuations and their dependence on the nanostructure of the sample.

2. Superconductivity and Magnetism in Oxide interfaces It has been found that when two insulating nonmagnetic perovskites form an epitaxial interface this interface can become highly conductive, magnetic and even superconducting. Using our laser deposition facility we are producing and studying such interfaces The gap amplitude as a function of charge carrier to find out the microscopic and macroscopic origin of conductivity, concentration in electron-doped cuprate superconductors superconductivity and magnetic effects. obtained by tunneling spectroscopy. This behavior is in strong contrast with the celebrated doping dependence of the pseudogap in hole-doped cuprates. 3. Local and macroscopic orders in electron-doped cuprates Electron-doped cuprates offer a unique laboratory for studying a variety of phenomena such as: superconductivity, quantum superconducting. It is not clear whether these criticality and density waves. While the undoped material is orders coexist and on what scale. We perform antiferromagnetic upon adding charge carriers the material becomes local and macroscopic tunneling study to clarify these issues that are eminent for understanding superconductivity in the cuprates.

References 1. M. Ben Shalom, C. W. Tai, Y. Lereah, E. Levy, A. Palevski, and Y. Dagan, Anisotropic magneto- transport effects at SrTiO3/LaAlO3 interfaces. arXiv:0902.2668 (2009 Submitted). 2. I. Diamant, R. L. Greene and Y. Dagan, single superconducting energy scale in electron-doped cuprates. (2009 Submitted) arXiv: 3. Y. Dagan and R. L. Greene, “Hole superconductivity in electron-doped cuprates”, Phys. Rev. B, 76, 024506 (2007). 4. Y. Dagan, R. Beck and R. L. Greene, “Dirty Superconductivity in the Electron-doped cuprate TEM image of 8 unit cell crystal of LaAlO3 grown on Pr2-xCexCuO4: Tunneling study”, Phys. Rev. Lett. 99, top of SrTiO3 crystal although these materials are nonmagnetic insulators the interface between them 147004 (2007). is superconducting and has anomalous magnetic 5. Y. Dagan, M. C. Barr, W. M. Fisher, T. Dhakal, A. properties. Insert: RHEED oscillations indicative of Biswas, R. Beck, and R. L. Greene, “Origin of the deposition of exactly 8 unit cells. anomalous low temperature upturn in resistivity in the electron-doped cuprates.” Phys. Rev. Lett., 94, Tel: (972)-3-6405554 057005 (2005). Fax: (972)-3-6422979 Email: [email protected] Personal Website: http://www2.tau.ac.il/Person/exact/physics/researcher. asp?id=adfjeecjh

15 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Guy Deutscher Physics Nanoscale Superconductivity

nanoscale coherence length is a key property of References high temperature superconductors. Point Contact 1. Andreev – Saint-James reflections: a probe of and STM spectroscopy can be used to reveal cuprate superconductors.G. Deutscher, Rev. Mod. Phys. 77, 110 (2005). the effect of nanoscale faceting on the order 2. Local and microscopic tunneling spectroscopy of parameter (1,2). These studies are fundamental YBaCuO films: evidence for a doping dependent is for the development of tunneling and Josephson or idxy component in the order parameter. devices.A Another kind of device being studied consists of a two 3. A.Sharoni, O. Millo, A. Kohen, Y. Daga, R. Beck, G. ferromagnetic nanowires connected to a superconducting base. Deutscher and G. Koren, Phys. Rev. B 65, 134526 They allow in principle to propagate the two electrons of a Cooper (2002). 4. Coupling superconducting – ferromagnetic point pair in physically separate channels, which can form the basis for contacts by Andreev reflections.G. Deutscher and producing entangled states for quantum computing (3). In these D. Feinberg Applied Physics Letters, 76, 81 (2000). devices, the distance between the two ferromagnetic wires must be 5. Insulator to superconductor transition I granular in the nanometer range. Another field of study is that of composite AluminumA.Gerber, A. Milner, G. Deutscher, M. metal/insulator mixtures, which behave as three dimensional arrays Karpowsky and A. Gladkich. Phys. Rev. Lett., 78, of weakly coupled metallic nanodots. Transport properties in these 4277 (1997). structures are extremely sensitive to the composition, they range from metallic to insulators, and can even be super-insulators when the metallic grains are superconducting due to the opening of the energy gap (4). They are model systems for the study of very low superfluid density condensates.

Tel: (972)-3-6408205 Fax: (972)-3-6422979 Email: [email protected] Personal Website: http://www2.tau.ac.il/Person/exact/physics/researcher. asp?id=acjljdegd

16 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Alexander Gerber Physics Nano-scale magnetism and Hall effect spintronics

1. Nanoscale magnetic systems a) Spin-dependent electronic transport in ultra-thin magnetic films and granular ferromagnet – normal metal and ferromagnet – insulator mixtures. b) giant magnetoresistance (GMR) and tunneling magnetoresistance (TMR). c) Extraordinary Hall effect in ultra-thin films and heterogeneous mixtures. d) Magnetic properties of single nanoscale magnetic clusters and their arrays. c) Development of new experimental techniques for nanoscale magnetometry, with a special emphasis on the extraordinary Hall effect technique. References d) development of new magnetic field sensors and memory devices 1. Milner, A. Gerber, M. Karpovsky and A. Gladkikh, based on the extraordinary Hall effect. Spin – Dependent Electronic Transport in Granular Ferromagnets.Phys. Rev. Lett. 76, 475-478 (1996). 2. Heterogeneous superconducting systems 2. Gerber, A. Milner, J. Tuaillon-Combes, M. Negrier, a) Localized superconductivity and insulator – superconductor O. Boisron, P. Melinon, and A. Perez. Probing Planar Arrays of Magnetic Nano-Particles by the transition in granular superconductors. Extraordinary Hall Effect. Jour. Magn. Magn. Matt. b) Superconducting fluctuations above and below the metal- 241, 340-344 (2002). insulator transition. 3. Gerber, A. Milner, M. Karpovsky, B. Lemke, H.-U. c) Proximity effect in superconductor – normal metal and Habermeier, J. Tuaillon-Combes, M. Negrier, O. superconductor – ferromagnet mixtures. Boisron, P. Melinon, and A. Perez Extraordinary Hall Effect in MagneticF ilms. Jour. Magn. Magn. Matt. 242, 90-97 (2002). This magnetic field response of an ultra-thin Ni film with lateral 4. Gerber, A. Milner, M. Karpovski, A. Tsukernik, dimensions 100 ´100 nm serves a prototype of the Hall effect – based A. Sulpice, J. Tuaillon-Combes, P. Melinon, and magnetic memory bit. A.Perez. Anomalous Magnetization of Nanoscale Ferromagnet/Normal-Metal Systems: Possible Evidence of the Electronic Spin Polarization. Phys. Rev. B 69, 134422 (2004).

Tel: (972)-3-6405405, (972)-3-6407023 Fax: (972)-3-6422979 Email: [email protected] Personal Website: http://www2.tau.ac.il/Person/exact/physics/researcher. asp?id=acimccdck

17 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Ron Lifshitz Physics

Nanomechanics & Quasicrystals References With recent advances in nanotechnology, state of the art 1. R. Lifshitz and M.C. Cross, “Nonlinear dynamics nanoelectromechanical systems (NEMS) can now be fabricated of nanomechanical resonators.’’ In Nonlinear Dynamics of Nanosystems, Eds. G. Radons, B. with lateral dimensions down to a few nanometers and combined Rumpf, and H.G. Schuster (Wiley-VCH, Weinheim, with self-assembled nanostructures such as carbon nanotubes, 2010) Ch. 8. achieving normal frequencies that exceed 1 GHz. As a consequence, 2. E. Kenig, B.A. Malomed, M.C. Cross, and R. Lifshitz, NEMS are no longer simply smaller and improved versions of MEMS “Intrinsic localized modes in parametrically-driven (microelectromechanical systems), but also offer great opportunities arrays of nonlinear resonators’,’ Phys. Rev. E 80 (2009) for the study of mechanics in physical regimes that previously had 046202. 3. K. Barkan, H. Diamant, and R. Lifshitz, “Stability of been inaccessible experimentally. The Lifshitz group—working in quasicrystals composed of soft isotropic particles,” contact with the groups of Michael Roukes and Michael Cross at (Preprint: arXiv:1005.5257). Caltech, the groups of Jan von Delft and Eva Weig at LMU-Munich, 4. B. Freedman, G. Bartal, M. Segev, R. Lifshitz, D.N. and the group of Eyal Buks at the Technion—is concerned with the Christodoulides, and J.W. Fleischer. “Observation of theoretical study of nanomechanical systems. These studies cover wave and defect dynamics in nonlinear photonic a broad range of topics, ranging from the mesoscopic physics of quasicrystals,” Nature 440 (2006) 1166. 5. Y. Bromberg, M.C. Cross, and R. Lifshitz, “Response phonons and their interaction with electrons, the classical nonlinear of discrete nonlinear systems with many degrees of dynamics of coupled nanomechanical systems, and the quantum freedom,” Phys. Rev. E 73 (2006) 016214. behavior of human-made nano-scale devices. 6. R. Lifshitz, A. Arie, and A. Bahabad, “Photonic The Lifshitz group is also involved in unrelated theoretical research quasicrystals for nonlinear optical frequency in the field of quasicrystals. These crystals—which are not periodic conversion,” Phys. Rev. Lett. 95 (2005) 133901. but nevertheless possess perfect long-range order—offer interesting 7. M.C. Cross, A. Zumdieck, R. Lifshitz, and J.L. Rogers, “Synchronization by nonlinear frequency pulling,” opportunities for studies at the nano-scale. Lifshitz is collaborating Phys. Rev. Lett. 93 (2004) 224101. with Haim Diamant of the School of Chemistry at TAU in studies of self- 8. M.C. Cross and R. Lifshitz, “Elastic wave transmission assembly of nano-scale molecules into soft quasicrystalline states; In a at an abrupt junction in a thin plate with application collaboration with the group of Ady Arie of the Faculty of Engineering to heat transport and vibrations in mesoscopic at TAU, Lifshitz is studying artificially fabricated nonlinear photonic systems,” Phys. Rev. B 64 (2001) 085324. quasicrystals for the purpose of optical frequency conversion; and 9. R. Lifshitz and M.L. Roukes, “Thermoelastic damping in micro- and nanomechanical systems,” Phys. Rev. in a collaboration with the group of Clemens Bechinger at the B 61 (2000) 5600-5609. University of Stuttgart, Lifshitz is studying the dynamics of optically- induced colloidal quasicrystals, used as model system to understand atomic dynamics on surfaces of solid-state quasicrystals.

Tel: (972)-3-6405145 Fax: (972)-3-6406953 Email: [email protected] Personal Website: http://www.tau.ac.il/~ronlif/

18 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Alexander Palevski Physics Quantum Transport in Nanostructures

1. One-dimensional quantum wires 4. Mesoscopic phenomena in SrTiO3/ We investigate electronic transport properties of V-grooved quantum LaAlO3 interfaces wires at low temperatures. In particular we focus our research on We investigate low temperature properties of weakly disordered quasi-ballistic wires exhibiting Luttinger liquid recently discovered two-dimensional electron behavior. We also investigate dephasing effect in Aharonov Bohm gas formed at the interface of two wide gap rings and the temperature dependence of long disordered quantum insulators SrTiO3/LaAlO3. The analysis of a variety wires exhibiting activated behavior at very low temperatures. of the observed mesoscopic effect allowed us to elucidate the mechanism of the dephasing and 2. Superconductor proximity effect in ferromagnetic to determine the dephasing rate and spin orbit junctions and bilayers. scattering rate. This research is performed in We investigate the direct and inverse proximity effect in ferromagnet collaboration with the group of Prof. Y. Dagan. superconductor junctions and bilayers. In transport experiments we observe oscillations of the critical current when the thickness of the References ferromagnetic layers is varied. The theory based on the formation 1. M. Ben Shalom, M. Sachs, D. Rakhmilevitch, A. of the π-junction in Josephson coupled structures containing Palevski, and Y. Dagan Tuning Spin-Orbit Coupling and Superconductivity at the SrTiO3/LaAlO3 ferromagnetic layers was verified. Interface: A Magnetotransport Study Phys. Rev. Our group in collaboration with the group from Stanford University Lett. 104, 126802 (2010). was the first to observe the magnetization induced in the 2. Jing Xia, V. Shelukhin, M. Karpovski, A. Kapitulnik, superconductor due to so-called spin screening effect. and A. Palevski Inverse Proximity Effect in Superconductor-Ferromagnet Bilayer Structures 3. Quantum Phase Transitions in ultrasmall Phys. Rev. Lett. 102, 087004 (2009). 3. E. Levy, A. Tsukernik, M. Karpovski, A. Palevski, superconductor cylinders B. Dwir, E. Pelucchi, A. Rudra, E. Kapon, Y. Oreg Our experimental groups in collaboration with the colleagues in WIS Luttinger liquid behavior in weakly disordered (Dr. H. Shtrikman and Prof. M. Heiblum) developed a new technology quantum wires, Phys. Rev. Lett. 97, 196802 (2006). to fabricate superconducting nanocylinders with the diameters as 4. Y. Blum, A. Tsukernik, M. Karpovski and A. Palevski, small as 50 nm. The quantum phase transition was recently observed Oscillations of the critical current in Nb-Cu-Ni- by our group in these structures Cu-Nb junctions, Phys. Rev. Lett.89, 187004-(1-4), (2002).

The typical nanostructures fabricated in our laboratory using the the nanofabrication facilities in the TAU Nano center: 1D quantum embedded in Aharonov Bohm interferometer (left) and Al nanocylinder with contacts (right).

Tel: (972)-3-6409456, (972)-3-6408193 Fax : (972)-3-6422979 Email: [email protected] Personal Website: http://www.tau.ac.il/~apalev/

19 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Ori Cheshnovsky Chemistry Nanoscale Optics using Raman Spectroscopy. Transport properties of Nanoparticles with STM

1. Nanoscale optics using Raman Spectroscopy An important consequence of electron-vibration interaction in molecular-junction-transport is heat generation, i.e., energy transfer to the underlying nuclear motions. In balance with heat dissipation, this has important implications on the issue of junction stability. Advancement in molecular electronics necessitates thorough understanding of these processes in molecular junctions. Such an understanding depends on the ability to monitor non-equilibrium occupancy of vibrational levels at current carrying junctions as a function of bias. We realize such a capability by utilizing the Stokes (S) and AntiStokes (AS) components of Surface Enhanced Raman Spectroscopy (SERS) fluctuations (0.5-2.2 eV) in Bismuth nanoparticles to probe the effective temperature of current carrying junctions. In which are temperature dependent. The high our specific junction, all Raman active modes show similar heating anisotropic conductance of Bi, facilitates the as a function of bias at room temperature, suggesting fast internal observation of these phenomena. At 80K, upon vibrational relaxation processes. These results demonstrate the power freezing of structural fluctuations, the anisotropy of direct spectroscopic probing of heating and cooling processes in of the BNPs is revealed as variations in band gap nanostructures. maps of individual particles. Similar methodology is being applied to other nanometric objects Nanoparticles bear the potential of exceeding such as grapheme and carbon nanotubes. the efficiency of bulk materials in converting We use our infrastructure in Raman spectroscopy in the service heat to electricity. With this challenge in mind, of challenging projects in other disciplines. We monitor micro in another set of experiments the group looks calcification in tissues (Medicine) develop methods to improve the for the thermoelectric properties of individual reading of ancient Orthicons (Archeology) or to monitor the quality of nanoparticles. interfaces between Carbon Nanotubes and neurons (Neuroscience). References 2. Transport properties of Nanoparticles and objects 1. Z. Ioffe T. Shamai, A. Ophir, G. Noy, I. Yutsis, K. Kfir, The effect of size and composition on the electronic, optical and O. Cheshnovsky, Y. Selzer. . Detection of Heating in Current Carrying Molecular Junctions by Raman conductance properties of nanoparticles is a subject of active Scattering. Nature Nanotechnology, Vol. 3, 2008, research. In contrast, the effect of dynamical structural changes and (pp. 727-732). anisotropy in nanoparticles on these attributes is much less known. 2. ZR Abrams, Z Ioffe, A Tsukernik, O Cheshnovsky, Y In many cases, when the net gain in surface energy, outweighs the Hanein. A complete scheme for creating predefined strain internal energy cost, nanoparticles fluctuate between different networks of individual carbon nanotubes. Nano crystal structures. Letters, Vol. 7, 2007, (pp. 2666-2671). 3. E. Flaxer, O. Sneh and O. Cheshnovsky. Molecular In our group we explore the resulting fluctuations in the electronic Light Emission Induced by Inelastic Electron band structure and conductance by using specially tailored scanning Tunneling. Science, Vol. 262, 1993, (pp 2012-2014). tunneling microscope (STM). Indeed we observe very high band gap

Tel: (972)-3-6405617, (972)-3-6408325, (972)-3-6408628 Fax: (972)-3-6405612 Email: [email protected] Personal Website: http://www2.tau.ac.il/Person/exact/chemistry/ researcher.asp?id=abhjlefek

20 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Haim Diamant Chemistry Theory of Complex Fluids

omplex fluids (or soft matter) is a general term References referring to a broad class of materials, which are 1. D. Frydel and H. Diamant, Long-range dynamic neither molecular liquids nor atomic or molecular correlations in confined suspensions, Phys. Rev. Lett. 104, 248302 (2010). Featured in Physical crystals. Examples include surfactant solutions, Review Focus 25, 23 (2010). polymer solutions, interfacial monolayers, 1. H. Diamant and O. Agam, Localized Rayleigh membranes, suspensions, and liquid crystals. The instability in evaporation fronts, Phys. Rev. Lett. 104, richC phase behavior and dynamic response of such materials stem 047801 (2010) from the existence of inner structures on an intermediate, nanometer- 1. N. Oppenheimer and H. Diamant. Correlated to-micron scale, between the molecular and the macroscopic scales diffusion of membrane proteins and their effect on membrane viscosity. Biophys. J. 96, 3041 (2009). (e.g., micelles, colloid particles, polymeric structures). The theoretical 1. H. Diamant. Hydrodynamic interaction in confined challenge is to account for the emergence of these structures, their geometries. J. Phys. Soc. Jpn. 78, 041002 (2009). effect on material properties, and their various instabilities. 1. E. Haleva and H. Diamant. Critical swelling of In the past several years we have been focusing on the dynamics particle-encapsulating vesicles. Phys. Rev. Lett. 101, and flow properties of complex fluids, and on various effects caused 078104 (2008). by micro- and nano-scale confinement. Recently studied systems 1. R. Hadgiivanova and H. Diamant. Premicellar aggregation of amphiphilic molecules. J. Phys. have included: (a) colloid suspensions in narrow channels; (b) Chem. B 111, 8854 (2007). heterogeneous fluid membranes; (c) particle-encapsulating vesicles; (d) curved liquid domains; (e) compressed surfactant monolayers; (f) surfactant aggregates (micelles); (g) liquid quasi-crystals.

Tel: (972)-3-6406967 Fax: (972)-3-6409293 Email: [email protected] Personal Website: http://www.tau.ac.il/~hdiamant

21 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Diana Golodnitsky Chemistry Nano Materials and Thin Films for Electrochemical Energy Storage and Conversion

ver-shrinking applications such as smart cards, miniature remote sensors, RFID tags, and medical implants are Fig.1 Schematic creating an ever-growing need for smaller and thinner presentation of the 3D-thin batteries to power the devices. Short ion diffusion path film microbattery on enables high-power capability of thin-film batteries. perforated substrate One of the key drawbacks of these batteries is limited scalabilityE for applications that demand high areal energy density. References The effective surface area of an electrode can be increased without 1. L. Gitelman, A. Averbuch, M. Nathan, Z. Schuss, increasing its physical size by depositing thin films on the high- D. Golodnitsky Stochastic Model of Lithium Ion aspect-ratio 3D-perforated substrates and using materials with Conduction in Poly(ethylene Oxide), Journal of Applied Physics (2010) JAP: MS #JR09-5752, in press. very fine particle size. This can boost both: the surface area of the 2. H. Mazor, D. Golodnitsky and E. Peled High-Power electrodes and their volume by orders of magnitude, enabling high Copper Sulfide Cathodes for Thin-film Microbatteries” current rates to be achieved in conjunction with high energy values Electrochemical and Solid-State Letters, 12, (2009) 12 per battery footprint. Our research is focused on the development A232-A235. of simple and inexpensive electrochemical synthesis of nanoparticle 3. Golodnitsky D. Electrolytes: Single Lithium Ion Conducting Polymers. In: Juergen Garche, Chris high-performance battery materials for coating of irregular surfaces, Dyer, Patrick Moseley, Zempachi Ogumi, David such as in three-dimensional thin-film microbatteries, which break Rand and Bruno Scrosati, editors. Encyclopedia of the classical battery energy-power compromise. Electrochemical Power Sources, Vol 5. Amsterdam: Enhancing the lithium-ion conduction of polymer electrolytes for all- Elsevier; 2009. pp. 112–128. solid-state lithium and lithium-ion batteries is by now an old theme, 4. S. Menkin, D. Golodnitsky, E. Peled Artificial solid- and there has been much research done over the years. However, the electrolyte interphase (SEI) for improved cycleability and safety of lithium–ion cells for EV applications, problem of obtaining polymer electrolytes (PE) with sufficiently high Electrochemistry Communications 11 (2009) 1789– conductivity (>1mS/cm) still persists, and is still relevant from both 1791. scientific and technological points of view. We recently presented a 5. T. Ripenbein, D. Golodnitsky, M. Nathan, E. Peled, procedure for orienting the polyethylene-oxide (PEO) helices in the Porous interlaced structures for 3D-microbatteries, perpendicular direction by casting the PEs under a magnetic field, Electrochimica Acta doi:10.1016/j. electacta.2009.01.057. which enhances the ionic conductivity of the plane perpendicular to 6. V. Yufit,D . Golodnitsky, L. Burstein, M. Nathan, E. the film by about one order of magnitude. The magnetic-field effect Peled. XPS and TOFSIMS study of electrodeposited is even more pronounced in polymer electrolytes with incorporated molybdenum oxysulfide cathodes for lithium and diamagnetic and ferromagnetic nano-fillers. Our current efforts address lithium-ion microbatteries, J Solid State Electrochem the original research approach for the development of single-molecule, (2008) 12, 273–285. orthogonally-oriented ion-conducting polymer channels (helices) 7. D. Golodnitsky, R. Kovarsky, H. Mazor, Yu. Rosenberg, I. Lapides, E. Peled, W. Wieczorek, A. Plewa, M. Siekierski, by the attachment of nanosize core-shell magnetic particles to the M.Kalita, L. Settimi, B. Scrosati, L. G. Scanlon Host- end groups of the polymer helix, followed by casting of a polymer Guest Interactions in Single-Lithium-Ion Polymer electrolyte film under a gradient magnetic field. Conductor, Journal of The Electrochemical Society, 154, (2007) 6, A547-A553. Current Main Projects (together with Prof. E. Peled): 8. D. Golodnitsky, M. Nathan, V. Yufit, E. Strauss, T. Ripenbein, I. Shechtman, S. Menkin, L. Burstein, A. n Superior power and energy density Li-on microbattery Gladkich E. Peled. Progress in Three-Dimensional n Novel High-Performance, Low-Cost and Safe Anode Materials for (3D) Li-Ion Microbatteries, Solid State Ionics, 177, Advanced Energy Storage (2006) 26-32, 2811-2819. n Single ion conducting channels 9. E. Livshits, R. Kovarsky, D. Golodnitsky, E. Peled, New insights into structural and electrochemical properties of anisotropic polymer electrolytes, Tel: (972)-3-6407820 Electrochimica Acta, 50, 2005, 3805. 10. E. Peled and D. Golodnitsky SEI on lithium, graphite, Fax: (972)-3-6422649 disordered carbons and tin-based alloys, in : SOLID- Email: [email protected] ELECTROLYTE INTERPHASE (Eds., P. Balbuena, Y. Personal Website: http://chemistry.tau.ac.il/ Wang) Imperial College Press and World Scientific Publishers, 2004, 1-70.

22 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Michael Gozin Chemistry Formation and Characterization of Stable Protein Complexes with Fullerene and its Derivatives

ver the past decade, research in the field of References fullerene chemistry has greatly increased 1. “Fabrication and Properties of Nanodevices Based due to a wide range of potential applications on Ferrocene-containing Molecules” Rosenberg, N.; Caster, A.; Gozin M.; Richter S., submitted. proposed for fullerene-based materials. These 2. “Interaction of [C60]-Fullerene and Carboxyfullerene applications span non-linear optical properties, with Proteins: Docking and Binding Site Alignment” superconductivity and the biological activity Benyamini, H.; Shulman-Peleg, A.; Wolfson, H. J.; and,O as industrial scale of fullerenes production approaches multi- Belgorodsky, B.; Fadeev, L.; Gozin, M., submitted. ton level per year, the human and environmental exposure to the 3. “Formation and Characterization of Stable Human carbonaceous nanomaterials will be undoubtedly increased. While Serum Albumin-Tris-malonic Acid [C60]-Fullerene Complex” Belgorodsky, B.; Fadeev, L.; Ittah, V.; most of the current research is focused on examination of tissue- and Benyamini, H.; Zelner, S.; Huppert, D.; Kotlyar, A. B.; cell-level nanomaterials influence, interaction on a molecular level, Gozin, M., Bioconjugate Chem. 2005, 16(5), 1058- with native proteins, remains mostly unexplored. 1062. As current research related to the toxicological and environmental 4. “Construction of Dithiol-based Nanostructures by a effects of carbonaceous nanomaterials is still in its infancy, there is Layer-exchange Process” Meshulam, G.; Rosenberg, a rapidly growing public concern regarding the potential impact N.; Caster, A.; Burstein, L.; Gozin M.; Richter S., Small 2005, 1(8-9), 848-851. of these nanomaterials on human health and on environment. We 5. “Synthesis and Water Solubility of Adamantyl-OEG- believe that our research is very important as it lays a foundation fullerene Hybrids” A. Bar-Shir, Y. Engel, M. Gozin, for better understanding of carbonaceous materials bio-delivery J.Org. Chem., 2005, 70 (7), 2660-2666. systems and potential effects of these nanomaterials on environment and on human health. In addition we wish to understand how these compounds are interacting on molecular level with various native proteins and other biomolecules. Not less fascinating are the potential applications of these hybrid materials as crucial components in the future nano-bioelectronic devices, nano-sensors and artificial organs, functioning as the biocompatible interface between biological and electronic systems.

Figure 1. (left): Proposed by docking algorithm location of the [C60]-fullerene ligand (red) inside BSA protein, relative to

position of the Trp214 residue (blue). (right): MALDI-TOF MS spectrume of purified BSA-[C60]-fullerene complex.

Tel: (972)-3-6405878 Fax: (972)-3-6405879 Email: [email protected] Personal Website: http://www.tau.ac.il/chemistry/gozin/

23 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Oded Hod Chemistry

anoscience and nanotechnology open a unique opportunity for the application of highly accurate theories to realistic material science problems. The research in my group focuses on the theoretical study of the mechanical, electronic, magnetic, and transport properties of systems at the nanoscale.N Using first-principles computational methods, we aim to characterize both ground state and dynamical properties of such systems. A combination of codes developed within our group along with commercial computational chemistry packages, operating on a highly parallelizable high-performance computer cluster, allows us to address the properties and functionality of a variety References of systems ranging from carefully tailored molecular structures up 1. D. Rai, O. Hod, and A. Nitzan, “Circular Currents in to bulk systems. On top of basic science questions, the design of Molecular Wires”, submitted (2010). technologically applicable nanoscale material properties for future 2. N. Marom, J. Bernstein, J. Garel, A. Tkatchenko, E. Joselevich, L. Kronik, and O. Hod, “Stacking and applications in fields such as nano-electronics, nano-spintronics, Registry Effects in Layered Materials: The Case of accurate and sensitive chemical sensing, and nano-mechanical Hexagonal Boron Nitride”, Phys. Rev. Lett., In press devices, is being pursued. (2010). 3. S. Hod and O. Hod, “Analytic treatment of the black- hole bomb”, Phys. Rev. D (Rapid Communication) 81, 061502(R) (2010). 4. O. Hod and G. E. Scuseria, “Electromechanical properties of suspended Graphene Nanoribbons”, Nano Letters 9, 2619-2622 (2009). 5. O. Hod and G. E. Scuseria, “Half-metallic zigzag carbon nanotube dots”, ACS Nano 2, 2243-2249 (2008). 6. O. Hod, J. E. Peralta, and G. E. Scuseria, “Edge effects in finite elongated graphene nanoribbons”, Phys. Rev. B 76, 233401 (2007). 7. O. Hod, V. Barone, J. E. Peralta, and G. E. Scuseria, “Enhanced Half-Metallicity in Edge-Oxidized Zigzag Graphene Nanoribbons”, Nano Letters 7, 2295-2299 (2007). 8. V. Barone, O. Hod, and G. E. Scuseria, “Electronic Structure and Stability of Semiconducting Graphene Nanoribbons”, Nano Letters 6, 2748-2754 (2006). 9. O. Hod, J. E. Peralta, and G. E. Scuseria, “First- principles electronic transport calculations in finite elongated systems: A divide and conquer approach”, J. Chem. Phys. 125, 114704 (2006). 10. O. Hod, E. Rabani, and R. Baer, “Magneto-resistance Tel: (972)-3-6405850 of nanoscale molecular devices”, Acc. Chem. Res. 39, 109-117 (2006). Fax: (972)-3-6405850 11. O. Hod, R. Baer, and E. Rabani, “Inelastic effects in Email: [email protected] Aharonov-Bohm molecular interferometers”, Phys. Personal Website: http://www.tau.ac.il/~odedhod/ Rev. Lett. 97, 266803 (2006).

24 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Joseph (Yossi) Klafter Chemistry Biological Processes on the Level of a Single Molecule

ingle molecule techniques offer a unique tool to study References in real-time the dynamical behaviour of individual 1. O. Flomenbom, K. Velonia, D. Loos, S. Masuo, M. molecules and provide the possibility to construct Cotlet, Y. Engelborghs, Hofkens, A.E. Rowan, R.J.M. Nolte, F.C. de Schryver and J. KlafterTemporal distributions from individual events rather than from Stretched Exponential Decay and Correlations in a signal stemming from an ensemble of molecules. the Catalytic behavior of Fluctuating Individual In biological systems, known for their complexity, Lipase MoleculesProc. Nat. Acad. Sci. (USA), 102, theseS techniques make it possible to gain insights into the detailed 2368-2372 (2005). spectrum of molecular conformational changes and activities. In 2. K. Velonia, O. Flomenbom, D. Loos, S. Masuo, M. collaboration with experimental groups in Europe we observed a Cotlet, Y. Engelborghs, Hofkens, A.E. Rowan, J. Klafter, R.J. M. Nolte and F.C. de SchryverSingle Enzyme single enzyme reaction for extended periods of time (hours), using Kinetics of CALB Catalyzed HydrolysisAngewandte confocal fluorescence microscopy. When adding a profluorescent Chemie 44, 560-564 (2005). Front cover substrate the monitored enzymatic activity appeared as a trajectory 3. O. Flomenbom, J. Klafter and A. SzaboWhat of on-state and off-state events. The waiting time probability density Can One Learn from Two-State Single Molecule function (PDF) of the off-state and the state-correlation function fit TrajectoriesBiophys. J. 88, 3780-3783 (2005). stretched exponentials, independent of the substrate concentration in a certain range. In addition, clusters of fast events were detected in the ordered off waiting times trajectory, indicating correlations in the activity. Our findings imply that a fluctuating enzyme model, which involves a spectrum of enzymatic conformations that interconvert on the timescale of the catalytic activity, best describes the observed enzymatic activity. The “text book” Michaelis–Menten scheme has been modified accordingly.

Tel: (972)-3-6408254 Fax: (972)-3-6406466 Email: [email protected] Personal Website: http://www.tau.ac.il/~klafter1/

25 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Gil Markovich Chemistry Synthesis and Physical Studies of Colloidal Nanostructures and their Assemblies he group uses various colloidal chemistry methods to prepare oxide nanocrystals, mostly magnetic, and study their magnetic and magneto-resistive properties, as well as various types of metal nanostructures. The group uses spin polarized transport in magnetite nanocrystal arrays to probe the Tmagnetization dynamics in such a strongly interacting dipolar system close to the magnetization freezing transition. This is done both on a single particle level in a variable temperature scanning tunneling microscope and in nanoscale solid state devices, in collaboration with the Majetich group from Carnegie Mellon University. Another aspect of the work on magnetism in nanocrystals is a search for defect induced ferromagnetism, which was theoretically predicted for diamagnetic oxides like magnesium oxide. The colloidal syntheses, done at relatively low temperatures are good candidates for trapping high defect concentrations in metal oxide nanocrystals. References

A study on nanoscale ferroelectricity in BaTiO3 nanocubes aims 1. E. Tirosh, B. Tsukerman, N. Taub, S. A. Majetich, G. at achieving better understanding of the electric polarization in Markovich, “Magnetoresistive telegraph noise in nano-ferroelectrics, the importance of the surface and magnitude Langmuir-Blodgett films of colloidal magnetite of electric fields within the nanocrystals. The major technique used nanocrystals probed by scanning tunneling for this study is electron holography, in collaboration with the Lichte microscopy”, Phys. Rev. B 80, 224427 (2009). 2. D. Azulai, T. Belenkova, H. Gilon, Z. Barkay, G. group from Dresden University. Markovich, “Transparent metal nanowire thin films In another project, a wet self-assembly chemistry technique is used prepared in mesostructured templates”, Nano Lett. for the growth of ultrathin metallic nanowire films on surfaces. These 9, 4246-4249 (2009). films act as highly transparent and conductive electrodes and will be 3. I. Lieberman, G. Shemer, T. Fried, E. M. Kosower, explored for application in photovoltaic cells. G. Markovich, “Plasmon Resonance Enhanced The combination of chirality and nanostructure is being explored Absorption and Circular Dichroism” Angew. Chem. Int. Ed. 47, 4855-4857 (2008). in various directions: 1. Induction of strong chirality in metal 4. E. Tirosh, G. Markovich, “Control of Defects and nanostructures by various chiral templates, such as DNA, in Magnetic Properties in Colloidal HfO2 Nanorods”, collaboration with the Kotlyar group from the Biochemistry Adv. Mater. 19, 2608 (2007). department at TAU. 2. Enhancement of circular dichroism in chiral 5. G. Shemer, O. Krichevski, G. Markovich, T. Molotsky, I. (bio) molecules using plasmonic nanostructures. Lubitz, A. B. Kotlyar, “Chirality of Silver Nanoparticles Synthesized on DNA”, J. Am. Chem Soc. 128, 11006 (2006). 6. P. Poddar, T. Fried and G. Markovich,, “First-Order Metal-Insulator Transition and Spin-Polarized Tunneling in Fe3O4 Nanocrystals”, Phys. Rev. B 65, 172405 (2002). 7. T. Fried, G. Shemer, and G. Markovich, “Ordered Two-Dimensional Arrays of Ferrite Nanoparticles”, Adv. Mater. 13, 1158-61 (2001). Tel: (972)-3-6406985 Fax: (972)-3-6405911 Email: [email protected] Personal Website: http://www.tau.ac.il/~gilgroup/

26 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Abraham Nitzan Chemistry Theoretical and Computations Chemical Dynamics

y research effort in the past few years has focused on particular types of interfacial systems and processes – those encountered in the evolving field of Molecular Electronics. The possibility that molecules and small molecular assemblies can replace conventional Mconductors and semiconductors in nano-scale electronic devices has become a subject of intense discussion. The new fundamental issues associated with such systems – the electronic structure, the charge transfer properties, energy transfer and relaxation and the capacitive properties (to name just a few), of molecules connected References to conducting leads, present new theoretical and experimental 1. A. Nitzan and Mark Ratner, Electron transport in challenges. Recent studies in our group aim at developing theoretical molecular wire functions: Models and Mechanisms Science, 300, 1384-1389 (2003). and numerical tools to study electron transmission through such 2. D. Segal, A. Nitzan and P. Hänggi, Thermal interfaces. A recent series of papers that focus on the electron conductance through molecular wiresJ. Chem. transmission properties of water, arguably the most important Phys. 119, 6840-6855 (2003). electron transmitting medium, has demonstrated a new resonance 3. M. Galperin and A. Nitzan, Current-Induced Light effect that explains the observed high efficiency of electron Emission and Light-Induced Current in Molecular- transmission through this medium. More recent work has focused on Tunneling Junctions Phys. Rev. Letters 95, 206802 (2005). analyzing the crucial issue of thermal relaxation and heating effects as well as heat conduction in molecular conductors that bear on the question of thermal stability of such systems, and on developing a theoretical framework for understanding inelastic tunneling features and phonon induced non-linear response of molecular conduction junctions. Our current studies aim at analyzing the possibility to probe and control of molecular junctions by light.

Tel: (972)-3-6408904 Fax: (972)-3-6423765 Email: [email protected] Personal Website: http://atto.tau.ac.il/~nitzan/nitzan.html

27 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Fernando Patolsky Chemistry

anoscale science holds extraordinary promises to References impact crucial issues of our era, such as improved 1. F. Patolsky, G. F. Zheng, O. Hayden, M. Lakadamyali, medical diagnosis and treatment, renewable X. W. Zhuang and C. M. Lieber.Electrical Detection of Single Viruses.PNAS, 101, 14017-14022 (2004). energy, more efficient information technology, and 2. F. Patolsky and C. M. Lieber. Nanowire Nanosensors. environmental protection. My research interests Materials Today, 8, 20-28 (2005). are concerned with ‘multifunctional’ systems 3. G. Zheng, F. Patolsky, Y. Cui, W. U. Wang, C. M. Lieber. ofN reduced dimensionality, and their applications for addressing Multiplexed, electrical detection of cancer markers important chemical, biochemical, physical and technological using nanowire sensor arrays. Nat. Biotechnol., 23, problems. Specifically, the research will focus on the synthesis, 1294-1301 (2005). 4. F. Patolsky, G. Zheng and C. M. Lieber. Nanowire- characterization of the fundamental physical and chemical properties, based transistor sensors Anal. Chem., 78, 65-76 and applications of integrated nanostructured materials that (2006). combine tuneable optical, electrical and magnetic properties, as well 5. F. Patolsky and C. M. Lieber. Nanosensors and Future as the study and understanding of the mutual interactions between MedicineNanomedicine, 1, 51-65 (2006). light, electricity, and magnetism at the nanometer scale. A major goal 6. F. Patolsky, G. Zheng and C. M. Lieber. Nanosensors of this research is to address the “structure-function” relationship, as and Future MedicineNature Protocols, accepted for publication, in press (2006). one of the most basic and central questions in materials chemistry. 7. F. Patolsky, B. P. Timko, G. H. Yu, Y. Fang, G. Zheng, A. A second and more central aspect of the research concentrates on B. Greytak and C. M. Lieber.Detection, stimulation, the application of nanowire-based electronic/optical devices in the and inhibition of neuronal signals with high- biological and chemical detection area, with the aim to explore and density nanowire transistor arrays.Science, 313, exploit the nano-scale potential advantages in answering ‘open 1100-1104 (2006). questions’ in biology.

Tel: (972)-3-6408327 Fax: (972)-3-6409293 Email: [email protected] Personal Website: http://www.tau.ac.il/chemistry/patolsky/

28 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Emanuel Peled Chemistry Nano Materials and Thin Films for Electrochemical Energy Storage and Conversion

n our group, four projects are related to nano science and References technology. We have developed a nano-porous proton- 1. E. Peled, V. Livshits and T. Duvdevani, High Power conducting membrane with a typical pore size of 1.5nm. Direct Ethylene Glycol fuel Cell (DEGFC) Based on Nanoporous Proton Conducting Membrane (NP- On the basis of this membrane we have developed a direct PCM). JPS 106, 245-248 (2002). methanol fuel cell and a direct ethylene glycol fuel cell which, 2. E. Livshits, R. Kovarsky, D. Golodnitsky, E. Peled, at time of writing, have demonstrated the highest recorded New insights into structural and electrochemical Ipower densities (0.5 and 0.32W/cm2 respectively). We are studying properties of anisotropic polymer electrolytes, synthesis routes for highly active nano-size platinum-alloy catalysts Electrochimica Acta, 50 (19): 3805-3814 JUN 30 (2-5nm in size) for use in hydrogen and in alcohol fuel cells (in 2005. 3. D. Golodnitsky, V. Yufit, M. Nathan, I. Shechtman, T. collaboration with Prof. Golodnitsky). We have developed and Ripenbein, E. Strauss, S. Menkin, E. Peled. Advanced demonstrated the first on-chip three-dimensional thin-film lithium- Materials for the 3D-Microbattery, J. Power Sources, ion microbattery (collaboration with Prof. Golodnitsky and with Prof. 2005, accepted. Nathan of the Faculty of Engineering). In collaboration with Prof. 4. E. Peled, V. Livshits, M. Rakhman, A. Aharon, T. Golodnitsky, Prof. Scrosati (Rome) and with Prof. Wieczorek (Warsaw) Duvdevani, M. Philosoph and T. Feiglin; 0.5W/cm2 we have developed and characterized a single-ion lithium polymer- Direct Methanol-Air Fuel Cell ESL 7 507- 510 (2004). 5. W. Wieczorek, R. Kovarsky, D. Golodnitsky, E. Peled, electrolyte conductor using anion nano traps. L.G. Scanlon, G.B. Appetecchi and B. Scrosati, Single- We were the first to develop a procedure for orienting the helices of Lithium Ion Highly Conductive Solid Polymer poly ethylene oxide (PEO) in the orthogonal direction by casting the Electrolytes J. Electrochem. Soc, 151, (2004) 10, film under magnetic field (MF), the result of which is a one-order- A1762-A1766. of-magnitude increase in polymer electrolyte (PE) conductivity and a similar decrease in PE/lithium electrode interfacial resistance (in collaboration with Prof. Golodnitsky).

Tel: (972)-3-6408438, (972)-3-6414126 Fax: (972)-3-6409293 Email: [email protected] Personal Website: http://www.tau.ac.il/chemistry/peled/

29 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Moshe Portnoy Chemistry Design and investigation of nanoscale dendritic composite materials for catalysis and biomedical applications

endrimers are branched, highly ordered macromolecules that are assembled in a modular, iterative fashion from polyfunctional building blocks. These macromolecules are not only aesthetically appealing, but offer chemists three- dimensional structures of nanometer-range size Dwith a variety of interesting architecture-dictated properties for a wide spectrum of applications. The modular mode of assembly and highly ordered nature of dendrimers make them especially suitable for the building of nanoscale devices. During the past few years, my group actively pursued the preparation of dendritic molecules on insoluble support as a platform for the generation of highly active and selective heterogeneous catalysts. We developed an efficient synthesis of new poly(arylbenzylether) dendrons on solid polymer support, functionalized their termini with catalytic units and explored their properties. An unprecedented positive dendritic effect on activity and chemoselectivity of a number of organometallic effects as well as improvement and perfection catalysts immobilized on such dendronized supports was revealed in of such systems for potential use. Recently, we a series of studies. Another group of catalysts that were immobilized began exploring dendrimers as platforms for on the dendronized supports are organocatalysts, small metal-free diagnostic agents for molecular imaging. moieties capable of promoting selectively organic transformations of considerable complexity. For instance, we demonstrated a References remarkable improvement in the efficiency and enantioselectivity of 1. K. Goren and M. Portnoy, Supported polymer-supported proline in the aldol and Mannich reactions upon N-alkylimidazole-decorated dendrons as dendritic spacer introduction. A tremendous increase in the catalyst heterogeneous catalysts for the Baylis-Hillman activity upon dendronization of the support was also demonstrated reaction, Chem. Commun. 2010, 46, 1965-1967. for polymer-bound N-alkylimidazole catalysts in the Baylis-Hillman 2. T. Kehat, K. Goren and M. Portnoy, Dendrons on reaction. Our research in the field of supported dendritic catalysis insoluble supports: synthesis and applications, New J. Chem. 31, 2007, 1218-1242. is aimed at both understanding the rationale behind the dendritic 3. T. Kehat and M. Portnoy, Polymer-supported proline-decorated dendrons: dendritic effect in asymmetric aldol reaction, Chem. Commun. 2007, 2823-2825. 4. A. Dahan and M. Portnoy, Pd catalysis on dendronized solid support: generation effects and the influence of the backbone structure, J. Am. Chem. Soc. 129, 2007, 5860-5869. 5. A. Dahan and M. Portnoy, Synthesis of poly(aryl- benzyl ether) dendrimers on solid support. Macromolecules 36, 2003, 1034-1038. 6. A. Dahan and M. Portnoy, A remarkable dendritic effect in the polymer-supported catalysis of the Tel: (972)-3-6406517, (972)-3-6406518 Heck arylation of olefins,Org. Lett. 5, 2003, 1197- 1200. Fax: (972)-3-6409293 7. A. Dahan, A. Weissberg and M. Portnoy, Preparation Email: [email protected] of novel polythioether dendrons on solid support, Personal Website: http://www.tau.ac.il/chemistry/portnoy/ Chem. Commun. 2003, 1206-1207.

30 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Eran Rabani Chemistry

Doping nanocrystals We have developed a method to dope semiconductor nanocrystals with metal impurities providing control of the band gap and Fermi energy. Two theoretical models for heavily doped nanocrystals have been proposed. These include a tight-binding model where impurities are localized due to the quantum confinement effect and an atomistic treatment of lattice disorder induced by the impurities leading to confined band tailing.

Multiexciton Generation at the Nanoscale Carrier multiplication by multiexction generation (MEG) is a process Transport in Correlated Systems where several charge carriers are generated upon the absorption The description of dynamics and transport in of a single photon in semiconductors. This process is of great nanoscale devices is fundamentally challenging. technological ramifications for solar cells and other light harvesting We have developed an exact real-time path technologies. We have developed a unified approach based on integral Monte Carlo method to fully describe Green’s function formalism to the treatment of MEG in nanocrystals. transport and dynamics in such systems where We showed that the description of multiexciton generation in simultaneous effects related to electron-electron, nanocrystals can be described as incoherent process and discussed electron-phonon and electron-photon scattering the scaling of multiexciton generation with respect to the photon are present and important. energy and nanocrystal size. Illustrations include three prototype systems: CdSe, InAs and silicon quantum dots. References 1. E. Rabani, D.R. Reichman, P.L. Geissler, and Self-Assembly L.E. Brus “Drying-Mediated Self-Assembly of Nanoparticles”, Nature 426, 271 (2003). The possibility of fabricating and controlling spontaneously organized 2. L. Mühlbacher and E. Rabani, “Real-Time Path nanoscale devices is one of the challenges of nanotechnology. We Integral Approach to Nonequilibrium Many-Body have been involved in the study of several aspects of self-assembly, Quantum Systems”, Phys. Rev. Lett. 100, 176403 including the development of a lattice-gas model to study the (2008). kinetics of drying-mediated self-assembly. Our approach puts down 3. E. Rabani and R. Baer, “Distribution of Carrier the theoretical foundation of dynamical assembly of nanoparticles. Multiplication Rates in CdSe and InAs Nanocrystals”, Nano. Lett. 8, 4488 (2008). It accounts for all experimentally observed spatial and temporal 4. D. Mocatta, G. Cohen, J. Schattner, O. patterns, and also predicts network structures that have yet to be Millo, E. Rabani and U. Banin, “Heavily Doped explored. We showed how different choices of solvent, nanoparticle Semiconductor Nanocrystal Quantum size (and identity) and thermodynamic state give rise to various Dots”, Science 332, 77 (2011). morphologies of the final structures.

Tel: (972)-3-6407599 Fax: (972)-3-6407042 Email: [email protected] Personal Website: http://www.tau.ac.il/~rabani/

31 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Shachar Richter Chemistry Bio- and Molecular Electronics

he research in our group focuses on several aspects References related to bio- and molecular electronics 1. Chemically controlled doping of gated molecular The on going projects are junctions. E. Mentovich, B. Belgorodsky, H. Cohen and S. Richter. Submitted. (i) Construction and characterization of molecular 2. Post CMOS transistors as a new platform for and bio-photonic based devices. We utilize a novel Molecular Electronics. E. Mentovich ans S. Richter. vertical molecular transistor to investigate key issues Submitted. Tin molecular electronics. Among the ongoing research projects are: 3. The electrical role of redox center in Azurin: a polaron formation, quantum capacitance, AC molecular transistors, molecular electronics study. E. Mentovich and S. molecular circuits and bio-inspired devices Richter. Submitted. 4. Evaluation of leakage currents and the gate oxide (ii) Bio-composites. The unique properties of some natural proteins in vertical molecular transistors. E. Mentovich and are exploited to prepare thin films bio-composites. These materials S. Richter. Jpn. J. of Appl. Phys. 49, 01AB04 (2010). show excellent electrical, mechanical and optical properties that 5. High-yield fabrication of molecular vertical might be used in future for various applications. junctions. E. Mentovich, N. Rosenberg-Shraga, I. Kalifa, A. Tsukernik, N. Hendler, M. Gozin and S. Richter. J. Nanosci. Nanotec. In Press. 6. Peptide-based Spherulitic Films-formation and properties. N. Sidelman,Y. Rosenberg; and S.Richter . J.Coloid. Interf. Sci. 387-391 (2010). 7. Nanometer-Sized Active-Channel Molecular Quantum-Dot Transistor E. Mentovich, B. Belgorodsky, M. Gozin and S. Richter Adv. Mater. 22, 1–5 (2010). Including cover page. 8. Polarizability of DNA Block Copolymer Nanoparticles Observed by Electrostatic Force Microscopy. M. Sowann, M. Faroum E. Mentovich, I. Ibrahim, F.E. Alemdaroglu, M. Kwak, S.Richter, Herrmann. Macromol. Rapid Comm. 31, 1242– 1246. (2010). Including Cover page. 9. Three Dimensional multifunctional molecular circuits. E. Mentovich, I. Kalif, N. Shraga, G. Arvushenko and S. Richter. J.Phys.Chem. Lett, 1574– 1579 (2010). 10. Plasmon enhancement of the photosystem I assisted by metal nanoparticle antennas. I Carmeli, I. Lieberman, L. Kraversky, A. Govorov, G. Markovich and S. Richter. nano. Lett. 10, 1374–1382 (2010). 11. Construction and operation of sub-10 nm vertical molecular transistors. E. Mentovich and Top (left) Molecular quantum dot transistor. Top (right) investigation of the S. Richter. Proceedeings of the 3rd International electrical properties of DNA-conjugated polymers micelles. Botomm (left) Nanoelectronics Conference (INEC), 646-647 Plasmon enhancement of Photosystem I-Au nanoparticles. Bottom (right) (2010). molecular-based circuit 12. Large-scale fabrication of 4-nm-channel vertical -proteins ambipolar transistor- Elad Mentovich, Tel: (972)-3-6405711 Bogdan Belgorodsky , Itsik Khalifa, S. Richter. Nano Lett., 9 1296–1300. (2009). Fax: (972)-3-6405612 Email: [email protected] Personal Website: http://www.tau.ac.il/~richter1/

32 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Yael Roichman Chemistry

he objective of our work is to further develop optical directions: along the line connecting a pentagon techniques to manipulate and image nanometer sized center to its vortices and perpendicular to that entities. For example, by extending the capabilities line (Fig. 1), which is in contrast to the theoretical of holographic optical trapping and fluorescence prediction. microscopy we wish to make and study novel all optical devices. By combining holographic imaging Hydrodynamic interactions between Tand microscopic shear cells we study the mechanical properties driven and confined colloidal particles of biological proteins. In addition, we complement our work by Hydrodynamic interaction between colloidal synthesizing specialized colloids with properties tailored for our particles are usually of little importance in self applications. assembly under quasi-equilibrium conditions, however, they could play an important role in Faceting and growth of droplets on micro-fabricated assembling structures in a driven system. In surfaces order to improve our understanding of the effect We look at the problem of morphology selection in faceting hydrodynamic interactions have on directed self and roughening of quasicrystals in equilibrium, which is virtually assembly we study a simple driven-dissipative uncharted territory. To this aim we use an analog system of liquid system of colloids confined to move on a ring. spreading on a textured landscape. Our aim in this ongoing study Surprisingly, we find that hydrodynamic is to understand how the symmetry, scale and composition of interactions lead these systems to exhibit the patterned substrate govern droplet spreading, shrinking, and behaviors ranging from periodic motion to translation. As part of this effort, we explore the influence of substrate intermittent motion to weakly chaotic motion symmetry on hydrophobicity, with potential applications for self- depending on temperature. Moreover, it seems cleaning surfaces and anti-bacterial coatings. that the diffusion of a single particle in the Initially we studied droplet shape formation on the different tilings. ensemble of rotating colloids is anomalous. We found that while on a square lattice and on a hexagonal lattice the droplet almost always adopts a symmetric shape, this is not the References case for the Penrose tiling. On a square lattice, octagons were readily 1. Optical forces arising from phase gradients, Yohai created, for Penrose tilings facets formed in two crystallographic Roichman, Bo Sun, Yael Roichman, Jessie Amato- Grill and David G. Grier, Phys. Rev. Lett., 100, 013602, (2008). 2. Anomalous collective dynamics in optically driven colloidal rings, Y. Roichman, G. M. Zaslavsky and D. G. Grier, Physical Review E 75, 020401(R) (2007). 3. Manipulation and assembly of nanowires with holographic optical traps, R. Agarwal, K. Ladavac, Y. Roichman, G. Yu, C. M. Lieber and D. G. Grier, Optics Express 13, 8906-8912 (2005). (cond-mat/0509297). 4. Optimized holographic optical traps, M. Polin, K. Ladavac, S. Lee, Y. Roichman and D. G. Grier, Optics Figure 1: Facet formation of a droplet spreading on a pillar array ordered in a 5-fold symmetric quasicrystal lattice, (a) parallel to the pentagon directions Express 13, 5831-5845 (2005). (cond-mat/0504203). (surprisingly), and (b) perpendicular to the pentagon directions (as was predicted). 5. Holographic assembly of quasicrystalline photonic heterostructures, Y. Roichman and D. G. Grier, Optics Express 13, 5434-5439 (2005). (cond-mat/0506283). Tel: (972)-3-6405848 Fax: (972)-3-6409293 Email: [email protected] Personal Website: http://lorentz.tau.ac.il/~yael/

33 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Yoram Selzer Chemistry Understanding the Physics and Chemistry of Single Molecule Junctions

he research in my group strives to construct measure Since typical energy scales of molecules are in the and understand the physics and chemistry of single optical and infrared regime, where today’s laser molecule electrical junctions. This research is crucial technology provides a wealth of coherent light for the advancement of future nanoelectronic devices. sources, future research in my group will focus Current research in the group is divided into two on the various ways by which lasers could be areas: used to affect and direct currents through single T molecule junctions. 1. Measurement of the thermophysical properties of molecular junctions such as thermovoltage, and heat conduction. References Understanding heat conduction through molecular junctions 1. Effect of local environment on molecular is important as heat capacity of molecules is extremely small as conduction: Isolated molecule versus self- assembled monolayer. Selzer Y., Cai, L. T., Cabassi, A. a result heat dissipation in molecular junctions is expected to M., Yao, Y. X., Tour, J. M., Mayer, T. S., Allara, D. L. Nano drastically affect their stability and performance. Lett. 2005, 5, 61. 2. Molecular spintronics: Theory suggests that the tunneling 2. Thermally activated conduction in molecular wires. magnetic resistance (TMR), i.e., the efficiency of spin tunneling Selzer Y., Cabassi A. M., Mayer T. S., Yao Y., Allara D. L. without flipping, in molecular junctions could be as high as J. Am. Chem. Soc. 2004, 126, 4052. 500%, while standard solid state devices are operating at 40%. 3. Temperature effects on molecular conduction. Selzer Y., Cabassi A. M., Mayer T. S., Allara D. L. Experimental verification of this prediction is underway. Highly Nanotechnology 2004, 15, S483. efficient TMR elements will enable to develop universal ‘on-chip’ memory technology.

A scheme of the experimental setup for thermovoltage measurement of a single molecule junction

Tel: (972)-3-6407361 Fax: (972)-3-6407362 Email: [email protected] Personal Website: http://www.tau.ac.il/chemistry/selzer/

34 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Doron Shabat Chemistry Self-Immolative Molecular Systems for: Drug delivery, Diagnostic assays, Signal amplification, NIR imaging

uring the course of our work at Tel-Aviv University, References we have developed novel molecular systems 1. Gopin, A., Pessah, N., Shamis, M., Rader, C., and with self-immolative capabilities. The ability of a Shabat, D. “A chemical adaptor system designed to link a tumor-targeting device with a prodrug and molecule to undergo spontaneous domino-like an enzymatic trigger”. Angew. Chem. Int. Ed. Engl., disassembly upon a stimulus event is referred as 2003, 42, 327-332. self-immolative feature. Initially, we developed 2. Amir, R.J., Pessah, N., Shamis, M., Shabat, D., “Self- Da chemical adaptor system for targeted prodrug approach. The Immolative Dendrimers”. Angew. Chem. Int. Ed. prodrug is disassembled of the targeting moiety to release the active Engl., 2003, 42, 4494-4499. drug upon a triggering event. Next, we developed dendrimers with 3. Shamis, M., Lode, H.N., Shabat, D. “Bioactivation of Self-Immolative Dendritic Prodrugs by Catalytic self-immolative capabilities and later, we extended this approach Antibody 38C2”, J. Am. Chem. Soc., 2004, 126, 1726- to linear polymers and comb polymers. We also introduced a novel 31. technique for exponential amplification of diagnostic signals. This 4. Haba, K., Popkov, M., Shamis, M., Lerner, R. A., technique is based on a distinctive dendritic chain reaction (DCR) Barbas C. F. III., Shabat, D., “Single-Triggered Trimeric and has the potential to detect a single molecule activity. Recently, Prodrugs”, Angew. Chem. Int. Ed. Engl., 2005, 44, we become interested in the field of Near-Infrared imaging. We 716-20. developed a novel paradigm for obtaining a Turn-ON mechanism in 5. Amir R. J., Popkov, M., Lerner, R. A., Barbas C. F. III., Shabat, D., “Prodrug Activation Gated by a cyanine dyes and demonstrate this concept for noninvasive optical Molecular OR Logic Trigger”, Angew. Chem. Int. Ed. imaging of inflammation in animal-model. Engl., 2005, 44, 4378-81. 6. Weinstain, R., Lerner, R. A., Barbas C. F. III., Shabat, D., “Antibody-Catalyzed Asymmetric Intramolecular Michael Addition of Aldehydes and Ketones to Yield the disfavoured Cis-Product” J. Am. Chem. Soc. 2005, 127, 13104-5. 7. Sagi, A., Weinstain, R., Karton, N., Shabat, D., “Self- Immolative Polymers” J. Am. Chem. Soc. 2008, 130, 5434-5. 8. Sella, E., Shabat, D., “Dendritic Chain Reaction”, J. Am. Chem. Soc. 2009, 131, 9934-6. 9. Weinstain, R., Segal, E., Satchi-Fainaro, R., Shabat, D., “Real-Time Monitoring of Drug Release”, 2010, Chem. Commun., 46, 553-5. 10. Sella, E., Lubelski, A., Klafter, J., Shabat, D., “Two- Self-immolative dendrimers, as shown in the picture, spontaneously release Component Dendritic Chain Reactions: Experiment all the end-group molecules (drug or diagnostic units) following a single and Theory”, J. Am. Chem. Soc., 2010, 132, 3945-52. activation event at the focal point. This triggering event induces a cascade of 11. Karton-Lifshin, N., Segal, E., Omer, L., Portnoy, M., self-eliminations, which leads to complete dissociation of the dendrimer into its Satchi-Fainaro, R., Shabat, D., “A Unique Paradigm separate building blocks. for a Turn-ON Near-Infrared Cyanine-Based Probe: Non-Invasive Intravital Optical Imaging of Hydrogen Peroxide”, J. Am. Chem. Soc., 2011, DOI: 10.1021/ja203145v.

Tel: (972)-3-8340 Fax: (972)-3-6406517 Email: [email protected] Personal Website: http://www1.tau.ac.il/~shabat/

35 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Michael Urbakh Chemistry Nanotribology (theory)

y research effort in the past few years has References focused on a molecular level description of 1. Z. Tshiprut, S. Zelner, and M. Urbakh, Temperature- processes occurring between and close to Induced Enhancement of Nanoscale Friction, Phys. Rev. Lett., 102, 136102 (2009). interacting surfaces which is needed to first 2. M. Urbakh, J. Klafter, D. Gourdon, and J. Israelachvili, understand, and later manipulate friction. The nonlinear nature of friction, Nature 430, 525- Friction is present in a great number of physical 528 (2004). Msystems and plays a central part in phenomena that take place at all 3. O. Dudko, A.E. Filippov, J. Klafter, and M. Urbakh, length scales, from micro- and nanomachines or biological molecular Beyond the conventional description of dynamic motors to the geophysical scales characteristic for earthquakes. force spectroscopy of adhesion bonds, Proc. National Academy of Sciences USA, 100, 11378– Despite the practical and fundamental importance of friction and 11381 (2003). the growing efforts in the field, many key aspects of dynamics of this phenomenon are still not well understood. The main challenge is posed by the complexity of highly non-equilibrium processes occurring in any tribological scenario that includes detachment and re-attachment of multiple microscopic contacts between the surfaces in relative motion. The most challenging directions of future research include: bridging the gap between the nano, micro and macro scales in friction, new approaches to control and modify frictional properties and nanomanipulations at interfaces.

Tel: (972)-3-6408324 Fax: (972)-3-6409293 Email: [email protected] Personal Website: http://www.tau.ac.il/~urbakh1/

36 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Ady Arie Engineering

he group of Prof. Arie is working on design, optical References characterization and applications of nonlinear 1. T. Ellenbogen, N. Voloch-Bloch, A. Ganany- photonic crystals. These are materials in which the Padowicz and A. Arie “Nonlinear generation and manipulation of Airy beams”, Nature Photonics 3, nonlinear coefficient is modulated, in either one 395-398 (2009). or two dimensions, while the linear susceptibility 2. A. Bahabad, A. Ganany-Padowicz and A. Arie remains constant. These structures are significantly “Engineering two-dimensional nonlinear photonic Tdifferent than the more common photonic crystals, in which the quasi-crystals”, Optics Letters 33, 1386-1388 (2008). linear susceptibility is modulated. 3. T. Ellenbogen, A. Ganany and A. Arie “Nonlinear Nonlinear processes in nonlinear photonic crystals are governed by photonic structures for all-optical deflection”, Optics Express 16, 3077-3082 (2008). the phase matching requirements. The modulation of the nonlinear 4. A. Arie, N. Habshoosh and A. Bahabad, “Quasi phase coefficient enables efficient frequency conversion by quasi-phase matching in two-dimensional nonlinear photonic matching. Moreover, it allows the realization of all optical effects. crystals”, Optical and Quantum Electronics 39, 361- Our group is studying all optical effects in these nonlinear photonic 375 (2007). crystals such as switching, polarization rotation, focusing and beam 5. D. Kasimov, A. Arie, E. Winebrand, G. Rosenman, A. shaping. Bruner, P. Shaier and D. Eger, “Annular symmetry nonlinear frequency converters”, Optics Express 14, 9371-9376 (2006). 6. R. Lifshitz, A. Arie and A. Bahabad, “Photonic quasicrystals for general purpose nonlinear optical frequency conversion”, Physical Review Letters 95 133901 (2005).

A nonlinear photonic crystal for converting a Gaussian pump beam at angular frequency ω to a second harmonic Airy beam at 2ω. The black and white regions of the nonlinear photonic crystal represent the sign modulation of the nonlinear coefficient of the Stoichiometric Lithium Tantalte crystal used in the experiment. For more details see Nature Photonics 3, 395-398 (2009).

Tel: (972)-3-6406627, (972)-3-6403508 Fax: (972)-3-6423508 Email: [email protected] Personal Website: http://www.eng.tau.ac.il/~ady/

37 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Alon Bahabad Engineering Nonlinear optics, extreme nonlinear optics, nanophotonics, quantum optics

e are interested in theoretical and experimental medium in the vicinity of the nano-hole array. research in various areas of physical optics. The ionized electron oscillates in the enhanced One of our major areas of research is the femtosecond laser field, gaining kinetic energy. generation of coherent light sources at very With some probability this electron can high photon energies (soft X-rays). For this recombine with the parent ion, releasing excess we employ the extreme nonlinear optical energy in the form of a high-energy photon. The processW of high-harmonic-generation (HHG). HHG is driven with an result is a coherent source of very short soft X-ray intense ultra-short light pulse which ionizes a gaseous medium. The pulses. The geometry of the nano-hole array can liberated electron is then oscillating in the laser field, gaining kinetic be designed to modify the characteristic of the energy. There is a small chance that the electron will encounter the soft X-ray radiation. ion from which it was liberated and would recombine with it. The excessive kinetic energy that was gained by the electron is released References in the form of a high energy photon. During such a process hundreds 1. Alon Bahabad, Margaret M. Murnane and Henry of the photons of the laser field can be converted to a single high C. Kapteyn, “Quasi Phase Matching of Momentum and Energy in Nonlinear Optical Processes”, Nature energy photon. We are interested in mediating this process by Photonics, 4, 570-575 (2010). employing Plasmon-assisted field enhancement. When the laser light 2. Tenio Popmintchev, Ming-Chang Chen, Alon interacts with a metallic nanostructure, electron oscillations on the Bahabad, Michael Gerrity, Pavel Sidorenko, Oren metal surface can lead to a significant field enhancement. This can be Cohen, Ivan P. Christov, Margaret M. Murnane utilized to assist with the process of HHG. In addition, the geometry and Henry C. Kapteyn, “Phase Matching of High of the metallic nanostructure can be used to control the beam shape Harmonic Generation Throughout the Soft and Hard X-Ray Regions of the Spectrum”, Proceedings and polarization state of the generated high harmonic radiation. of the National Academy of Science, 106, 10516- 10521 (2009). Plasmon-assisted high-harmonic-generation 3. Alon Bahabad and Ady Arie, “Generation of Optical A femtosecond laser pulse interacts with a metallic nano-hole array. Vortex Beams by Nonlinear Wave Mixing”, Optics This interaction enhances significantly the field within the nano- Express, 15, 17619-17624 (2007). holes allowing for the ionization of an atom (or a molecule) in a gas 4. Alon Bahabad, Noa Voloch, Ady Arie, Ariel Bruner and David Eger, “Unveiling Quasi-periodicity through Nonlinear Wave Mixing in Periodic Media”, Physical Review Letters, 98, Issue 20, 205501 (2007). 5. Ron Lifshitz, Ady Arie and Alon Bahabad, “Photonic quasicrystals for general purposes nonlinear optical frequency conversion”, Physical Review Letters, 95, Issue 13, 133901 (2005).

Tel: (972)-3-6409423 Fax: (972)-3-6423508 Email: [email protected] Personal Website: http://www.eng.tau.ac.il/~alonb/

38 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Zahava Barkay Engineering Surface characterization methods based on scanning electron microscopy

1. Nano-scale crystallographic characterization References Study of crystallographic phase and orientation on the nano-scale 1. E. Bormashenko, Y. Bormashenko, A. Musin, Z. using backscattered electron diffraction (EBSD) provides unique Barkay, “On the Mechanism of Floating and Sliding of Liquid Marbles”, Chemphyschem., in press (2009) information unavailable by ordinary methods. Its implementation 2. E. Bormashenko, R. Pogreb, G. Whyman, A. Musin, was shown on various crystalline materials including nano Y. Bormashenko, Z. Barkay, “Shape, vibrations,

structures. Results were reported for low TC superconducting CS- and effective surface tension of water marbles”, 1-2 doped WO3 crystals (from Prof. Reich lab, WIS). Langmuir 25(4): 1893-1896 (2009). 3. Z. Barkay, I. Rivkin, R. Margalit, “Three dimensional characterization of drug-encapsulating particles 2. STEM – 3D information using STEM detector in FEG-SEM”, Micron, in press A method for transforming projected two-dimensional (2D) (2009). bright-field scanning transmission electron microscopy (STEM) 4. Z. Barkay, E. Grunbaum, G. Leitus and S. Reich, “Study images into three-dimensional (3D) thickness images was of the superconducting Cs-doped WO3 crystal established by combining STEM imaging and theoretical models surface by electron backscattered diffraction”, J. for electron-specimen interaction. Its implementation was shown3 of superconductivity and novel magnetism 21(2): for submicron biological systems such as drug-encapsulation 145-150 (2008). 5. Z. Barkay, E. Grunbaum, A. Gholinia, S. Reich, particles (from Prof. Margalit lab, TAU). “Characterization of superconductors by electron backscattered diffraction in SEM”, invited talk and 3. Surface wettability and liquid marble properties paper, MMT-2008, Israel, 8-10 Sept. (2008). Static and dynamic experiments in environmental SEM (ESEM) 6. E. Bormashenko, Y. Bormashenko, T. Stein, G. are carried out for sub-micron characterization of wettability4-5 Whyman, R. Pogreb, Z. Barkay, “ESEM Study of the properties on various surfaces (polymer, semiconductor or nano- Fine Structure of the Triple Line and Cassie-Wenzel Wetting Transition for Sessile Drops Deposited on tube), and in particular for the triple line structure. Alternative the Rough Polymer Substrates”, Langmuir 23(8); approach to super-hydrophobic surfaces is the modification of 4378-4382 (2007). liquid interface with hydrophobic colloidal particles leading to 7. D. Aronov, G. Rosenman, Z. Barkay, “Wettability formation of “liquid marbles”. These are of current investigation6-7 Study of Modified Silicon Dioxide Surface Using in ESEM due to their special physical and chemical properties as Environmental Scanning Electron Microscopy”, J. well as being potential carriers in microfluidic devices. Appl. Phys. 101 084901 (2007).

(a) EBSD pole figure of (0001) plane orientation for Cs-doped

superconducting phase in CsXWO3 crystal (b) Environmental SEM image of liquid marble surface coated with polydenefluoride (PVDF) 100nm particles

Tel: (972)-3-6407818 Fax: (972)-3-6422649 Email: [email protected] Personal Website: http://www.tau.ac.il/institutes/wamrc/

39 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Raymond (Reuven) Boxman Engineering Electrical Discharge and Plasma Lab n Pulsed air arc deposition of carbon nano-tubes (in open air, on References room temperature substrates). 1. V.N. Zhitomirsky, I. Grimberg, L. Rapoport, N.A. n Submerged arc synthesis of nano-particles. Travitzky, R.L. Boxman, S. Goldsmith and B.Z. Weiss, “Vacuum arc deposition of TiN, NbN and TiN/ n directed growth of nano-structures using an imposed electric NbN multilayer coatings”, Surface and Coatings field. Technology, Vol. 120-121, pp. 2199-225, 1999. n Nano-structured thin films and coatings for improved mechanical 2. R.L. Boxman, V.N. Zhitomirsky, I. Grimberg, L. properties. Rapoport, S.Goldsmith, and B.Z. Weiss, “Structure and hardness of vacuum arc deposited multi- component nitride coatings of Ti, Zr and Nb”, Surface and Coatings Technology, Vol. 125, pp. 257- 262, 2000. 3. N. Parkansky, B. Alterkop, S. Goldsmith, and R.L. Boxman, “Effect of an applied voltage during annealing on the resistivity and transparency of the amorphous tin oxide films”, J. Vac. Sci. Technol. Vol A21, pp. 1923-6, 2003. 4. N. Parkansky, B. Alterkop, S. Goldsmith, R.L. Boxman, H. Wulff, M. Quaas, and A. Quade, “Nano organization of thin titanium films by an electric field during vacuum arc deposition”, Thin Solid Films 377-378, pp. 507-511, 2000. 5. N Parkansky, R L Boxman, B Alterkop, I. Zontag, Y Lereah, Z Barkay, “Single-Pulse Arc Production of Carbon Nanotubes in Ambient Air” J. Phys. D: Appl. Phys. Vol. 37, pp 2715-19, 2004. 6. N. Parkansky, B. Alterkop, R.L.Boxman, S. Goldsmith, Z. Barkay, Y Lereah, “Pulsed discharge production Figure 1. “Forest” of erect multi-wall carbon nano-tubes desposited on a Ni-coated of nano- and micro-particles in ethanol and their glass substrate at room temperature in open air, by a single 20 ms arc discharge. characterization” Powder Technology Vol. 150 (2005) pp. 36-41.

Tel: (972)-3-6407364 Fax: (972)-3-6410189 Email: [email protected] Personal Website: http://www.eng.tau.ac.il/~boxman/index.html

40 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Noam Eliaz Engineering The Biomaterials and Corrosion Laboratory

n line with the demands of modern society, the multidisciplinary collisions and to attack by atomic oxygen. The Biomaterials and Corrosion Laboratory is conducting strategic project is conducted in collaboration with the R&D on advanced materials ranging from biomaterials and Space Environment Group at Soreq NRC. nanomaterials, to materials for space applications, and alloy deposition. The Lab also provides materials selection, quality References control and failure analysis services, serving and collaborating 1. J. J. Elsner, Y. Mezape, K. Hakshur, M. Shemesh, with industrial, medical and defense organizations. Among the lab’s A. Shterling and N. Eliaz. Wear rate evaluation of I a novel polycarbonate-urethane cushion form internationally renowned achievements are: bearing for artificial Hip joints. Acta Biomater. 2010; n The development of novel electrochemically-deposited 6: 4698-707. hydroxyapatite (HAp) coatings for orthopedic and dental 2. K. Mendel, N. Eliaz, I. Benhar, D. Hendel and N. implants. Coatings prepared in the lab have demonstrated higher Halperin. Magnetic isolation of particles suspended performance than the commercial plasma-sprayed coatings with in synovial fluids for diagnostics of natural joint respect to osseointegration and occurrence of cracking. chondropathies. Acta Biomater. 2010; 6: 4430-8. 3. A. Naor, N. Eliaz and E. Gileadi. Electrodeposition n The magnetic isolation of bone, cartilage, metals, synthetic of alloys of rhenium with iron-group metals from polymers, minerals and carbon nano-spheres and nano-rods aqueous solutions. J. Electrochem. Soc. 2010; 157 from a variety of liquids, including synovial fluids, ethanol and (7):D422-7. bovine serum. The applications include diagnosis of osteoarthritis, 4. N. Eliaz, S. Shmueli, I. Shur, D. Benayahu, D. Aronov determination of the efficacy of drug treatment, and for and G. Rosenman. The effect of surface treatment monitoring the wear of artificial joints (either in the design stage on the surface texture and contact angle of electrochemically deposited hydroxyapatite or during service in vivo). The lab is the only one outside the US to coating and on its interaction with bone-forming have this capability (by means of Bio-Ferrography). cells. Acta Biomater. 2009; 5: 3178-91. n Electroplating and electroless plating of Re-based alloys. These 5. R. Verker, E. Grossman, I. Gouzman and N. Eliaz. projects are conducted in collaboration with Prof. Eliezer Gileadi POSS-Polyimide nanocomposites: Effect of from the TAU School of Chemistry, and are intended for aircraft, chemical structure on mechanical properties. aerospace, nuclear, chemical, electrical, biomedical and other Composites Sci. Technol. 2009; 69: 2178-84. 6. D. Lakstein, W. Kopelovitch, Z. Barkay, M. Bahaa, D. applications. Hendel and N. Eliaz. Enhanced osseointegration of n The development of hybrid nano-composites with unique grit-blasted, NaOH-treated and electrochemically mechanical and electrical properties and improved durability hydroxyapatite-coated Ti-6Al-4V implants in in space, for example, with higher resistance to space debris rabbits. Acta Biomater. 2009; 5: 2258-69.

Left: Bone forming cells attached to electrochemically deposited hydroxyapatite. Right: Electron backscatter diffraction (EBSD) demonstrating the reorientation of copper during tensile test.

Tel: (972)-3-6407384 Fax: (972)-3-6407617 Email: [email protected] Personal Website: http://www.eng.tau.ac.il/~neliaz/

41 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Ilan Goldfarb Engineering Surface Science and Nanostructures Laboratory

rof. Goldfarb is mainly interested in self-assembled upon the sample while it is being scanned and self-organized growth of epitaxial nanostructures and continuously imaged during growth. inside STM. One way to self-assemble nanostructures Furthermore, bias-dependent STM imaging and is to introduce strain into the growing layer by scanning tunneling spectroscopy (STS) have carefully controlling the mismatch between the been instrumental in studying the nanostructure crystalline lattices of the layer and the substrate electronic properties, such as their local density (heteroepitaxy).P Relaxation of mismatch strain drives the self- of states (LDOS), for exploration of the observed assembled formation of nanocrystal arrays [1-4], which can be used quantum size effects (QSE’s). in quantum-dot and -wire devices, provided the size and shape distribution of the nanocrystals in the array is sufficiently narrow, and References their degree of crystalline perfection is high. Nanostructure ordering 1. G. Cohen-Taguri, O. Sinkevich, M. Levinshtein, A. can be achieved by self-organization on naturally provided mesas, Ruzin, I. Goldfarb, Atomic structure and electrical properties of In(Te) nanocontacts on CdZnTe(110) such as periodic step-bunches on vicinal surfaces [4]. Since self- by scanning probe microscopy, Adv. Funct. Mater. assembly and self-ordering of nanostructures are thermodynamically 20, 215 (2010). and/or kinetically determined, only deep understanding of these 2. I. Goldfarb, Step-mediated size-selection tendencies (that occur naturally during growth) can provide the and ordering of heteroepitaxial nanocrystals, means to control them and hence tailor-on-demand. Therefore, the Nanotechnology 18, 335304 (2007). projects carried out in the laboratory are aimed at exploring epitaxial 3. I. Goldfarb, L. Banks-Sills, R. Eliasi, Is the elongation of Ge huts in a low-temperature regime really materials systems with varying mismatch and ability to order, such governed by kinetics?, Phys. Rev. Lett. 97, 206101 as Ge/Si [1-3] and Co/Si [4], as well as other refractory metal silicides, (2006). and compound semiconductors, e.g., In/CdZnTe [5] (see the figure 4. I. Goldfarb, Effect of strain on the appearance of below). The goal is to gain a sufficient degree of understanding of subcritical nuclei of Ge nanohuts on Si(001), Phys. the nanostructure-surface interactions for developing a generic Rev. Lett. 95, 025501 (2005). approach for controlling the nanostructure behavior on surfaces, 5. I. Goldfarb, P.T. Hayden, J.H.G. Owen, G.A.D. Briggs, Nucleation of “hut” pits and clusters during gas- towards implementation in realistic devices. One of the strengths source molecular-beam epitaxy of Ge/Si(001) in in- of the laboratory is the rare ability to observe the evolution of the situ scanning tunneling microscopy, Phys. Rev. Lett. growing epilayers in real-space and -time by STM, due to state-of- 78, 3959 (1997). the-art UHV SPM Microlab where the deposition flux is incident

Scanning tunneling microscopy (STM) micrograph of self-assembled pyramidal Ge/Si(001) nano-huts (left) [1-3], self-organized CoSi2/Si(111) nano-islands (middle) [4], and their LDOS (right). Rightmost image on the black background: In(Te) nanocontacts on a CdZnTe(110) substrate [5].

Tel: (972)-3-6407079, (972)-3-6405931 Fax: (972)-3-6407617 Email: [email protected] Personal Website: http://www.eng.tau.ac.il/~ilang/

42 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Yael Hanein Engineering Brain machine interface, engineered neural networks, nanotube – neuron interfaces

ur research activity concerns with the References development of electronic nano devices which 1. Yael Hanein, Carbon nanotube integration into are designed to interface with brain cells and MEMS devices, physica status solidi, In Press, 2010. 2. Sarit Anava, Alon Greenbaum, Eshel Ben Jacob, Yael to record their activity. These devices have far Hanein and Amir Ayali, The regulative role of neurite reaching applications in the realm of treating mechanical tension in network development, understanding brain disorders, the effect of drugs Biophysical Journal, Vol.96, pp. 16611670, 2009. onO the brain and the possibility to build implantable electronic brain 3. Asaf Shoval, Christopher Adams, Moshe David- chips. In particular we use nano materials to construct recording Pur, Mark Shein, Yael Hanein and Evelyne and stimulation electrodes for neuro-prosthetic applications such as Sernagor, Carbon nanotube electrodes for effective interfacing with retinal tissue, Frontiers in retinal implants. Unlike many contemporary devices, our nano based Neuroengineering, Vol 2, pp. 4, 2009. systems are flexible, and have superior electro-chemical properties. 4. Ze’ev R. Abrams, Zvi Ioffe, Alexander Tsukernik, Ori Cheshnovsky and Yael Hanein,A Complete Scheme Our research also utilizes micro and nano miniaturization techniques for Creating Large Scale Networks of Carbon for the realization of new devices. In addition to neuronal interfaces Nanotubes, Nano Letters, 7 (2007) 2666 -2671. we also explore bio-mimetic approaches to construct functional 5. Tamir Gabay, Moti Ben-David, Itshak Kalifa, Raya Sorkin, Ze’ev R. Abrams, Eshel Ben-Jacob, and Yael devices such as sensitive accelerometers and radiation sensors based Hanein,Electro-chemical and biological properties on nanoantennas. of carbon nanotube based multi-electrode arrays, Nanotechnology, 18 (2007) 035201-035206. 6. Ze’ev R. Abrams and Yael Hanein, Tube-Tube and Tube-Surface Interactions in Straight Suspended Carbon Nanotube Structures, Journal of Physical Chemistry B, 2006. 7. Compact self-wiring in cultured neural networks, Raya Sorkin, Tamir Gabay, Pablo Blinder, Danny Baranes, Eshel Ben-Jacob and Yael Hanein, Journal of Neural Engineering, Vol. 3 pp. 95-101, 2006.

A flexible carbon nanotube based neuro electrodes

Tel: (972)-3-6407698, (972)-3-6407698 Fax: (972)-3-6423508 Email: [email protected] Personal Website: http://www.eng.tau.ac.il/~hanein/

43 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Slava Krylov Engineering Micro- and nanoelectromechanical systems (MEMS/ NEMS), micro- and nano sensors and actuators

icrosystems or MEMS (Microelectromechanical experimental investigation carried out in the Systems) are the batch-fabricated integrated laboratory serves as a basis for generating new microscale systems converting various designs and operational concepts of micro physical (mechanical, optical, electromagnetic) devices. and chemical stimuli to electrical signals and vice versa. Microsystems find application in References various areas of engineering due to their low fabrication cost, low 1. S. Krylov and N. Dick, “Dynamic Stability of M Electrostatically Actuated Initially Curved Shallow energy consumption and high or unique performance. To date, a Micro Beams,” Continuum Mechanics and large variety of micro systems based applications were reported and Thermodynamics, 22(6), pp. 445-468, 2010. several MEMS based products were successfully commercialized. 2. S. Krylov, N. Dick, “Pull-In Dynamics of In light of the unabated progress in micro technologies and Electrostatically Actuated Bistable Micro Beams,” escalation in complexity and diversity of micro-devices, modeling in Advanced Materials and Technologies for Micro/ issues that were ignored in the past have become of primary Nano-devices, Sensors and Actuators, NATO importance. The ability to predict possible failure mechanisms Science for Peace and Security Series – B: Physics and Biophysics, Edited by E. Gusev, E. Garfunkel, A. and performance of batch-fabricated devices at early stages of the Dideikin,. Springer 2010, pp. 117-128. design is among the most important requirements to modeling 3. Y. Gerson, S. Krylov and B. Ilic, “Electrothermal tools. The increasing device performance requirements of a highly Bistability Tuning in a Large Displacement competitive industry have resulted in the emergence of more Micro Actuator,” Journal of Micromechanics and sophisticated designs that exploit more complex physical effects. Microengineering, 20, paper 112001, 2010. In our research we develop new actuation and sensing approaches 4. S. Krylov, Y. Gerson, T. Nachmias, U. Keren, “Excitation of Large Amplitude Parametric Resonance and their implementation in micro devices along with investigation by the Mechanical Stiffness Modulation of a of complex nonlinear electromechanical phenomena which are Microstructure,” Journal of Micromechanics and intrinsic in microstructures but are not encountered naturally in Microengineering, 20, 015041 (12pp), 2010. conventional large-scale structures. A better understanding of 5. Ya’akobovitz, S. Krylov, “Toward Sensitivity physical phenomena gained during extensive theoretical and Enhancement of MEMS Accelerometers Using Mechanical Amplification Mechanism,” IEEE Sensors Journal, 10(8), pp. 1311-1319, 2010. 6. Ya’akobovitz, S. Krylov, Y. Hanein, “Nanoscale Displacement Measurement of Electrostatically Actuated Micro- Devices using Optical Microscopy and Digital Image Correlation,” Sensors and Actuators A-Physical, 162, pp.1-7, 2010. 7. Y. Linzon, S. Krylov, B. Ilic, D. Southworth, R. Barton, B. Cipriany, J. Cross, J. Parpia, H. Craighead, “Real- Time Synchronous Imaging of Electromechanical Resonator Mode and Equilibrium Profiles,” Optics Letters, 35(15), 2010 8. Ilic, S. Krylov, and H. G. Craighead, “Young’s Modulus and Density Measurements of Thin Atomic Layer Deposited Films using Resonant Nanomechanics,” Journal of Applied Physics, 108, paper 044317, 2010.

Tel: (972)-3-6405930 Fax: (972)-3-6407617 Email: [email protected] Personal Website: http://www.eng.tau.ac.il/~vadis/

44 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. David Mendlovic Engineering Silicon nano-photonic dynamic devices

he research activity in Prof. Mendlovic Lab deals with Our results so far include the design of a novel silicon nano-photonic devices for telecommunications ultra small beam-splitting waveguide junction, applications. The main objectives of the research are design and fabrication of high-Q 1D PhC cavities design and fabrication of highly efficient passive and fabrication of 2D PhC waveguides. In the devices and application of dynamic properties using future we intend to expand our research to other different physical phenomena \ materials. Currently fields such as incorporation of CNTs on the optical Twe are working on three projects. The first is tunable optical filters silicon chip. based on 1D photonic crystal (PhC) cavities. In this project we design high quality passive cavities that form a shaped filter then use thermal References modulation to tune the filter’s center frequency. The second project 1. Damian Goldring, Evgeny Alperovich, Uriel Levy is about producing ultra fast EO modulators using 2D PhC cavity. In and David Mendlovic, “Analysis of Waveuide- Splitter-Junction in high-index silicon-on-insulator this project we compare two different methods of modulations (both waveguides”, Optics Express, 13, 2931-2940 (2005). use carrier injection) and optimize each system both in optical design 2. Damian Goldring, David Mendlovic, “High quality and material design. In the third project we design and fabricate a 1D Photonic Crystal cavity for optical filters” – to be tunable Dispersion Compensator Based on ring resonators. published. As part of our research activity we have developed a fabrication 3. Damian Goldring, David Mendlovic, “Tunable nano- process as well as a suitable test system so we are able to get photonic optical filters” – to be published. experimental results.

Tel: (972)-3-6408245, (972)-3-6408139 Fax: (972)-3-6423508 Email: [email protected] Personal Website: http://www.eng.tau.ac.il/~mend/mendelov.html

45 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Naum Parkansky Engineering

1. Nanoparticles production, characterization and application. References 2. Pulsed air arc surface treatment: surface modification and coating. 1. Parkansky N, Alterkop B, Boxman RL, et al.,Magnetic 3. Electro erosion of different electro conducting materials in liquid properties of carbon nano-particles produced by a pulsed arc submerged in ethanol, CARBON Volume: and gas: possibility of control and application. 46 Issue: 2 Pages: 215-219 Published: FEB 2008. 4. Influence of electric current passing on the mechanical properties 2. Parkansky N, Glikman L, Beilis II, et al.,W-C synthesis of magnetic and non magnetic materials. in a pulsed arc submerged in liquid, PLASMA 5. Submerged arc liquids processing: contamination breakdown CHEMISTRY AND PLASMA PROCESSING Volume: 28 and other applications. Issue: 3 Pages: 365-375 Published: JUN 2008. 3. Parkansky N, Frenkel G, Alterkop B, et al., Influence of pulsed arc parameters on powder production in ethanol, POWDER TECHNOLOGY Volume: 162 Issue: 2 Pages: 121-125 Published: MAR 1 2006. 4. Parkansky N, Goldstein O, Alterkop B, et al., Features of micro and nano-particles produced by pulsed arc submerged in ethanol, POWDER TECHNOLOGY Volume: 161 Issue: 3 Pages: 215-219 Published: FEB 3 2006.

Tel: (972)-3-6408176, (972)-3-6408221 Fax: (972)-3-6429540 Email: [email protected] Personal Website: http://www.eng.tau.ac.il/index.php?option=com_wrapp er&view=wrapper&Itemid=119&language=he-IL

46 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Gil Rosenman Engineering

1. Studies of nanodomain reversal effect in ferroelectrics. High Voltage Atomic Force Microscope (HVAFM) and Indirect Electron Beam Writing Methods (IEB) for tailoring of 1D and 2D ferroelectric domain configurations in nanometer scale. Development of new generation of nonlinear photonic devices, lasers in short wavelength region and new methods of nanolithography based on nanodomain structures. Atomic Force Microscopy and Kelvin Probe Microscopy studies of ferroelectric domains, electronic properties of domains and domain boundaries. Investigation of pyroelectric, piezoelectric and photovoltaic properties of ferroelectric with nanometer resolution. References 2. Studies of physical properties of biological and biomimetic 1. G. Rosenman, P. Urenski, A. Agronin, Y. Rosenwaks, materials in nanometer scale. Bones: Collagen and Hydroxyapatite. M. Molotskii, Submicron Ferroelectric Domain Nanoscale piezoelectric studies of bones. Nanoscale imaging of Structures Tailored by High Voltage Scanning Probe ferroelectric properties in bones. Microscopy, Appl. Phys. Lett., 82, 103 (2003). hydroxyapatite. Semiconductor properties of Hydroxyapatite, 2. M. Molotskii, A. Agronin, P. Urenski, M. Shvebelman, electronic structure and optical properties. New method of G. Rosenman, and Y. Rosenwaks, Ferroelectric domain breakdown, Phys. Rev. Lett, 90, 107601 wettability modification and bioactivation of bones implants. (2003). Wettability engineering for biocells adhesion. Wettability patterning 3. G. Rosenman, Y. Rosenwaks, P. Urenski, “Tailoring and arrayed Hydroxyapatite in micro- and nanometer scale. Domain Engineered Structures in Ferroelectric Materials, US Patent No. 6,653,630, Nov. 25, 2003. 4. G. Rosenman, E.Weinbrand, “Ferroelectric domain reversal by indirect charged particle beam”, Provisional Patent, November, 2004. 5. C. Halperin, S. Mutchnik, A. Agronin, M. Molotskii, P. Urenski, M. Salai, G. Rosenman, Piezoelectric properties of bones studied in nanometer scale, Nanoletters, 4, 1253 (2004).

Tel: (972)-3-6407446 Fax: (972)-3-6423508 Email: [email protected] Personal Website: http://www.eng.tau.ac.il/~gilr/

47 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Yossi Rosenwaks Engineering Nano probing, Electrical Measurements Using Scanning Probe Microscopy

rof. Rosenwaks is heading a research group of 10 References graduate students and scientists and his current 1. E. Koren, N. Berkovich, and Y. Rosenwaks, “Measuring research interests include: nanoscale electrical the active dopant distribution and diffusion constant in Silicon nanowires”, Nanoletters, 10, measurements using mainly Kelvin probe force 1163-1167, (2010). microscopy, nanowires and nanowire devices, organic 1. L. Sepunaru, I. Tsimberov, L. Forolov, C. Carmeli , I. and molecular transistors, charge carrier dynamics Carmeli, and Y. Rosenwaks, “ Picosecond Electron andP transport in semiconductors, image restoration in Kelvin probe Transfer From Photosysnthetic Reaction Center microscopy, novel photovoltaic devices based on inorganic and Protein to GaAs “, Nanoletters, 9, 2751-5, (2009). organic materials. The laboratory includes 5 KPFM systems operating 1. O. Tal, N. Tessler, C. K. Chan, A. Kahn, and Y. Rosenwaks, “Direct determination of the hole density of states in air, controlled humidity, and ultra-high vacuum environments. in undoped and doped amorphous organic films with high lateral resolution”, Phys. Rev. Lett., 95 256405-8, (2005). 1. M. Molotskii, P. Urenski, A. Agronin, M. Shvebelman, G. Rosenman, and Y. Rosenwaks “Ferroelectric Domain breakdown”, Phys. Rev. Lett., 90, 107601-4, (2003).

Tel: (972)-3-6406248 Fax: (972)-3-6423508 Email: [email protected] Personal Website: http://www.eng.tau.ac.il/~yossir/

48 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Jacob Scheuer Engineering Nano-Photonic devices for telecommunication and sensing

egardless of the specific application, the key References requirements from any optical system are compactness 1. Y. Huang, G. T. Paloczi, J. Scheuer and A. Yariv, “Soft and low loss. Nano-scale optical components enable lithography replication of polymeric microring optical resonators”, Opt. Express. Vol. 11 (2003) 2452. the realization of dense, highly functional integrated 2. J. Scheuer, W. M. J. Green, G. DeRose and A. Yariv, optical circuits while low-loss improves the efficiency “Low Threshold Two-Dimensional Annular Bragg and performances of the system. Our research is Lasers”, Opt. Lett. 29, 2641 (2004). focusedR on achieving these characteristics by developing novel 3. J. Scheuer, W. M. J. Green, G. DeRose and A. Yariv, wave guiding concepts and optical materials. Currently there we are “InGaAsP annular Bragg lasers: theory, applications working in two main directions. The first direction is achieving tight and modal properties”, IEEE J. Sel. Top. Quantum Electron., Vol. 11 (2005) 476. confinement of light using distributed feedback. The objective is to 4. J. Scheuer, W. M. J. Green, G. DeRose and A. Yariv, develop components such as waveguides, resonators etc. that are “Lasing from a circular Bragg nanocavity with an capable of confining light in sub-micron dimensions. The applications ultra-small modal volume”, Appl. Phys. Lett. Vol. 86 are ultra-dense photonic processors for telecom and sensing (2005) 251101. applications. The second project deals with the development of new 5. J. Scheuer, G. T. Paloczi and A. Yariv, “All-Optically optical polymeric materials and soft-lithography molding methods Tunable Wavelength-Selective Reflector Consisting of Coupled Polymeric Microring Resonators”, Appl. capable of fabricating nanometer-scale features. Phys. Lett. Vol. 87 (2005) 251102. Our results so far include the demonstration of the world smallest 6. W. Green, J. Scheuer, G. DeRose and A. Yariv, “Ultra- semiconductor laser, an ultra-sensitive biochemical sensor and a Sensitive Biochemical Sensor Based on Circular novel tunable reflector based on electro-optic polymer micro-cavities. Bragg Micro-Cavities”, CLEO/QELS 2005, Baltimore, In the future we intend to expand our activity to 3D polymeric nano- Maryland, paper CPDA7 (post deadline). photonic components and integration of sensor-arrays with micro- fluidic channels.

Left: SEM image of an InP Nano-laser; Right: Polymeric optical chip

Tel: (972)-3-6407559 Fax: (972)-3-6423508 Email: [email protected] Personal Website: http://www.eng.tau.ac.il/~kobys/

49 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Yosi Shacham-Diamand Engineering Nano-chemical processes for Microelectronics and integration of biological material on chip for acute toxicity detection

ano-chemistry for electronics applications – Physical and electrical characterization of electronic devices for CMOS technologies made by various chemical techniques such as self assembled monolayers and surface catalyzed auto catalytic electrochemical processes. The research (a) Array of eight 100nL electrochemical cells on a silicon involves studying of the basic chemistry and electrochemistry of chip. The chip is glued to the tailored PCB platform, and N the chip’s gold pads are wire bonded to the gold PCB’s those structures as well as the fabrication steps and the integration onto CMOS compatible structures that can be used for electronics electrodes. The PCB board enters directly to the socket of an external sensing circuit. and nano-bio interfacing applications. (b) Electrochemical-cells on chip consist of three embedded Interconnects applications for ULSI – nano-scale Cu Damascene electrodes: gold working lectrode (30nm2), gold counter interconnect structures, Cu deposition on nano structures with electrode (300nm2), and Ag/AgCl reference electrodes. high aspect ratio, barrier and capping layers, deposition on low-k (low dielectric constant) insulating materials. Electroless plating References of Cu wires, Co and Nickel alloy barriers on low-dielectric constant 1. Rachela Popovitzer, Tova Neufeld, Dvora Biran, materials. The group main research activities are on the following Eliora Z. Ron, Judith Rishpon, and Yosi Shacham- topics: Electrical properties of interconnect structures, materials Diamand “Novel Integrated Electrochemical Nano- properties – composition, texture, morphology, field effect transistors Biochip for Toxicity Detection in Water”, NANO applications, electrical characterization, physical modeling, electrical LETTERS 2005 Vol. 5, No. 6 1023-1027. 2. M. Yoshino a, Y. Nonaka, J. Sasano, I. Matsuda, Y. modeling. The main applications that are being investigated today: Shacham-Diamand, T. Osaka , All-wet fabrication 1. Cell on chip applications – integration of cells on bio-chips process for ULSI interconnect technologies, for functional sensing of molecular components in aqueous Electrochimica Acta 51 (2005) 916-920 solutions. The cells are genetically engineered to generate a readily 3. A. Inberg, A. Ruzin, I. Torchinsky, V. Bogush, N. detectable electrical signal upon sensing toxicants; this signal will Croitoru, Y. Shacham-Diamand, Annealing influence be detected by either nano-electrodes or the ion-sensitive field on electrical transport mechanism of electroless deposited very thin Ag(W) films, Thin Solid Films , effect transistors, amplified, interpreted and broadcast by the in press (2005). electronic circuitry.Both nano-electrodes and the transistors will 4. Hila Einati, Vadim Bogush, Yelena Sverdlov, Yuri be made using self assembled techniques. Rosenberg, Yosi Shacham-Diamand, The effect of 2. directed metallization of cells for integrated electrochemical nano- tungsten and boron on the Cu barrier and oxidation biochip – electroless deposition in two levels: molecularlevel and properties of thin electroless cobalt-tungsten- cellular level and studying the impact of metal deposition of boron films, Microelectronic Engineering , in press (2005). cells on integrated biochip. It will be followed by experimental 5. E. Glickman a, A. Inberg , V. Bogush , G. Aviram , R. section which includes enzyme/cell metallization and activity Popovitz , N. Croitoru , Y. Shacham-Diamand, “Role experiments, evaluation of the immobilization of the metallized of local microchemistry and surface structure in cells and electrochemical measurement of the metallized cells. electrical resistivity of 50 nm electroless films Ag- W-oxygen”, Microelectronic Engineering, in press (2005).

Tel: (972)-3-6408064 Fax: (972)-3-6423508 Email: [email protected] Personal Website: http://www.eng.tau.ac.il/~yosish/

50 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Natan T. Shaked Engineering

n Biomedical Optical Microscopy and Nanoscopy. can be sub-nanometric. These low-cost and n optical Imaging and Therapy using Nano-Particles in Biological high-accuracy methods have been shown to be Cells. sensitive enough for early detection of diseases n optical Interferometric Systems (including Interferometric Phase such as cancer and Alzheimer’s disease. Plasmonic Microscopy, Optical Coherence Tomography and Endoscopic metal nano-particles that are adequately excited Interferometric Systems). by external sources are able to add specificity n optical Signatures of Cancer and Alzheimer’s Disease. to the interferometric measurements, which n Three-Dimensional Optical Imaging and Holography for enables nano-tracking, biological imaging below Biomedical Applications. the diffraction limit, and directed nano-therapy. Microscopic biological specimens, such as biological cells, are dynamic These novel techniques have a great potential as objects, continuously adjusting their three-dimensional sizes, shapes diagnostic tools for clinical applications, and thus and other biophysical features. Microscopy and nanoscopy of these we also examine the integration of the proposed specimens can provide a powerful research tool for cell biology techniques into a novel endoscopic fiber bundle studies, as well as a means for medical diagnosis and monitoring of probes, enabling in-vivo measurements and diseases. Many biological specimens, however, are mostly-transparent clinical implementations. objects, and thus imaging them with conventional bright-field light microscopy fails to provide adequate image contrast. For this reason, References exogenous contrast agents such as fluorescent labels are widely used 1. N. T. Shaked, L. L. Satterwhite, G. A. Truskey, M. J. in biomedical microscopy. However, these exogenous agents might Telen,and A. Wax, “Quantitative microscopy and nanoscopy of sickle red blood cells performed be cytotoxic in the long run and there is a possibility that they will by wide field digital interferometry,” Journal of influence the specimen behavior. Additionally, fluorescent agents Biomedical Optics Letters, Vol. 16, No. 3, 030506, tend to photobleach, potentially limiting the imaging duration. 2011. Novel optical interferometric and spectroscopic methods are able 2. Y. Zhu, N. T. Shaked, L. L. Satterwhite, and A. to uniquely characterize biological cells in vitro or in vivo, without Wax, “Spectral-domain differential interference microscopy,” Optics Letters, Vol. 36, Issue 4, pp. 430- 432, 2011. 3. N. T. Shaked, L. L. Satterwhite, N. Bursac, and A. Wax, “Whole-cell-analysis of live cardiomyocytes using wide-field interferometric phase microscopy,” Biomedical Optics Express, Vol. 1, Issue 2, pp. 706- 719, 2010. 4. N. T. Shaked, J. D. Finan, F. Guilak, and A. Wax, “Quantitative phase microscopy of articular chondrocyte dynamics by wide-field digital using any contrast agents or sample preparation. For example, interferometry,” Journal of Biomedical Optics interferoemtric phase microscopy using low coherence light sources Letters, Vol. 15, Issue 1, 010505, 2010. provides a fully quantitative tool for recording the three-dimensional 5. N. T. Shaked, M. T. Rinehart, and A. Wax, “Dual structure of cells, as well as the extremely fast dynamics associate interference channel quantitative phase with them (with rates of up to several thousands of full frames per microscopy of live cell dynamics,” Optics Letters, second), where the accuracy of measurement in the axial dimension Vol. 34, Issue 6, pp. 767-769, 2009.

Tel: (972)-3-6407100 Fax: (972)-3-6407100 Email: [email protected] Personal Website: www.tau.ac.il/~nshaked

51 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Meital Zilberman Engineering Polymeric biomaterials and implants, controlled drug release, tissue engineering

ctive implants can provide life-giving help to many systems in the body. When made of a biodegradable polymer, the degradation of such implants occurs by hydrolytic cleavage and the end products (carbon dioxide and water) are non- toxic. These implants can remain intact in the body forA a predicted period of time – from weeks to years – and then degrade obviating the need for a removal surgery. We have been developing and studying novel fiber- and film-based bioresorbable SEM micrograph of multi-reservoir microsphere structures loaded with various bioactive agents. These structures are loaded with protein molecules. designed to be used as basic elements of implants and scaffolds for tissue regeneration applications. In addition to their regular role of References support, these implants also release bioactive agents in a controlled 1. Adi Rachelson and Meital Zilberman, “Highly manner and thus, induce healing effects. We are investigating the Porous Nano and Micro-Structured Films Loaded effects of the process’ kinetic and thermodynamic parameters on with Bioactive Agents for Biomedical Applications: the nano- and micro-structural features of these implants and on Structure – Release Profile Effects”, Advanced Engineering Materials (Advanced Biomaterials), 11 the resulting properties (mainly drug release profile, mechanical (8), B122-128 (2009). and physical properties). The results of our studies thus have great 2. Jonathan J. Elsner and Meital Zilberman, ”Antibiotic- medical relevance and provide solutions to basic needs in the fields Eluting Bioresorbable Composite Fibers for Wound of medical implants and tissue regeneration. Healing Applications: Microstructure, Drug Delivery and Mechanical Properties”, Acta Biomaterialia, 5, Current main projects 2872-2883 (2009). 3. Amir Kraitzer, Yoel Kloog and Meital Zilberman, n Wound dressings with controlled release of antibiotics for “Novel Farnesylthiosalicylate (FTS) – Eluting treatment of patients with large burns, diabetic ulcers and Composite Structures”, European Journal of pressure sores. Pharmaceutical Sciences, 37, 351-362 (2009). n highly porous scaffolds for bone regeneration with growth factor 4. Yael Shifrovitch, Itzhak Binderman, Hila Bahar, Israela release. Berdicevsky and Meital Zilberman, “Metronidazole- n Core/shell fiber structures loaded with antiproliferative agents for Loaded Bioresorbable Films as Local Anti-Bacterial Treatment of Periodontal Pockets”, Journal of vascular stents and local cancer treatment. Periodontology, 80 (2), 330-337 (2009). n A new class of bioactive and biodegradable soybean-base 5. Amir Kraitzer, Yoel Kloog and Meital Zilberman, scaffolds for tissue regeneration applications. “Approaches for Prevention of Restenosis”, Journal n Novel drug-eluting soft tissue adhesives and hard tissue adhesives of Biomedical Materials Research Part B: Applied based on natural polymers. Biomaterials, 85 (B), 583-603 (2008). 6. Meital Zilberman and Jonathan Elsner, “Antibiotic- Eluting Medical Devices for various Applications – A review”, Journal of Controlled Release, 130, 202- 215 (2008). 7. Amir Kraitzer, Lia Ofek, Reut Schreiber and Meital Zilberman, “Long-Term In-Vitro Study of Paclitaxel Eluting Bioresorbable Core/Shell Fiber Structures”, Journal of Controlled Release, 126, 139-148 (2008). Tel: (972)-3-6405842 Fax: (972)-3-6407939 Email: [email protected] Personal Website: http://www.eng.tau.ac.il/~meitalz/

52 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Azem Abdussalam Life Sciences Protein folding and Unfolding by Molecular Chaperones

haperone protein, as their name implies, accompany sorted into mitochondria. Protein import into proteins, during synthesis, translocation, and stress- the matrix space requires the activity of the induced denaturation, to prevent misfolding and mitochondrial hsp70 (mhsp70) chaperone. aggregation and subsequently facilitate their MtHsp70 is an ATP-hydrolyzing component, correct refolding. They carry out their task and are which acts together with other subunits of not retained as part of the final protein complex. the so-called translocation motor to execute ManyC chaperone proteins are also classified as heat-shock proteins the final steps of translocation across the (hsp), due to the fact that their expression is generally up-regulated inner membrane. Since the motor associates at temperatures that are elevated relative to the normal growth with the TIM23 complex in order to carry temperature of an organism. Five basic families have been described out its task, our research includes studying and classified by their molecular weights: hsp100, hsp70, hsp60/10, the molecular mechanism of function of the hsp40, and small heat-shock proteins. complete TIM23 complex and its associated The research in our group aims at obtaining greater insight into the motor components. molecular mechanism behind the function of molecular chaperones. We are interested in two aspects of the function of molecular References chaperones. 1. Marom, M., Safonov, R., Amram, S., Avneon, i. The mechanism of function of mitochondrial and chloroplast Y., Nachliel, E., Gutman, G, Zohary, K., Azem, A. and Tsfadia, Y. (2009). The Interaction of Tim44 chaperonins. The ultimate function of this group of proteins is C-terminal Domain with Negatively-Charged in mediating the folding of newly translated, imported and stress Phospholipids. Biochemistry. 48, 11185-95. denatured proteins. We are trying to determine the unique 2. Parnas, A., Nadler, M., Nisemblat, S., Horovitz, A., structural and functional properties of the mitochondrial and Mandel, H., and Azem,, A. (2009) The MitCHAP-60 chloroplast chaperonins that distinguish them from the bacterial Disease is due to Entropic Destabilization of the homolog and make them suitable for specific roles within these Human Mitochondrial Hsp60 oligomer. J. Biol. Chem. 284, 28198-28203. organelles. 3. Airapetov, L., Zohary, L., Popov-Čeleketić, D., Mapa, K., Hell, K., Neupert, W., Azem, A., and Mokranjac, D. (2009). Interaction of Tim23 with Tim50 is essential for protein translocation by the mitochondrial TIM23 complex. J. Biol. Chem. 284, 4865-4872. 4. Slutsky-Leiderman, O., Marom, M., Iosefson, O., Levy, R., Maoz, S. and Azem, A. (2007). The interplay between components of the mitochondrial protein translocation motor studied using purified components. J. Biol. Chem. 282, 33935-33942. 5. De Los Rios, P., Ben-Zvi, A., Slutsky, O., Azem, A., Goloubinoff, P. (2006)H sp70 chaperones accelerate ii. The mechanism of function of molecular chaperones that protein translocation and the unfolding of stable protein aggregates by entropic pulling. Proc. Natl. mediate protein import into the mitochondrial matrix. Nuclear- Acad. Sci. USA. 103, 6166-6171. encoded mitochondrial proteins (~800-1000 proteins in yeast) 6. Azem, A., Kessel, M. and Goloubinoff, P. (1994) are synthesized in the cytosol as precursors and then imported/ Characterization of a functional GroEL14(GroES7)2 chaperonin hetero-oligomer. Science 265, 653-656.

Tel: (972)-3-6409007 Fax: (972)-3-6406834 Email: [email protected] Personal Website: http://www.tau.ac.il/lifesci/departments/biochem/ members/azem/azem.html

53 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Ari Barzilai Life Sciences The molecular mechanism of optic nerve degeneration and regeneration

illions of people throughout the world become promote RGC survival and axonal regeneration. blind as a result of devastating disease or (i) Spatial and temporal controlled secretion trauma. In the Western world, the main factors from specially designed nano-structures that will leading to blindness are diseases such as implanted in the optic nerve. (iii) Implantation diabetes, age related macular degeneration of nano-chips and electrodes in the optic nerve (AMD) and glaucoma, or traumas such as in order to generate biofeedback necessary to Mcar and work accidents, terrorism and wars. In the third world, maintain homeostatic conditions. malnutrition as well as infective and toxic alimentation are the leading factors of blindness. Our work is based on our hypothesis References that retinal ganglion cells (RGC) are capable of growing their axons 1. Shirvan, A., Ziv, I., Fleminger, G., Shina, R., He, Z., following injury; however, the non-permissive environment prevents Brudo, I., Melamed, E., and Barzilai, A., Semaphorins as mediators of neuronal death. J. Neurochem. 73 them from doing so. We further hypothesize that removal of the 961-971 (1999). non-permissive cures and supplement the RGCs with axonal growth 2. Shirvan, A., Melamed, E., and Barzilai, A., Induction promoting substances will lead to axonal functional regeneration. of neuronal apoptosis by semaphorin 3A derived Based on these hypotheses we intend to use holistic approach that peptide. Brain Res. Mol. Brain Res. 83 81-93 (2000). combines nanotechnological methodologies that will supplement 3. Shirvan, A., Kimron, M., Holdengreber, V., Ziv, I., the neurons with the necessary cues that will accelerate their growth. Melamed, S., Melamed, E., Barzilai, A., and Solomon, A.S., Anti sema3A antibodies resuce retinal Our specific aims are: (i) Implantation of biodegradable three- ganglion cells from cell death induced by optic dimensional scaffold in the optic nerve and assessing its ability to nerve axotomy. J. Biol. Chem. 277 49799-49807 (2002).

Tel: (972)-3-6409782, (972)-3-6407129 Fax: (972)-3-6407643 Email: [email protected] Personal Website: http://www.tau.ac.il/lifesci/departments/neuro/ members/barzilai/barzilai.html

54 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Itai Benhar Life Sciences Targeted drug-carrying phage nanoparticles

acteriophages (phages) have been used for over specific peptide, recombinant antibody or a century for (un-orthodox) therapy of bacterial other target-specifying entity) on their surface. infections (also known as “phage therapy”), for nearly The drugs are chemically conjugated to the half a century as tools in genetic research, for nearly bacteriophages through labile linkages that are two decades as tools for discovery of specific target- subject to controlled cleavage. In the conjugated binding proteins (mainly antibodies and peptides, state the drug is kept in an inactive prodrug state knownB as “phage display”), for nearly a decade as tools for vaccination and is released and concomitantly re-activated or as gene delivery vehicles and very recently as tools for assembly of at the target. As such, the drug-carrying phage electronic materials by nanofabrication. nanoparticles may be useful as targeted drug Filamentous phages (Inovirus) comprise a family of bacterial viruses delivery vessels for the treatment of various that have only about 10 genes and grow in well-characterized hosts, pathological conditions. the Gram-negative bacteria. Structurally, the filamentous phage is The targeted drug carrying phage nanoparticles a particle of nanometer dimensions comprising a sheath of several have a large drug-carrying capacity in excess of thousand identical alpha-helical coat proteins in a helical array that 104 drug molecules/target site. We have provided during phage maturation, self-assemble around a single-stranded POC of this approach toward the elimination of circular DNA molecule at the core. A few minor proteins cap the pathogenic bacteria cancer cells in closed culture particle at each end. systems and are now evaluating the potential We present a novel technology related to the field of targeted drug of the approach in small animal disease models. delivery in the form of targeted drug-carrying phage nanoparticles. In 2010 we initiated a study of targeting the Our approach is based on genetically-modified and chemically pathogenic fungus, Aspergillus fumigatus using manipulated phages. The genetic manipulation endows the phages our approach which is carried out in collaboration with the ability to display a host-specificity-conferring ligand (target- with Dr. Nir Oshrov from the Medical School.

References 1. Yacoby, I. and Benhar, I. (2008) Potential of Antibacterial Nanomedicines. Nanomedicine 3(3):329-41. 2. Bar, H., Yacoby, I. and Benhar, I. (2008) Killing cancer cells by targeted drug-carrying phage nanomedicines. BMC Biotech. 8:37. 3. Yacoby, I. and Benhar, I. (2008) Targeted Bacteriophages as Therapeutic Agents. Expert Opin Drug Targets. 5(3):321-329. 4. Yacoby, I. and Benhar, I. (2007) Targeted anti bacterial therapy. Infectious Diseases Drug Targets. 7(3):221-9. 5. Yacoby, I., Bar, H. and Benhar I. (2007) Targeted drug-carrying bacteriophages as anti bacterial Targeted drug-carrying phage nanoparticle: general scheme nanomedicines. Antimicrob Agents Chemother. 51(6):2156-63. 6. Yacoby Y., Shamis, M., Bar, H., Shabat, D. and Benhar, I. (2006) Targeting anti bacterial agents by drug- Phone: (972)-3-6407511, (972)-3-6407510 carrying filamentous bacteriophages. Antimicrob. Fax: (972)-3-6405829 Agents & Chemother. 50(6):2087-2097. E-mail: [email protected] Personal Website: http://www.tau.ac.il/lifesci/departments/biotech/ members/benhar/benhar.html

55 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Chanoch Carmeli Life Sciences Application of the Photosynthetic Reaction Center Proteins, PS I in the Fabrication of a Novel Nano-Bio-Photovoltaic Devices

hotovolteic devices are fabricated by assembling when the oriented self assembled monolayer of the highly efficient photosynthetic reaction center PS I on metal electrode was capsulated in a nitride protein in solid state scaffolds. The assembly of the micro cell and toped with the transparent indium soft protein-made photosystem I (PS I) into a solid tin oxide electrode. These photovoltaic devices state scaffold without damaging the activity is very are being used for development of cost effective challenging therefore the robust chlorophyll-protein solar cells. It can be applied in the development PSP I reaction centerfrom cyanobacteria was selected. Induction of bio-nano-photo-sensors, in artificial vision and of cysteine mutants in the outer loops of this membrane protein as photo-switches in molecular electronics. enabled fabrication of oriented self assembled monolayer by formation of sulfide bonds to metal electrodes as determined by References AFM. In the biological membranes the efficient PS I generates light- 1. Frolov, L.; Rosenwaks, Y.; Carmeli, C.; Carmeli, I. induced vectorial charge transfer across nano size protein creating Fabrication of Photo-Electronic Device by Direct Chemical Binding of the Photosynthetic Reaction a potential of 1 V in 200 ns at quantum efficiency of 1 and energy Center Protein to Metal Surfaces. Adv. Mater. 2005, conversion efficiency of 58%. It was found that the self assembled dry 17, 2434-2437. PS I retained its activity as it generated a reversible photovoltage of 1 V 2. Pending # 60/654,502, (2005) Fabrication of nano- as measured by KPFM1,2. A photocurrent of 0.35A/cm2 was measured photoelectrical device from photosystem I.

Figure: Light induced charge separation in protein-chlorophyll reaction center-PS I drives current in a solid state scaffold. The nano-particles are attached to bottom metal electrode inside a nano-cavity drilled in a Si3N4 layer. A conductive and transparent protective InSnO2 is sputtered on top.

Tel: (972)-3-6409826, (972)-3-6415053 Fax: (972)-3-6406834 Email: [email protected] Personal Website: http://www.tau.ac.il/lifesci/departments/biochem/ members/carmeli/carmeli.html

56 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Avigdor Eldar Life Sciences

Sub-micron light-guided protein localization and will use these systems to explore aspects of super-resolution microscopy for studying division and differentiation and protein localization during signaling in bacteria sporulation. My interest is in understanding symmetry breaking and its relation with cell signaling and differentiation on multiple temporal and spatial Division septum assembly and site- scales. The main model system in my lab is the sporulation process selection of the bacteria Bacillus subtilis. Using it we will study differentiation Bacterial cytokinesis (division) is guided by decisions, symmetry breaking in cell division and signaling across a the assembly of a membrane bound ‘ring’ of septum. the tubulin-like protein ftsZ. The subcellular localization of this ring is guided by a complex 1. Light guided systems for studying signaling and molecular network of inhibitors that restrict its localization. assembly in living cells at the cellular and sub-cellular resolution During growth, a single cytokinetic ring is usually Several systems have been developed recently for using light to restricted to the middle of the bacteria. Upon guide gene expression and protein localization in living cells. We sporulation, two rings are formed at the two distal ends of the bacteria but only one of them continues through cytokinesis while the other disassembles. We will explore the re-localization of the ring and the symmetry breaking event it goes through by re-designing the membrane binding protein that link the ftsZ filaments to the membrane to allow membrane localization by light. This will allow us to guide the position of localization and the number of localization sites at a diffraction limiting resolution of 300nm. We will combine this technique with time-lapse microscopy of fluorescently tagged ftsZ to monitor the assembly and dissociation dynamics, the interaction between assembly sites and the dependence of the system on various proteins that modify the preferred localization. Studying cell division dynamics and site selection using light regulated localization. (A) The formation of the division ring can be followed by fluorescent protein reporter fused to the main component of the ring, ftsZ (marked Z in B,C). Sporulation decision making (B) Wild type ring protofilament consist of ftsZ and the membrane anchoring The decision to sporulate is guided by a complex protein ftsA (marked A). A light regulated system for membrane localization will regulatory system, involving many feedbacks at be incorporated into the ftsA membrane. The two components bind and unbind the cellular and inter-cellular levels. We will use a depending on wavelength. (C) Using this system we will control z-ring assembly at sub-micron resolution and monitor its formation dynamics and dependence light-activated gene expression system to control on additional proteins. gene expression in time and space in order to understand the basic logic of this system and the way it guides symmetry breaking on the multi- Tel: (972)-3-6407492 cellular level. Fax: (972)-3-6409407 E-mail: [email protected] 2. Super-resolution techniques for studying Personal Website: http://www.tau.ac.il/lifesci/departments/biotech/ complex formation across septa members/eldar/eldar.html Asymmetric septation during sporulation is

57 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

followed by the differentiation of the two cells, which is guided by References signaling between them across the septa. This system serves as a 1. Eldar, A., et al., Partial penetrance facilitates simple model to analyze direct interaction between cells. Membranal developmental evolution in bacteria. Nature, 460 (7254): 510-4 (2009). proteins involved in cross-septal signaling are characterized by 2. Eldar, A. and N. Barkai, Interpreting clone-mediated asymmetric distribution on the two sides, by coupled formation of perturbations of morphogen profiles. Dev Biol, complexes on the two sides and by the formation of fine-resolution 2005. 278 (1): p. 203-7. patterns. Most of these characteristics cannot be examined by regular 3. Eldar, A., B.Z. Shilo, and N. Barkai, Elucidating light-microscopy because of the nanometric scale of the system. mechanisms underlying robustness of morphogen We will use STORM (stochastic optical reconstruction microscopy) gradients. Curr Opin Genet Dev, 2004. 14 (4): p. 435-9. super-resolution techniques to reconstruct the signaling apparatus 4. Eldar, A., et al., Self-enhanced ligand degradation underlies robustness of morphogen gradients. Dev at the 10nm resolution and analyze their dependence on interaction Cell, 2003. 5 (4): p. 635-46. and signaling. While a one-color STORM is sufficient to analyze the 5. Eldar, A., et al., Robustness of the BMP morphogen interdependence of localization across the septa, two colors are gradient in Drosophila embryonic patterning. needed to resolve co-localization of proteins within the compartment Nature, 2002. 419 (6904): p. 304-8. and such methods will be explored.

58 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Amihay Freeman Life Sciences Biologically active metal-enzyme and metal-cell hybrids and their integration with electrodes and biochips

ew methods were developed for the fabrication of References novel enzymatically active, soluble and stabilized 1. Wine Y, Cohen-Hadar N, Lamed R, Freeman A, enzymes and binding proteins for their integration Frolow F (2009). Modification of protein crystal packing by systematic mutations of surface with electrodes and biochips. residues. Biotechnology and Bioengineering 104: This project is carried out in collaboration with 444-457 Prof. Shacham from The Department of Physical 2. Vernick S, Moscovich-Dagan H, Porat-Ophir C, Electronics,N Faculty of Engineering, and Prof. Rishpon from our Rishpon Y, Freeman A, Shacham-Diamand Y. department. (2009). Directed metallization of single enzyme molecules with preserved enzymatic activity. IEEE Protein crystals as biotemplates for the fabrication of Transactions 8: 95-99. 3. Cohen-Hadar N, Wine Y, Lagziel-simis S, Dror novel composite materials Y, Frolow F, Freeman A (2009). Protein crystal The use of protein crystals as highly ordered biotemplate enabling mediated biotemplating. J Porous Media 12: 213- “filling” of its nano-structured voids array was established. Novel 220. approaches for restructuring of the porosity of a given protein 4. Ben Yoav H, Freeman A. (2008). Enzymatically crystal were developed along with methods for the stabilization of attenuated in situ release of silver ions to combat bacterial biofilms. J Drug Delivery Science and the protein biotemplate and monitoring of the filling process were Technology 18: 25-29. demonstrated. 5. Wine Y, Cohen-Hadar N, Freeman A, Frolow F (2007). This project is carried out in collaboration with Prof Frolow from our Elucidation of the mechanism and end products department. of glutaraldehyde crosslinking reaction of protein crystal by X- ray structure analysis. Biotechnology and Bioengineering 98: 711-718. 6. Moscovich-Dagan H, Cohen – Hadar N, Porat C, Rishpon J, Shacham-Diamand Y, Freeman A. (2007). Wiring of the catalytic site of novel molecular enzyme-metal hybrids to electrodes. J Physical Chem C 111: 5766-5769. 7. Lagziel-Simis S, Cohen-Hadar N, Moscovich-Dagan H, Wine Y, Freeman A (2006). Protein mediated nano-scale biotemplating. Currents Opinins in Biotechnology, 17: 569-573. 8. Cohen-Hadar N, Wine Y, Nachliel E, Huppert D, Gutman M, Frolow F & Freeman A (2005). Biotemplating of synthetic gels by stabilized protein crystals. Biotechnology and Bioengineering, 94: 1005-1011.

Crystal porosity modification by site-directed mutagenesis

Tel: (972)-3-6409054 Fax: (972)-3-6405147 Email: [email protected] Personal Website: http://www.tau.ac.il/lifesci/departments/biotech/ members/freeman/

59 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Ehud Gazit Life Sciences Self-Assembly of Short Aromatic Peptides: from Amyloid Disease to Nanotechnology

he self-assembly of well-ordered amyloid fibrils is their biological compatibility and remarkable the hallmark of several diseases of unrelated origin, mechanical, and chemical stability, may provide including Alzheimer’s disease, Type II diabetes, very important tools for future nanotechnology and Parkinson’s disease. We suggested, based applications. We recently demonstrated the on experimental and bioinformatical analysis, ability of the nanotubes to serve in advanced thataromatic stacking interactions may provide electrochemical sensing. Tenergetic contribution as well as order and directionality in the self- assembly process. Our model recently gained experimental and References theoretical support from leading groups and it serves as the basis for 1. Reches, M., & Gazit, E. (2003) Casting Metal the development of novel therapeutic agents to treat the disorders. Nanowires within Discrete Self-Assembled Peptide Nanotubes. Science 300, 625-627. In the path of our reductionist approach toward the identification 2. Reches, M., & Gazit, E. (2004) Formation of Closed- of the shortest motifs that mediate the assembly of the fibrils, we Cage Nanostructures by Self-Assembly of Aromatic demonstrated that the diphenylalanine core-recognition motif of Dipeptides. Nano Lett. 4, 581-585. the Alzheimer’s β-amyloid contains all the molecular information 3. Yemini, M., Reches, M., Rishpon, J., & Gazit, E. (2005) needed for efficient assembly into well-ordered, stiff, and elongated Novel Electrochemical Biosensing Platform Using nanotubes with a remarkable persistence length, that could serve Self-Assembled Peptide Nanotubes. Nano Lett. 5, 183-186. as a mold for the fabrication of nanoscale inorganic material. We 4. Kol, N., Abramovich, L., Barlam, D., Shneck, R. Z., later reveal that diphenylglycine, a highly similar analogue and the Gazit E. , & Rousso, I. (2005) Self-Assembled Peptide simplest aromatic dipeptide, forms spherical nanometric assemblies. Nanotubes Exhibit Unique Mechanica Stiffness. These properties of the peptide nanostructures, taken together with Nano Lett. 5, 1343 -1346.

Peptide nanotubes on a carbon electrode used for biosensors application

Tel: (972)-3-6409030, (972)-3-6407536 Fax: (972)-3-6405448 Email: [email protected] Personal Website: http://www.tau.ac.il/lifesci/departments/biotech/ members/gazit/gazit.html

60 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Jonathan Gershoni Life Sciences Nano-optical sensing of protein: Protein interactions

e work to elucidate the molecular References mechanisms of bio-recognition, especially 1. Gershoni, J.M. 2008 Molecular decoys: antidotes, those related to the interplay between therapeutics and immunomodulators. Curr. Opin. Biotech. 19: 644-651. viruses and the immune system. Our main 2. Ozkumur, E, JW Needham, DA Bergstein, R goals focus on understanding the specific Gonzalez, M Cabodi, J.M. Gershoni, BB Glodberg, interaction between viral proteins, their MS Unlu 2008 Label-free and dynamic detection cognateW receptors and the antibody response against them. The of biomolecular interactions for high-throughput insights gained are applied towards the development of novel microarray applications. Proc. Natl. Acad. Sci USA vaccines, therapeutics and immunodiagnostics. The latter aspect of 105: 7988-7992. 3. Bergstein, DA, E Ozukumur, AC Wu, A Yalcin, JR our work incorporates the development of new optical biosensors. Colson, JW Needham, RJ Irani, J.M. Gershoni, BB Spectral Reflectance Imaging Biosensing (SRIB) is a nanophotonic Goldberg, C DeLisi, MF Ruane, MS Unlu 2008 platform that supports multiplex protein arrays in which binding Resonant cavity Imaging: a means toward high events are detected label-free. The schematic of the SRIB system thoughput label free protein detection Selec. Top. used at Tel Aviv University and an explanation of SRIB principles are Quantum Electronics 14: 131139. provided. 4. Gershoni J.M., A. Roitburd-Berman, D.D. Siman- Tov, N. Tarnovitski Freund, Y. Weiss 2007 Epitope mapping: the first step in eveloping epitope-based vaccines. BioDrugs 21: 1-12. 5. Bublil, E.M., N. Tarnovitski Freund, I. Mayrose, O. Penn, A. Roitburd-Berman, N.D. Rubinstein, T. Pupko, J.M. Gershoni 2007 Stepwise prediction of conformational discontinuous B-cell epitopes using the Mapitope alghorithm. Proteins 68: 294- 304.

Tel: (972)-3-6408981 Fax: (972)-3-6402046 Email: [email protected] Personal Website: http://www.tau.ac.il/lifesci/departments/cell_r/ members/gershoni/gershoni.html

61 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Alexander Kotlyar Life Sciences DNA – based Organic Nano Wires

NA is a fascinating soft material that naturally conducting wire itself. Finally we hope to establish expresses two of the three main features required first prototype single-DNA-based electronic from molecular nanoelectronic components, devices. Several experimental and theoretical namely recognition and specific structuring groups working in Israel and Europe are working (sequence, length). The third additional property as a team towards the realization of the goals of that is needed in order to implement DNA- this interdisciplinary project. Dderivatives for electrical device applications is conductivity. The central objective of this multidisciplinary project is, thus development References of DNA-based conductive nanowires for nanoelectronics. There are 1. A. Kotlyar, N. Borovok, T. Molotsky, L. Fadeev, M. two main goals of this the project. The first is to produce double- Gozin, “In Vitro synthesis of uniform Poly(dG)- Poly(dC) by Klenow exo-fragment of Polymerase I.”, stranded [1,2], triple–stranded [3] and G4-DNA [4] molecular Nucleic Acid Research 33, 525 (2005). nanowires as well as complexes of the above wires with various redox 2. E. Shapir, J. Yi, H. Cohen, A. Kotlyar, G. Cuniberti, D. active ions and to characterize their electrical properties. We recently Porath, “The Puzzle of Contrast Inversion in DNA succeeded to produce for the first time a novel 4G-DNA nanowires STM Imaging” , J. Phys. Chem. B 108, 14270 (2005). that show encouraging conductivity signals while preserving the 3. A. Kotlyar, N. Borovok, T. Molotsky, D. Klinov, B. Dwir, structuring and recognition qualities. The second goal of the project E.Kapon “Synthesis of novel poly(dG)-poly(dG)- poly(dC) triplex structure by Klenow Exo- fragment is development of model nanoelectronic devices on the basis of the of DNA Polymerase I “ Nucleic Acid Research (2005) above DNA-Based wires. Our strategy is to use specific alterations in press. of the sequence and inclusions of hybrid inorganic elements to 4. A. Kotlyar, N. Borovok, T. Molotsky, H. Cohen, E. pre-planned locations in the conducting wire. A device resulting Shapir, D. Porath, “Novel Long Monomolecular G4- from this approach will be nanometric in size and embedded in the DNA Nanowires”, Adv. Mater. 17, 1901 (2005).

Tel: (972)-3-6407138 Fax: (972)-3-6406834 Email: [email protected] Personal Website: http://www.tau.ac.il/lifesci/departments/biochem/ members/kotlyar/kotlyar.html

62 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Rimona Margalit Life Sciences Biomaterial-based targeted particulate drug carriers: biophysical properties, cell-particle interactions and therapeutic responses

ur efforts in the drug delivery arena focus on three structural, physicochemical and biochemical drug delivery technologies that are inventions of properties of the drug-carrier systems selected for our group. All are based on biomaterials, and can a given task. In cell cultures we explore cell–carrier form vesicular-shaped particles. The particles interactions with particular emphasis on: kinetics of one technology are named Bioadhesive and thermodynamics of cell-carrier binding, Liposomes (BALs), consisting of regular liposomes cellular localizations of carrier and drug, the –O hence their shell is a lipid bilayer membrane. Surface-modification mechanisms by which carrier-mediation affects by covalent binding of target-recognition agents such as hyaluronan, drug entry into cells, and therapeutic activity. The collagen, EGF or gelatin to the liposomal surface, renders them in vivo studies focus on pharmacokinetics, drug bioadhesive. The particles of the second technology are named and carrier biodistributions, adverse effects, and gagomers (GAGs), their shell is made of hyaluronan, and their interior therapeutic responses. contains water and lipids. The particles of the third technology are named collagomers, their shell is made of collagen and their interior Selected Publication from collagen-lipid conjugates. The goal is to apply these particles 1. Rivkin I, Cohen K, Koffler J, Melikhov D, Peer as drug carriers for the treatment of pathologies such as tumors, D, Margalit R. (2010) Paclitaxel-clusters coated with hyaluronan as selective tumor-targeted infectious diseases, diabetes and inflammatory diseases, in order to nanovectors. Biomaterials 31, 7106-7111. improve deficiencies of treatment with free drugs, as the latter lead 2. Dekel Y, Glucksam Y, Margalit R (2010) Novel to poor therapeutic responses and to treatment failures. The choice fibrillar insulin formulations for oral administration: of more than one carrier technology allows for the match of carrier Formulation and in vivo studies in diabetic mice. J. species, size and route of administration that best-fits the designated Cont. Rel. 143, 128-135. therapy. Our conceptual approach, for any project, is to start at the 3. Elron-Gross I, Glucksam Y, Margalit, R (2009) Liposomal dexamethasone-diclofenac combinations for local molecular level and proceed systematically to studies in cell cultures, Osteoarthritis treatment. Intl. J. Pharma. 376, 84-91. and then to animal studies. At the molecular level we investigate 4. Margalit R, Peer D (2009) Lipidated glycosaminoglycan particles and their use in drug and gene delivery for diagnosis and therapy. US patent # 7,544,374. 5. Barkay Z, Rivkin I, Margalit R. (2009) Three- dimensional characterization of drug- encapsulating particles using STEM detector in FEG-SEM. Micron 40, 480-485. 6. Elron-Gross I, Glucksam Y, Biton IE, Margalit, R (2009) A novel Diclofenac-carrier for local treatment of Osteoarthritis applying live-animal MRI. J. Cont. Rel. 135, 65-70. 7. Glucksam Y, Elron-Gross I, Raskin A, Gombein P, Keller N, Margalit R, Schumacher I. (2008). Control Drug delivery to tumor cells mediated by targeted nano carriers. Left-hand side: and prevention of bacterial infections in burns by Bioadhesive Liposomes bound to mouse melanoma cells. Drug load (fluorescein, green fluorescence) is localized at the cell membrane. Right-hand side: Gagomers new formulations based on drug/carrier systems. J (red fluorescence) bound to mouse leukemia cells. Drug load (doxorubicin, red Israeli Military Med, 5, 66-70. fluorescence) is localized inside the cell. 8. Elron-Gross I, Glucksam Y, Melikhov D, Margalit R (2008) Cyclooxygenase inhibition by diclofenac formulated in bioadhesive carriers. Biochim Tel: (972)-3-6409822 Biophys Acta. 1778, 931-936. Fax: (972)-3-6406834 9. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Email: [email protected] Langer R. (2007) Nanocarriers: Emerging Platforms Personal Website: http://www.tau.ac.il/lifesci/departments/biochem/ for Cancer Therapy. Nature Nanotechnology 2, 751- members/margalit/margalit.html 760.

63 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Iftach Nachman Life Sciences

ur goal is to understand how cells within a Differentiation dynamics in size- population reach developmental decisions at the controlled embryoid bodies phenotypic and mechanistic level. How do cells In-vitro differentiation of embryonic stem cells “decide” to change their state? Why do similar into defined cell types is a field of immense cells respond differently to the same signal? What importance for both regenerative medicine properties of the cell affect its decision? Our lab and for basic understanding of development. willO study these fundamental questions in two model systems using Embryoid bodies (EB’s), three dimensional methods from live cell fluorescent imaging, microfluidics, statistical aggregates of differentiating embryonic stem and computational analysis. cells, have been the method of choice for in-vitro differentiation into many cell types, including motor neurons, hepatocytes and cardiomyocytes. We are developing a microfluidic-based system for controlled EB formation, for generation and imaging of both uniform and variable size and shape EB’s. We will study correlates of specific cell fate differentiation and cell movement patterns in EB’s by imaging large numbers of such systems, in conjunction with protein reporter and lineage tracing fluorescent constructs. The project will enhance our basic understanding of cell movement and rules of differentiation during development, and can lead to improved protocols of in-vitro differentiation.

Signal perturbations with spatial or Propagation of information through signaling and temporal gradients in microfuidic transcriptional pathways devices Cell populations in the nature face different cues from the environment a. A microfluidic flow cell capable of generating that change in different frequencies. For example, a yeast colony in a stable concentration gradient, shown in the the vineyard senses different levels of heat, humidity, osmolarity and insets on the right. By combining this device with nutrient levels changing at different rates. Effective response to these time varying inputs, we create a signal pulse with fluctuating cues raises several challenges. Can the cells distinguish a spatial gradient. b. Using the setup above, we between a fleeting cue and a consistent change? Can they filter out measured the meiosis decision time as a function the former to avoid mistaken decisions? How do their signaling and of the spike glucose level. The results show an transcriptional networks handle these complex fluctuations? We increase in decision time and variability which study responses to signal fluctuations in the yeast meiosis process depend on the fluctuation strength over a limited using live cell microscopy and custom-designed microfluidic devices range. c. By gradually changing the flow pressures capable of generating spatial and temporal signal gradients. in the two inputs of a Y-shaped flow channel, we obtain different spike durations along the

Tel: (972)-3-6405900, (972)-3-6409442 width of the channel. Multiple Y channels allow Fax: (972)-3-6409422 measurement of different conditions in parallel. Email: [email protected] Personal Website: http://www.tau.ac.il/lifesci/departments/biochem/ members/nachman/nachman.html

64 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

References 1. ZD. Smith*, I. Nachman*, A. Regev, A. Meissner (2010). Dynamic single- cell imaging of direct reprogramming reveals an early specifying event. Nature Biotechnol. 2010 May; 28 (5): 521-6. 2. I. Nachman, A. Regev (2009). BRNI: Integrated modular analysis of transcriptional regulatory programs. BMC Bioinformatics, 10: 155. 3. I. Nachman, A. Regev, S. Ramanathan (2007). Dissecting Timing Variability in Yeast Meiosis. Cell 131 (3), 544-556. 4. I. Nachman, A. Regev, N. Friedman (2004). Inferring Quantitative Models of Regulatory Networks from Expression Data. Bioinformatics 20: I248– I256. 5. I. Nachman †, G. Elidan †, N. Friedman (2004). “Ideal Parent” Structure Learning for Continuous Variables Networks. Proc. 20th Conference on Uncertainty in Artificial Intelligence (UAI). 6. N. Friedman, I. Nachman (2000). Gaussian Process Networks. Proc. 16th Conf. on Uncertainty in Artificial Intelligence (UAI). 7. N. Friedman, M. Linial, I. Nachman, D. Pe’er (2000). Using Bayesian Networks to Analyze Expression Data. J. Computational Biology 7 (3, 4), 601-620. 8. A. Ben-Dor, L. Bruhn, N. Friedman, I. Nachman, M. Schummer, Z. Yakhini (2000). Tissue Classification with Gene Expression Profiles. J. Computational Biology 7 (3, 4), 559-583. 9. N. Friedman, I. Nachman, D. Pe’er (1999). Learning Bayesian Network Structure from Massive Datasets: The Sparse Candidate Algorithm. Proc. 15th Conf. on Uncertainty in Artificial Intelligence (UAI). 1. (* equal contribution)

65 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Peer Dan Life Sciences Laboratory of Nanomedicine

ur lab is studying how to manipulate cells’ We are particularly engaged in the following functions in order to generate novel strategies projects: to treat inflammatory diseases and cancers. We n Developing novel strategies for targeted are combining multidisciplinary approaches nanoparticulate drug delivery systems. including immunology, cell and molecular n Probing and manipulating the immune biology, genetics, protein engineering, material system with nanomaterials. sciences,O nanotechnology and computational techniques for n Studying the role of cell cycle regulators drug discovery and potentially for therapeutics. In addition, we are during inflammatory bowel diseases and developing nanomedicines by designing highly selective targeting blood cancers. moieties and novel nanocarriers, with an ultimate goal to translate n Investigating novel cancer multidrug some of our findings into clinical settings. resistance inhibitors. n Studying novel approaches to target adult stem cells (hematopoietic; bulge, cancer). n harnessing RNAi as a tool for drug discovery and for therapeutic applications. n Developing tools to study immuno- nanotoxicity.

Selected Publications 1. Mizrahy S and Peer D (2011). Polysaccharides as building blocks for Nanotherapeutics. Chemical Society Reviews. In press. 2. Moghimi M., Peer D. , and Langer R. (2011). Reshaping the Future of Nanopharmaceuticals:. ACS Nano. In press. 3. Mizrahy S, Raz SR, Hasgaard M, Liu H, Soffer-Tsur N, Cohen K, Dvash R, Landsman-Milo D, Bremer MG, Moghimi SM, Peer D. (2011).Hyaluronan-coated nanoparticles: The influence of the molecular weight on CD44-hyaluronan interactions and on the immune response. Journal of Controlled Release, In press.

Selective targeting of siRNAs (red) into activated lymphocytes (green) using fusion protein that target conformation-selective integrin LFA-1. Naive cells (not stained) do not uptake siRNAs.

Tel: (972)-3-6405926, (972)-3-6405600 Fax: (972)-3-6405926 Email: [email protected] Personal Website: www.tau.ac.il/~peer/ Editorial board: Nanotechnology

66 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Judith Rishpon Life Sciences Application of nano technologies in electrochemical Biosensors

Carbon nanotubes on amperometric electrodes gold electrodes. The system respond to estrogen We have effectively exploited the unique electronic properties of or testosterone at physiological concentrations. carbon nanotubes (CNT) in electrochemistry as a means of promoting Moreover, it enables the detection of the electron transfer reaction for the development of enzyme based xenohormones like xenoestrogens that are a sensors. CNT were attached to gold or carbon electrodes and applied health risk in the environment [2]. in a sensitive detection of hydrogen peroxide employing the enzyme horse reddish peroxidase immobilized on a CNT modified electrode. Lab on a Chip This sensor was capable to measure enzymatic activity released from We developed an innovative electrochemical ‘lab the mycobacteria smegmatis (a model system for mycobacteria on a chip’ system that integrates the applicability tuberculosis). CNT attached to electrodes were also exploited in a of physiological reactions to serve as biosensors highly sensitive electrochemical enzyme immunosensors. with the advantages of micro electro mechanical systems (MEMS). The novel specific design and Peptide nanotubes on amperometric electrodes process of the nano-biochip adjusted to an In addition, we have examined the possibility of employing peptide exclusive biochemical process enables highly nanotubes (PNT) as catalytic elements in amperometric biosensors accurate, sensitive and rapid diagnosis of [1]. Voltammetric and time based amperometric techniques physiological reactions by a hand held miniaturize were applied to demonstrate the significantly improvement device [3]. This system was used in the detection electrochemical parameters by the PNT. These findings clearly show the response of microorganisms to acute toxicity that this novel class of peptide nanotubes provides an attractive in water. component for future electroanalytical biosensors. References Lipid nanolayer on gold electrode 1. M. Yemini, P. Xu, J. Rishpon, and D. Kaplan, Collagen- We have investigated interactions between receptors and hormone like Peptide as a Matrix for Enzyme Immobilization in Electrochemical Biosensors. Electroanalysis. Vol by following the impedance changes in 5-7nm thick lipid bilayers on 18, (21) 2047-2054, 2006. 2. R. Popovtzer, T. Neufeld, E. z. Ron, J. Rishpon, and Y. Shacham-Diamand, Electrochemical detection of biological reactions using a novel nano-bio-chip array, Sensors and Actuators B: Chemical, vol. 119 pp.664-672, 2006. 3. T. Neufeld, D. Biran, R. Popovtzer, T. Erez, E. Z. Ron, and J. Rishpon, Genetically engineered pfabA pfabR bacteria: an electrochemical whole cell biosensor for detection of water toxicity, Analytical Chemistry, vol. 78, pp. 4952-4956, 2006. 4. M. Yemini, M. Reches, E. Gazit, and J. Rishpon, Peptide nanotube-modified electrodes for enzyme-biosensor applications, Analytical Chemistry, vol. 77, pp. 5155-5159, 2005. 5. V. Lirtsman, R. Ziblat, M. Golosovsky, D. Davidov, R. Pogreb, V. Sacks-Granek, and J. Rishpon, Surface- plasmon resonance with infrared excitation: Studies of phospholipid membrane growth, Tel: (972)-3-6409366, (972)-3-6407525 Journal of Applied Physics, vol. 98, 2005. Fax: (972)-3-6409407 6. V Sacks-Granek and J. Rishpon, Environ. Sci Tech., Email: [email protected] 36, 1574-1578 (2002). Personal Website: http://www.tau.ac.il/lifesci/departments/biotech/ 7. M. Yemini, M. Reches, J. Rishpon and E. Gazit, Nano members/rishpon/rishpon.html letters 5: 83-186 (2005).

67 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. David Sprinzak Life Sciences Probing intercellular signaling at the nano scale level

ur main research goal is to understanding how between the cells affect signaling. To address these cells coordinate their differentiation in space and questions we need to develop tools that would time during embryonic development to form allow us to measure the dynamic distribution of complex patterns of differentiation. To perform Notch receptors and Delta ligands on the plasma these patterning processes cells use extracellular membrane, to characterize and control the signaling to communicate with their neighbors as properties of the boundary between cells, and to wellO as intracellular genetic circuitry to interpret signaling and make quantitatively measure the interaction between cell fate decisions. We are focusing on developmental patterning Notch and Delta across cellular boundaries. processes in which neighboring cells adopt different fates (such as differentiation of neural precursors into neurons and glia). In Our effort in these directions will focus metazoans, the canonical signaling pathway that coordinates such on the following goals: processes is the Notch signaling pathway. Notch signaling pathway 1. Mapping the spatial distribution of is used for transferring information between neighboring cell: Notch and Delta on the membrane and Delta ligands in one cell can interact and activate Notch receptors on the boundary between cells. The spatial in a neighboring cell. Notch signaling misregulation often leads to distribution and dynamics of the Notch and disease states such as cancer and developmental disorders. Delta proteins on the cell membrane is While we know a lot about the molecular mechanisms of the Notch largely unknown. Several tools may allow us signaling pathway, we have very little understanding of how the to image these distributions. First, we would Notch and Delta find each other across the boundary between like to develop an AFM based technique cells, whether Notch and Delta are evenly distributed or localized in in which Delta (Notch) can be attached to subdomains at the membrane, and how the properties of boundary the AFM tip and would probe Notch (Delta) distribution on membrane plasma. A second approach would be to label Delta or Notch with photoactivatable fluorescent protein and use super resolution techniques such as PALM to map the spatial distribution of Notch and Delta in high resolution. In particular it would be interesting to follow the dynamics of Notch and Delta at the plasma membrane and in the boundary between neighboring cells. 2. Develop tools to characterize and control the boundary between cells. How cell- Visualizing dynamics of Notch signaling in single cells. Quantitative time lapse micrscopy of CHO cells expressing Notch receptors responding to trans-Delat cell signaling is affected by the geometrical, (Delta plated on the cells) and to cis Delta, expressed in the same cell (Red mechanical, and molecular properties of the fluorescence). Notch reporter (green fluorescence) turns on when the level of cis- boundary between cells? To address this Delta goes below a threshold. Analysis of such movies allows the characterization question we will develop a set of tools that of the input-output response function of the Notch signaling pathway. This analysis showed that cells can either be ‘senders’ or ‘receivers’ but not both. would allow characterization of the boundary between cells using super resolution imaging techniques, control of geometry of the boundary using surface patterning, and Tel: (972)-3-6405218, (972)-3-6405699 control of the molecular properties of the Email: [email protected] Personal Website: http://www.tau.ac.il/~davidsp/ boundary by controlling cell morphology regulators. We will also use nano-fabrication

68 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Simulations of developmental patterning processes. (Top) A model for generating lateral inhibition patterns from an intially uniform field of cells. Neighboring cells inhibit each other’s Delta activity the Notch signaling. The resulting multicellular feedback can generate an alternating patterns of differentiation (bottom) where one ‘high Delta’ cell suppresses its neighbors. The process is studied through analytical methods and numerical simulations.

techniques to measure and apply forces on the boundary References between cells and monitor its affect of intercellular signaling. 1. Cis interactions between Notch and Delta generate These tools will be combined with current and future tools to mutually exclusive signaling states, D. Sprinzak, A. Lakhanpal, L. LeBon, L. A. Santat, M. E. Fontes, G. A. monitor intercellular signaling. Anderson, J. Garcia-Ojalvo, M. B. Elowitz, Nature. 3. Quantitative measurement of Notch and Delta interactions 2010 May 6; 465(7294): 86-90. across cell boundary. While techniques to track proteins at 2. Reconstruction of genetic circuits, D. Sprinzak and the cell membrane are currently available, we do not currently M. Elowitz, Nature 438 (7067), 443-8 (2005) Review. have ways to measure the interaction between proteins across cell boundary. We therefore propose to develop such molecular tools such as fluorescent complementation assay to study the interaction between Notch and Delta across cell boundaries.

The combination of these techniques will provide a powerful set of tools for understanding the interplay between intercellular signaling and cell morphology.

69 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Zeev Schuss Mathematics Ionic permeation in protein channels of biological membranes and applications to models of neurons and cardiac myocytes

y activity concerns construction of References mathematical models of ionic permeation, 1. B. Nadler, Z. Schuss, A. Singer, R.S. Eisenberg, selectivity, and gating in protein channels “Diffusion through protein channels: from molecular description to continuum equations”, of biological membranes and their analysis. I Nanotech 3, pp.439-442 (2003). integrate the channel and gating models in 2. A. Singer, Z. Schuss, “Brownian simulations and uni- models of neurons and cardiac myocytes to directional flux in diffusion”, Phys. Rev. E 71, 026115 Manalyze and predict their function under given physical, chemical, (2005). and biological conditions. My models, which have been borne out 3. A. Singer, Z. Schuss and R. S. Eisenberg, “Attenuation by experiment, include the increased conductivity of potassium of the Electric Potential and Field in Disordered Systems’’, J. Stat. Phys. 119 (5-6), pp.1397-1418 channels under the influence of low frequency (cca 16Hz) low (2005). intensity magnetic fields (pico to micro Tesla), the lowering of cytosolic 4. B. Nadler, Z. Schuss, and A. Singer, “Langevin calcium in cardiac myocytes, and the shortening of the QT interval in trajectories between fixed concentrations,’’ Phys. rat and Guinea pig EKG. More theoretical work includes a theory of Rev. Lett. 94 (21) 218101 (2005). Brownian and Langevin simulations of permeation, formulation of evolution equations for the non-equilibrium density of interacting ions, and other related problems in statistical physics. The theoretical work is based on asymptotic methods that I developed for the analysis of stochastic differential equations. I have two Ph.D. students in applied mathematics, one in electrical engineering in TAU working on this project. I cooperate with researchers in the departments of biomedical engineering and physiology in TAU and also with applied mathematicians and neuro-physiologists in the WIS (Brain Research Center).

Tel: (972)-3-6408827 Fax: (972)-3-5472440 Email: s [email protected] Personal Website: http://www.math.tau.ac.il/~schuss/

70 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Dafna Benayahu Medicine How to Nano-Manipulate Stem cells Differentiation

anomedicine is medical treatment at the level of Stem cell has a broad use in cell therapy and tissue single molecules or molecular assemblies that engineering. Mesenchymal stem cells derived provide structure, control, signaling, homeostasis, from the bone marrow are able to differentiate and motility in cells, i.e., at the “nano” scale of about to various lineages: osteogenic, chondrogenic 100 mm or less. There have been many scientific and muscle cells or behaves more plastic and and technological advances in both physical differentiates to other tissues. Before stem cells andN biological sciences over the past several years that make nano can be used for cell therapy, the definition medicine research particularly attractive at this time. New tools are of their identity and culturing conditiones being developed that permit imaging of structure at this scale, high- needs to be explored. The research conducted speed measurement of the dynamic behavior of these molecular at the laboratory is to answer the question assemblies, and the forces produced by molecular machines as of mesenchymal stem cells (MSC) identity.We are well as the forces needed to disrupt them. These advances are using animal models of to retrieve mesechymal complemented, on the biological side, by the dramatically expanded tissues and to culture MSCs to analyze their knowledge of the human genome, a greater understanding of the gene profiling. Micro array used to explore the pathophysiology of specific diseases at the molecular scale, the need gene expression and analysis of growth factor, to develop more specific treatments of disease, and the desire to hormone, and genes of signaling pathway understand the dynamic behavior of dysfunctional cellular machinery involved in cell activation and differentiation in the context of the total cell machinery. The need for more precise according to tissue source and profiling. measurements of the behavior of the nanomachinery within cells combined with the expanding array of tools capable of making these References measurements led to the identification of Nanomedicine theme of 1. Ron A, Singh RR, Fishelson N, Shur I, Socher R, “New Pathways to Discovery”. Benayahu D, Shacham Diamand Y. 2008. Cell- based screening for membranal and cytoplasmatic markers using Dielectric spectroscopy. Biophysl Chem 135: 59 2. Akavia UD, Veinblat O, Benayahu D, 2008. Comparing the transcriptional profile of mesenchymal cells to cardiac and skeletal muscle cells. J Cell Physiol 216:663-672 3. Akavia UD, Benayahu D, 2008. Meta-Analysis and Profiling of Cardiac Expression Modules. Physiological Genomics 35:305- 4. Ron A, Shur I, Singh RR, Daniel R, Fishelson N, Croitoriu N, Benayahu D, Shacham-Diamand Y 2010. Dielectric screening of early differentiation patterns in mesenchymal stem cells induced by steroid hormones. Bioelectrochemistry. 78(2):161-72

Tel: (972)-3-6406187 Fax: (972)-3-6407432 Email: [email protected] Personal Website: http://www2.tau.ac.il/Person/medicine/researcher. asp?id=agfhjdhld

71 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Rafi Korenstein Medicine Electrical enhancement of drug nano-carriers; Nanoscale cell membrane dynamics

he activity of research group in the field of nanoscience References and nanotechnology addresses two main topics: (1) 1. Scheffer, L., Bitler, A., Ben Jacob, E. and Korenstein, Electrical enhancement of delivery of nanoparticles R. (2001) Atomic Force Pulling: Probing the local elasticity of the cell membrane. Eur. J. Biophys. carrying drugs into cells (electroendocytosis) and 30:83-90. toxicology of nanoparticles; (2) Nanoscale dynamics 2. Goldstein M, Leibovitch I, Levin S, Alster Y, of the cell surface of cells. In order to achieve more Loewenstein A, Malkin G, Korenstein R. (2004) Red Teffective therapies while eliminating the potential for both under- blood cell membrane mechanical fluctuations and overdosing, we have developed a novel methodological in non-proliferative and proliferate diabetic platform to induce highly efficient transfer of specifically designed retinopathy. Graefes Arch Clin Exp Ophthalmol. 242: 937-43. nanoparticles carrying drugs into cells. The method is based on 3. Antov, Y. Barbul, A.Mantsur H.and Korenstein, R exposure of cells to trains of low unipolar electric fields which leads (2005) Electroendocytosis: Exposure of cells to to an efficient uptake of macromolecules and nanoparticles into pulsed low electric fields enhances adsorption and cells. One application of this methodology is the treatment and cure uptake of macromolecules. Biophys J. 88: 2206-23. of solid tumors in mice bearing different types of metastatic cancer. 4. Plotnikov A, Tichler T, Korenstein R, and Keisari Y. The study of nano-scale local dynamics of the cell surface addresses (2005) Involvement of the immune response in the cure of metastatic murine CT-26 colon carcinoma two major directions (i) Understanding the relationship between by low electric field enhanced chemotherapy. Int. the molecular structure of the membrane-skeleton complex and J. Cancer 117: 816-824 (2005). nano-scale cell membrane fluctuations under physiological and pathological situations; (ii) The non-linear analysis of time series of cell membrane fluctuations and their use as specific “signature” patterns for diagnosis employing a “cell on chip” configuration. This study involved the development of novel methodologies to monitor nano-scale cell membrane fluctuations.

Tel: (972)-3-640604 Fax: (972)-3-6408982 Email: [email protected] Personal Website: http://www2.tau.ac.il/Person/medicine/researcher. asp?id=afelkfdkj

72 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Ruth Nussinov Medicine

urrently there is increasing interest in nanostructures References and their design. Nanostructure design involves the 1. Tsai CJ, Zheng J, Zanuy D, Haspel N, Wolfson H, ability to predictably manipulate the properties of Alem.n C, Nussinov R.Principles of nanostructure design with protein building blocks.Proteins. 2007 the self-assembly of autonomous units. Autonomous (in press). units have preferred conformational states. The units 2. Haspel N, Zanuy D, Zheng J, Aleman C, Wolfson H, can be synthetic material science-based or derived Nussinov R. Changingthe charge distribution of fromC functional biological macromolecules. {beta}-helical based nanostructures can providethe Autonomous biological building blocks with available structures conditions for charge transfer. Biophys J. 2007 (in provide an extremely rich and useful resource for design. For proteins, press). 3. Haspel N, Zanuy D, Alem.n C, Wolfson H, Nussinov the structural databases contain large libraries of protein molecules R. De Novo TubularNanostructure Design Based and their building blocks with a range of shapes, surfaces, and chemical on Self-Assembly of beta-Helical ProteinMotifs. properties. The introduction of engineered synthetic residues or short Structure. 14: 1137-48, 2006. peptides into these can expand the available chemical space and 4. Aleman C, Zanuy D, Jim.nez AI, Cativiela C, Haspel enhance the desired properties. Our work focuses on the principles N, Zheng J, CasanovasJ, Wolfson H, Nussinov R. of nanostructure design with protein building blocks. Concepts and schemes for the re-engineering ofphysical protein modules: generating nanodevices via targetedreplacements with constrained amino acids. Phys Biol. 3: S54-62, 2006.

Tel: (972)-3-6407967, (972)-3-6409034 Fax: (972)-3-6405168 Email: [email protected]

73 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Eran Perlson Medicine Nanomotors and microfluidic platforms reveal neurodegeneration mechanisms

euron cell death and synapse disruption seen in neurodegenerative diseases like ALS. It is a non-cell- autonomous process and involve a multi system progression. Neurons are highly polarized cells with very long axons. In order to maintain healthy and function properly the neurons depends on accurateN and efficient long distance communication mechanism. Consequently, the precise targeting and delivery of cellular signals to specific, distinct sub-cellular compartments in neurons is largely achieved via axonal transport mechanisms. Axonal transport is the Vesicles live cell imaging reveals distinct mode of transport cellular process of moving proteins, organelles, vesicles, RNA and other cellular factors to (retrograde) and from (anterograde) the References neuron cell body. The molecular motor kinesin drives anterograde 1. Perlson, E., Hendricks, A., Holzbaur, E. Microtubule Tethering by Dynein and NCAM Facilitates Synaptic transport while the dynein motor drives the retrograde transport. Stabilization. Revision in “Nature”. 2. Perlson, E., Maday, S., Fu, M., Moughamian, A., Holzbaur, E. (2010) Retrograde Axonal Transport: Pathways To Cell Death? Trends in Neuroscience. 33 (7), 335-44. 3. Hendricks, A. */Perlson, E.*. Ross, J.*, Schroeder, H., Tokito, M., Holzbaur, E. (2010) Motor coordination via tug-of war mechanism drives bidirectional vesicle transport. Current Biology. 20(8), 697-702. *Equally contributing authors 4. Perlson, E., Jeong, GB., Ross, JL., Dixit, R., Wallace, KE., Kalb, RG., Holzbaur, EL. (2009) A Switch in Retrograde Signaling From Survival to Stress Leads to Rapid Onset Neurodegeneration. The Journal of In-vitro microfluidic platform with motor neuron cell bodies on one side and Neuroscience 29 (31); 9903-9917. muscle cells on the other, creating a powerful system to study axonal transport 5. Perlson, E., Holzbaur, EL. (2008) Myosin learns to and neurodegeneration mechanisms recruit AMPA receptors. Cell 135 (3); 414-5. 6. Perlson, E., Holzbaur, EL. (2007) The Role of We combine state of the art multidisciplinary approaches such as Molecular Motors in Axonal Transport. “Protein single molecule live imaging techniques and microfluid-co-culture Trafficking in the Neuron” Andrew Bean editor. chambers to understand basic mechanisms of axonal transport and Elsevier Publishing. motor proteins regulations and to elucidate the roles its play in: 7. Perlson, E., Hanz, S., Ben-Yaakov, K., Segal-Ruder, Y., 1. Cell survival; 2. Synapse stability Seger, R., Fainzilber, M. (2005) Vimentin dependent spatial translocation of an activated MAP kinase in injured nerve. Neuron 45(5):715-726. 8. Perlson, E., Medzihradszky, KF., Darula, Z., Munno, DW., Syed, NI., Burlingame, AL., Fainzilber, M. (2004) Differential proteomics reveals multiple components in retrogradely transported axoplasm after nerve injury. Mol Cell Proteomics. 3(5):510-20. Tel: (972)-3-6408743 9. Hanz, S., Perlson, E., Willis, D., Huerta, J.J., Massarwa, Fax: (972)-3-6409113 R., Zheng, JQ, Kohler, M, van Minnen J., Koltzenburg, M., Twiss J.L., Fainzilber M., (2003) Axoplasmic Email: [email protected] importins enable retrograde injury signaling in Personal Website: http://www2.tau.ac.il/Person/medicine/researcher. asp?id=adkmhfekh lesioned nerve. Neuron 40:1095-104.

74 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Ronit Sagi-Eisenberg Medicine Nano scale functional genomics and proteomics analyses of mast cell activation

llergic diseases including allergic rhinitis and conjunctivitis, urticaria, food allergy and asthma have reached epidemic proportions affecting more than 30% of the world population. Mast cells are central players in mediating allergic responses. Moreover, rapidly accumulating data clearly indicate implicate mastA cells as major participants in chronic inflammatory diseases and autoimmune diseases. However, mast cells do also play a beneficial role in innate and adaptive immunity during bacteria infections. Thus, given the pleiotropic function of mast cells and their involvement in many major diseases, it is of great importance to elucidate the machineries and molecular mechanisms associated with mast cells activation. Thus, it is the focus of our research to decipher the molecular signaling networks linked with mast cell activation. Towards this end, we have taken three experimental approaches. The first approach involves a nano scale functional genomics high-throughput analyses of mast cell activation. Specifically, this approach involves the transfection of mast cells with GFP-tagged mutant protein cDNAs, alongside RFP-tagged reporters for mast cell activation. Both single cell and average readout image analyses are then performed and the data recapitulated in models that correlate the dynamics of cellular proteins with the state of activation. The second complementary References approach follows specifically, the dynamics of selected essential 1. Melnikov S. and Sagi-Eisenberg, R.” Down- proteins. Particularly, we correlate ERK activation with its nano-scale Regulating Protein Kinase C alpha: Functional organization. Finally, our third approach involves the production of Cooperation between the Proteasome and the cell permeable peptides directed against intracellular targets. ALL1 Endocytic System”. Cell Signal. 21,1607-1619 (2009). is such peptide that targets the G-protein Gi3. Notably, this peptide, 2. Shefler, I., Zavaro, O., Raz, T. Baram, D. and Sagi- Eisenberg, R. “Inhibition of basic secretagogues- which displays remarkable inhibitory activity against mast cells both induced signaling in mast cells by cell permeable in vitro and in vivo self-assembles to form nano structures. Whether Gαi -derived peptides.” Int. Arch. Allergy. 145,131- these structures contribute or rather reduce the activity of ALL1 is 140 (2008). currently under investigation. 3. Haberman, Y., Ziv, I., Gorzalczany, Y., Hirschberg, K., Mittleman, L., Fukuda, M. and Sagi-Eisenberg, R. “Synaptotagmin (Syt) IX is an essential determinant for protein sorting to secretory granules in mast cells”. Blood. 109, 3385-3392 (2007). 4. Kapp-Barnea, Y., Ninio-Many, L., Hirschberg, K., Fukuda, M., Jeromin, A. and Sagi-Eisenberg, R. “Neuronal Calcium Sensor-1 (NCS-1) and PI4Kβ stimulate ERK1/2 signaling by accelerating recycling through the endocytic recycling compartment (ERC).” MBC. 17, 4130-4141 (2006). Tel: (972)-3-6409500 Fax: (972)-3-6407432 Email: [email protected] Personal Website: http://www2.tau.ac.il/Person/medicine/researcher. asp?id=agehciflc

75 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Ronit Satchi-Fainaro Medicine Multivalency of polymer therapeutics used for the integration of anti-angiogenic therapy with chemotherapy

umors consist of three general compartments: tumor Identifying new molecular markers on tumor cells, tumor vasculature and non-endothelial tumor endothelial cells in order to develop better stroma. The ability of cancers to grow is dependent on drugs and better targeting moieties. the formation and maintenance of new blood vessels 2. Design of novel nanocarriers as strategies from pre-existing vasculature in a complex process to target angiogenesis inhibitors to tumor referred to as Angiogenesis (Figure 1). Tumors may vasculature. To improve the therapeutic index of remainT small and dormant if unable to elicit functional angiogenesis. chemotherapeutic and antiangiogenic agents Consequently, the microvascular endothelial cell, recruited by a tumor, by conjugation to polymeric nanocarriers. has become a paramount factor in tumor progression and metastases 3. Investigation of the mechanism of action of formation making both the tumor cells and their surrounding stroma angiogenesis inhibitors (endogenous and a target for combined anticancer and anti-angiogenic therapy. pharmacological inhibitors). Selective therapy remains a key issue for successful treatment in 4. Intravital non-invasive molecular imaging of cancer therapy. Prolonged administration of effective concentrations treated tumor-bearing mice to follow tumor of chemotherapeutic or anti-angiogenic agents is usually not possible progression, pharmacodynamics and pharma- because of dose-limiting systemic toxicities involving non-malignant cokinetics of the synthesized nanomedicines. tissues. Therefore, a constant effort has been the development of 5. Shedding light on the molecular basis of new drug delivery systems that mediate drug release selectively at tumor dormancy using polymer therapeutics. the tumor site. Our strategy for advancing the field of vascular biology and the References development of vascular targeting nanomedicines is by: 1. Eldar-Boock A, Miller K, Sanchis J, Lupu R, Vicent

1. Characterization of tumor vasculature for tailored-made therapy. MJ and Satchi-Fainaro R, Integrin-assisted drug delivery of nano-scaled polymer therapeutics bearing paclitaxel, Biomaterials, 32, 3862-3874 (2011). 2. Segal E, Pan H, Benayoun L, Kopečková P, Shaked Y, Kopeček J and Satchi-Fainaro R, Enhanced safety profile and antitumor activity of targeted HPMA copolymer-alendronate-TNP-470 nanoconjugate in the treatment of bone malignances, Biomaterials, 32 (19), 4450-4463 (2011). 3. Miller K, Erez R, Segal E, Shabat D and Satchi-Fainaro R, A novel bi-specific agent based on a polymer- alendronate-taxane conjugate to target bone metastases, Angew Chem Int Ed Engl 48, 2949- 2954 (2009). 4. Segal E, Pan HZ, Udagawa T, Kopeckova P, Kopecek J and Satchi-Fainaro R, A novel combined Figure 1. The angiogenic switch and the use of nanomedicines such as Polymer targeted anticancer and anti-angiogenic polymer Therapeutics (A), to treat angiogenic tumors (B-C). The enhanced permeability and retention (EPR) effect allows nanoconjugates to extravasate through the therapeutic, PLoS One, 4 (4):e5233 (2009). tumor leaky vessels (D-E), accumulate in the tumor bed selectively and internalize 5. Stern L, Perry R, Ofek P, Many A, Shabat D and Satchi- into the tumor epithelial and tumor endothelial cells via endocytosis (F). Fainaro R, A novel antitumor prodrug designed to be cleaved by the endopeptidase legumain, Bioconjugate Chemistry, 20(3), 500–510 (2009). Tel: (972)-3-6407427 6. Satchi-Fainaro R, Puder M, Davies J, Tran H, Greene Fax: (972)-3-6409113 AK, Corfas G and Folkman J, Targeting angiogenesis Email: [email protected] with a conjugate of HPMA copolymer and TNP-470, Personal Website: http://www2.tau.ac.il/Person/medicine/researcher. Nature Medicine, 10 (3), 255-261 (2004). asp?id=adkkiefci

76 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Ella Sklan Medicine

epatitis C virus (HCV) is an important cause of worldwide liver disease. Current therapies are inadequate for most patients. Improving the understanding of the life cycle of this virus may provide opportunities for new antiviral strategies. HCV is a small, positive single-stranded RNA virus; theH viral particles have a uniform diameter of 50nm and contain a 9.6kb genome encoding a single ~3000 amino acid polyprotein. This polyprotein is proteolytically processed into structural proteins that compose the mature virus and non-structural (NS) proteins that are involved in replicating the viral genome. We are interested in identifying and characterizing interactions of these viral proteins with the host cell, using yeast screens and proteomic approaches as our major tools. In addition to identifying new viral-host interactions we aim to develop high-throughput screens (using Quantum dots based Bioluminescence Resonance Energy Transfer (BRET) and Fluorescence Resonance Energy Transfer (FRET)) for small molecule inhibitors of our previously identified and confirmed interactions such as the interaction between Hepatitis C non-structural protein (NS5A) and a host protein (TBC1D20) [1, 2] that was found to be essential for Hepatitis C replication (see figure). The small molecules identified in this powerful cell based assay could serve as novel antiviral compounds.

References 1. Sklan, E.H., R.L. Serrano, S. Einav, S.R. Pfeffer, D.G. Lambright, and J.S. Glenn, TBC1D20 Is a Rab1 GTPase-activating protein that mediates Hepatitis C virus replication. Journal of Biological Chemistry, 2007. 282(50): p. 36354- 36361. Depletion of TBC1D20 inhibits HCV RNA replication. 2. Sklan, E.H., K. Staschke, T.M. Oakes, M. Elazar, M. Winters, B. Aroeti, T. Wn is a colony formation assay using HCV subgenomic Danieli, and J.S. Glenn, A Rab-GAP TBC domain protein binds Hepatitis replicons. These replicons are fully competent for viral- C virus NS5A and mediates viral replication. Journal of Virology, 2007. RNA genome replication but lack the viral structural 81(20): p. 11096-11105. proteins and instead carry a neomycin selection gene. Co-transfection of these replicons into Huh7 hepatoma cells together with siRNAs depleting TBC1D20 showed that HCV replication is dramatically inhibited as a result of impairing the expression of TBC1D20.

Tel: (972)-3-6409872 Fax: (972)-3-6409160 Email: [email protected] Personal Website: http://www2.tau.ac.il/Person/medicine/researcher. asp?id=adlheibfh

77 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Dr. Inna Slutsky Medicine Information processing: From nano-scale single synapse to memory function

t is widely believed that memory is grounded in synaptic References connections. However, the principles regulating encoding, 1. Slutsky, I., Wu, L.J., Li, B., Govindarajan, A., Zhuo, M., storage and retrieval of information in synaptic networks Tonegawa, S., Liu, G. Reversal of Memory Decline and Reconfiguration of Synaptic Network by remain elusive. Our research is focused on the endogenous Magnesium Ion (submitted). mechanisms controlling memory capacity in adult brain. Our 2. Slutsky, I., Sadeghpour, S., Li, B., Liu, G. (2004). main target is to determine how the quality and quantity of Enhancement of Synaptic Plasticity through Iongoing neuronal activity affect the properties of individual pre- and Chronically Reduced Ca2 Flux during Uncorrelated post-synaptic compartments, neural connection (few synapses), Activity. Neuron 44:835-849. synaptic network (thousands of synapses), and the whole system. To 3. Slutsky, I., Wess, J., Gomeza, J., Dudel, J., Parnas, I., Parnas, H. (2003). Use of Knockout Mice Reveals fulfill this goal, we are applying combination of electrophysiology, Involvement of M2-Muscarinic Receptors in functional quantitative imaging, molecular biology, and behavioral Control of the Kinetics of Acetylcholine Release. J. techniques. Our recent results indicate that uncorrelated pattern of Neurophysiol. 89: 1954-1967. neuronal activity plays a key role in synaptic network organization 4. Slutsky, I., Rashkovan, G. Parnas, H., Parnas, I. (2002). and memory function. Ca2 -independent feedback inhibition of ACh release in the frog neuromuscular junction. J. Neurosci. 22, 3426-3433.

Tel: (972)-3-6406021 Fax: (972)-3-6409113 Email: [email protected] Personal Website: http://www2.tau.ac.il/Person/medicine/researcher. asp?id=dbjdgdcdk

78 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Researchers

Prof. Ilan Tsarfaty Medicine

reast cancer is the most common malignant disease in western women. In the majority of cases the cause of death in cancer patients is not the primary tumors, but complications derived from metastases at distant sites. The met proto-oncogene product (Met – a receptor tyrosine kinase) and its ligand, hepatocyte growth factor/scatterB factor (HGF/SF), mediate cell motility and proliferation in vitro and tumorigenicity, angiogenesis and metastasis in vivo. Aberrant Met signaling has been widely implicated in most types of human cancers including breast cancer. HGF/SF transgenic mice Mimp Localization in Mitochondrial cells develop a broad array of histologically distinct tumors. Mutations (Red inner mitochondria marker, Green in the Met tyrosine kinase domain have been identified in both Mimp-GFP) hereditary and sporadic forms of human papillary renal carcinoma. Mimp/Mtch2, a mitochondrial carrier homologue cloned in our lab, is induced by Met-HGF/SF signaling and is involved in metabolic and bioenergetic processes. Mimp/Mtch2 reduces cells proliferation in vitro and tumor growth in vivo. Over expression of Met and HGF/ SF is associated with poor prognosis in several major solid tumor types. Several anti Met targeted therapies are in development and some have entered phase III clinical trials. We have previously shown that activation of Met by HGF/SF induces an increase in tumor blood volume in a dose-dependent manner. The goal of our studies is to further understand the role of Met- Mimp/Mtch2 in cancer progression and metastasis, and to develop Met Localization in Blebbing Cells molecular imaging modalities for personalizing targeted Met therapy. somatostatin conjugate in a mouse xenograft Using quantum dots and confocal microscopy we have shown that model. Int J Cancer 122:2044-9, 2008. HGF/SF is bound and internalized by Met expressing DA3 breast 3. Tiran Z, Oren A, Hermesh C, Rotman G, Levin adenocarcinoma cells in vitro. Fluorescent tagged–Met proteins were Z, Amitai H, Handelsman T, Beiman M, Chen A, used to study Met mitogenic effect on cells. Met molecular imaging Landsman-Milo D, Dassa L, PeresY, Koifman C, demonstrated that Met signaling modulation plays a major role in Glezer S, Rinat Finkelstein, V Bahat K, Pergam T, breast cancer tumor growth and development. These emerging MI Israel C, Horev J, Tsarfaty I and Ayalon-Soffer M, Novel Recombinant Soluble Splice Variant of Met modalities may help tailor Met-targeted therapy. is a Potent Antagonist of the HGF⁄SF−Met Pathway, Clinical Cancer Research 14: 4612-21, 2008. References 4. Qian, C. N., Berghuis, B., Tsarfaty, G., Bruch, M., 1. Golan M, Hizi A, Resau, J. H, Yaal-Hahoshen N, Reichman H, Keydar I, Kort, E. J., Ditlev, J., Tsarfaty, I., Hudson, E., Jackson, Tsarfaty I, Human endogenous retrovirus (HERV-K) reverse transcriptase D. G., Petillo, D., Chen, J., Resau, J. H., and Teh, B. T. as a breast cancer prognostic marker, Neoplasia 10:521-33, 2008. preparing the “soil”: the primary tumor induces 2. Kostenich G, Oron-Herman M, Kimel S, Livnah N, Tsarfaty I, Orenstein vasculature reorganization in the sentinel lymph A. Diagnostic targeting of colon cancer using a novel fluorescent node before the arrival of metastatic cancer cells. Cancer Res, 66: 10365-10376, 2006. Tel: (972)-3-6407015 5. Moshitch-Moshkovitz, S. Tsarfaty, G. Kaufman, D.W. Fax: (972)-3-6409160 Stein, G. Y. Shichrur, K. Resau, J.H. Vande Woude, G.F. and Tsarfaty I. In vivo direct molecular imaging Email: [email protected] of early tumorigensis and malignant progression Personal Website: http://www2.tau.ac.il/Person/medicine/researcher. asp?id=aghihfeif induced by transgenic expression of GFP-Met. Neoplasia 8:353-363, 2006.

79 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY

Progress Reports (in alphabetical order)

PROGRESS reports

Prof. Azem Abdussalam Protein Folding and Unfolding by Chaperone Proteins

ver the past year, the focus of research in our laboratory has been the molecular mechanism of function of three chaperone systems.

Oi The function of the mitochondrial translocation motor This Hsp70 chaperone system mediates protein unfolding during the process of protein import across the mitochondrial inner membrane. Structural and mechanistic aspects of this chaperone system were investigated. Our work focused on investigating protein-protein interactions that form during protein import across membranes. A more detailed description of our research on this topic can be found in our recently published manuscript (1) Models for the structure of chloroplast co-chaperonins ii The molecular function of chloroplast chaperonins In this project, we investigated the structure and function of were screened in-vivo for the ability to work chloroplast chaperonins from A. thaliana. Most plants harbor multiple together with GroES to rescue an E. coli strain genes for chaperonin proteins, making analysis of plant chaperonin in which the endogenous chaperonin complex systems more complicated than the bacterial GroEL-GroES system. was silenced,. The screen led to the isolation of We decided to focus on the chaperonins from A. thaliana since the two mutants, whose mutations are located at the genome of this plant has been well defined and many materials are apical domain of mHsp60 and not in positions available which can help facilitate studies using this system. Our that directly contact the co-chaperonin mobile work included cloning, purification, and characterization of the loop. Currently, we are conducting additional chloroplast cpn60 subunits, and biophysical studies of their protein work to determine the structural basis for the folding function. Parts of this work have already been published in effect of the isolated mutations. (2) and (3). Future work in this system will focus on tracking protein folding inside plant chaperonin nanocages using FRET and additional References fluorescent methods. 1. Marom, M, Azem, A and Mokranjac, D. (2011) Understanding the molecular mechanism of iii The molecular function of the mammalian protein translocation across the mitochondrial inner mitochondrial chaperonin system membrane: Still a long way to go. Biochem. Biophys. Despite the high sequence homology among chaperonins, the Acta (Biomembranes). 1808, 990-1001. 2. Vitlin, A., Weiss, C., Demishtein-Zohary, K. Rasouly, A., mitochondrial chaperonin system (4) has developed unique Levin, D., Pisanty-Farchi, O., Breiman, A., Azem, A. (in properties that distinguish it from those of the chloroplast and press) Chloroplast β chaperonins from A. thaliana the widely-studied bacterial (GroEL and GroES) systems. The most function with endogenous cpn10 homologs in intriguing difference is that, in contrast to the bacterial chaperonins, vitro. Plant Mol. Biol. which are able to refold denatured proteins with the help of co- 3. Weiss, C., Bonshtien, A., Farchi-Pisanty, O., Vitlin, A. chaperonins from any source, mitochondrial chaperonins are capable and Azem, A. (2009) Cpn20: Siamese twins of the chaperonin world. Plant Mol. Biol (review). 69, 227- of refolding denatured proteins only with the help of mitochondrial 238. co-chaperonins. We endeavored to elucidate the structural basis for 4. Parnas, A., Nadler, M., Nisemblat, S., Horovitz, A., this specificity. To this end, we used a directed evolution approach on Mandel, H., and Azem,, A. (2009) The MitCHAP-60 the human mitochondrial Hsp60 (mHsp60) to identify mutations that Disease is due to Entropic Destabilization of the will allow it to function with the bacterial GroES. mHsp60 mutants Human Mitochondrial Hsp60 oligomer. J. Biol. Chem. 284, 28198-28203.

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Prof. David Andelman Phase behavior of polymer thin films

hin polymer films have attracted over the years abiding Nano-Imprint Lithography – NIL interest due to their various industrial applications, Nano-Imprint Lithography (NIL) is a new method such as coating of solid surfaces and controlling for macroscopic alignment of BCPs on molecular adhesion. In particular, in recent years much effort scales. It can be used as a tool for locally controlling have been devoted to understand thin films of block the self-assembly of BCPs and determining the copolymers (BCPs), which can self-assemble into precise position of the phase-separated domains. Tordered nanostructures with characteristic length scale (periodicity) The effect of NIL setup on in-plane BCP ordering in the 10-100 nm range, as is determined by the monomer size and is clearly demonstrated by our studies. chain architecture. In thin film geometry, the BCP nanostructure has to fill in the gap between two bounding solid surfaces with an inter- Electric Field Effects surface separation that can be a non-integer multiple of the natural Electric fields can be employed to re-orient and BCP periodicity. These combined constraints cause a complex and control morphology of BCP films. We study the interesting phase behavior of BCP films. role of added ionic impurities, as they have been shown to have a large effect on film morphology. BCP thin films with free interface When the BCP film is exposed on one side to a vapor phase or References another immiscible liquid, this surface should be regarded as a free 1. X. K. Man, D. Andelman, H. Orland, P. Thebault, P.-H. surface, and the film can adjust its thickness locally. We numerically Liu, P. Guenoun, J. Daillant, S. Landis, Organization of Block Copolymers using NanoImprint Lithography: investigate the overall wetting effect on the self-assembly of BCP Comparison of Theory and Experiments, films as induced by the substrate nano-patterning and the free Macromolecules 44, 2206 (2011) polymer/vapor interface. The obtained results suggest a complex 2. X. K. Man, D. Andelman, H. Orland, Block Copolymers film behavior with meaningful deviations from planar film behavior. at Nano-Patterned Surfaces, Macromolecules 43, 7261 (2010) 3. Y. Tsori and D. Andelman, Coarse Graining in Block Copolymer Films, J. Polym. Science – Polymer Physics 44, 2725 (2006)

(a) Perpendicular BCP lamellae with NIL mold; and, (b) without NIL mold. Perfect perpendicular is obtained in (a), while many in-plane defects appear in (b).

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Prof. Ady Arie Nonlinear Generation and Control of Accelerating Airy Beams

ccelerating Airy beams are beams whose transverse beams, that cannot be achieved using linear amplitude dependence at origin is defined by optics. One option that was experimentally the Airy function. These beams have generated demonstrated in [3] is all-optical shaping of the significant interest recently [1] owing to their unique caustic of the Airy beam. By changing the quasi- properties: They are termed “non-diffracting” since phase matching conditions, e.g., the crystal the infinite Airy wave-packet does not spread as temperature or pump wavelength, one can alter itA propagates, and “accelerating”, since this wavepacet is centered the location of the Airy beam peak intensity along around a parabolic trajectory in space. These unique features are still the same curved trajectory. observed to a large extent with truncated, finite energy Airy beams, in Another application of the nonlinear response is which the Airy function distribution is multiplied by either a Gaussian to all-optically control the acceleration direction or an exponential window. Possible applications of Airy beams include of the beam by relying on the physical difference optical micro-manipulation of small particles, generation of curved between up-conversion and down-conversion plasma channels in air and generation of Airy-Bessel light bullets. processes [4]. The phase mismatch values for For generating an Airy beam, it is useful to manipulate first the up-conversion and down-conversion processes Fourier transform of the beam, which in the case of the Airy function usually have opposite signs, so phase-matching is characterized by cubic phase dependence. Usually the cubic phase terms with corresponding opposite signs are is added to a Gaussian beam by a linear phase mask, followed by an required by the nonlinear structure. Switching optical Fourier transformation using a lens. Here we discuss a different from one process to the other by choosing proper approach, in which a specially designed asymmetric nonlinear pump beams that satisfy the corresponding QPM photonic crystal converts the frequency of an input pump beam, and conditions will therefore generate an Airy beam simultaneously adds a cubic phase to the harmonically generated that accelerates to the opposite direction. We wave. To generate the Airy beam, we designed and fabricated have demonstrated this concept experimentally, an asymmetric quadratic nonlinear photonic structure [2] having as shown in Fig. 1, by generating in the same periodic modulation, with spatial frequency fx, in the propagation crystal an upconverted Airy beam by second direction and cubic modulation, with coefficient fc, in the transverse harmonic generation (SHG) of a Nd:YLF laser as 3 direction, in the form dijsign[cos(πfxx+fcy )], where dij is an element of well as a down-converted Airy beam by difference the quadratic susceptibility tensor. frequency generation (DFG) between a frequency

A stoichiometric LiTaO3 nonlinear photonic crystal with 1/fx=7.38 μm, doubled Nd:YAG laser and a Nd:YLF laser. The two -7 -3 fc=1.9x10 μm was used to generate an Airy beam by frequency processes were phase matched at different crystal doubling a Nd:YLF pump laser and Fourier transforming its output temperatures, thereby enabling to characterize using a lens. each one of the two processes independently. In addition to frequency conversion, the nonlinear interaction provides new possibilities for manipulating and controlling Airy References 1. I. Dolev, T. Ellenbogen, and A. Arie, “Switching the acceleration direction of Airy beams by a nonlinear optical process,” Opt. Lett. 35, 1581-1583 (2010). 2. T. Ellenbogen, N. Voloch-Bloch, A. Ganany-Padowicz, and A. Arie, “Nonlinear generation and manipulation of Airy beams,” Nature Photonics 3, 395-398 (2009). 3. I. Dolev, T. Ellenbogen, N. Voloch-Bloch and A. Arie, “Control of free space propagation of Airy beams generated by quadratic nonlinear photonic crystals,” Appl. Phys. Lett. 95, 201112 (2009). Fig. 1 Controlling the acceleration direction of the generated Airy beams. Beams 4. G. A. Siviloglou, J. Broky, A. Dogariu, and D. N. propagate from bottom to top, normalized intensity scale. (a), (b) DFG and SHG Christodoulides, “Observation of Accelerating Airy experimental results, respectively. Inset: Simulation results. Beams,” Phys. Rev. Lett.. 99, 213901 (2007).

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Prof. Uri Ashery From Neuron to Network: The Roles of Synaptic Proteins in Neuronal Network Activity

Lavi Ayal, Sheinin Anton, Ashery Uri We have developed a novel platform to study the effects of genetic manipulations, such as overexpression or knock-down, on the spontaneous activity of neuronal networks. A combination of viral Fig. 2. DOC2B overexpression induces an increase in burst infection and fluorescent time-laps imaging is employed to study duration. Burst duration begins to significantly increase ~5 h after DOC2B introduction. GFP-overexpressing networks the kinetics of the overexpression and the effects are measured showed no change in these parameters (not shown). using MicroElectrode Array (MEA) recordings. Our preliminary results Raster plots of spontaneous activity before (A) and after show that manipulations of specific synaptic proteins alter the spike (B) overexpression of DOC2B. bursting activity of dissociated cortical neuronal networks. The plasticity of the brain plays a key role in shaping our behavior, performed 12-14 days after dissection. Proteins learning and memory. It is well known that plasticity is associated overexpression is achieved by viral infection and with alteration in synaptic strength and efficacy. Some of these effects fluorescent-microscopy combined with long- correlate with changes in the levels of synaptic proteins [1]. However, term time-lapse imaging is employed to study the implications of genetic alteration in synaptic proteins on the the kinetics of the overexpression (Fig. 1). network activity of neurons are not known. We examine the effects of Overexpression of DOC2B leads to a distinctive DOC2B, a synaptic neuronal Ca2+ sensor that enhances exocytosis and increase in the durations of neuronal network vesicle refilling, on spontaneous network activity expecting to detect spikes bursting activities (Fig. 2). This unique a role in neurons during high frequency stimulation periods [2]. combination of genetic manipulation on the We use MicroElectrode Array (MEA) technology to simultaneously neuronal network level complements and record action potentials from multiple neurons in ex vivo neuronal extends our understandings of the role of DOC2B network. Cortical murine neurons are extracted from postnatal in synaptic transmission. It has been previously mice and plated at a density of ~3000cell/mm2. Experiments are suggested that synchronized bursting activities may be templates for modifications of network- wide neuronal plasticity. Together, we suggest a novel role for DOC2B – tuning of synaptic plasticity to allow imprint of activity patterns.

Acknowledgements We thank The Joan and Jaime Constantiner Institute for Molecular Genetics, The Rabin Institute for Neurobiology and the Adams Super Center for Brain Studies for participating in financial support.

References 1. Friedrich, R., Groffen, A.J., Connell, E., van Weering, J.R., Gutman, O., Henis, Y.I., Davletov, B., and Ashery, U. (2008). DOC2B acts as a calcium switch and Fig. 1. Recording from a neuronal network on a Micro-Electrode enhances vesicle fusion. J Neurosci 28, 6794-6806. Array (MEA) overexpressing DOC2B. We established the MEA 2. Littleton, J.T., Bai, J., Vyas, B., Desai, R., Baltus, A.E., recording system (A, left) and successfully recorded different Garment, M.B., Carlson, S.D., Ganetzky, B., and patterns of spontaneous burst activity (A, right). Each bar Chapman, E.R. (2001). synaptotagmin mutants corresponds to a spike in a single neuron. One of the bursts is boxed in red. (B) Neurons expressing DOC2B-IRES-EGFP. In reveal essential functions for the C2B domain in addition, the expression efficiency of DOC2B was found to be Ca2+-triggered fusion and recycling of synaptic very high, starting as early as 3-5 h after infection (C). vesicles in vivo. J Neurosci 21, 1421-1433.

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Dr. Zahava Barkay

Introduction A method for wettability study using The investigation of wetting properties of surfaces at nano-scale transmitted electrons in environmental spatial resolution and high temporal resolution is an emerging scanning electron microscope field both from theoretical and practical aspects. The driving force A quantitative method for wettability study stems from fundamental theories of nucleation and growth as well at nanoscale was developed1. It is based on as from nanofluidic technological requirements in biotechnology measuring transmitted electrons through and materials sciences. Device miniaturization would require the nanodroplets using wet scanning transmission understanding of the physical phenomena associated with the electron microscope (wet-STEM) detector in nano-scale and in particular the role of boundary conditions. The environmental scanning electron microscope. development of innovative experimental methods for the nano- The quantitative information of the nanodroplet scale and the in-situ dynamic nanofluidic characterization is the shape and contact angle is obtained by fitting motivation for this research. Monte Carlo simulation results for transmitted electrons through spherical cap geometry with the experimental wet-STEM results using calibration polystyrene particles. The characterization was demonstrated for the initial stages of water droplet condensation over self- supported nano-thick liquid films, which were produced in the holes of a holey carbon TEM grid (Fig. 1).

Dynamic study of nanodroplet nucleation and growth on self- supported nano-thick liquid films The dynamics of water condensation on self- supported thin films was studied2 with 10nm spatial resolution and 1sec temporal resolution using transmitted electrons in an environmental scanning electron microscope. The initial stages of nucleation and growth over nano-thick water films have been investigated. Irregularities at the water film boundaries constituted nucleation sites for asymmetric dropwise and filmwise condensation. Nanodroplet growth was associated with center of mass movement and the dynamic growth power law dependence was explored for the nano-scale (Figs. 2 & 3).

References 1. Z. Barkay, “Wettability study using transmitted Fig. 1: Polystyrene water diluted spheres on grid (scale bar is 1mm) (a) 2° C and electrons in environmental scanning electron 1.1 torr (b) nanodroplet condensation at 2° C and 5.4 torr (c) calibrated profile microscope”, Appl. Phys. Lett. 96, 183109 (2010). along the center of the nanodroplet and the calibration particle together with 2. Z. Barkay, “Dynamic study of nanodroplet nucleation the MC simulations (inset – schematic diagram of spherical cap droplet model and growth on self-supported nano-thick liquid for the x-z plan) films”, Langmuir. 26, 18581 (2010).

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Fig. 2: (a-f) Wet-STEM in ESEM images of a sequence of dropwise nucleation and growth stages on a self-supported water film (scale bar is 1 micron). (a) t=0 sec, (b) t=6 sec, (c) t=13 sec, (d) t=27 sec, (e) t=42 sec, (f) t=49 sec. ESEM environmental conditions are 2° C and 4.4-5.3 torr.

Fig. 3: The droplet growth radius at constant 94% RH for two nanodroplets (signed as “1” and “2” in Fig. 2b).

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Prof. Ari Barzilai Reduced Synchronization Persistence in Neural Networks derived from Atm-Deficient Mice

oss or inactivation of ATM, which is a master regulator of network theory analyses methods revealed kinase leads to the severe genomic instability the spontaneous formation of synchronization syndrome, ataxia-telangiectasia (A-T). This syndrom is cliques composed of highly synchronized central characterized by progressive cerebellar degeneration, nodes in both networks. In addition, the analysis immunodeficiency, genome instability, gonadal revealed that Atm deficiency leads to reduced dysgenesis, extreme radiosensitivity, and high incidence synchronization persistence – the changing of ofL lymphoreticular malignancies. The most devastating symptom of clique members over time – a phenomenon the A-T syndrome is the neurological impairments including sever that significantly intensified following chemically loss of motor coordination and movement synchronization. The imposed DNA damage. Whereas, in comparison, causal link between DNA damage, Atm deficiency and subsequent WT networks showed sustained synchronization neuronal abnormalities remains elusive. Here we report comparative even following induced DNA damage. studies between the activity of in vitro neural networks taken from wild type (WT) mice and the activity of networks taken from Atm- Phase Synchronization Matrices and /- mice. The networks were grown on multi-electrode-arrays (MEA) synchronization networks for system level simultaneous recordings of tens of neurons. The use In (a) we show a typical phase synchronization dendrogram for a specific 30 minutes window prior to NCS addition, for one of the WT networks (see SI3). The distinct synchronization cliques are the clusters of highly synchronized neurons. In (b) we show the corresponding synchronization networks presented on top of the real space diagram of the MEA electrodes. Here, the phase synchronization is represented by color coded lines between the nodes (neurons). The neurons are color coded (blue for low and red for high) according to their centrality (see SI3). One clique is marked by a red square in (a), the same clique is now marked by a red ellipse in (b). This shows that the synchronization clique is indeed formed by proximate neurons. The synchronization endurance is illustrated in (c) and (d) by the similarity of the synchronization matrices [using the same dendrogram order as in (a)], evaluated at different time windows before NCS treatment (c) and after (d). Performing similar comparison for the Atm -/- networks reveals reduced synchronization persistence – the dendrogram obtained post NCS (f) is somewhat different than the one obtained pre NCS addition (e).

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Prof. Eshel Ben Jacob The effect of natural and made-man nanoprticles on water

ater as the Fabric of Life: Many share the feeling that we are at the beginning of a paradigm shift in our perception of water; a shift from the current molecular-level based approach (focusing on individual or several molecules) that underpinned our Wperception of water, into a new, systemic view of water. A paradigm in which water is perceived as an active substance which adaptively responds to external and internal constraints, and signals, responses that can have singular effects on substances immersed in water and in particular on the functioning of biological constituents, from molecules to living cells. The special volume will present evidence and reflect on the question weather we are at the doorstep towards a systemic view of water as an active substance imbued with life- giving properties. And that the notion of water as “life’s solvent” should give way to the new realization of water as an active “Fabric of Life”; continuously engaging and interacting with bio-molecules in complex subtle ways [1].

We found [2] that radio-frequency (rf) irradiation of zinc sulfate solutions can dramatically affect the deposition patterns generated during electrochemical deposition in thin circular cells. For some growth parameters (voltage and concentrations), the rf-treatment can even induce morphology transitions between the dense The effect of Man-made doped nanoparticle on Electro- branching morphology and dendritic growth. We found that the chemical deposition [2]. Top control and bottom in the presence of doped nanoparticles effects of rf-treatments can last for a long time hours). In addition, detailed studies using electron microscopy observations reveal that We found [3] that waters from natural sources, the effects span on all scales, from the micrometer-scale organization including bottled spring water and tap water, to the self-organization of the macroscopic pattern. We propose contain a significant density of naturally- that these changes of patterning on all scales resulted from singular occurring nanoparticles – about 1011-1012 effects of gas-filled submicrometer bubbles or nanobubbles, which particles/ml. The shapes and chemical content are generated by the rf-irradiation. The idea is that hydration shells of the nanoparticles were investigated using an around the nanobubbles induce water ordering that acts as a aberration corrected and monochromated High new singular perturbation mechanism in the solution. The latter Resolution TEM, which enable both physical is in addition to the well studied microscale singular perturbation and chemical analyses of the nanoparticles. mechanisms in the deposit surface tension and attachment kinetics. The nanoparticle have spherical shapes with We also studied electrochemical deposition in zinc sulfate solutions typical size of 10-50nm. Their chemical content prepared from water that is doped with nanoparticles under rf- is consistent with calcium carbonate (CaCO3) irradiation, and found similar and even amplified effects in such Man- nanoprticles with some additional trace chemicals made nanoparticle doped solutions. Moreover, the nanoparticle that vary between the different types of natural doping stabilizes the effects—they are retained months after the water. The HRTEM measurements also indicate solutions were prepared. that the nanoparticles are homogeneously

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Naturally occurring nanoparticles in natural water. Left in tap water and right in Eden mineral water spread in the natural water solutions with about 0.5mm -1.5 mm effect on a wide range of chemical and biological mean distances between particles. Hence, we refer to such water aquatic processes with far reaching implications. as natural, nanoparticle-doped water or N-NPD water. In contrast, purified drinking water (e.g., Aqua Nova) contains much lower References density of nanoparticles, and in ultra pure water (UPW) only very 1. “Towards a systemic view of water as the fabric of few nanoparticles are observed. The shape and chemical contents Life”, Eshel Ben Jacob, WATER: A multidisciplinary Research Journal. Vol 2 (2010). of most of the naoparticles in these waters are different from the 2. “The Effect of rf-Irradiation on Electrochemical shape and chemical contents of the nanoparticles in N-NPD water. Deposition and Its Stabilization by Nanoparticle We found that N-NPD water have significant buffering capacity Doping” Yael Katsir, Lior Miller, Yakir Aharonov, and both for acids and bases, dilution buffering effect, stabilization salt Eshel Ben Jacob, J. of the Electrochemical Society precipitation and broken chiral symmetry. Noteworthy, we found Vol 154 (2007). that the N-NPD water exhibit protection of DNA-polymerase activity 3. “Protection of DNA-polymerase Activity by Water with Naturally-Occurring Aquatic Nanoparticles” (protection of the Taq polymerase against thermal stress) and have a Liat Buzaglo, Lior Miller, Gabor Harmat, Regina remarkable effect on bacteria growth and colony development. We Aharonov-Nadborny, Eshel Ben Jacob, INTERFACE of propose that the observations indicate the existence of multi-scale the Roy Soci (reviewed). (nanometers to microns) water order induced by the nanoparticles. If it exists, such induced order in natural water can have significant

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Prof. Itai Benhar

ne nano activity our group was engaged in can form stable complexes between phages that is the ongoing project of evaluating targeted are biotinylated via the same BirA tag displayed drug-carrying bacteriophages and potential on the N-terminus of the p3 minor coat protein, nanomedicines. Bacteriophages (phages) have through an avidin bridge to the biotinylated IgGs. been used previously for therapy of bacterial In this study, the drug Amphotericin B is to be infections, for genetic research, for discovery linked to the phages by means of chemical ofO specific target-binding proteins, as tools for vaccination or as conjugation through a genetically engineered potential gene delivery vehicles. We evaluated the possibility of labile linker subject to controlled release by applying filamentous bacteriophages as targeted drug carriers for digested as a result of proteolytic activity of the two modalities: 1) the eradication of pathogenic bacteria as a means fungal protease Alp1. We are currently working of to meet the challenge of spreading antibiotic resistance among drug conjugation of the drug to the phages. pathogenic bacteria. 2) Application of the phages as anti tumor The second nano activity we are involved in is agents. having provided proof-of principle of the potential of both carried out in collaboration with the group of Prof. the anti-bacterial and the anti-cancer phages in cell culture systems Yosi Shacham-Diamand from the department (published 2006 and 2007). of physical electronics, school of electrical Our recent research if looking to develop targeted drug carrying engineering, and faculty of engineering at Tel- bacteriophages as anti fungal nanomedicines. Specifically, the Aviv University. In this study, we are evaluating study is based on our ability to genetically engineer and chemically the potential of various forms of recombinant modify filamentous phages that display or form a stable complex antibodies in biosensors for explosives. To that with a target-specific antibody on their coat and are used to deliver end we isolated from an antibody phage display cytotoxic drugs to target cells. The antibodies in this case are specific library antibodies that specifically bind TNT, and for binding the pathogenic fungus – Aspergillus fumigatus (AF). We are in the process of isolating antibodies specific applied antibody phage display to isolate a panel of anti AF single- to PETN and RDX. Once isolated, the antibodies are chain antibodies. We converted the scFvs to full IgG format, and added expressed in the from of either a small single-chain a BirA tag to the C-terminus of the antibody heavy chains to facilitate antibody (mw 25 kDa) or IgG (mw 150 kDa) and site-specific biotinylation of the antibodies. We have shown that we applied onto an EIS sensor. A biologically modified electrolyte-insulator-semiconductor (EIS) in an impedance-measurement configuration. The method is based on changes in the overall impedance of the system as a result of accumulation of charged molecules at the surface. The Biological elements (antibodies in this instance) are cross linked to the sensor’s surface. The measurement inspects potential changes which take place in the area between the solution and the sensor and related to binding events between the antibodies and the relevant antigens in the solution. By measuring the voltage shift, the analyte concentration or composition to be detected can be determined.

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Prof. David J. Bergman Strong-field magneto-transport in a composite medium

hen the Hall resistivity is greater than the amplification by stimulated emission of radiation) Ohmic resistivity in at least one constituent concept a patent application was finally approved of a composite medium, which always [2]. Work on extraordinary optical transmission by happens when the magnetic field is strong arrays of sub-wavelength holes or indentations in enough, the macroscopic magneto- a thin metal film has continued [3], with particular transport exhibits surprising new behavior: attention to the effect of applying a strong dc TheW local distribution of electric field and current density simplifies magnetic field [4]. This last study was conducted greatly, becoming much simpler than even in the absence of a in collaboration with a group at Bar Ilan University magnetic field. This was so surprising and unexpected that we had and another group in Moscow. to verify it by comparing those predictions with some detailed numerical computations of the relevant fields in some composites Nano-physical processes in the with a periodic microstructure. Consequently, simple closed form physiology of the Oriental hornet asymptotic expressions were obtained for some elements of the Studies of physical processes in the life of the macroscopic resistivity tensor. Those are correct to leading order Oriental hornet continued, even after the passing of the small Ohmic-to-Hall resistivity ratio. New critical points and away of Professor Jacob S. Ishay, together with singular behavior are predicted to occur in such systems in the limit his last PhD student (Marian Plotkin). It was where that ratio is much less than 1. However, significant critical established that the yellow nano-granules in the behavior is predicted to appear already when that ratio is 0.1. cuticle, made of Xanthopterin, play the role of photo-voltaic material in harvesting ultraviolet Nano-optics and nano-plasmonics energy from solar radiation and transforming it In the wake of our discovery in 2003 of the SPASER (surface plasmon into electric power.

Current distribution for a simple-cubic array of cubical or spherical inclusions: Numerical computations

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References 7,569,188 (filed January 5, 2004; approved August 4, 1. D. J. Bergman and Y. M. Strelniker, Exact asymptotics for the strongfield 2009); assigned to Ramot at Tel Aviv University and macroscopic magneto-transport of a composite medium, Phys. Rev. B The Georgia State University Research Foundation. 82(17), 174422 (19 pp.) (16 Nov. 2010). 6. M. Plotkin, S. Volynchik, N. Y. Ermakov, A. Benyamini, 2. M. Plotkin, I. Hod, A. Zaban, S. A. Boden, D. M. Bagnall, D. Galushko and D. J. D. J. Bergman, and J. S. Ishay, Xanthopterin in the Bergman, Solar Energy Harvesting in the Epicuticle of the Oriental Hornet Oriental Hornet (Vespa orientalis): Light absorptance (Vespa orientalis), Naturwissenschaften 97, 1067-1076 (2010). is increased with maturation of yellow pigment 3. Y. M. Strelniker and D. J. Bergman, Y. Fleger, M. Rosenbluh, A. O. granules, J. Photochem. Photobiol. 85, 955-961. Voznesenskaya, A. P. Vinogradov, and A. N. Lagarkov, Manipulating the 7. M. Plotkin, S. Volynchik, R. Hiller, D. J. Bergman and transparency and other optical properties of meta-materials by applying J. S. Ishay, The Oriental hornet Vespa Orientalis a magnetic field, Physica B 405, 2938–2942 (2010). (Hymenoptera: Vespinae) cuticular yellow stripe as 4. D. J. Bergman, Plasmonics, nano-plasmonics, and SPASER’s, in Perspectives an organic solar cell: a hypothesis, In Photobiology: of Mesoscopic Physics, Dedicated to Yoseph Imry’s 70th Birthday— Principles, Applications and Effects, Editors: Lon N. Chapter 2, eds. A. Aharony and O. Entin Wohlman (World Scientific, Collignon and Claud B. Normand, Nova Science Singapore, 2010), pp. 45–56. Publishers, Inc., New York, 2009. 5. M. I. Stockman and D. J. Bergman, Surface plasmon amplification by stimulated emission of radiation (SPASER), United States Patent No.

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Prof. R. L. Boxman, Prof. R. Avivi, Prof. B. Alterkop, Dr. N. Parkansky, Dr. V. Zhitomirsky, Dr. E. Cetinorgu-Goldenberg Nano-structured TiON Photo-Catalytic Membranes for Water Treatment

verall objective is to develop a solar energized water treatment system which does not require any consumables, for deployment in remote areas of developing countries. The Plasma Lab’s task is to develop and deposit photocatalytic coatings unto membranes which will be the heart of the systemO (Boxman, Avni, Cetinorgu-Goldenberg, Chayoun). Micrographs of Ni-C nano-particles Nano-composite and nano-layered coatings of Al-O/Zr-O Objective is to deposit and characterize nano-composite and nano- layered coatings of alumina and zirconia, as well as each component. References The coatings are intended for protecting components from wear, 1. Sun Kyu Kim, Vinh Van Le, R. L. Boxman, Z. N. especially at high temperatures. Nano-structuring is expected to Zhitomirsky, Jeong Yong Lee, “Cathodic arc plasma increase hardness and high temperature stability. In cooperation deposition of nano-multilayered Zr-O/Al-O thin films”, Surf. Coat. Technol. 204, (2010), pp 1697-1701. with Ulsan University (S. Korea) and NRC-Negev (Boxman, Zukerman, 2. V.N. Zhitomirsky, S.K. Kim, L. Burstein and R.L. Goldberg, Cetinorgu-Goldenberg). Boxman “X-ray photoelectron spectroscopy of nano-multilayered Zr-O/Al-O coatings deposited by cathodic vacuum arc plasma”, Appl. Surface Sci. 256 (2010) 6246–6253. 3. I. Zukerman, V.N. Zhitomirsky, G. Beit-Ya’akov, R.L. Boxman, A. Raveh, S.K. Kim, Vacuum arc deposition of Al2O3–ZrO2 coatings: arc behavior and coating characteristics, J Mater Sci (2010) 45:6379–6388, DOI 10.1007/s10853-010-4734-7.

HRTEM photographs of samples deposited with bias of -50 V and substrate temperature of 400 °C showing embedded ZrO2 (left) and Al2O3 (right) nano- crystals. Submerged Arc Production and Characterization of Nano-particles Pulsed arc discharges are produced between a pair of electrodes submerged in a liquid, e.g. water or alcohol. A plasma bubble is produced, composed of vaporized liquid and electrode material, which condenses in the form of nano-particles. In particular, Ni-C and C particles have been produced, and their magnetic properties examined (Parkansky, Alterkop, Boxman).

Novel Wear Resistant TiN-C60 Coatings Deposited Using Combination of Filtered Vacuum Arc and Effusion Cell Techniques Nano-composite coating comprised of vacuum arc deposited

TiN and effusion cell generated C60 fullerenes were synthesized and characterized. Addition of C60 was not found to improve the tribological properties of the films. (Valsky, Zhitomirsky, Boxman).

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Prof. Chanoch Carmeli Naotechnology of Photosynthetic Reaction Centers

he reaction center photosystem I (PSI) is membrane Hybrids of carbon nano tubes – PSI are fabricated protein-chlorophyll complexes. PSI functions like by activation of the nano tubes and attachment photodiode converting light quanta to electrical of the unique cysteine in the engineered protein charges of 1 V at quantum efficiency of ~100%. through small bifunctional molecules. PSI that We investigate the novel properties of hybrid PSI- has cysteine on both oxidizing and reducing ends metals, -metal nanoparticles, -semiconductors and of the protein forms junctions either between T–nanotubes devices. The interaction between PSI and the solids and nano tubes or between the nanotubes and metal the efficiency of charge transfer through the fabricated electronic electrodes. A order of magnitude enhancement in junctions are being studied. photo conductance in the nanotubes is induced Oriented monolayer of PS I is self-assembled by the formation of by PSI in the hybrid PSI-nanotubes devices. a sulfide bond between unique cysteine mutants of genetically These finding lay the basis for the development modified PSI from the cyanobacteria and metal surfaces. The dry of photovoltaic and light sensors devices based layers generate photo potential and when toped by transparent on PSI as the active optoelectronic element. electrode photocurrent is detected. The absorption can be enhanced by fabrication of oriented multilayer through formation, References by autometalization, of metal junction connecting the serial layers. 1. L. Sepunaru, I. Tsimberov, L. Forolov, C. Carmeli, Itai Oriented layers are self assembled on semiconductors by the use Carmeli, and Yossi Rosenwaks. Picosecond Electron Transfer From Photosynthetic Reaction Center of small bifunctional connecting molecules that form junctions Protein to GaAs. Nano Lett. 2009, 9, 2751-2755. between the surfaces and PSI. These junction mediate fast, ps time 2. X-M. Gong , Y. Hochman , T. Lev , G. Bunker , C. scale charge transfer in the hybrid devices. The extremely fast charge Carmeli, The Structure of Genetically Modified Iron– transfer is mediated through a pathway that was selected by the Sulfur Cluster Fx in Photosystem I as Determined by evolution for the input of electron to PSI from donor proteins. X-ray Absorption Spectroscopy. Biochim. Biophys. Acta, 2009, 1787, 97–104. 3. L. Frolov, O. Wilner, C. Carmeli and I. Carmeli, Fabrication of Oriented Multilayers of Photosystem I Proteins on Solid Surfaces by Auto-Metallization, Adv. Mater. 2008, 20, 263–266. 4. L. Frolov, Y. Rosenwaks, S. Richter, C. Carmeli and I. Carmeli, Photoelectric Junctions Between GaAs and Photosynthetic Reaction Center Protein, J. Phys. Chem. C. 2008, 112, 13426-13430. 5. I. Carmeli, M. Mangold, L. Frolov, B. Zebli, C. Carmeli, S. Richetr and A. Holleitner, Photosynthetic Reaction Center Covalently Bound to Carbon Nanotubes, Adv. Mater. 2007, 19, 3901–3905. 6. I. Carmeli, L. Frolov, C. Carmeli and S. Richter, Photovoltaic Activity of Photosystem I-Based Self- Assembled Monolayer, J. Am. Chem. Soc., 2007, 129, 12352-12353. 7. L. Frolov, Y. Rosenwaks, C. Carmeli, & I. Carmeli, Fabrication of a Photoelectronic Device by Direct Chemical Binding of the Photosynthetic Reaction Picosecond charge transfer through the electronic in hybrid PSI – semiconductor Center Protein to Metal Surfaces, Adv. Mater. 2005, surface 17, 2434–2437.

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Prof. Ori Cheshnovsky

Large band gap fluctuations and anisotropic conductance in single semiconducting Bismuth nanoparticles (with Y. Selzer and Y. Larea) The effect of size and composition on the electronic, optical and conductance properties of nanoparticles is a subject of active research. In contrast, the effect of dynamical structural changes and anisotropy in nanoparticles on these attributes is much less known. In many cases, when the net gain in surface energy, outweighs the strain internal energy cost, nanoparticles fluctuate between different crystal structures. The configurational space of these particles is densely populated due to shallow free-energy surfaces with a multiplicity of local minima. Detection of micro calcification in tissue Here we report on dynamic structural fluctuations in Bi nanoparticles, by Raman spectroscopy (with S. Einav) as observed by transmission electron microscope (TEM). The resulting A new microscope, designed to automatically fluctuations in the electronic band structure and conductance obtain a Raman spectral map of rough biological are studied by scanning tunneling spectroscopy and shown to be tissues, was engineered and constructed. The temperature dependent. The high anisotropic conductance of Bi, experimental setup enabled 3D scans of ex-vivo facilitates the observation of these phenomena. At 80K, upon freezing artery samples on and below the surface and the of structural fluctuations, the anisotropy of the BNPs is revealed as presentation of spatial spectral maps that can be variations in band gap maps of individual particles. (see Fig) related to the specific molecular structure of the sample. Our method enabled nondestructive quantification of minute (10μm diameter) cellular- level micro calcifications in the thin cap fibrous atheroma, and a coarse measurement of their depth in the tissue down to 200 micron below surface .Unlike previous diagnostic tools, we could image post-mortem tissues, with simultaneous creation of chemical maps of all chemicals involved, along with emphasis on the detection of the hydroxyapatite content of the tissue. Our ability to identify small hydroxyapatite crystals below surface calls for the development of a catheter version of the system, with prospects for research on the mechanism of acute coronary events, as well as the early detection of endangered patients.

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Prof. Yoram Dagan

The Perovskite based Superconductor-Ferromagnetic Superconductivity and Magnetism on Field effect Transistor the nanoscale It has been recently discovered that the interface between the two Superconductivity is a macroscopic quantum non-magnetic insulators: LaAlO3 and SrTiO3 is highly conducting phenomenon. Long range order is established and has the properties of a two dimensional electron gas. It has also over a coherence length-scale, ξ. However, when been demonstrated that in some samples this interface exhibits the superconducting specimen is constituted superconductivity with transition temperature Tc ≈ 350mK, and of weakly connected nano-grains whose size is in others ferromagnetism. The main parameter responsible for the smaller than ξ, or when the coherence length various phases seems to be the number of charge carriers. In our becomes of the size of the crystal unit cell many laboratory we are navigating through the phase diagram of this interesting physical phenomena occur. The first interface by varying the number of charge carriers using gate voltage case is realized in granular superconductors and via proximity to other superconductors. Utilizing the facilities at (GSC), and High Tc cuprate superconductors the nanocenter such as the FIB, and e-beam lithography we are able (HTCS) fit to the second. This research explores to fabricate small devices which enable us to observe electronic a possible analogy drawn between these two coherent effects in this fascinating new system. types of superconductors in order to understand fundamental questions in the physics of Tuning Superconductivity in Perovskites Using Organic superconductors in general and HTCS in particular. monolayers Nernst effect in superconductors is one of the In a material undergoing a superconducting transition, the most sensitive probes for vorticity. In the High electrons condense into a macroscopic ground state below a critical Tc cuprates superconductors the vortex Nernst temperature Tc. We use organic molecular and bio-inspired thin films effect anomalously persists well above the critical in order to control the properties of high Tc cuprate superconductors temperature and field. and other perovskite superconductors. This will be done by chemical We study the Nernst effect in the granular and opto-electrical tuning of the electronic properties of the superconductor Al-Al2O3 where phase superconductor surface using bio-optical active proteins and polar fluctuations can be tuned using the grain size self assembled monolayers. This ability may be useful both from the and inter-grain resistance as control parameters basic science and application perspectives. and in SrTiO3 \LaAlO3 interfaces. No vortex-

Magnetoresistance at low temperatures can Magnetoresistance curves at 20mK and field The doping dependence of the be explained by weak localization applied parallel to a SrTiO3\LaAlO3 interface. superconducting gap Δ and Tc in electron- The low field behavior is governed by doped cuprates. In marked contrast with hole- superconductivity. While the high field regime doped cuprates Δ and Tc follow the same by the spin-orbit interaction doping dependence.

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like excitations were found above Tc for the granular material near Femtosecond quasiparticle and phonon dynamics optimum oxygen concentration. Lower oxygen content may result in superconducting YBa2Cu3O7 studied by in a broader fluctuation regime. Large anomalous Nernst effect is ultrabroadband terahertz spectroscopy, Phys. Rev. Lett. (In press) found in the oxide heterostructure. The origin of this effect is yet to 6. M. Ben Shalom, M. Sachs, D. Rakhmilevitch, A. be understood. Palevski and Y. Dagan, Tuning spin-orbit coupling and superconductivity at the SrTiO3/LaAlO3 References interface: a magneto-transport study. Phys. Rev. 1. S. Finkelman, M. Sachs, J. Paglione, G. Droulers, P. Bach, R.L. Greene and Y. Lett. 104, 126802 (2010). Dagan, On the resistivity at low temperatures in electron-doped cuprate 7. A. Lusakowski, M. Gorska, J. R. Anderson, Y. Dagan, superconductors, Phys. Rev. B (submitted). and Z. Golacki, Magnetic contribution to the 2. D. Rakhmilevich, M. Ben Shalom, M. Eshkol, A. Tsukernik, A. Palevski, and Y. specific heat of Pb1-xGdxTe, Jour. Phys. Cond. Mat. Dagan, Phase coherent transport in SrTiO3=LaAlO3 interfaces (Submitted) 21, 265802 (2009). 3. I. Diamant, R. L. Greene, and Y. Dagan, Doping and temperature 8. I. Diamant, R. L. Greene, and Y. Dagan, Single dependence of the superconducting energy gap in electron doped superconducting energy scale in electron-doped cuprates, Physica C (In Press). cuprate superconductor Pr2-xCexCuO4-δ, Phys. 4. M. Sachs, D. Rakhmilevitch, M. Ben Shalom, S. Shefler, A. Palevski, andY . Rev. B, 80, 012508 (2009). Dagan, Anomalous magneto-transport at the superconducting interface 9. M. Ben Shalom, C. W. Tai, Y. Lereah, M. Sachs, E. Levy, D. Rakhmilevitch, A. Palevski, and Y. Dagan, Anisotropic between LaAlO3 and SrTiO3, Physica C (In Press). 5. A. Pashkin, M. Porer, M. Beyer, J. J. Hees, K. W. Kim, C. Bernhard, X. Yao,Y. magnetotransport at the interface between SrTiO3 Dagan, R. Hackl, A. Erb, J. Demsar1, R. Huber, and A. Leitenstorfer, and LaAlO3, Phys. Rev. B 80, 140403(R) (2009).

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Prof. Guy Deutscher

Long range triplet order parameter with equal spin spontaneously split zero-bias peaks and spectra pairing in diffusive Co/In contacts with un-split peaks. The former showed enhanced We have pursued the development and application of nano-scale split with field, and the latter showed threshold planar superconductor/ferromagnetic (S/F) contacts mentioned in splitting above finite fields. Although both field our 2008 Progress Report (see S. Hacohen-Gourgy, B. Almog and G. evolutions can be described in terms of screening Deutscher, Appl. Phys. Lett. 92, 15202 (2008)). and orbital supercurrents, within the framework Our efforts have been directed at the fabrication and study of nano- of a complex pairing symmetry, the enhanced scale multi-terminal devices where current is passed through one of the splitting is only compatible with an is component S/F contacts and the non-local voltage at a different one is measured in addition to the main d component. Our results as a function of the applied current. The non local conductance is the have direct implications on the local stability result of several processes. Here we have focused on its dependence of broken time-reversal symmetry in cuprate on the relative signs of the magnetization on the nearby ferromagnetic superconductors. legs of the two contacts, and have shown that it is larger in the parallel J. H. Ngai, R. Beck, G. Leibovitch, G. Deutscher and J. Y. T. state than in the anti-parallel one. This result was unexpected because Wei, Phys. Rev. B 82 (054505 (2010). it is incompatible with singlet pairing and implies the existence of triplet superconductivity near the S/F contacts on a length scale of the Origin of weak-link behavior of grain order of the superconducting coherence length. According to theory, boundaries in superconducting the only components of the triplet state that can extend up to such a cuprates and pnictides length scale are equal spins components. Superconducting cuprates and pnictides

It thus appears that equal spin triplet pairing can, under certain composed of CuO2 or AsFe planes, respectively, conditions, extend on the S side of S/F contacts over a long range. with intercalated insulating layers, are at the crossroads of three families of crystalline solids: B. Almog, S. Hacohen-Gourgy, A. Tsukernik and G, Deutscher, Phys. Rev. B 80, metals, doped Mott insulators and ferroelectrics. 220512 (2009). The metallic and doped Mott insulator approaches to high temperature superconductivity are Current driven transitions in ferromagnetic/insulator/ essentially electronic ones, while in ferroelectrics superconductor narrow stripes atomic displacements play a key role, as proposed We have studied superconducting to normal state current-driven in the Bond Contraction Pairing model. We show transitions in ferromagnetic Co/Co oxide/superconducting In stripes of that pairing by contraction of in-plane Cu-O (or Fe- widths ranging from 3 to 20 micron. The critical current of the narrower As) bonds is prevented at grain boundaries by the stripes can be controlled by modifying the domain structure of the Co tensile strain generated by dislocations. This explains line through the application of different field cycles leading to different why the weak link behavior of grain boundaries sets magnetization states, either homogeneous (small magnetic domain in already at small grain misorientation. density) or inhomogenenous (large magnetic domain density). In the latter case the current driven transition is preceded by a number of G. Deutscher, Appl. Phys. Lett. 96, 122502 (2010). steps where the resistance is only partially restored. These steps have been ascribed to the formation of finite size normal domains in the In stripe generated by the stray fields of Neel domain walls.

S. Hacohen-Gourgy, B. Almog, G. Leibovitch, R. G. mints and G. Deutscher, Appl. Phys. Lett. 95, 122507 (2009). Local tunneling probe of (110) YCaBaCuO thin films in a magnetic field Scanning tunneling spectroscopy was performed on (110) oriented thin films of Ca-overdopedY BCO films at 4.2K to probe the local evolution of Andreev – Saint-James surface states in a c-axis magnetic field. In zero field we observed conductance spectra with

100 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY PROGRESS reports

Prof. Haim Diamant

Dynamic correlations in confined suspensions Instability of curved liquid domains Confined suspensions are encountered, for example, in porous The Rayleigh instability of slender liquid bodies, media, micro- and nano-fluidic devices, blood vessels, and various driven by surface tension, is part of everyday other biological channels. In such confined geometries mutual drag experience. We have demonstrated the unusual forces between particles (hydrodynamic interactions) are widely occurrence of a localized instability in a curved presumed to be cut off (“screened”) when the distance exceeds the liquid filament supported on a solid substrate. channel width. We have shown, however, using a simple analytical Instead of the usual breaking into many droplets, theory and hydrodynamic simulations, that the picture becomes the filament narrows locally at the curved qualitatively different once the time-dependent response and finite region. This instability plays a central role in the compressibility of the host liquid are taken into account. Prior to the evaporation of nanometer-thick wetting films off steady, screened state, the velocities of the confined particles are solid surfaces [6]. correlated over extremely large distances. The correlations decay The work has been done in collaboration with slowly (only as t –3/2), and the many-particle dynamics during this time Oded Agam (Hebrew University). It is supported is highly cooperative [1]. by the Israel Science Foundation. This work has been done by Derek Frydel (post-doctoral researcher). It is supported by the Israel Science Foundation. Localized folds in compressed supported layers Dynamics of heterogeneous membranes When an elastic sheet is laterally compressed, it Proteins or nano-domains embedded in bilayer membranes move buckles globally (the Euler instability). However, in a correlated way due to flows that their motions induce within if the sheet is supported on a heavy liquid or the membrane and in the surrounding liquid. In addition, their an elastic substrate, it spontaneously focuses presence modifies the membrane response to stresses – its effective its unstable response onto localized, narrow viscosity – much like the way colloid particles modify the viscosity folds. Such a folding instability is observed of a suspension. We have derived the coupling diffusion coefficients in monomolecular layers lying at the water- of pairs of such inclusions, along with their dependence on the air interface and mimicking the surfactant concentration of inclusions and the effect of that concentration on monolayer covering the surface of the lung. the response of the membrane [2]. We have extended the theory to We have developed an analytical theory that membranes supported on a solid substrate, as encountered in many explains this nonlinear, localized instability and natural and practical scenarios [3]. the resulting pressure-displacement relation [7]. The work has been done by Naomi Oppenheimer (PhD student). It is The work has been done in collaboration with supported by the Israel Science Foundation. Tom Witten (University of Chicago). It is supported by the US–Israel Binational Science Foundation. Kinetics of surfactant aggregation The formation of nano-sized aggregates (micelles) in dilute solutions Nonequilibrium attraction between of amphiphilic molecules is a ubiquitous and useful phenomenon. We driven colloid particles have developed a new coarse-grained formalism for the kinetics of Non-interacting identical particles, driven through formation of micelles, in which the various stages (nucleation, growth, a liquid by the same force, can nonetheless final relaxation) are treated on a single footing – as constrained paths get closer to one another if the symmetry of on a single free-energy landscape. We have addressed both closed their hydrodynamic drag forces is somehow and open systems, showing that the two cases should exhibit very broken. Using optical-tweezers experiments, different kinetics [4,5]. hydrodynamic simulations, and a simple The work has been done by Radina Hadgiivanova (PhD student) in analytical model, we show that such a pairing collaboration with David Andelman (Tel Aviv University). It is supported effect is obtained when the particles are driven by the American Chemical Society Petroleum Research Fund. simply along a curved path (specifically, around

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an optical ring). We analyze this purely nonequilibrium interaction, References its influence on the collective mobility of particle assemblies, and the 1. R. Hadgiivanova, H. Diamant, and D. Andelman, effect of temperature [8]. Kinetics of surfactant micellization, in preparation. 2. T. A. Witten and H. Diamant, Localized folds in The work has been done by Yulia Sokolov (MSc student) and Derek compressed supported layers, in preparation. Frydel (post-doctoral researcher) in collaboration with Yael Roichman 3. Y. Sokolov, D. Frydel, Y. Roichman, and H. Diamant, (Tel Aviv University). It is supported by the Israel Science Foundation. Nonequilibrium pair attraction between driven colloidal particles, in preparation. Liquid quasicrystals 4. K. Barkan, H. Diamant, and R. Lifshitz, Stability of Several new structures with quasicrystalline (dodecagonal) symmetry, quasicrystals composed of soft isotropic particles, submitted. formed by nano-scale isotropic aggregates in solution, have been 5. D. Frydel and H. Diamant, Long-range dynamic discovered in the past few years. We have derived a coarse-grained correlations in confined suspensions, Phys. Rev. Lett. free energy for such a system, which depends on the details of 104, 248302 (2010). Featured in Physical Review the inter-particle pair potential and the thermodynamic variables. Focus 25, 23 (2010). Analytical and numerical analyses have revealed simple criteria for 6. H. Diamant and O. Agam, Localized Rayleigh the stabilization of dodecagonal quasicrystals, thus explaining the instability in evaporation fronts, Phys. Rev. Lett. 104, 047801 (2010). stability of the observed soft structures [9]. 7. N. Oppenheimer and H. Diamant, Correlated The work has been done by Kobi Barkan (MSc student) in collaboration diffusion of membrane proteins and their effect on with Ron Lifshitz (Tel Aviv University). It is supported by the Israel membrane viscosity, Biophys. J. 96, 3041 (2009). Science Foundation. 8. N. Oppenheimer and H. Diamant, Correlated motion of inclusions in a supported membrane, submitted. 9. R. Hadgiivanova and H. Diamant, Premicellar aggregation of amphiphilic molecules: aggregate lifetime and polydispersity, J. Chem. Phys. 130, 114901 (2009).

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Prof. Noam Eliaz

Introduction properties at elevated temperatures. Acta Materialia, In line with the demands of modern society, The Biomaterials 57 (2009) 1112-1119. and Corrosion Laboratory at Tel Aviv University is developing and Electrocrystallization of Hydroxyapatite studying advanced materials for a variety of applications, including and other Calcium Phosphates for biomedical, space, and harsh environments. Biomedical Applications The effect of a Simulated Low Earth Orbit Environment on Apatite is the primary inorganic constituent of the Durability of Polyhedral Oligomeric Silsesquioxane all mammalian skeletal and dental tissues. In its (POSS)-Polyimide Hybrid Nanocomposites synthetic form, hydroxyapatite (HAp) and some In collaboration with the Space Environment Section at Soreq NRC other calcium phosphates (CaP) are typically (headed by Dr. Eitan Grossman). A laser-driven flyer system was used bioactive ceramics, which are more osteoconductive to accelerate aluminum flyers to impact velocities of up to 3 km/s at than solid metal surfaces, and form direct bonds temperatures ranging from –60 to 100°C. Subsequently, the chemistry, with adjacent hard tissues. Prof. Eliaz has studied structure and morphology of the materials were analyzed. An different aspects of electrocrystallization of HAp intermolecular POSS-POSS condensation reaction was identified as a on commercially pure Ti and Ti–6Al–4V alloy, key factor, affecting the mechanical properties of the nanocomposite including its nucleation and growth; the effects via aggregate formation. The amount and density of the aggregates of bath chemistry and operating conditions; were shown to be composition dependent. A model based on the corrosion behavior of the coated samples; formation and coalescence of voids during tensile tests was suggested the effect of surface pre-treatments and post- to explain the effect of the POSS content on the POSS-PI mechanical treatments on the composition, phase content, response. The POSS-PI/MWCNTs nanocomposite films were found surface morphology and wettability of the coating to be a material with many beneficial properties for applications in as well as on its interaction in vitro with bone- the space environment, such as improved AO durability, mechanical forming cells and Staphylococcus aureus bacteria; properties, and increased electrical conductivity. and its in vivo performance. It was concluded that the EDHAp coatings were more biomimetic than References coatings produced by other technologies such as 1. R. Verker, E. Grossman, I. Gouzman and N. Eliaz. TriSilanolPhenyl plasma spraying. The nucleation of CaP exhibited POSS-polyimide nanocomposites: Structure-properties relationship. heteroepitaxy behavior, similarly to that observed Composites Science and Technology, 69 (2009) 2178-84. in biomineralization. 2. R. Verker, E. Grossman and N. Eliaz. Erosion of POSS-polyimide films under hypervelocity impact and atomic oxygen: The role of mechanical References 1. D. Lakstein, W. Kopelovitch, Z. Barkay, M. Bahaa, D. Hendel and N. Eliaz. Enhanced osseointegration of grit-blasted, NaOH-treated and electrochemically hydroxyapatite-coated Ti-6Al-4V implants in rabbits. Acta Biomaterialia, 5 (2009) 2258-2269. 2. N. Eliaz, S. Shmueli, I. Shur, D. Benayahu, D. Aronov and G. Rosenman. The effect of surface treatment on the surface texture and contact angle of electrochemically deposited hydroxyapatite coating and on its interaction with bone-forming cells. Acta Biomaterialia, 5 (2009) 3178-3191.

Ferrography: From Helicopters to the Human Body Ferrography is a method of particles separation onto a glass slide based upon the interaction Figure 1: AFM images of pristine (a and c) and AO exposed (b and d) PI and 15 between an external magnetic field and the wt% POSS-PI samples (note different z scale for image d). Scan size 1 µm × 1 µm; Z scale 25 nm (a-c) and 75 nm (d). Source: PhD dissertation of Ronen Verker magnetic moments of the particles suspended

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in a flow stream. The method was developed by Westcott et al. in the early 1970s to investigate the occurrence of ferrous wear particles in lubricated dynamic components. Bio-ferrography is a recent modification of conventional analytical ferrography that was specifically developed to allow magnetic isolation of target cells or tissues. Our lab is one of four labs worldwide, and the only one outside the Figure 2: ESEM image revealing prismatic hexagonal USA, which operates a bio-ferrograph. We have developed a method hydroxyapatite single crystals, approximately 300 nm in for isolating bone and cartilage wear particles suspended in the diameter, that were formed by electrocrystallization on Ti synovial fluid of the hip, knee and ankle joints of humans suffering substrate pre-treated by soaking in NaOH solution. from different levels of osteoarthritis, based on specific magnetization cartilage wear particles captured by bio-ferrography. of collagens I and II. The relations between the level of the disease Acta Biomaterialia, 7 (2011) 848-857. and the number, dimensions, shape and chemical composition of the 3. J.J. Elsner, Y. Mezape, K. Hakshur, M. Shemesh, A. particles were established. Shterling and N. Eliaz. Wear rate evaluation of a novel polycarbonate-urethane cushion form Next, an MSc student in our group, Keren Hakshur, used bio- bearing for artificial hip joints. Acta Biomaterialia, 6 ferrography to capture magnetically labeled cartilage and bone (2010) 4698-4707. debris from the synovial fluid in human knees before each of four hyaluronan (Euflexxa™) injections. The wear particles were counted Electrochemical and Electroless and characterized microscopically and chemically. Bio-ferrography Deposition of Rhenium-Based Alloys showed a reduction in the concentration of both cartilage and bone The unique combination of physical, mechanical particles, with a minimum after the third hyaluronan injection. The and chemical properties of rhenium and its alloys advantages of bio-ferrography as a primary assessment tool was makes it extremely attractive as a coating in a demonstrated. The results indicated that while hyaluronan treatment diverse range of defense and civilian industries that may temporarily slow the wear rate to an extent beyond a placebo include aerospace, nuclear, electrical, chemical effect, it does not prevent joint degradation altogether. production, and biomedical. The objectives of our A third project was carried out in collaboration with Active Implants research is to study the deposition mechanisms, Corp. Liners based on polycarbonate-urethane (PCU) mimic the identify promising bath chemistries and operation natural synovial joint more closely than ultrahigh molecular weight conditions that yield uniform films with high Re- polyethylene (UHMWPE) by promoting fluid-film lubrication. In content and little or no cracking, and characterize this study, we used a physiological simulator to evaluate the wear the resulting coatings. The kinetics of Re-Me alloy characteristics of a compliant PCU acetabular liner, coupled against deposition (where Me = Ni, Fe or Co) has been a cobalt–chrome femoral head. The wear rate was evaluated over studied for different bath chemistries, along with 8 million cycles gravimetrically, as well as by wear particle isolation the microstructure, chemical composition and using filtration and bio-ferrography. Bio-ferrography was found to be thickness of the coatings. The possible role of Me more sensitive towards the detection of wear particles compared to has been suggested for electrodeposition of Re- the conventional filtration method, and less prone to environmental Me alloys. fluctuations than the gravimetric method. PCU demonstrated a low particle generation rate with the majority of wear particle mass lying References above the biologically active range. Thus, PCU offers a substantial 1. A. Naor, N. Eliaz and E. Gileadi. Electrodeposition advantage over traditional bearing materials, not only in its low wear of alloys of rhenium with iron-group metals from rate, but also in its osteolytic potential. aqueous solutions. Journal of the Electrochemical Society, 157 (2010) D422-D427. References 2. N. Eliaz, E. Gileadi and A. Naor. Rhenium 1. K. Mendel, N. Eliaz, I. Benhar, D. Hendel and N. Halperin. Magnetic isolation nanostructures. US provisional patent application of particles suspended in synovial fluid for diagnostics of natural joint 61/260,089, filed 11 November, 2009. chondropathies. Acta Biomaterialia, 6 (2010) 4430-4438. 3. A. Naor, N. Eliaz, E. Gileadi and S.R. Taylor. Properties 2. K. Hakshur, I. Benhar, Y. Bar-Ziv, N. Halperin, D. Segal and N. Eliaz. The effect and applications of rhenium and its alloys. The of hyaluronan injections into human knees on the number of bone and AMMTIAC Quarterly, 5 (2010) 11-15.

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Prof. Amihai Freeman Protein Mediated Nano-Scale Biotemplating

ur research is focused on the development of new methodologies for the preparation of nanostructured novel composite materials by protein mediated biotemplating [1]). The research program is divided into two arms: The first is focused on the use of single, soluble protein Omolecules as core for biotemplating leading to biologically active molecular protein-metal hybrids. The second is focused on the use of stabilizd protein crystals as biotemplates for the fabrication of novel composite materials by ‘filling’ their 3D intermolecular voids arrays with organic or inorganic materials. In the first arm we developed a new approach to direct electroless deposition of silver and palladium to the surface of the enzyme glucose oxidase (see Figures 1&2 and [2, 3]). The resulting enzymatically active soluble hybrids were successfully nano-wired to Figure 1: High Resolution Electron Microscope (Philips platinum electrode allowing glucose determination in the absence Tecnai F20) micrographs, obtained without staining for of oxygen (a study carried out in collaboration with Prof. Y. Shacham- silver-glucose oxidase hybrid. The chemical identity of the silver deposit was confirmed by EDX (inserts). Diamand from the Faculty of Engineering and Prof. J. Rishpon from our faculty). The silver-glucose oxidase hybrid was also used as a new antibacterial agent to combat biofilms by enzymatically attenuated in situ silver release [4]. The methodology developed for the production of silver-enzyme hybrids was recently successfully expanded for the preparation of avidin-silver and IgG-silver hybrids (Mor et al (2010), submitted). The ‘wiring’ approach of metal-enzyme hybrids to electrodes was recently successfully expanded to wire intracellular enzymatic activities of whole bacterial cells to gold electrodes (Dagan-Moscovich (2010) manuscript in preparation). In the second arm we continued our studies aiming at the establishment of methodologies for the monitoring of the ‘filling’ process of a protein crystal biotemplate [5] with elucidation of the mechanism of protein crystal stabilization by chemical crosslinking by glutaraldehyde – a prerequisite for biotemplating without template Figure 2: High Resolution Electron Microscope (Philips distortion – and resolution of its end products by x-ray analysis [6] Tecnai F20) micrographs, obtained without staining for and demonstrated the construction of a 3D metal nanoparticles array palladium-glucose oxidase hybrid. The chemical identity of the palladium deposit was confirmed by EDX (inserts). formation within the crystals voids array (see figure3 and [7]). To gain control on the voids array of the protein crystal biotemplate we have concluded studies involving three three approaches: in the first, the capability to alter the geometry of the crystal’s voids array by chemical modification of the protein ‘building block’ with purification of the modified protein prior to crystallization (Cohen-Hadar et al (2010), submitted); in the second the use of co-addition of modifying agents into the crystallization medium was demonstrated (7), and in the third, the use of site directed point mutations (see Figure 4 and ref.

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Figure 3: Scanning electron microscope photographs (X50,000-300,000) showing the 3D array of silver grains formed within the pores of stabilized ConcanavalinA crystal.

molecules with preserved enzymatic activity. IEEE Transactions on Nanotechnology. In press. 4. Ben Yoav, H, Freeman A. (2008) Enzymatically attenuated in situ release of silver ions to combat bacterial biofilms: a feasibility study. J Drug Delivery Sci Technol 18: 25-29. 5. 2, Dagan-Moscovich H, Cohen-Hadar N, Porat C, Post modification Pre modification Rishpon J, Shacham-Diamant Y, Freeman a (2007) Figure 4: Modification of protein crystal’s porosity by site directed mutagenesis (8). Nanowiring of the catalytic site of novel molecular enzyme-metal hybrids to electrodes. J Phys Chem 8). These studies were carried out in collaboration with Prof. F. Frolow C, 111:5766-5769. from our faculty. 6. Wine Y, Cohen-Hadar N, Freeman A, Frolow F (2007) Elucidation of the mechanism and end products of glutaraldehyde crosslinking reactions by X-ray References structure analysis. Biotechnol Bioeng 98: 711-718. 1. Wine Y, Cohen-Hadar N, Lagziel-Simis S, Dror Y, Frolow F, Freeman A (2010) 7. Lagziel-Simis S, Cohen-Hadar N, Moscovich-Dagan Adjustment of protein crystal porosity for biotemplating: chemical and H, wine Y, Freeman A (2006) Cur Opin Biotechnol 17: protein engineering tools. AIP Con Pro 1254:198-203. 569-573. 2. Wine Y, Cohen-Hadar N, Lamed R, Freeman A, Frolow F. (2009) Modification 8. Cohen-Hadar N, Wine Y, Nachliel E, Huppert D, of protein crystal packing by systematic mutations of surface residues: Gutman M, Frolow F, Freeman A (2006) Monitoring implications on biotemplating and crystal porosity. Biotechnol Bioeng the stability of crosslinked protein crystals 104:444-457. biotemplates: a feasibility study. Biotechnol Bioeng 3. S. Vernik, H. Moscovich-Dagan, C. Porat-Ophir, J. Rishpon, A. Freeman, 94: 1005-1011. Shacham-Diamand Y. (2008) Directed metallization of single enzyme

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Prof. Ehud Gazit

Physical Properties of Peptide Nanostructures Natural-Synthetic Malleable Composite Nadav Amdursky, Ph.D. student Hydrogel Hybrid for Tissue Engineering In our studies we report for the first time in the bio-organic world Moran Aviv, Ph.D. student on the direct observation of quantum confined nanocrystalline Development of malleable polymeric nanofibers structure at various peptide nanostructures (PNS). These highly constracts is of a great scientific and technological ordered building blocks of the structures have been observed from interest due to their wide-range applications optical studies where pronounced quantum confinement (QC) and in biomedicine and biotechnology. Particularly, photoluminescence, which results in an intense blue emission, have composite nanofibers derived from natural and been revealed. We found a step-like optical absorption behavior, synthetic polymers, combining the favorable which is a distinguished feature of 2D-QC, and a spike-like behavior, biological properties of the natural polymer and which is a feature of 0D-QC. By calculations we have estimated the the mechanical strength of the synthetic polymer, dimension of those crystalline regions to be at the order of only ~1 represents a major advantageous advancement nm, a size that is most difficult to achieve at the inorganic world using in tissue engineering and regenerative medicine. common deposition techniques. These data directly indicates on the Our work is focus on the development and presence of fine crystalline structure at the PNS and allows relating characterization of an innovative natural-synthetic these PNS to self-assembly ceramic-like nanostructural bio-inspired polymeric nanofiber hydrogel hybrid comprised material. By following the formation of the exciton we could follow the of hyaluronic acid (HA) and the self-assembled self-assembly process of the structures. The nanocrystalline structure, peptide, FmocFF (fluorenylmethoxycarbonyl- in addition to the P61 crystal symmetry of the peptide nanotubes, diphenylalanine). HA, a biodegradable, promoted us to assume the existence of piezoelectric properties nonimmunogenic, and biocompatible natural and second harmonic generation (SHG) in these structures. From our polymer, which represent remarkable viscoelastic piezoelectric measurements we indeed found a strong longitudinal properties, is an attractive biomaterial for cells in and shear piezoelectric response where d15 shear piezoelectric tissue engineering. FmocFF is a short peptide (FF- coefficient has reached 70-100 pm/V. We have also found strong diphenylalnine) with a protected group (FmocFF), SHG from the peptide nanotubes. In addition to the strong SHG, which can self assembled into nanotubes and a pronounced threshold for the two photon luminescence was form hydrogels as macrostructure. The mixing observed, this indicate on the possibility of the nanotubes to serve between these two components, without as a lasing material. using any chemical crosslinkers agents, results The new physical findings, which were previously found mainly in in hydrogels that are characterized both by a inorganic materials, may pave the way for the incorporation of bio- remarkable rigidity in comparison to HA, and inspired PNS toward green devices, such as: LEDs, lasers and actuators. biocompatibility in comparison to FmocFF alone.

Figure A. The intrinsic blue luminescence of PNS, which composed of 2D-QC structure. Figure B. AFM image of peptide quantum dots (0D-QC). Figure C. The formation of an exciton at the peptide quantum dots.

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These innovative hybrids present a unique, rainbow of agents (in into various nano-metric structures in the nano respect to the ratios of the basic two components), remarkable scale depending on the basic molecule structures rheological, viscoelastic, swelling and biodegradability properties and solvent composition. In our research we that has multifunctional properties supporting growth of all kinds are using the BocFF peptide which forms in of cultures. The design combines the technological advances in specific condition nano-spheres that are very biocompatible polymers and nanofibrous matrices with significantly stable and uniform at various pH conditions and improved mechanical and biological properties. temperatures, in order to obtain new insight on its conformation, stability and manipulate his Ultra-Sensitive Biosensor for Environmental spheric structure for using it as a new approach Monitoring, Combining Electrochemistry and Surface for drug delivery system. The spheres are very Modification Using Aromatic Dipeptide Nanostructure stable after lyophilization (Figure 1) after adding and Carbon Nanotubes to the powder only water. Lihi Adler-Abramovich, Ph.D. student We also wanted to see if the spheres could In this study the researchers aimed to increase the sensitivity of an be fluorescently labeled and delivered into environmental sensor, for the detection of phenol by combining both cell culture. We labeled the nano-spheres CNT and peptide nanotubes on the same electrode. An amperometric with fluorescein and checked its emission in enzyme-based biosensor was designed by decorating standard fluorescent microscope (Figure 2). electrodes with both CNT and peptide nanotubes, consequently improving the sensor sensitivity 13-times, in comparison to the absence of the nanostructures. The work was extended and sensors based on various nanostructures, all member of the aromatic dipeptide nanostructures family were designed. Cyclic voltammetric and time-based amperometric techniques demonstrated that the integration of dinaphthylalanine peptide nanotubes or Boc-Phe- A Phe-OH peptide nanospheres into biosensor electrodes, increased sensitivity of the electrochemical measurements. Notably, electrode coated with nanoforest, vertically aligned peptide nanotubes, showed the highest sensitive phenol detection, 17-times than a bare electrode.

Reference 1. Adler-Abramovich, L., Badihi-Mossberg, M., Gazit, E., Rishpon, J. (2010) Characterization if Peptide Nanostructures Modified Electrodes and their Application for Ultra- Sensitive Environmental Monitoring. Small 7, 825- 831.

Stability of Peptide Nano Structures for Drug Delivery Applications Hadar Cohen, M.Sc. student & Lihi Adler Abramovich, Ph.D. student Various organic and inorganic self assembled nanostructures have B been suggested to have a potential key role in nano technological devices and applications. Various biological molecules such as Electrode modified with a nanoforest of vertically aligned FF peptide nanotubes. Comparison between untreated peptides have demonstrated the ability to self assemble into well and nanoforest modified electrode. A) CV of 1mM quinone ordered nano-structures. The diphenylalanine peptide self assembles obtained at a scan rate of 50mV s-1. B) Scanning electron microscopy image of the nanostructures

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Prof. Alexander (Sasha) Gerber

Monitoring magnetization reversal and perpendicular anisotropy in nanoscale magnetic systems Ferromagnetic films with perpendicular magnetic anisotropy attract significant attention as strong candidates for realizing ultra- high density recording systems. For this, detailed information on the magnetization reversal mechanisms and determination of the magnetic anisotropy constants are particularly important. We developed a novel experimental technique particularly suitable for studies of nano-scale magnetic objects with magnetic moment too small to be detected by conventional magnetometric tools. We measure two magnetotransport properties of ferromagnetic materials: the extraordinary Hall effect and anisotropic magnetoresistance to monitor the normal and in-plane projections of the magnetization their spin angular momentum to the localized in ultra-thin Co/Pd multilayers with perpendicular anisotropy. By spins of the ferromagnet, resulting in a spin reconstructing the normalized magnetization vector we were able to torque acting on the magnetization. The critical distinguish between the coherent rotation and domain nucleations currents at which current-induced excitations or during the process of magnetization reversal. We found that under magnetization reversal was observed depend fields canted beyond a certain critical angle the complete cycle of on the layer thickness and on the magnetic field, magnetization reversal takes place by a coherent rotation with an which is on the order of 108 – 5´108 A/cm2. It intermediate sharp flip-flop of the out-of-plane component. has been recently reported by I.Ya.Korenblit that the electromagnetic (relativistic) interaction of D. Rosenblatt, M. Karpovski and A. Gerber. Jour. Appl. Phys. 108, 043924 (2010). the electron current with the field of the spin

wave in ferromagnetic conductors with large Reversal of the extraordinary Hall effect polarity in extraordinary Hall effect can lead to current ultra-thin Co/Pd multilayers induced instability at critical unpolarized currents Thin Co/Pd multilayers, with room temperature perpendicular significantly smaller than predicted by the anisotropy and an enhanced surface scattering, were studied for the exchange interaction models. We performed the possible use in the extraordinary Hall effect (EHE) – based magnetic first and rather preliminary study of current- and memory devices. Polarity of the EHE signal was found to change from temperature-assisted magnetization reversal in negative in thick samples to positive in thin ones. Reversal of EHE sign two types of magnetic systems: thin Ni films with was also observed in thick samples with aging. The effect is argued an enhanced extraordinary Hall coefficient and to be related to the dominance of surface scattering having the EHE planar arrays of Co nanoclusters embedded in a polarity opposite to that of the bulk. nonmagnetic Pt matrix. In Ni we have identified D. Rosenblatt, M. Karpovski and A. Gerber. Appl. Phys. Lett., 96, 022512 (2010). at least three features inconsistent with the “thermal-only” scenario that can be considered as Non-thermal magnetization reversal assisted by evidence of destabilization of magnetization by unpolarized current unpolarized electric current. Current induced switching of the magnetization and spin-wave excitations in magnetically inhomogeneous systems has attracted O. Riss, A. Gerber, I. Ya. Korenblit, M. Karpovsky, S. considerable attention over the last decade stimulated by prospects Hacohen-Gourgy, A. Tsukernik, J. Tuaillon-Combes, P. Melinon and A. Perez. Phys. Rev. B 82, 144417 (2010). of possible practical applications of current driven high-density magnetic storage media, as well as by the fascinating physical phenomena accompanying this effect. When a spin-polarized current passes through a ferromagnetic layer, the electrons transfer

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Prof. Jonathan Gershoni

Molecular mechanisms of biorecognition Much of biology depends on the ability of proteins to interact with their surroundings with exquisite specificity. Receptors bind hormones and neurotransmitters, antibodies bind antigens, enzymes react with their substrates and viruses target specific cells -- all as a result of proteins being able to identify, bind and discriminate between an endless diversity of molecular nano-structures. The question is, therefore, how do proteins recognize their counterparts and can a deep understanding of these mechanisms be translated into the design and production of novel protein based therapeutics? The ultimate goal of our research is to elucidate the mechanisms of biorecognition of proteins and their ligands with a special emphasis on the interaction between antibodies and their corresponding antigens. Currently our research deals with better understanding the antibody response towards viral infections, such as AIDS, Hepatitis, Influenza and SARS. In each case we attempt to identify epitopes (the nano- molecular structures bound by antibodies) of the viruses that are targeted by the immune system with the ultimate goal of designing novel drugs, vaccines and diagnostics. The following are summaries of the ongoing projects in our lab:

Reconstituting epitopes of therapeutic potential: When viruses enter our body, B-cells react and produce antibodies that recognize the virus and bind it. This binding can interfere with virus infectivity and in the best case scenario antibody binding leads to virus inactivation, ie neutralization. Thus a major objective is to understand the molecular structure of those viral epitopes that should be targeted for the production of effective protective Reconstitution of bridging sheet of HIV gp120: vaccines. For this we have developed a novel approach where we The bridging sheet of the envelope protein gp120 of HIV consists of 4 anti-parallel beta strands. Two of the strands produce hundreds of millions of epitope variants expressed on the are linked at their base via cysteine residues 119 and surface of filamentous bacteriophages. This collection of epitopes is 205 as is illustrated in the figure. In order to reconstitute then subjected to screening against the antibody that naturally binds a native structure it is necessary to link the two strands via a linker that will allow the strands to form a network the virus and neutralizes it. The antibody thus serves as a template of hydrogen bonds between them. We are currently for the selection of epitopes that best mimic the native viral structure. constructing libraries of alpha and beta strands linked via This approach has been applied to specific targets in HIV, SARS CoV combinatorial linkers of different lengths and composition and recently in influenza. The long term goal of these efforts is to and testing these for their ability to reconstitute the native conformation. Functionally reconstituted structures will produce prophylactic vaccines. then be characterized for their immunological activity.

Profiling the complete antibody response in human blood Antibodies are produced against various immunological insults and act to remove them from our bodies. Well after antibodies have acted they remain in the blood as “foot-prints” telling the tale of past

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encounters. Hence the ability to profile the repertoire of antibodies generate read-outs indicating the presence of present in serum (the fluid of blood without cells) is extremely specific antibodies in a blood sample. Here we informative, revealing what pathogens may have been encountered have been developing a novel nano-photonic and how they were successfully removed and inactivated. The ability method whereby antibodies or antigens are to identify the specificities of antibodies can often be extremely immobilized on silicon wafers and illuminated complicated and tedious. We are currently developing a novel by a laser over a range of wavelengths. The technological platform that enables one to measure the spectrum beam is reflected from the surface of the chip of antibody specificities in a single blood sample. This new method and a reference interface below, thus generating should prove very useful in elucidating mechanisms of the immune an interference pattern. Phase determination response towards viral infections and suggest new approaches for enables one to measure the optical thickness diagnosis and treatment. of the surface at 0.1nm resolution. This allows one to monitor binding of antibodies to their Interferometric measure of antibody antigen corresponding antigens without the need for interactions enzyme-tagged reagents. This new technology One of the basic means to diagnose disease is to measure the coined SRIB is currently being developed for the presence of antibodies in blood. Standard methods, such as ELISA purpose of multiplex optical sero-diagnostics. tests, require multiple steps using enzyme tagged reagents to

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Prof. Ilan Goldfarb

Surface Science and Nanostructures Laboratory The main research directions throughout this period were three-fold: (a) self-organization of silicide nanocrystals on vicinal Si surfaces, (b) nanocontacts on CdZnTe surfaces, and (c) cross-sectional (X-sectional) STM of III-V superlattice-based devices. We have experimented primarily with cobalt-silicide and titanium-silicide islands on vicinal Si(111) surfaces, though recently we have initiated experiments with iron-silicide, as well. This has been an interdisciplinary collaborative effort (with E. Rabani from TAU Chemistry and W.D. Kaplan from Materials at the Technion), funded by ISF, where the samples are self-assembled and in-situ analyzed in Goldfarb’s lab, ex-situ HR-TEM- analyzed by Kaplan’s group at the Technion, and modeled by the Rabani group. Up until now, the main findings indicate, that self- ordering of the silicide nanoislands by preferential decoration of the periodic step-bunches at the vicinal Si(111) surface, is better at low initial metal coverage, improves with temperature, and that of cobalt- Scanning tunneling microscopy (STM) micrograph In-Te silicide islands is superior to that of titanium-silicide islands in the nanocontacts on CdZnTe(110) identical coverage & temperature ranges (submitted for publication). In addition, we have found evidence of an interesting quantum-size effect in these silicide islands, known as “electronic growth”, namely that height and shape of the islands are stabilized by the energy of the electrons quantum-confined in the island (rather than the more familiar surface/interface and elastic strain energies). These findings have been published in J. Mater. Sci. (2010 (DOI 10.1007/s10853-010- 4393-8). For the nanocontacts work, we used indium on cleaved (110) surfaces of CdZnTe (CZT) crystals used for radiation detectors. We have established, that In reacts with the Te atom rows at the CZT surface already at RT, and these indium-telluride complexes form epitaxial finger-like nanocontacts (pink in the figure below) parallel to the Te-rows (green stripes in the figure below). While normally indium on n-type CZT creates ohmic contact, surprisingly these In(Te) nanocontacts were of the Schottky-type [Adv. Funct. Mater. 20, 215 (2010)]. In view of the tiny nanocontact size, the latter could only be established using sophisticated scanning probe technique with high spatial resolution, such as torsion-resonance AFM (TR-TUNA), in an ISF-funded collaboration with Electronic Measurements Laboratory of A. Ruzin (EE at TAU).

Finally, in collaboration with Y. Rosenwaks (EE ay TAU) and SemiConductor Devices (SCD) company (which also provides partial funding for the project), we have recently initiated a project at a Ph.D. level, aimed at characterizing cleaved multilayered structures by STM and KPFM.

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Dr. Michael Gozin

Natural Nanoreactors – Organic Reactions Promoted by protein backbone, plays an important role in the Mucin Glycoproteins hydrolytic activity of these glycoproteins. Mucins are glycoproteins that comprise 80% of the organic The discovered property of mucins to accelerate components of mucus, which coats many organs, including organic chemical reactions provides a new and respiratory, digestive, and reproductive tracts, and, in some amphibia, unique example of natural non-enzymatic proteins the skin. It is believed that the main function of these glycoproteins capable of promoting reactions of hydrophobic is to protect epithelial cells from infection, dehydration, as well as materials in aqueous solution. As heavily- from physical and chemical injuries. Although mucins exhibit a broad glycosylated mucins showed unique properties range of adhesive interactions with various hydrophobic materials, in comparison to various oligosaccharides, including Polycyclic Aromatic Hydrocarbons (PAHs), there has been we propose that mucins perform a task of no clear evidence that mucins are capable of promoting chemical hydrophobic compounds dissolution (with reactions. subsequent promotion of organic reactions) We demonstrated that under physiological conditions, two by folding of their amorphous oligomeric representative mucins, Bovine Submaxillary Mucin Type I (BSM) and structure, in order to create local hydrophobic Porcine Gastric Mucin Type III (PGM), accelerated the rate of fatty environments, in which such reactions can take acid ester hydrolysis up to 337 times compared to the mucin-free place. Furthermore, our results would lead to a reference reactions. Moreover, under the same reaction conditions, a better understanding of how various therapeutic Diels-Alder (DA) reaction was promoted by these glycoproteins. The agents undergo metabolic processes in a mucus latter reaction does not occur in aqueous media without mucins and layer. Studies of mucin chemical reactivity are the rate was accelerated up 200 times in the presence of a mucin, also relevant to development of biocompatible over the rate of the reference process performed in chloroform. materials for implantable devices, such as birth Mucins are comprised of branched oligosaccharide chains attached control devices, orthodontic devices, digestive to a protein backbone. This unique structure was discovered to be tract implantable devices and contact lenses that critically important to the rate acceleration, as various cyclic and non- have surfaces that come into direct, long-term cyclic oligosaccharides were far less efficient in promoting the same interaction with mucus. reactions. To assess the influence of the glycosidic moieties on the capability of References mucins to promote hydrolytic reactions; we compared the rate of ester “Organic Reactions Promoted by Mucin Glycoproteins” hydrolysis in the presence of BSM and PGM glycoproteins with that Shraga, N.; Belgorodsky, B.; Gozin, M. J. Am. Chem. Soc. 2009, 131(34), 12074-12075. in the presence of various oligosaccharides under the same reaction conditions. Our findings strongly suggest that spatial arrangement of glycosidic moieties, resulting from their attachment to mucin

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Prof. Yael Hanein

Neuro-prosthetic devices, nanotube-based MEMS, nano-fabrication Nano materials have unique functionalities which are being harnessed in many applications ranging from electronic devices to bio-imaging. In the field of brain-machine interfacing, nano materials and light addressed electrodes. This research is are particularly attractive and are now helping to resolve decades- aimed to achieve neuro-prosthetic devices. Such old challenges. Primarily, bio-nano-materials facilitate seamless link devices are developed with the vision to restore between artificial systems and neuronal tissue. Owing to their unique function due to neurological dysfunction. In mechanical, chemical, optical and electrical properties, quantum particular, we are developing a technology suited dots and nanotubes are especially promising and can be used as for the realization of novel retinal interfaces. excellent interfaces. Engineered neuronal systems are also being Over the past several years, we have pioneered the use of carbon explored in our lab. We construct systems that nanotube technology for neuronal interfacing applications. Our help us learn how neuronal systems function so efforts focus on the realization of high efficacy recording and the underlying mechanisms that govern these stimulation electrodes. More recently we have expanded our efforts systems can be revealed. to develop a flexible platform suited for implantable applications Our research also utilizes micro and nano miniaturization techniques for the realization of new devices. In addition to neuronal interfaces we also explore bio-mimetic approaches to construct functional devices such as sensitive accelerometers and radiation sensors based on nanoantennas

References 1. Assaf Ya’akobovitz, Slava Krylov and Yael Hanein, Digital image correlation algorithm for nanoscale displacement measurements by means of optical microscopy of electrostatically actuated devices, Sensors & Actuators: A. Physical, In Press, 2010. 2. Sarit Anava, Alon Greenbaum, Eshel Ben Jacob, Yael Hanein and Amir Ayali, The regulative role of neurite mechanical tension in network development, Biophysical Journal, Vol.96, pp. 16611670, 2009. 3. Raya Sorkin, Alon Greenbaum, Moshe David- Pur, Sarit Anava, Amir Ayali, Eshel Ben Jacob, and Yael Hanein, Process entanglement as a neuronal adhesion mechanism, Nanotechnology, Vol. 20, pp. 015101, 2009. 4. Asaf Shoval, Christopher Adams, Moshe David-Pur, Mark Shein, Yael Hanein and Evelyne Sernagor, Carbon nanotube electrodes for effective interfacing with retinal tissue, Frontiers in Neuroengineering, Vol 2, pp. 4, 2009. 5. Ze’ev R. Abrams, Zvi Ioffe, Alexander Tsukernik, Ori Cheshnovsky, and Yael Hanein, A Complete Scheme for Creating Large Scale Networks of Carbon Nanotubes, Nano Letters, Vol. 7, pp. 2666-2671, 2007.

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Dr. Oded Hod

Boron Notride Nanotubes of first-principle calculations. Furthermore, we are We are studying the electro-mechanical properties of multi-walled developing a molecular-dynamics code with an boron-nitride nanotubes (BNNTs). These systems have unique appropriate force-field that will enable us to study properties in the sense that each layer has a Young’s modulus similar the electromechanical response of large multi- to that of carbon nanotubes, yet the interlayer coupling is much walled boron-nitride nanotubes. The project is stronger due to the polarized nature of the BN bond. The strong held in collaboration with Prof. Ernesto Joselevich interlayer coupling is expected to considerably increase the Q-factor and Prof. Leeor Kronik from the Weizmann of nanoscale oscillators based on these molecules allowing them to Institute, and Dr. Alexandre Tkatchenko from the serve as key components in future Nano Electro-Mechanical Systems Fritz-Haber-Institut in Berlin, Germany. (NEMS). Thus far, we have studied the interlayer sliding processes in planar hexagonal BN sheets. It was found that van der Waals forces Graphene Based Ultra Sensitive serve to “anchor” the layers at a fixed distance, whereas electrostatic Chemical Sensors interactions dictate the optimal stacking mode and the interlayer The electronic response of graphene nanoribbons sliding energy. A nearly free-sliding path has been identified, along to the chemisorption of external molecular which bandgap modulations of ~0.6 eV have been obtained. We species is investigated. We aim to investigate have proposed a simple geometrical model that quantifies the the sensitivity, specificity, selectivity, and registry matching between the layers and captures the essence of the reliability of these systems as chemical sensors. corrugated h-BN interlayer energy landscape. The simplicity of this The project relies on the recently developed phenomenological model opens the way to the modeling of complex density functional theory divide-and-conquer layered structures, such as carbon and boron nitride nanotubes. We approach. We are currently implementing the are now in the process of extending the study towards double-walled method within the real space density functional boron-nitride nanotubes. The geometric model has been extended theory code PARSEC (see below). As a first step to treat such structures and is currently being compared to results we are performing a comprehensive study of the adsorption of lithium atoms on the surface and edges of armchair graphene nanoribbons. These atoms will serve as anchoring sites for the adsorption of target molecules to be sensed. The understanding of the physics and chemistry of the adsorption of Li on graphene is thus of high importance. Divide and Conquer Approach in 2 and 3 Dimensions We have started the implementation of the one-dimensional divide-and-conquer method within the real-space density functional theory code PARSEC. As a first step, we have written a non-self-consistent code for the calculation of the electronic transport through molecular constrictions based on absorbing imaginary potentials. During the implementation it was found that the ARPACK package is performing poorly when executing the partial diagonalization of non-Hermitian matrices. Therefore, we have developed an alternative method that avoids the

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need to form the (huge) Green’s function matrix representation of the system and is based on an efficient algorithm to solve an energy- dependent system of equations. The method has been implemented and tested within a tight-binding code and is currently being inserted into PARSEC. Once this stage is finished the conductance code will be tested and expanded to perform self-consistently and with open shell systems. In parallel, the divide and conquer method will be implemented and expanded to perform in two and three dimensions. The project is run in collaboration with Prof. Leeor Kronik from the Weizmann Institute, and Prof. Tamar Seideman and Prof. References Mark Ratner from Northwestern University. 1. D. Rai, O. Hod, and A. Nitzan, “Circular Currents in Molecular Wires”, J. Phys. Chem. C, In press (2010). Time-domain-real-space electron dynamics in open 2. N. Marom, J. Bernstein, J. Garel, A. Tkatchenko, E. systems Joselevich, L. Kronik, and O. Hod, “Stacking and We develop a new method for the time-domain description of Registry Effects in Layered Materials: The Case electron dynamics in molecular junctions. The method is based of Hexagonal Boron Nitride”, Phys. Rev. Lett. 105, 046801 (2010). on propagating the Kohn-Sham equations within the framework 3. S. Hod and O. Hod, “Analytic treatment of the black- of time-dependent density functional theory. The Hamiltonian hole bomb”, Phys. Rev. D (Rapid Communication) 81, is augmented with complex potentials that serve to absorb the 061502(R) (2010). electronic wave-packet as it propagates deep into the leads. The 4. O. Hod and G. E. Scuseria, “Electromechanical first stage of this project involves the study of simple wave-packet properties of suspended graphene nanoribbons”, propagation schemes in the context of electronic transport. Once Nano Letters (Letter) 9, 2619-2622 (2009). we develop understanding of the relation between the steady state solutions and the dynamical scattering description of the systems at hand the method will be implemented within the real-space density functional theory code PARSEC. The project is run in collaboration with Prof. Leeor Kronik from the Weizmann Institute of Science.

Silicon nanowires and nanotubes We are investigating the electronic and mechanical properties of ultra-narrow silicon nanowires (SiNWs) and nanotubes (SiNTs). The energetic stability of SiNWs grown along different crystallographic directions is studied. We find considerable differences in the electronic character of pristine SiNWs and SiNTs the later possessing considerable larger bandgaps. The effect of chemical doping, such as fluorine passivation, on the electronic properties of the systems is investigated in order to identify and characterize possible routes to control and tailor the electronic functionality of these systems.

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Prof. Alexander Kotlyar

Application of novel DNA-based nanostructures in Binding of Thiazole orange to the wires leads to a molecular electronics and devices tremendous (more then 1000 times) increase in The main goal of the this work is – to develop new conductive fluorescence of the dye. molecular nanowires based on G4-DNA and complexes of the G4- Specific binding of Thiazole orange to non- DNA with photoactive interacaltors and to use them as building canonical DNA forms with respect to a double blocks in electronic switches, molecular-sensors and molecular- stranded one may provide a useful tool for optoelectronic devices. selective highly sensitive fluorescent detection of We have recently synthesized nanowires composed of single self- these structural motifs in genome of living cells. folded poly(G) strands of thousands of bases [1-3]. These G4-wires We have shown that that the mechanism the comprise a large number of stacked guanine tetrads providing better above dyes binding includes their intercalation conditions for π overlap compared to base-pairs of the canonical between each pair of successive G-tetrad planes double stranded DNA. A high content of guanines, which have the in the G4-DNA. The π-stacking between the lowest ionization potential among DNA bases, also makes charge G-tetrads and the dyes within the G4-DNA- migration through the DNA highly probable. We have shown by dye complexes might promote conductivity of electrostatic force microscopy that the quadruplex DNA, in contrast the wire. In addition the intercalators are pho- to the double stranded one, exhibit strong signal [4]. These data electroactive and are capable of abstracting an indicate that the conductivity of G4-DNA is potentially better than electron at electrical potentials much lower than that of dsDNA, making G4-wires a valid alternative to dsDNA to the ground state. When complexed with G4-DNA develop DNA-based nano-electronics. the intercalated molecules will carry the current We have also investigated the interaction of G4-wires with various through the polymer at relatively low applied organic molecules. It is known that small aromatic molecules, which electrical potentials only in the presence of light. molecular dimensions resemble those of a G-tetrad, are capable of This property is essential for the development binding to telomeric structures which composed of a small number molecular electro-optical devices. of stacked G-tetrads. Such structures are found in the nucleus of a cell To achieve the above goals, we collaborate closely at the ends of chromosomes. We have demonstrated that incubation with European and Israeli groups specialized in: of long (hundreds of nanometers) G4-DNA wires with porphyrins surface chemistry, nanoelectronics nanooptics, and Thiazole orange results in the formation of very stable high scanning probe microscopy, and electrical affinity intercalative complexes between the DNA and the dyes [5,6]. transport measurements.

Figure 1: A – Schematic representation of a G-tetrad structure. B – Self-assembling of G-strands into a G4-DNA wire. C – AFM image of a G4-wire.

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References 1. I. Lubitz, D. Zikich, A. Kotlyar, Specific high- affinity binding of Thiazole Orange to Triplex and G-quadruplex DNA, Biochemistry, Vol. 49, pp. 3567- 3574, 2010. 2. N. Borovok, N, Iram, D. Zikich, J. Ghabboun, G. Livshits D. Porath, A. Kotlyar, Assembling of G-strands into novel tetra-molecular parallel G4-DNA nanostructures using avidin-biotin recognition, Nucl. Acid Res., Vol. 36, pp. 5050-5060 2008. 3. N. Borovok, T. Molotsky, J. Ghabboun, D. Porath, A. Kotlyar, Efficient procedure of preparation and properties of long uniform G4-DNA nanowires, Anal Figure 2: Schematic representation of a G4-wire with porphyrin (TMPyP) Biochem., Vol. 374, pp. 71-78, 2008. molecules 4. H. Cohen, T. Sapir N., Borovok, T. Molotsky, R. Felice, A.B. Kotlyar, D. Porath, Polarizability of G4- DNA Observed by Electrostatic Force Microscopy Measurements, Nano Letters, Vol. 7, pp. 981-986, 2007. 5. I. Lubitz, N. Borovok, A.B. Kotlyar, Interaction of monomolecular G4-DNA nanowires with TMPyP: evidence for intercalation, Biochemistry, Vol. 46, pp. 12925-12929, 2007. 6. A.B. Kotlyar, N. Borovok, T. Molotsky, H. Cohen, E. Shapir, D. Porath, Long Monomolecular G4-DNA Nanowires, Adv. Materials, Vol. 17, pp. 1901-1905, 2005.

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Prof. Slava Krylov

Introduction general results providing the criteria of bistability In light of the unabated progress in micro and nano technologies and of these kinds of devices were obtained. Dynamic escalation in complexity and diversity of micro- and nano-devices, stability criteria for an electrostatically actuated modeling issues that were ignored in the past have become of primary bistable beam was obtained in 1,‎ 2.‎ An approach importance. The increasing device performance requirements of a allowing efficient control of stability properties highly competitive industry have resulted in the emergence of more of bistable actuators was demonstrated sophisticated designs and fabrication approaches that exploit more theoretically and experimentally in ‎3. Micro complex physical effects. Our research is focused on development technology can be viewed as a very convenient of new actuation and sensing approaches and their implementation and versatile experimental platform mainly due in micro devices along with investigation of complex nonlinear to the large number of structures with varying electromechanical phenomena which are intrinsic in micro and parameters that can be simultaneously fabricated nanostructures but are not encountered naturally in conventional and characterized. The characterization of large-scale structures. microstructures provides unique experimental data unavailable at the macro scale and illustrates Dynamics and stability of electrostatically actuated the influence of various parameters on the microstructures device behavior. An approach allowing efficient One of the distinguishing features of electrostatically actuated parametric excitation of large-amplitude stable microstructures is that they are inherently nonlinear. Since the generic oscillations of a microstructure along with nonlinearities encountered in microstructures are often related to the results of a theoretical and experimental the small scale of the devices, and mainly due to the forces acting investigation of the device were presented in in these systems, results and approaches obtained for conventional ‎4 (see Fig. 1). The suggested approach can be structures are often not directly applicable to the micro devices. efficiently used for excitation of various types of The research provides new theoretical and experimental results microdevices – micro and nano resonators, mass shedding light on the dynamic behavior and stability of micro and and inertial sensors – where stable resonant nano structures in general and bistable and multistable structures as operation combined with robustness and large well as parametrically excited devices in particular. Recently, several vibrational amplitudes are desirable.

Figure 1. Parametrically excited micro struxture: (a) the frame-type structure, fabricated from a silicon on insulator (SOI) substrate using deep reactive ion etching (DRIE) –optical microscope micrograph; (b)-(e) snapshots of the device at differing actuating frequencies; (f) expeimental resonant curves built by means of image processing and experimentally mapped regions of parametric instability (inset) of the device.

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Figure 2. (a) Scanning Electrom Microscope micrograph of the fabricated device. The mechancial amplification mechanism is shown in the inset. (b) Experimental results of sensing element output voltage versus external acceleration (dots), linear fit (solid line) and estimation of the output voltage of the proof mass (dashed line) based on the amplification ratio extracted from the static experiment. Mechanical inertial actuation using an external PZT transducer was implemented.

Long displacement micro actuators and inertial sensors research, performed in collaboration with Prof. The development of new concepts of long displacement micro Yael Hanein, new types of CNT based sensors actuators (e.g., see [3]) and inertial sensors (angular rate sensors were be developed and implemented based and accelerometers) is essentially based on the results of more on already accomplished feasibility studies that fundamental theoretical and experimental research. As an example, demonstrate the CNT/MEMS fabrication process one can mention the recently developed micro accelerometers and motion sensing using CNTs. It shouold be incorporating mechanical amplifying elements [5] (see Fig. 2). noted that recent progress achieved in the fields In this work, the novel architecture and operational principle of micro and nanoelectromechanical systems of microelectromechanical accelerometers, which may lead to demands a reliable method for high resolution enhanced sensitivity achieved through mechanical amplification characterization of nano scale motion of actuated of a proof mass displacements was reported. The integrated devices. The technique of optical detection of amplification mechanism transforms small out-of-plane motion of nanoscale displacements of micro actiators using the proof mass into significantly larger motion of a tilting element digital image correlation (DIC) algorithms was whose displacements are sensed to extract acceleration. The device reported in [6]. Using the DC-DIC, the resolution was fabricated from silicon-on-insulator wafer and is distinguished was enhanced significantly and displacement by a robust single-layer architecture and simple fabrication process. measurements with nanoscale accuracy were Theoretical and experimental results, which are in a good agreement captured using simple optical and processing with each other, indicate that the motion amplification scheme tools. realized in the framework of the suggested architecture results in larger detectable displacements. Nano oscillators for biosensing applications Integration of nano scale and micro scale devices The research carried out in collaboration with Nano scale devices, e.g. carbon nanotubes (CNT) based sensors, Prof. Harold Craighead and Dr. Rob Ilic from exhibit unique properties which are very attractive for the Cornell University, USA, was focused on the implementation in MEMS sensors. However, their integration actuation of biologically functional micro- into much larger MEMS structures is challenging. Recently, some and nanomechanical structures using optical new approaches allowing for the integration of CNTs into MEMS excitation, the exploration of new sensing sensors were successfully implemented. In the framework of the approaches [7] as well as the use of nano

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resonators for measurements of mechanical properties of ultrathin Dideikin,. Springer 2010, pp. 117-128. films [8]. This is an emerging area of research that couples the 3. Y. Gerson, S. Krylov and B. Ilic, “Electrothermal fields of optics, fluidics, electronics, and mechanics with potential Bistability Tuning in a Large Displacement Micro Actuator,” Journal of Micromechanics and for generating novel chemical and biological sensors. For example, Microengineering, 20, paper 112001, 2010. material properties of atomic layer deposited (ALD) thin films are 4. S. Krylov, Y. Gerson, T. Nachmias, U. Keren, “Excitation of interest for applications ranging from wear resistance to high-k of Large Amplitude Parametric Resonance dielectrics in electronic circuits. In [8] we demonstrated, for the by the Mechanical Stiffness Modulation of a first time, the ability to simultaneously measureY oung’s modulus Microstructure,” Journal of Micromechanics and and density of 21.2–21.5 nm ALD hafnia, alumina, and aluminum Microengineering, 20, 015041 (12pp), 2010. 5. A. Ya’akobovitz, S. Krylov, “Toward Sensitivity nitride ultrathin films by observing vibrations of nanomechanical Enhancement of MEMS Accelerometers Using cantilever beams. Our approach is based on an optical excitation and Mechanical Amplification Mechanism,” IEEE Sensors interferometric detection of in-plane and out-of plane vibrational Journal, 10(8), pp. 1311-1319, 2010. spectra of single crystal silicon cantilevers before and after a conformal 6. A. Ya’akobovitz, S. Krylov, Y. Hanein, “Nanoscale coating deposition of an ALD thin film. Experimental results obtained Displacement Measurement of Electrostatically for the measured films were in excellent agreement with numerical Actuated Micro- Devices using Optical Microscopy and Digital Image Correlation,” Sensors and simulations as well as with the data available in literature. Actuators A-Physical, 162, pp.1-7, 2010. 7. Y. Linzon, S. Krylov, B. Ilic, D. Southworth, R. Barton, References B. Cipriany, J. Cross, J. Parpia, H. Craighead, “Real- 1. S. Krylov and N. Dick, “Dynamic Stability of Electrostatically Actuated Time Synchronous Imaging of Electromechanical Initially Curved Shallow Micro Beams,” Continuum Mechanics and Resonator Mode and Equilibrium Profiles,” Optics Thermodynamics, 22(6), pp. 445-468, 2010. Letters, 35(15), 2010 2. S. Krylov, N. Dick, “Pull-In Dynamics of Electrostatically Actuated Bistable 8. B. Ilic, S. Krylov, and H. G. Craighead, “Young’s Modulus Micro Beams,” in Advanced Materials and Technologies for Micro/Nano- and Density Measurements of Thin Atomic Layer devices, Sensors and Actuators, NATO Science for Peace and Security Deposited Films using Resonant Nanomechanics,” Series – B: Physics and Biophysics, Edited by E. Gusev, E. Garfunkel, A. Journal of Applied Physics, 108, paper 044317, 2010.

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Dr. Yossi Lereah

Quasi melted state in Nano-particles 2. Measurements of Strains in Core-Shell Nano-Particles in Nano-Containers he influence of temperature Heteroepitaxial Semiconductor Nanowires. on the interaction (wetting angle) between nano-particle (Pb), the The effect of strains on band gap and on container content (Ga) and the container walls (SiO) was studied mobility of electrons and holes is becoming quantitatively. The results (Fig. 1) indicate a continuous change crucial issue in low dimensions systems. We from non wetting state at low temperature to wetting state at high used a Geometrical Phase analysis of High temperature. These findings are consistent with the proposed “quasi- Resolution Electron Micrograph in order to liquid State” phase of nano-particles. It is interesting to note the detect the strains in core-shell nanowires. Fig wetting angle of 90º at the melting temperature of the nanoparticle 2 shows the HREM (left) and the the strain i.e. there is a convex to concave morphology. This work is obtained distribution (right) in InAs-GaAs Nano-wires, in collaboration with the group of Prof. Richard Kofman from Nice prepared by Hadas Shtrikman from Weizmann University (France). For more details: M. Allione, R. Kofman, F. Celestini Institude. Similar analysis was obtained on Si- and Y. Lereah EPJD 52, 207 2009. Ge nano wires prepared by Moshit Ben Ishai 1. Surface diffusion in nano-particles The reconstruction of the from the school of chemistry. For more details: surface in Bi nano-particles was study in correlation with the Yossi Lereah, Moshit Larbony Ben Ishai, Ronit characteristics phenomena of “quasi melted state”. The study was Popvich and Hadas Shtrikman. Submitted to obtained by High Resolution Transmission Electron Microscopy ICM 17. on Bi nano-particles that are synthesized by the group of Prof. Yoram Selzer from the school of chemistry. Preliminary results indicate a correlation between the surface diffusion and angle rotation of the nano-particles. An experiment in mm scale was design in order to simulate the hard core effect of limited number of atoms oin the characteristics of quasi melted state. For more details: Sigal Jarby, Debora Marchak and Yossi Lereah Submitted to ICM17

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Prof. Ron Lifshitz

Bifurcation-Topology Amplification dramatic changes in the overall response. We have Since the advent of the transistor, amplification has been a major quest implemented a Bifurcation-Topology Amplifier in modern science and technology. Our ongoing investigations of the (BTA) using a pair of parametrically-driven high- nonlinear dynamics of nanomechanical resonators, in collaboration frequency nanoelectromechanical systems with the groups of Michael Roukes and Michael Cross at Caltech [1- (NEMS) resonators, demonstrating robust and 6], have led us to the discovery of a novel and generic amplification reliable small-signal amplification. The simple and mechanism based on inducing dynamical changes to the topology generic principles underlying the BTA suggest its of a simple bifurcation diagram [7]. Previous amplification schemes applicability to a wide variety of physical systems, utilized static bifurcations in nonlinear dynamical systems—biasing such as laser cavities, superconducting resonators, the operation at points where the response of a device is highly coupled Josephson junctions, and possibly even sensitive to input. In our new device, tiny variations in an input signal to oscillating chemical and biological systems. change the actual topology of the bifurcation diagram, inducing Our discovery was recently highlighted and reviewed by Dykman [8].

References 1. M.I. Dykman. “Signal amplification through bifurcation in nanoresonators,” Physics 4 (2011) 16. 2. R.B. Karabalin, R. Lifshitz, M.C. Cross, M.H. Matheny, S.C. Masmanidis, and M.L. Roukes. “Signal amplification by sensitive control of bifurcation topology,” Phys. Rev. Lett. 106 (2011) 094102. 3. R. Lifshitz and M.C. Cross, “Nonlinear dynamics of nanomechanical resonators.’’ In Nonlinear Dynamics of Nanosystems, Eds. G. Radons, B. Rumpf, and H.G. Schuster (Wiley-VCH, Weinheim, 2010) Ch. 8. 4. E. Kenig, B.A. Malomed, M.C. Cross, and R. Lifshitz, “Intrinsic localized modes in parametrically-driven arrays of nonlinear resonators,” Phys. Rev. E 80 (2009) 046202. 5. E. Kenig, R. Lifshitz, and M.C. Cross. “Pattern selection in parametrically-driven arrays of nonlinear resonators,” Phys. Rev. E 79 (2009) 026203. 6. Y. Bromberg, M.C. Cross, and R. Lifshitz, “Response (a) Experimental measurement of the parametric response of two uncoupled of discrete nonlinear systems with many degrees of nanomechanical beams (shown in the inset), confirming the pitchfork bifurcation freedom,” Phys. Rev. E 73 (2006) 016214. (in red and black). (b) With a constant coupling input signal larger than the noise 7. M.C. Cross, A. Zumdieck, R. Lifshitz, and J.L. Rogers, floor, the response to upward frequency sweeps deterministically follows the “Synchronization by nonlinear frequency pulling,” upper or lower curves [red and black curves in (a)] depending on the sign of the Phys. Rev. Lett. 93 (2004) 224101 input. (c) Repeated upward frequency scans with no coupling, show that each of 8. M.C. Cross and R. Lifshitz, “Elastic wave transmission the two possible branches are followed with equal probability. (d) Repeated scans at an abrupt junction in a thin plate with application with a coupling input signal of 3 mV, show that a majority of the scans follow the to heat transport and vibrations in mesoscopic upper response curve, yet because the noise amplitude is greater than 3 mV, some systems,” Phys. Rev. B 64 (2001) 085324. scans still follow the lower response curve. Reproduced from Ref. [7].

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Prof. Rimona Margalit Carrier-mediated drug delivery in inflammatory diseases and in cancer Inflammatory diseases

Liposomal dexamethasone-diclofenac combinations for Targeting regular and hyaluronan- local Osteoarthritis treatment modified liposomes to macrophages Conventional chronic and acute treatments for osteoarthritis (OA) for treatment of inflammatory diseases: are by oral NSAIDs (such as diclofenac) and intra-articular injected drug delivery at the cellular and sub- glucocorticosteroids (such as dexamethasone). In free form, cellular levels and impact on TNF-α diclofenac and dexamethasone generate severe adverse effects production with risks of toxicity. To reduce these drawbacks, we investigated Macrophages are pivotal cells in the processes local injections of liposomal formulations for diclofenac and of onset and progression of inflammation, hence dexamethasone (each alone, and their combination). Bioadhesive primary targets for anti-inflammatory treatment. liposomes carrying hyaluronan (HA-BAL) or collagen (COL-BAL) as Liposomes, front-line candidates for treatment of their surface-anchored ligand were used for the task. Each drug alone inflammatory disease as drug delivery systems or their combination showed high efficiency encapsulations (≥80%) can improve targeting and avoid adverse effects. and performance as slow-release depots (half lives in the range of 1-3 Our hypothesis was to manipulate liposome size days under the fastest conditions). Employing RIA and immunoblot and surface properties in order to deliver drugs to assay techniques, it was verified that the encapsulated drugs retained their molecular loci of action, inside the cell or on their biological activities: inhibitions of Cyclooxygenases enzyme- the cell membrane. We investigated four liposome activity (diclofenac) and of Cyclooxygenases protein- expression species. Two of them regular (conventional) (dexamethasone). Using live-animal MRI (figure 1), a single intra- liposomes, denoted RL-ULV and RL-MLV for the articular injection of each liposome-drug(s) formulation sufficed to small and large systems, respectively. The other reduce knee joint inflammation in OA rats over a time span of 17 two are our previously-developed bioadhesive days, HA-BAL better than COL-BAL. The most effective treatment was liposomes in which the liposomal surface is by the combination of both drugs in HA-BAL, a single dose reducing modified by covalently-anchored hyaluronan the inflammation volume down to 12.9% from initial over that time (HA) denoted HA-ULV and HA-MLV, respectively. span. We find all three HA-BAL formulations worthy of further studies. We measured liposome-macrophage interactions

Figure 1: MRI of Osteoarthritic rat knees as function of time (days 0, 3, 10 and 17 post treatment) and treatment, each image is one of 24 taken per animal, per time point. Day zero is defined as the day of treatment administration, taking these images prior to treatment. Upper panels: Images from an untreated animal Bottom panels: Images from an animal receiving a single treatment of intra-articular injection of SD-DEXA-encapsulating HA-BAL at the drug dose of 1 mg/kg body weight. The white arrows point to the inflammation, which is observed through the water accumulation that appears as red, light-yellow and pale-blue regions.

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free SB distributes randomly and is prone to fast metabolism. Also, to maintain the chronic state, continuous daily SB dosing is required. Our hypothesis is that the deficiencies of free SB can be overcome by formulating it in our tumor- targeted hyaluronan bioadhesive liposomes. In this liposomal formulation SB should be protected from fast metabolism, therapeutic drug doses can concentrate at the target, slow drug release can reduce dosing frequency, and these formulations are suitable for the patient- friendly oral route of administration. The major findings are: (1) High-doses of SB, up to 160 mM, were encapsulated in the tumor-targeted liposomes, with slow release – half life of 3.6 days. (2) Applied to cultures of human colon carcinoma Figure 2: The effects of internalization inhibitors on RL-MLV binding to, and cells (HT-29), SB increased the activity of alkaline internalization by, macrophages (RAW264.7 cells). A. Binding affinity and phosphates, a marker of differentiation (peak capacity, without inhibitor and with 2DOG, LY2 and Wt. Calculations of binding activity at 10 mM SB). (3) Comparing inhibition parameters, bar averages and standard deviations were all similar to those of cell proliferation in vitro in cancer cells, by described for figure 3. B-D. confocal microscopy as described for figure 3, except: B. 2DOG. C LY2 and D. Wt. free drug vs. the same drug in a targeted carrier, is done to verify that the encapsulated drug has combining binding equilibria and liposome cellular localizations. not lost its activity. It is rare that a benefit for the Using the macrophage cell line RAW264.7. We also showed that the targeted system is already seen in vitro, as the in inhibitors – 2-deoxyglucose (2DOG), LY294002 (LY2) and Wortmannin vitro system is static and biased towards the free (Wt) – influence particle internalization by macrophages (figure 2) drug. Nevertheless, in the present case in cultures and that the liposomes themselves do not elicit cell death or TNF-α of the HT-29 cells, the targeted liposomes not only production in LPS-activated and non-activated macrophages. showed retention of drug activity, the liposomal formulations were better than the free drug. Turning colon cancer from acute to chronic disease by treatment Exposure of the cells to 2.5 mM SB for 144 hours with sodium butyrate (SB) formulated in tumor-targeted hyaluronan resulted in proliferation of inhibitions of 50% and bioadhesive liposomes “Differentiation therapy” is an alternative of 70% for the free and carrier-encapsulated drug, method for cancer treatment, aimed to turn it from an acute to a respectively. The results are encouragement to chronic disease. Sodium butyrate (SB), a bacterial fermentation continue in 2 directions: to further explore the SB- product of dietary fibers digested in the large intestine, has potential induced differentiation mechanisms, especially in as a differentiation therapeutic agent in human colon cancer. Despite the targeted carrier; to proceed with the targeted this potential, it cannot be applied to date, due to severe drawbacks carrier formulation to studies in mice bearing of its current dosage form which is free SB. Millimolar concentrations colon cancer. are needed for effective therapy, but those cannot be achieved as

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Prof. Gil Markovich

Colloidal Nanocrystals Laboratory boiling point organic solvent. It was found The Markovich group focuses on studies of various types of physical that by tuning synthesis conditions, i.e., type phenomena related to inorganic nanocrystals. In the last year the of solvent and surfactants, temperature, the group has been working on several nanocrystal systems: concentration of defects in the nanocrystals could be controlled, turning a small part of Studies of spin-polarized electron transport properties the nanocrystals into ferromagnetic for the with emphasis on the nanoscale magnetization higher defect concentrations. Currently, a high- dynamics resolution electron microscopy study, performed In one study, the films were deposited in small gaps between in collaboration with Cheuk-Wai Tai and Yossi two electrodes defined by electron beam lithography. Magneto- Lereah is aimed at identifying the exact nature of transport measurements revealed relatively large magnetoresistance these defects and defective nanocrystals. values (10-25%) at temperatures >200K and their magnetic field and temperature dependence indicated the dominance of inter-particle Studies of the interactions of tunneling in the contribution to the measured magnetoresistance. chiral molecules with surface In a second study, a multilayer film was deposited on a gold film plasmon excitations of noble metal and studied by a variable-temperature, ultra-high vacuum scanning nanoparticles tunneling microscope. In this project, temperature dependent We have used colloidal silver nanoparticles, in the noise in the tunneling current was observed and correlated to the size range of 10-50 nm to enhance the absorption dynamics of magnwtic moment switching of the nanocrystals. of chromophore molecules, attached through a short tri-peptide (glutathione) to the particles’ Studies of defect induced ferromagnetism in surfaces. The absorption of the chromophores, magnesium oxide nanocrystals in resonance with the surface plasmon excitation of the silver particles, was enhanced by about In this project, colloidal HfO2 nanocrystals were produced using thermal decomposition of organometallic precursors in a high two orders of magnitude. In addition, we have studied the circular dichroism induced at the achiral chromophore molecules by attachment to the chiral peptide. This weak circular dichroism response was also enhanced by two orders of magnitude on binding to the silver particles.

Studies of nanoscale ferroelectricity in

BaTiO3 nanocubes

Ferroelectric BaTiO3 nanocubes in the size range of 20-100 nm were synthesized and studied by x-ray diffraction, Raman spectroscopy and transmission electron microscopy, in particular with electron holography, a technique that is able to image the ferroelectric polarization fields within the nanocrystals with nanometric resolution. These studies revealed nanocrystal size dependence in the polarization fields, as well as insight into the polarization behavior near the nanocrystal surfaces.

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Metal nanowire films formed on surfaces using wet References chemistry as transparent electrodes 1. A. Dror-Ehre, A. Adin, G. Markovich, H. Mamane, A technique for the deposition of very thin films containing networks “Control of biofilm formation in water using molecularly capped silver nanoparticles”, Water of high aspect ratio gold/silver nanowires has been developed. The Research 44, 2601-2609 (2010). technique involves the preparation of a growth solution containing a 2. I. Carmeli, I. Lieberman, L. Kraversky, Z. Y. Fan, A. mixture of gold and silver salts and a reducing agent in the presence O. Govorov, G. Markovich, S. Richter, ”Broad Band of high concentrations of surfactant molecules. After its preparation Enhancement of Light Absorption in Photosystem the solution is spread on various surfaces with a controlled thickness I by Metal Nanoparticle Antennas”, Nano Lett. 10, and then let dry. While drying the surfactant molecules form tubular 2069-2074 (2010). 3. T. Molotsky, T. Tamarin, A. Ben Moshe, G. Markovich template structures in which the metal nanowires grow. These and A. B. Kotlyar “Synthesis of Chiral Silver Clusters nanowire network films are highly conductive, as well as transparent on a DNA Template”, Accepted to J. Phys. Chem. C due to the low volume filling of the nanowires. (2010) (special issue – “Protected Metallic Clusters, Quantum Wells and Metal-Nanocrystal Molecules Synthesis of silver nanocapsules Symposium”). Colloidal hollow silver nanoparticles are produced by a fast 4. N. Taub, A. Tsukernik, G. Markovich, “Inter-particle Spin Polarized Tunneling in Arrays of Magnetite transformation reaction of silver oxide nanoparticles. These particles Nanocrystals”, J. Mag. Mag. Mater. 321, 1933-1938 are surprisingly single crystalline, have almost perfect spherical (2009). shells and hold water in their core. Several characteristics of 5. A. Heyman, I. Medalsy, O. Dgany, D. Porath, G. the transformation reaction, such as high sensitivity to reactant Markovich, O. Shoseyov “Float and Compress: A concentration, indicate that the mechanism leading to the formation Honeycomb like Array of a Highly Stable Protein of the nanocapsules is a variant of the Kirkendall effect, which in the Scaffold”, Langmuir 25, 5226 (2009). 6. A. Dror-Ehre, H. Mamane, T. Belenkova, G. Markovich, present case primarily involves outward diffusion of dissolved silver A. Adin, “Silver nanoparticle–E. coli colloidal ions due to the moderate solubility of silver oxide. interaction in water and effect on E. coli survival”, J. Colloid Interface Sci., 339, 521-526 (2009). 7. D. Azulai, T. Belenkova, H. Gilon, Z. Barkay, G. Markovich, “Transparent metal nanowire thin films prepared in mesostructured templates”, Nano Lett. 9, 4246-4249 (2009). 8. E. Tirosh, B. Tsukerman, N. Taub, S. A. Majetich, G. Markovich, “Magnetoresistive telegraph noise in Langmuir-Blodgett films of colloidal magnetite nanocrystals probed by scanning tunneling microscopy”, Phys. Rev. B. 80, 224427 (2009).

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Dr. Iftach Nachman

ur lab studies how cells within a population reach generating spatial and temporal signal gradients. developmental decisions at the phenotypic and We have started to characterize the responses of mechanistic level, and how does information the glucose and nitrogen sensitive transcription processing done by signaling pathways affect factors controlled by the PKA and TOR signaling these decisions. This year we have started to pathways. study these fundamental questions in two modelO systems using methods from live cell fluorescent imaging, Temporal-spatial quantification of microfluidics, statistical and computational analysis. Below is a the Wnt canonical/Non canonical description of projects in our lab that involve the use of microfluidics: balance required for cardiomyocyte differentiation. A microfluidic approach for probing propagation of Myocardial infarction (MI) remains the most information through signaling pathways frequent cause of death in the developed The yeast Saccharomyces cerevisae senses its environment and reacts world. Development of directed differentiation to changes in nutrient availability by changing its metabolism, techniques of stem cells into cardiomyocytes have transcriptional profile and developmental program. These pathways raised hopes for cell therapy based treatment of appear to involve functional duplications and/or redundancy of MI survivors. However, gaps in understanding of transcription factors, as some of the transcription factors are activated the mechanisms that regulate the differentiation or suppressed through the same signals. We are asking three major process limit the use of cell therapy. Previous questions: studies have characterized the competition 1. Why do cells need multiple transcription factors that are activated between the Wnt canonical and non-canonical through the same combination of signals? signaling pathways and their activation at specific 2. What is the purpose of intermediate-level signal merging? Why time and space windows during cardiomyocyte does the cell need crosstalk at multiple levels between sensing differentiation as the main factor in determining pathways? cell fate. We are studying the process of cardiac 3. Do the cell’s signaling pathways encode dependencies between differentiation using ES cells in which different nutrients in its natural habitat? Wnt signaling components are fluorescently To study these questions we follow localization dynamics of tagged, quantifying inter-correlations between downstream transcription factors under various signal combinations pathway activation, signal levels and cell fates. in single cells. We also examine how these dynamics are altered upon We have developed several microfluidic designs, manipulation of the signaling network structure. To this end we design in which clusters of ES cells (called embryoid and fabricate microfluidic devices capable of dynamically changing bodies) can be formed (Fig 3, left), grown and

Figure 1: Y-shaped microfluidic channels allow dynamic changes in external conditions of yeast cells. Right: Delocalization of Msn2 protein from the cytoplasm (left) to the nucleus (right) as a result of nutrient change.

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imaged for long periods of time (days/weeks) under controlled conditions.

Microfluidic devices for two-cell interaction assays We have started a collaboration with Prof. Yoel Kloog’s lab in a project that studies the transfer of RAS between different cell types in the immune system (B-cell to T-cell). To image this process, we have designed microfluidic cells with H-traps (Fig 2, right) that allow the controlled insertion of a pair of different cells into the same trap. We will optimize this assay to study the dynamics of RAS Figure 2: Microfluidic devices for the controlled formation and imaging of cell groups. Left: A design for a device with “U”- transfer by live cell imaging. shaped traps, used to form clusters of embryonic stem (ES) cells. Right: Part of a design for a device containing “H”-shaped traps, in which one can insert two types of cells in the same trap by reversing the direction of flow.

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Prof. Abraham Nitzan

y research at Tel Aviv University deals with b. The internal current distributions in theoretical of molecular conduction. In the molecular loops significantly depend particular I focus on the tight-binding steady on the positions of the electrodes. Internal state quantum approach to the molecular currents, i.e., bond currents can be larger conduction, which involve solving Schrödinger (“magnification effect”) than the source- equation with boundary conditions necessary drain current and change direction under Mfor steady state current through the molecular wire. The basis of certain condition. Current magnification our approach can be found in the references [1, 2, 3]. We include effect is seen to be an important feature of the interaction of molecule with the environments, leading to the current conduction process in the molecular decoherence (dephasing), by recasting the steady state equations in wire with loops. the density matrix formulation that essentially makes use of Liouville c. Amongst the molecular systems studied, equation and the boundary conditions.[3] Within the tight-binding azulene and naphthalene are demonstrated, steady state quantum approach, we studied the following: for a particular choice of electrodes’ position, to act as a balanced molecular 1. Scattering in the presence of dephasing at a single impurity site Wheatstone’s bridge characterized by zero in a linear wire. current in the bridging bond. Furthermore, 2. Correspondence between the steady state theory of current in naphthalene, for the meta position of transfer and scattering theory in the coupled wires, and the electrodes (with respect to the bridging effects of dephasing. bond), a circumscribing circular current is 3. Current conduction through molecular wires with loop structures, observed with zero current in the bridging e.g., benzene, biphenyl, azulene, naphthalene and anthracene. bond. This peculiar feature (circular current Internal current distribution, circular currents, effects of in a balanced Wheatstone’s bridge) will not dephasing and the induced local magnetic fields. be observed in the conventional electrical 4. Magnetic field effects on the internal current distribution in circuits. molecular loop wires, control of molecule-metal coupling, d. dephasing reorganizes internal current external magnetic field and gate voltage on the current distribution and smooth out the otherwise conduction characteristics, and magnetic torque on molecular step-like current-voltage characteristics. wires. 4. a. Externally applied magnetic field does not have any significant effects on current The main results of the aforementioned studies are summarized as conduction for strong metal-molecule follows: coupling unless the field is unrealistically 1. For an impurity level lying inside the energy band in a linear wire high (> 5000 T). On the other hand, for with an impurity, the transmission coefficient diminishes with weak coupling, field effects can be seen at increasing dephasing rate, while the opposite holds for impurity moderate field strength ~ 5 Tesla or even energy outside the band. less. 2. For weak inter-wire coupling in the coupled wire systems, both b. The metal-molecule coupling crucially calculations (based on current transfer theory and scattering influences the transmission spectrum that theory) give nearly identical results, except at singular points has periodic structure with the period of

associated with band edges, and the efficiency of current magnetic flux quantum 0 . Lowering the transfer is found to decreases with an increase in dephasing rate. coupling strength shifts the transmission 3. a. Circular current exists in molecular loops, even in the peaks toward low fields, which makes it absence of externally applied magnetic field, and the associated possible to control current conduction by local magnetic field can be as strong as, for instance, 0.23 Tesla at magnetic field of magnitudes < 5 Tesla. 2V bias at the center of meta-connected benzene ring. c. The magnetic field is not seen to control

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current conduction (“I-V characteristics”) in a symmetrically The results of the first two studies have been connected molecular ring (para-connected benzene) and, communicated in the form of a research article, furthermore, the effect in the other molecules such as biphenyl, now under peer review [4]. A manuscript naphthalene, is weak although field dependent changes in the representing (3) is in preparation and will be internal current distribution is observed also for such molecules. communicated soon. The results of the work d. Magnetic field control on current conduction through outlined in (4) will be communicated separately a molecular ring is more evident in a three-terminal device in the next few weeks. with one input and two output terminals. Depending on the direction of field applied (into the ring or out of the ring), metal- References molecule coupling strength, and the position of the electrodes, 1. V. Ben-Moshe, D. Rai, S.S. Skourtis and A. Nitzan, the output currents can be equal, or vary reciprocally for low submitted to J. Chem. Phys. (arXiv:1002.2775v1) 2. V. Ben-Moshe, A. Nitzan, S. S. Skourtis, and D. N. field strength which become equal above certain field values, or Beratan, J. Phys. Chem. C 114, 8005 (2010). vary reciprocally throughout the field range. 3. A. Nitzan, Chemical Dynamics in Condensed Phases e. A suitable combination of magnetic field, coupling strength (Oxford University Press, 2006). and gate voltage can control current conduction characteristics 4. A. Di Carlo, A. Pecchia, L. Latessa, Th. Frauenheim of single-molecule electronic devices. and G. Seifert on Tight-Binding DFT for Moelcular Electronics (gDFTB), Introducing Molecular Electronics (Springer Berlin, 2005). 5. D. Segal, A. Nitzan, Chem. Phys. 268, 315 (2001).

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Prof. Alexander Palevski

Quantum electronic transport in nanostructures n The Quantum Phase Transition was observed in In our research laboratory at the Department of Condensed Matter ultrasmall diameter superconductor cylinders. we currently conduct experimental research related to nanoscience The recovery of the normal state resistance at in the following three directions: half integer flux quanta was observed for the n Inversed proximity effect in ferromagnetic and normal first time. junctions Three invited lectures on the above subjects were our group in collaboration with the group of Prof. Kapitulnik from presented at the international scientific meetings Stanford University were the first to observe the appearance of and conferences in New Orleans (APS 2008), the ferromagnetic order in the superconductor. This effect was Tokyo (IX Int. Conference on Superconductivity, predicted theoretically just few years before our experiments. 2009), Sardinia (FTM 2009), St Petersburg n One-dimensional quantum wires and mesoscopic effects (Nanotechnology Conference 2010) Electronic transport properties are studied at low temperatures in V-grooved quantum wires. Anderson localization in long wires References and the dephasing are studied. 1. Jing Xia, V. Shelukhin, M. Karpovski, A. Kapitulnik, n Metal-superconductor quantum phase transition in and A. Palevski. “Inverse Proximity Effect in Superconductor-Ferromagnet Bilayer Structures”. nanocylinders Phys. Rev. Lett. 102, 087004 (2009). our experimental groups in collaboration with the collegues in 2. Aharon Kapitulnik, Jing Xia, Elizabeth Schemm and WIS developed a new technology to fabricate superconducting Alexander Palevski. „Polar Kerr effect as probe for nanocylinders with the diameters as small as 50 nm. The quantum time-reversal symmetry breaking in unconventional phase transition was recently observed by our group in these superconductors“. New J. Phys. 11, 055060 (2009). structures. 3. I. Sternfeld , R. Koret , H. Shtrikman , A. Tsukernik , M. Karpovski and A.Palevski. “Quantum phase transition in ultra small hollow superconducting Achievements cylinders”. Physica C 468, 90 (2008). n Theoretically predicted phenomenon of the induced magnetization in the superconductor due to spin screening was observed for the first time.

Fig. 1. The typical nanostructures fabricated in our laboratory using the the nanofabrication facilities in the TAU Nano center: 1D quantum embedded in Aharonov Bohm interferometer (left) and Al nanocylinder with contacts (right).

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Prof. Fernando Patolsky

1. New approaches for the synthesis of multicomponent Composition, Morphology and Electrical Properties nanoparticles and the applications. of Si(1-x)Gex Nanowires”. J. Phys. Chem. C, 114, 4331- 2. The synthesis and characterization of a new family of Si and Si/ 4335 (2010). 8. N. Shpaisman, U. Givan and F. Patolsky. Ge highly controlled nanotubular structures. We are currently “Electrochemical Synthesis of Morphology- applying this nanotubular structures in biosensing and Controlled Segmented CdSe Nanowires”. ACS Nano, nanofluidic studies. 4, 1901-1906 (2010). 3. The development of photovoltaic future devices based on 9. M. Ben Ishai and F. Patolsky. “A Route to High-Quality nanoscale light collectors arrays. Crystalline Coaxial Core/Multishell Ge@Si(GeSi) 4. The development of highly efficient fuel cells of ultra-low cost (n) and Si@(GeSi)(n) Nanowire Heterostructures”. Advanced Materials, 8, 902-906 (2010). based on cheap nanocatalyst elements. 10. A. Pevzner, Y. Engel, R. Elnathan, T. Ducobni, M. Ben- 5. Biosensing of a broad range of diseases based on large scale Ishai , N. K. Reddy, N. Shpaisman, A. Tsukernik, M. nanowires-based FET arrays. Oksman and F. Patolsky. “Knocking Down Highly- 6. The development of novel approaches for the assembly of ultra- Ordered Large-Scale Nanowire Arrays”. NanoLetters, large arrays of nanowires elements. 10, 1202-1208. (2010). 7. The development of homeland-security directed sensor arrays. 11. M. Devika, N. K. Reddy, A. Pevzner and F. Patolsky. “Heteroepitaxial Si/ZnO Hierarchical Nanostructures 8. The discovery of a new approach for the clinical diagnosis of for Future Optoelectronic Devices”. ChemPhysChem, cancer at early stages based on immune-system responses and 11, 809-814 (2010). optical means. 12. M. Ben Ishai and F. Patolsky. “Shape and Dimension- 9. The development of nanotube-based electrical sensing devices. Controlled Single-Crystalline Silicon and SiGe 10. The research group consists of 21 researchers and a vast spectrum Nanotubes: Towards NanoFluidic FET Devices”. J .Am of facilities, including fully equipped clean rooms. .Chem. Soc., 131, 3679–3689 (2009). 13. U. Givan and F. Patolsky. “Pressure-Modulated Alloy

Composition in Si(1-x)Gex Nanowires”. NanoLetters, 9, References 1775–1779 (2009). 1. M. Kwiat, A. Peretz and F. Patolsky. “Preparation of Highly-Ordered and 14. M. Ben Ishai and F. Patolsky. “Tube-in-Tube and Controlled Large-Scale Neuronal Networks of Individual Cells”. Submitted Wire-in-Tube NanoBuilding Blocks: Towards the for publication (2010). Realization of Multifunctional Nanoelectronic 2. N. Shpaisman, U. Givan, M. Kwiat, A. Pevzner and F. Patolsky. “Controlled Devices”. Angew. Chem. Int. Ed., 46, 8699-8702, Synthesis of Room-Temperature Ferromagnetic Semiconducting Silicon Accepted as Hot Paper (2009). Nanotubes”. ACS Nano, submitted for publication (2010). 15. D. M, Reddy, N.K. Reddy, K. Ramesh, F. Patolsky and 3. M. Ben-Ishai and F. Patolsky. “Controlled and Wall-Selective Chemical Gunasekhar KR. “Weak rectifying behaviour of p-SnS/ Alteration of Silicon Nanotubes”. J. Am. Chem. Soc., submitted for n-ITO heterojunctions”. Solid State Electronics, 53, publication (2010). 630-634 (2009). 4. M. Devika, N. K. Reddy, A. Pevzner, M. Ben-Ishai and F. Patolsky. “CdSe-ZnO 16. N. A. Kotov, J. O. Winter, I. P. Clements, E. Jan, B. P. Hierarchal heterostructures”. J. Mater.Chem. in Revision (2010). Timko, S. Campidelli, S. Pathak, A. Mazzatenta, C. M. 5. Y. Engel, R. Elnathan, G. Davidi, E. Flexer and F. Patolsky. “Supersensitive Lieber, M. Prato, R. V. Bellamkonda, G. A. Silva, N. W. Shi Explosives Detection by NanoNose Arrays”. Angew. Chem. Int. Ed., 49, Kam, F. Patolsky, L. Ballerini. “Nanomaterials for Neural 6830-6835, (2010) Accepted as Hot Paper with Cover Page. Interfaces”. Advanced Materials, 21, 3970-4004 (2009). 6. E. Granot, B. Filanovsky, R. Dirawi and F. Patolsky. “Nanotextured Copper 17. D. M, Reddy, N.K. Reddy, K. Ramesh, F. Patolsky and K. Substrates as Highly Effective and Long-Lasting Fuel Cell Anodes”. Angew. R. Gunasekhar. “Temperature dependent structural Chem. Int. Ed., Provisionally Accepted for Publication (2010). properties of nanocrystalline SnS structures”. Appl. 7. U. Givan and F. Patolsky. “The Influence of Doping on the Chemical Phys. Lett., 95, 261907 (2009).

133 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY PROGRESS reports

Dr. Dan Peer

Selective targeting and reprogramming of cells using with their niche, HSCs should be studied in their fully degradable nanomedicines natural microenvironment, therefore there is a We are studying how to manipulate cells’ functions in order to need to devise strategies that will enable to target generate novel therapeutic strategies to treat inflammatory diseases specifically HSCs in their BM environment. and cancers. We operate in a two-arm approach. In the first, we design, RNA interference (RNAi) is a ubiquitous and highly fabricate, develop and characterize novel nanocarriers for selective specific mechanism of gene silencing. RNAi has systemic targeting to variety of cell types involved in inflammatory emerged as a powerful tool for elucidating gene diseases and different types of cancers. In the second, we utilize our function and identifying potential drug targets. technologies for drug discovery, and personalized medicine approach. RNAi can also be exogenously activated by In both arms, we are combining multidisciplinary approaches introducing short double-stranded RNAs (siRNAs) including immunology, cell and molecular biology, genetics, protein or MicroRNAs (miRNAs) into the cell cytoplasm. To engineering, material sciences, nanotechnology and computational realize the full potential of RNAi, there is a need to techniques to develop innovative therapeutics to target specific cells overcome the considerable hurdle of intracellular within the immune system and special epithelial cells. Our ultimate delivery into specific cells. RNAi are not taken up goal is to translate some of our findings into clinical settings. into most cells in the absence of a transfection reagent. For many cells, mixing RNAi with a lipid Developing novel strategies to target hematopoietic transfection reagent can efficiently induce gene stem cells silencing. However, some cells such as HSCs Hematopoietic stem cells (HSCs) are rare cells that sit atop a hierarchy are notoriously difficult to transduce with RNAi. of progenitors that can progressively differentiate to several lineages Thus, there is a need to devise strategies that and give rise to over a billion new mature blood cells including will enable the efficient transfection of RNAi into red blood cells, myeloid and lymphoid cells every day. During HSCs, preferentially in vivo, in their BM niche, as a homeostasis, HSCs are mostly present in a quiescent stage in the tool to study gene expression and potentially as bone marrow (BM). When they enter the cell cycle, they have a therapeutic. unique ability to self-renew by dividing asymmetrically, producing The aim of this project is to devise a strategy an additional HSC and a progenitor cell. HSCs can be identified and to target RNAi into HSCs and early progenitors isolated from mice by monoclonal antibodies directed to specific (HSPCs) in their natural niche. Using this strategy surface markers such as stem cell antigen-1 (Sca-1), c-kit (CD117) and we plan to identify key genes responsible for HSCs signal-lymphocyte-activating molecule (CD150). HSCs depend on self-renewal properties. It will provide a powerful their microenvironment, the BM niche, for regulation of quiescence, technique to investigate the contribution of self-renewal and differentiation. As a result of the essential interaction individual genes in maintaining the phenotypic

Schematic describtion of the preparation steps of the integrin-targeted and stabilized nanoparticles (I-tsNP). Multilamellar vesicles (MLV) are extruded into nano-scale unilamellar vesicles (ULV) then they are surface-modified with high molecular weight (850KDa) hyaloronan (HA). The HA-modified liposomes are coupled to mAb using an amine-coupling method, and then the I-tsNPs are purified and lyophilized. The siRNAs entrapment procedure is done by rehydrating the lyophilized I-tsNPs with nucleases-free water containing protamine-condensed siRNAs.

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and functional properties of HSCs, and may provide a way to improve it is possible to direct the silencing of any target engraftment during transplantation and preserve HSCs self-renewal gene of interest. Harnessing RNAi through the capacity during homeostasis or under chemotropic stress. introduction of exogenous siRNAs has emerged We have made substantial advances in this project and could as a powerful tool for gene function analysis and demonstrate selective delivery of RNAi payloads to HSCs and their the identification of potential drug targets. Since progenitors. host proteins are inherently more genetically stable than viral targets, therapies directed at Investigating the Immuno-nanotoxicity generated by host factors may prove more difficult for the virus different types of nanocarriers to circumvent. Our collaborators have recently Delivery of nucleic acids with positively charged lipid nanoparticles completed an RNAi-based full genome screen ((+)NPs) are widely used as research reagents and potentially for to better understand the host dependencies therapeutics due to their ability to deliver nucleic acids into the of HIV and to identify novel therapeutic targets. cell cytoplasm. However, in most reports little attention has been This screen led to the identification of over 230 made to their toxic effects. We performed comprehensive analyses novel host factors required for HIV-1 replication, of the potential toxicity associated with (+)NPs. Mice treated with many of which acted in early stages of the (+)The results suggest that a careful attention must be made when viral lifecycle. These results have encouraged different types of (+)NPs are being developed as nanotherapeutics. us to characterize several of these factors in This laid the foundation of tests needed for immuno-charcaterization more depth to better understand how they of nanocarriers in vivo (See publication, Biomaterials 2010). We are interact with the HIV lifecycle and to determine now testing different types of nanocarriers (gold, carbon nanotubes, if they would be suitable therapeutic targets nanodiamonds and others) to show their systemic immuno-toxicity for an siRNA-based anti-HIV microbicide. The for potential medical uses. development of siRNAs as a suitable and effective anti-HIV microbicide is a multistep process. This Developing targeted siRNA delivery as an anti-HIV involves the identification and characterization of microbicide potential therapeutic targets, the development Infections of the mucosal surfaces, such as the vaginal mucosa, of effective siRNA delivery strategies, and the in constitute the predominant natural mode of HIV transmission. Sexual vivo characterization of the efficacy and safety transmission occurs when either cell-free or cell associated virus of the siRNA-mediated silencing reagents and infects lymphocytes (macrophage, dendritic cells and activated T cells) the delivery reagents in an appropriate model present in the mucosal tissues. After this initial exposure, the virus is system. To that end we have developed a phased quickly disseminated throughout the body. research plan. In the initial phase we will be Although an HIV vaccine that induces sterilizing immunity would characterizing several of the HIV dependency be the most advantageous method or controlling the spread of HIV, factors (HDFs) to assess if they are suitable targets thus far this has been an elusive goal. As a result, the search for novel for an HIV-1 siRNA-based microbicide. This will microbicidial approaches remains a high priority. involve the characterization of these factors in RNA interference (RNAi) is a highly conserved endogenous relevant tissue culture model systems, as well así mechanism that uses small RNA species to guide the sequence- in primary CD4+ T lymphocytes and macrophage. specific silencing of gene expression. The discovery that RNAi In parallel with these studies, we will be testing functions in mammalian cells to regulate important cellular the in vitro efficacy and safety of a novel cell-type processes suggested that harnessing these endogenous gene- specific siRNA delivery system. In the second silencing pathways can prove to be an effective method for the phase of the program, we will take the results targeted silencing of gene expression. By mimicking the structure from the first phase (the therapeutic targets and of the small RNA molecules that serve as the effector molecules the optimized delivery vehicle) and test them in for RNAi, in particular, the 21-23-nt small interfering RNAs (siRNAs), a humanized mouse model of HIV-1 infection for

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their potential utility as a microbicide. We already developed a robust gut of animals with experimentally induced colitis nano- platform to target leukocytes and have recently shown that we suggests that integrin β7 may be a promising target can systemically target leukocytes under HIV infection and reduce the for radioimmunodetection of colitis, which would propagation of the virus (see publication, Molecular Therapy, 2010). aid diagnosis, assessment and therapy guidance of this disease (See publication, IBD 2010; clinical trials Developing and studying novel approaches to target are expected to be launched early 2011). cancer stem cells Breast tumor-initiating cells (BT-IC or “cancer stem” cells) not only References 1. Kim S-S*, Peer D* , Kumar P *, Wu H, Asthana D, give rise to the tumor, but also are relatively resistant to chemo/ Habiro K, Yang Y-G, Manjunath N, Shimaoka M, radiotherapy and may be responsible for tumor recurrence and Shankar P (2010). RNAi-mediated CCR5 silencing by metastases. The let-7 microRNA (miR) family regulates stem cell LFA-1-targeted nanoparticles prevents HIV infection properties and tumor formation of primary breast cancer cells sorted in humanized mice. Molecular Therapy, 18, 370-376. 2. Weinstein S., and Peer D (2010). RNAi Nanomedicines: + -/low for the breast cancer stem cell phenotype (CD44 CD24 ). let-7 is challenges and opportunities within the immune markedly reduced in BT-IC and increases with differentiation, acting system. Nanotechnology, 21(23), 232001, 1-13. as a master regulator of “stemness’ of BT-IC. Therefore a drug that 3. Kedmi R*, Ben-Arie N*, and Peer D (2010). The systemic toxicity of positively charged lipid- mimics let-7 might be able to differentiate BT-IC into less malignant nanoparticles and the role of Toll-like receptor 4 in and potentially more chemosensitive. Small RNAs can be designed to immune activation. Biomaterials 31, 6867-6875. function as miR mimetic. However, cells do not readily take up these 4. Rivkin I, Cohen K, Koffler J, Malichov D, Peer D‡ molecules. We have developed a strategy to target these molecules and Margalit R‡ (2010). Paclitaxel-clusters coated with hyaluronan as selective tumor-targeting into specific cell types by entrapping them in novel lipid nanoparticles nanovectors. Biomaterials 31, 7106-7114 (NPs) previously shown to deliver chemotherapies into CD44+ tumor 5. Dearling JJ, Voss S, Dunning P, Park EJ, Fahey F, cells in xenotransplant models (see publication, Biomaterials 2010). Treves T Solapino S., Shimaoka M, Packard AB, Peer D (2010). Detection of Intestinal Inflammation by PET Imaging Using a 64Cu-Labeled Anti-β7 Integrin Early detection of colitis using a targeted system with Antibody. Inflammatory Bowel Disease., In press. PET/ CT screen 6. Peer D (2010). Induction of therapeutic gene silencing The primary function of integrin β7 is the recruitment and retention in leukocyte-implicated diseases by targeted and stabilized nanoparticles: an overview of RNAi delivery of lymphocytes to the inflamed gut. The aim of this study was to to leukocytes. Journal of Controlled Release. In press. investigate the possibility of imaging colitis radioimmunodetection 7. Cohen-Kupie R, Weinstein S, Peer D, and Weil by targeting the β7 integrin with a radiolabeled antibody. FIB504.64, M (2010). IKAP/hELP1 down-regulation in a monoclonal antibody against β7 integrin, was conjugated with a neuroblastoma cells causes enhanced cell adhesion 64 mediated by Contactin over –expression. Cell bifunctional chelator and labeled with Cu. The antibody (50 µg, 7 Adhesion & Migration, In press. MBq) was injected into experimentally induced colitis C57BL/6 mice 8. Peer D‡., and Shimaoka M‡ (2009) Systemic siRNA with dextran sodium sulphate (n = 6). MicroPET images were collected delivery to leukocyte-implicated diseases. Cell Cycle at 1, 24, and 48 hours post-injection, and the biodistribution was 8, 853-9. 9. Peer D. (2009). Nanocarriers delivering RNAi to measured at 48 hours by tissue assay. Data were also obtained for a cancer cells: from challenge to cautious optimism. 64Cu-labeled non-specific isotype-matched antibody in mice with Therapy. 6, (3), 293-296. colitis, and 64Cu-labeled FIB504 in healthy mice (n = 5 – 6). The microPET 10. Kedmi R., and Peer D (2009). RNAi nanoparticles in the service of personalized medicine. Nanomedicine, images showed higher uptake of 64Cu-labeled FIB504 in the gut of mice 4(8), 853-855. treated with DSS than for either of the controls. This observation was confirmed by the 48 hour ex vivo biodistribution data: %ID/g ± SD (large intestine) DSS-treated mice with 64Cu-labeled FIB504, 6.49 ± 2.25; non- treated mice with 64Cu-labeled FIB504, 3.64 ± 1.12; DSS-treated mice, 64Cu-labeled non-specific antibody 3.97 ± 0.48 %ID/g (p <0.05 between groups). The selective uptake of 64Cu-labeled FIB504 antibody in the

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Prof. Emanuel Peled and Prof. Diana Golodnitsky

Laboratory of Electrochemical Power Sources PE under applied gradient MF (Fig.1.) Despite the The main research activities of our group over the report period large number of grains FF-PNT do not impede have been focused on 3 main topics: development of ordered solid grain-boundary conductivity, possibly because polymer electrolytes, electrochemical synthesis of electrode materials of the intimate contact with helical PEO chain for 3D-MB applications, and nano-size Pt alloy crystals as catalysts for and formation of shish-kebab superstructure fuel cells. of polymer electrolyte. Multichannel wall of the In the frame of BSF project “Single-molecule ion conducting single PNT can provide additional free paths to Li+ channels” we studied the effect of modification of polyethylene and increase of bulk ionic conductivity. oxide (PEO)-based polymer electrolytes (PE) by aromatic peptide In the frame of EU FP7 project we continued nanotubes decorated by ferrofluid (FF-PNT) on the structure- the development of simple and inexpensive conductivity relationship. It was expected that casting under electrochemical syntheses routes, which are magnetic field of such PEs would result in an improved orientational preferable for irregular surfaces, such as exist in order and enhanced Li+ ionic mobility. We have found that at near three-dimensional microbatteries. Electroless, ambient temperature range the total conductivity of composite PE electrodeposition and EPD methods were used containing only 1% of FF-PNT and cast under gradient magnetic field for the preparation of thin-film nanoparticle- is one order of magnitude higher than ionic conductivity of PE with size V2O5, FeOxS2-x and CuS cathodes, composite 14% 8nm–size maghemite filler. The PNT-modified PE cast under MF membrane and anode materials. Characterization exhibits high thermal stability. Even after 1 month of storage at 70°C of the materials is carried out by ESEM, XRD, it retains the conductivity values close to those of the freshly cast film. XPS and HRTEM and electrochemical tests. The For PNT-modified PEs the applied magnetic field improved mostly cathodes prepared by electrochemical synthesis the bulk conductivity, while the interchain ion transport was almost are capable of delivering a peak power greater uninfluenced. Opposite to other para- and ferromagnetic nanofillers, than 100mW/cm2 (Fig.2a) and 1.5-10mWh/ studied by us before, modification of PEs by FF-PNTs increases the rate cm2 energy density – adequate for the needs of nucleation of lamellae crystals and eliminates formation of large of Microsystems. The 3D-microbatteries ran spherulites. Highly homogeneous fine grained morphology with more that reversible 400 cycles at 100% Faradaic well-defined ~1.5micron-size crystallites develops in this composite efficiency (Fig.2b) A Ru core – Pt shell, XC72 supported catalyst was synthesized in a two-step process: first, by deposition of Ru on XC72 by the polyol process and then by deposition of Pt on the XC72 supported Ru, with NaBH4 as reducing agent. TEM examination (Fig. 3a) showed a good dispersion of the metallic nanoparticles on the carbon support. In addition, examination of the local composition of the catalyst particles revealed that the atomic ratio Pt:Ru at the edges of the particles was ≈ 1.5, while the same atomic ratio in the particle centers was ≈ 0.5. These physicochemical analyses reveal that, while the predominant metal in the catalyst is ruthenium (according to XRD-Fig.3b, and EDS), only the core is highly enriched with ruthenium while the shell is highly enriched with platinum, a b both in nano-powder and in ink (according to XPS Fig.1. SEM micrographs of pristine (a) and FF-PNT-modified (b) LiCF3SO3:P(EO)3 polymer electrolytes and TEM). In fact, it proves that the homemade

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a b Fig.2. Pulse power capability (a) and cycleability (b) of 3D-MB with nanosize-particles CuS cathodes catalyst has the intended Rucore – Ptshell structure. The methanol Glycol Oxidation, JPS accepted 8-2010. and ethylene glycol oxidation activities of the core-shell catalyst were 3. L. Gitelman, A. Averbuch, M. Nathan, Z. Schuss, D. studied at 80°C and compared to those of a commercial catalyst. Golodnitsky STOCHASTIC MODEL OF LITHIUM ION CONDUCTION IN POLY(ETHYLENE OXIDE), J. Appl. Our catalyst was found to be significantly better (in terms of Ag-1 Phys. 107, 064318 (2010). of Pt) in the case of methanol oxidation and worse in the case of 4. Y. Vilenchik, E. Peled and D. Andelman; Kicking the ethylene glycol oxidation, probably as a result of too-low ruthenium oil addiction; Physics World January (2010). 5. E. Peled, D. Golodnitsky, H. Mazor, M. Goor and content of the surface. Although the concept of the Rucore – Ptshell catalyst was proven to be successful, in seeking the goal of enhanced S. Avshalomov. Parameter Analysis of a Practical oxidation activity, it needs further optimization of the surface Ru/Pt Lithium- and Sodium-Air EV Battery; JPS accepted 9-2010. composition ratio. 6. E Peled, A Blum, and M Goor, Hydrogen–Bromine Fuel Cells, Encyclopedia of Electrochemical Power References Sources, Vol 5. Amsterdam: Elsevier; 2009. 1. R. Kovarsky, D. Golodnitsky, E. Peled, Y. Friedman, S. Greenbaum Study 7. Golodnitsky D. Electrolytes: Single Lithium Ion of highly conductive Magnetic Field Oriented Polymer Electrolytes with Conducting Polymers. In: J. Garche, C.Dyer, P. nanosize fillers, Electrochimica Acta, 2010, submitted. Moseley, Z. Ogumi, D. Rand and B. Scrosati, Editors. 2. Dima Kaplan; Meital Alon; Larisa Burstein, Yuri Rosenberg; Emanuel Peled, Encyclopedia of Electrochemical Power Sources, Vol Study of Core-Shell Platinum-Based Catalyst for Methanol and Ethylene 5. Amsterdam: Elsevier; 2009. pp. 112–128.

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Prof. Moshe Portnoy

he research interest of the group includes the fields amino-ureas, -carbamates and -guanidines), of dendrimer chemistry, organic synthesis on solid N-heterocyclic carbene and imidazole catalysts. support (a.k.a. solid-phase synthesis or SPS) and For instance, we prepared a series of polymer- catalysis. bound chiral amino-urea catalysts, incorporating an amino acid spacer, which are capable of SPS is applied in our group for the preparation of promoting nitro-Michael addition of ketones Tdendritic templates on polymeric supports, leading to dendron- and aldehydes with extraordinary efficiency functionalized resin and dendron-based nanoscale devices. We and enantioselectivity. Moreover, these catalysts developed unique synthetic schemes for the divergent synthesis of showed very promising results in some domino five new types of dendrons on solid support and additional routes reactions, such as Robinson annulation. towards other dendritic systems on polymers are being explored. We also mapped routes for other multivalent oligomers on solid support, We also demonstrated a remarkable improvement such as brush-like linear oligomers and dendronized oligomers. in the efficiency and enantioselectivity of an organocatalyst proline in the aldol and Mannich reactions, due to the introduction of dendritic spacers between the polymer core and the catalytic units. A tremendous increase in the catalyst activity upon dendronization of the support was recently demonstrated for polymer- bound N-alkylimidazole catalysts in the Baylis- The dendronized supports, prepared using the aforementioned Hillman reaction. Our research in the field of technique, are converted into supported dendritic catalysts and the supported dendritic catalysis is aimed at both dendritic effect on the catalytic performance is being investigated. understanding the rationale behind the dendritic Thus, few years ago we demonstrated dramatic improvement in effects as well as improvement and perfection of the catalytic performance in the Pauson-Khand, Heck and Suzuki such systems for potential use. reactions due to the introduction of dendritic templates between the support and catalytic units.

A new group of supported catalysts, being explored in our group, consists of small metal-free organic molecules termed organocatalysts. We are developing SPS routes to and investigate organocatalytic processes with bifunctional catalysts (e.g. proline derivatives,

139 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY PROGRESS reports

Prof. Eran Rabani

Electrostatic Force Microscopy Study of Single Au-CdSe Hybrid Nanodumbbells: Evidence for Light-Induced Charge Separation Electrostatic Force Microscopy was used to study light induced charging in single hybrid Au-CdSe nanodumbbells. Such a detailed study of charging effects in a single particle is only possible because of the high quality of the well-defined hybrid metal-semiconductor nanodumbbells (NDBs). NDBs exhibit negative charging under illumination, in contrast to mild positive charging for CdSe rods and Au particles in similar conditions. This behavior is assigned to a charge separation taking place in the NDBs following optical excitation, where the electron is transferred to the metal tips and the hole remains in the semiconductor part of the nanoparticles, and eventually extracted by tunneling interactions with the underlying substrate. This assignment gains support from the observation that the negative charging is strongly affected by the substrate and its ability to donate electrons to the system: increasing the insulating polymer thickness or switching to a p-type substrate blocks the charge transfer, while changing the substrate to n-type silicon leads to enhanced charging of up to eight electrons. The light induced negatively charged state persists for over an hour, even after the irradiation has been turned off. This charge retention allows the when the matrix elements of W are small activation of the NDBs for photocatalytic actvity in the dark as has compared to the phonon self-energy. Note that been demonstrated for an ensemble of NDBs in solution. The process a systematic weak coupling treatment requires of light-induced charge separation at the metal-semiconductor a consistent treatment of both the couplings interface is key for the photocatalytic activity of such hybrid metal- between single and biexcitons and between the semiconductor nanostructures. single excitons themselves, but not between the biexcitons themselves (which leads to higher Theory of multiexciton generation in semiconductor order contributions). The resulting expression nanocrystals for the photon absorption rate enables a We have developed a unified approach to the treatment of MEG natural dissection to the rate of absorption in nanocrystals. Our approach is based on the Green’s function into single and biexcitons. The results of this formalism, which in principle, leads to an exact description of MEG. approach were compared, theoretically and It accounts for the screened Coulomb couplings between single numerically, to those of previous work which and biexcitons, and between the exciton manifolds themselves. In was based on an incoherent master equation addition, the formalism allows for the description electron–phonon approach. Excellent agreement between the two couplings that are crucial for a complete description of MEG. approaches indicates that MEG can be described Within this formalism, the efficiency of MEG is calculated from the as incoherent process. rate of photon absorption. In practice, the solution of the full Green’s We have also discussed the scaling of the MEG function formalism is difficult and several approximations need to with respect to the size and composition of the be introduced. Common to all treatments, is the assumption that nanocrystals, and with respect to the energy of the phonon self-energy can be described within the wide band the absorbed photon. The efficiency increases limit and the value of its imaginary part is taken from experimental with energy, as expects, with an onset that is given work. The weak Coulomb coupling limit provides a solid framework by the crossover between DOSX and DOSXX. The

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effective Coulomb coupling is largely independent of energy, which 3. Excitation into the ee3–eh1 bands suggests implies that the scaling of the efficiency of MEG comes from the that only one charge multiplication event change in the density of states. In addition, at a scaled energy the can occur at photon energies slightly above efficiency of MEG increases with decreasing NC’s size and is largely 2Eg, since e-h symmetry is broken, consistent materials independent. At the NC sizes relevant for experiments, with experiments.3 Contrary, excitation theory predicts that MEG efficiency is small, on the order of <20%, into the symmetric ee2–eh2 could lead to the not sufficient to push the efficiency of thin film solar cells way above generation of two multiplication events, the SQ limit. one by the electron and one by the hole, if We would like to add a positive view. Recent experiments by impact excitation would be allowed from the

Gabor et al. reported highly efficient generation of electron–hole ee2–eh2 bands, giving rise to 300% efficiencies pairs in single-walled carbon nanotube p–n junction photodiodes. at photon energies of 2Eg, which is not seen Theoretical analysis of these experiments reveals the importance of experimentally. the diode field along with the interplay between phonon emission, 4. Our proposed mechanism also provides an field acceleration, and multiexciton generation. These results are explanation to the absence of cascade of encouraging and call for further investigation of the MEG in confined charge carrier multiplication, since multiple system. carriers are generated at lower bands. Thus, even if these carriers are accelerated by the Can Impact Excitation Explain Efficient Carrier diode field, energy conservation restricts Multiplication in Carbon Nanotube Photodiodes? carrier multiplication by impact excitation We proposed a mechanism based on impact excitation which from these bands. accounts for highly efficient multiple e–h pair generation in CNT 5. We predict an onset temperature to observe photodiodes. The mechanism involves photoexcitation into a quasi- carrier multiplication that scales as, which bound exciton which breaks into an e-h pair in the ee3–eh1 bands. implies that the phenomena can occur at The excited charge carriers are then accelerated by the diode field room temperatures for short enough CNTs under phonon induced friction. The carrier dynamics were described (L<500nm). by a Langevin equation where the interplay between the field and The present work provides a minimalist model the rate by phonon decay (which is temperature dependent) sets for carrier multiplication in CNT photodiodes. the maximal energy reached by the charge carriers. At low frictions Despite its simplicity, it captures the hallmarks (low temperature), the charges are accelerated to high enough of current experimental observations. Future energies where charge carrier multiplication is highly efficient. The work will focus on assessing prediction made photocurrent efficiency was described by a drift equation with a sink with more elaborate models. The present work term, where the rate of charge multiplication was calculated within also calls for additional experiments to verify a Fermi Golden rule within an extended Hückel electronic structure the hypothesis and predictions made here model. Several conclusions can be drawn from our work: (asymmetric excitation, role of substrate, onset 1. Impact excitation (trion formation) can explain highly efficient temperature and length scaling). carrier multiplication in CNTs photodiodes, but only for electrons

in the ee3 band or higher. Equivalently, a similar process can occur Lattice Gas Model for the Drying- for holes excited to bands with high enough energy. Excitation Mediated Self-Assembly of Nanorods

into the ee2–eh2 bands cannot lead to carrier multiplication by We have developed a lattice gas model to treat impact excitation. the drying-mediated self-assembly of nanorods 2. The proposed mechanism provides an onset energy to observe which accounts for the drying kinetics and the

carrier multiplication slightly above 2Eg, since below there is not rotational and translational diffusion motion

sufficient photon energy to excite the system into the ee3–eh1 of the nanorods. Two distinct realizations of band. self assembly experiments of nanorods were

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Simulating lattice spin models on GPUs Lattice spin models are useful for studying critical phenomena and allow the extraction of equilibrium and dynamical properties. Simulations of such systems are usually based on Monte Carlo (MC) techniques and the main addressed: a random initial orientation corresponding to drop difficulty often being the large computational casting experiments and pre-alignment of the nanorods by capillary effort needed when approaching critical points. forces at the air-solvent interface. Analysis of the results was based on In this work it is shown how such simulations introducing the oriented cluster size distribution, PC(n), the overall can be accelerated with the use of NVIDIA angular distribution, P(θ), and the coarsening of nanorod domains. Graphics Processing Units (GPUs) using the CUDA We find that the mobility of nanorods reduces markedly with programming architecture. We have developed increasing diameter and with increasing aspect ratio. This leads to two different algorithms for lattice spin models, morphologies that are typically determined by the sluggish motion the first useful for equilibrium properties near of the nanorods rather than by the rate of solvent fluctuations. a second order phase transition point and the Coarsening follows the typical scaling of ta, with an exponent that second for dynamical slowing down near a glass depends strongly on the aspect ratio and reduces from 1/3 to 1/20 transition. The algorithms are based on parallel when the aspect ratio increases to 4. MC techniques and speedups from 70 to 150 For nanorods with an aspect ratio above 5/2, the time scale fold over conventional single-threaded computer accessible by simulations is too short to observe the crossover from codes are obtained using consumer-grade the intermediate scaling to the long time behavior of t1/3, providing hardware. an explanation as to why experimentally it is impossible to reach the thermodynamic stable ordered structure on time scale accessible by References simulations or experiments. These observations are consistent with 1. O. Kletenik-Edelman, C.G. Sztrum-Vartash, and E. the general picture that in drop casting experiments (random initial Rabani,”Coarse-Grained Lattice Models for Drying- Mediated Self-Assembly of Nanoparticles”, J. Mater. orientation), only local orientational order is observed. Our analysis Chem. 19, 2872-2876 (2009). shows that the range of order scales with the aspect ratio of the 2. R. Costi, G. Cohen, A. Salant, E. Rabani and U. Banin, nanorods as long as time is scaled by the exponent R, i.e., when order “Electrostatic Force Microscopy study of Single Au- is measured at similar domain sizes. CdSe Hybrid Nanodumbbells : Evidence for Light Induced Charge Separation”, Nano. Lett. 9, 2031- 2039 (2009). 3. R. Baer and E. Rabani, “Can Impact Excitation Explain Efficient Carrier Multiplication in Carbon Nanotube Photodiodes?”, Nano Lett. 10, 3277-3282 (2010). 4. C.G. Sztrum-Vartash and E. Rabani,”Lattice Gas Model For the Drying-Mediated Self-Assembly of Nanorods”, J. Phys. Chem. C 114, 11040-11049 (2010). 5. E. Rabani and R. Baer, “Theory of Multiexciton Generation in Semiconductor Nanocrystals”, Chem. Phys. Lett. 496, 227-235 (2010). 6. T. Levy, G. Cohen and E. Rabani, “Simulating Lattice Spin Models on GPUs”, J. Chem. Theory. Comput., 6 3293-3301 (2010).

142 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY PROGRESS reports

Dr. Shachar Richter

Molecular-quantum dot transistor Bio-inorganic plasmonics Using our previously demonstrated molecular- transistor (Central – The photosystem I (PS I) protein is one of nature’s Gate Molecular Vertical Transistor, C-Gate MolVet) we have constructed most efficient light harvesting complexes and and investigated the transport mechanisms of molecular quantum exhibits outstanding optoelectronic properties. dot device. This C60-based device has been operated in two new We have demonstrated how metal nanoparticles modes: voltage-controlled switching and gate-controlled hysteresis. which act as artificial antennas can enhance A polaron-based model was used to explain the operation of the the light absorption of the protein. This hybrid transistor and to introduce some general rules for the construction of system shows an increase in light absorption and polaronic molecular transistors. of circular dichroism over the entire absorption band of the protein rather than at the specific Spherulites films-mechanisms of formation plasmon resonance wavelength of spherical Peptide nanotube-based spherulitic films are a recently discovered metal nanoparticles (NPs). This is explained phenomenon, which was demonstrated in the case of the self- by broad-resonant and nonresonant field assembled peptide nanotubes. We have investigated the formation enhancements caused by metal NP aggregates, of such films and showed that they can be implemented with other by the high dielectric constant of the metal, and peptides. We have also demonstrate that a critical physical parameter, by NP-PS I-NP antenna junctions which effectively an elevated level of environmental hydration, is required for film enhance light absorption in the PS I. growth and suggested a possible formation mechanism

Figure 1 The Polaronic transistor. Left. artist view of the transistor as (Advanced materials 2010). Middle device structure. Right. Transistor characteristics at the switching mode

Figure 2 A Maltese cross pattern observed in peptide Figure 3. Left Molecular structure scheme of the PS I attached to metal colloids. Spherulites films when viewed using polarized light Calculated local Nano Particle enhancement factors in the PS I regime are presented as microscopy. background descending color gradient from red to light blue. Right. Light absorption enhancement of the PS I-Ag colloid hybrid system. Enhanced absorption of light by the hybrid system (black curves) is reduced (red curves) upon addition of replacing compound. Inset. Adsorption spectra of the PSI in solution.

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Prof. Judith Rishpon Highly Sensitive NanoParticles Modified Electrodes for Fast medical and environmental Diagnostics

Carbon nanotubes modified electrodes for the detection of drugs efficacy: We developed an electrochemical biosensor for the detection of formaldehyde in aqueous solution, based on the coupling of the enzyme formaldehyde dehydrogenase and a carbon nanotubes (CNT)-modified screen-printed electrode (SPE). We monitored the amperometric response to formaldehyde released from U251 human glioblastoma cells situated in the biosensor chamber in response to treatment with various anticancer prodrugs of formaldehyde and butyric acid. The current response was higher for prodrugs that Figure 2: Scheme of CRP detection release two molecules of formaldehyde (AN-193) than for prodrugs that release only one molecule of formaldehyde (AN-1, AN-7). Homologous prodrugs that release one (AN-88) or two (AN-191) this method, CRP was quantitatively detected - molecules of acetaldehyde, showed no signal. The sensor is rapid, within 10 min down to concentration of 0.5 ng ml 1. sensitive, selective, inexpensive and disposable, as well as simple to Other performances data, including intra-assay manufacture and operate. variation and interference study, also met the requirements for clinical use. The rapid availability of results and the simplicity of the experimental setup could make this sensor an option for point- of-care testing device

Detection of bacteria Previously we have shown that electrochemical measurements enzymatic activity expressed in bacteria can be applied for identification enumeration of bacteria. Here we report the application of nanoparticles for enhanced sensitivity of E. Coli determination

Application of electrode modified with peptide nano tubes for Environmental Analysis Figure 1: Measurement scheme and results of formaldehyde release from cancer cells in response to of the drug AN 88 We demonstrated organized incorperation of novel biocompatible organic nanostructures into An Electrochemical sensors in medical diagnostics: extremely sensitive amperometric biosensors. C-reactive protein (CRP) is a nonspecific marker of inflammation that Peptide nanoforest (FF) biosensors for phenol can be used as a prognostic risk marker of cardiovascular diseases. detection were 17-fold more sensitive than We developed a new sensor based on heterogeneous sandwich uncoated electrode and more sensitive than those immunoassay for high sensitivity CRP (hs-CRP) measurement. This modified with carbon nanotubes or combined common immunoassay method was optimized by modifying coating. The high sensitivity reported may screen-printed electrodes with multi-walled carbon nanotubes provide a novel platform for biosensors design and using protein A to ensure oriented immobilization of anti-CRP and fabrication for environmental monitoring, antibodies. These modifications have significantly enhanced the homeland security, and other applications. sensitivity, activity, and reproducibility of the prepared sensor. With

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Figure 3: Amprometric response of β galactosidae in e-coli

Figure 4: Sensitive phenol detection using peptide nanotube and carbon nanotubes modified electrode. a, Scanning electron microscopy images of screen printed electrode. b, Electrode modified with self assembled FF peptide nanotubes. c, Electrode modified with CNT. d, Cyclic voltammogram of a screen printed electrode, obtained at a scan rate of 100mV/sec, of 1mM K4Fe(CN)6 of untreated, CNT and FF peptide nanotubes modified electrodes. e, Amperometric response of a screen printed electrode modified with varied FF peptide nanotubes layers, to 100, 500 and 1000 nM phenol.

145 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY PROGRESS reports

Dr. Yael Roichman

esearch in soft condensed matter is concerned with as an analog system to 2D crystal faceting, in order materials whose basic units consist of mesoscopic to the roughening transition in quasycrystals. To building blocks. Examples include complex fluids this end we have fabricated textured surfaces such as biological gels, emulsions, polymer solutions, made of polymer pillars on a glass substrate. and colloidal suspensions, as well as granular materials. These pillars, which are 50µm wide and are spread Some of these systems are studied for their interesting 200µm apart, are ordered in different patterns statisticalR mechanics properties whereas others are studied as model (Figure 1.). A liquid droplet, made of an ethanol/ system for a broader class of materials. During the paFigurest year we water mixture, is then dropped onto the textured have been working on projects of both kinds. surface and its spreading is recorded with a high speed camera (Figure 2). Faceting and growth of droplets on micro-fabricated surfaces The liquid droplets start out as spherical and Our aim in this ongoing study is to understand how the symmetry, spread due to impact forces. Spreading then scale and composition of a patterned substrate govern the spreading continues if the mixture sufficiently wets the of a liquid droplet on it. Specifically, we would like to use this system substrate, resulting in a faceted shape. The final

Figure 1: Glass surfaces covered with polymer (SU8) pillars. (a)-(c) top view, (d) an Figure 2: Experimental setup SEM side view image.

Figure 3: Droplet facets and their crystallographic direction on a quasiperiodic Figure 4: Droplet facets and their crystallographic direction lattice. on asquare lattice.

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shape the droplet adopts is then faceted, with a number of facets Active microrheology of actin networks reflecting the symmetry of the underlying structure. A closer look at Complex fluids usually respond non-linearly to the facets and their crystal direction was achieved by viewing the applied forces. It is becoming increasingly clear droplet spreading with an optical microscope. Surprisingly, facets that this non-linear behavior is used by the cell to formed both in the theoretically predicted direction as well as in some transmit mechanical signals along its backbone. new directions for both crystal structures (Figures 3 and 4). We are Due to its economic use of samples and non- currently working on the derivation of the free energy of this system destructive nature, microrheology has emerged which will be able to account for the unpredicted facet direction as a desired tool to study cell mechanics. The both analytically and numerically. At the same time we are exploring viscoelastic properties of the investigated the possibility that this facet formation in a result of dynamics in the materials are inferred from the motion of a tracer droplet deposition. particle in that media. However, microrheology is restricted to work in the linear regime since its Limit Cycles and Chaos on Optical Vortexes analysis is based on linear response. Hydrodynamic interaction between colloidal particles are usually of We believe that knowing the nonlinear elasticity of little importance in self assembly under quasi-equilibrium conditions, the cell skeleton will lead to better understanding however, they could play an important role in assembling structures of mechanotrunsduction. To this end, we have in a driven system. In order to improve our understanding of the been developing an imaging system that can effect hydrodynamic interactions have on directed self assembly we monitor a large number of particles, in three study a simple driven-dissipative system of colloids confined to move dimensions, at high speeds (>1000 fps). Active on a ring. microrheology will be done by using holographic optical tweezers to drive the tracer particles.

Figure 5: Simulation results. At low temperatures colloidal particles driven on a ring interact vie hydrodynamic interactions to form pairs (1)-(3). This coupling increases their average angular velocity. At some threshold temperature the pairs dissolve and the angular velocity decreases dramatically this happen both for a ring with four particles (N=4) and for a ring with two particles (N=2).

147 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY PROGRESS reports

Prof. Gil Rosenman

New Generation of Energy Storage Devices Based on Peptide Nanotubes In cooperation with Prof. E. Gazit Supercapacitors are promising energy storage devices due to their unique combination of high power density and relatively large energy density. We report on environmentally clean bio-supercapacitors based on peptide nanotubes (PNT)-modified electrodes. Short aromatic dipeptides can self-assemble into ordered structures at the nano-scale. These assemblies include nanotubes, nanospheres, nano-plates and hydrogels with nano-scale order (Reches, Gazit, Science, 2003; Nature Nanotechology, 2006, 2007). Peptide nanotubes represent a novel class of nanotubes of biological origin as an appealing alternative to carbon nanotubes. It has been observed Photoluminescence of peptide nanofibers that these biological nanostructures possess paramount properties of different origin allowing to find at the intersection Biology-Physics- Bio-Inspired Nanostructures Light Engineering new advanced nanotechnological applications using Sources the PNT building blocks. In cooperation with Prof. E. Gazit The basis for the new nanotechnology presented in this report is We discover pronounced quantum confinement recently developed new biomolecules deposition method which (QC) and photoluminescence (PL) phenomena allows to drastically change the previous PNT deposition technology, in self-assembled peptide nanostructures based on peptide evaporation from aqueous or organic solutions. of different origin diphenylalanine (FF) The method may be applied to PNT coatings on unlimited area with nanotubes deposited by a vapor deposition high density and homogeneity, controllable thickness as well for method, hydrogels self-assembly of short fabricating patterned PNT structures. Fmoc (N-fluorenylmethoxycarbonyl)-based We found that vertically oriented peptide nanotubular bio-inspired molecules into fibrous formation, nanospheres structures demonstrate new surprising physical properties such as self-assembled from Fmoc-FF or Boc-(Di-tert- dielectric, electrochemical, and wettability which affords to develop butyl dicarbonate)-FF monomers and natural environmentally clean nanodevices. A new PNT-based technology self assembly of amyloidogenic proteins. Our has been applied to development of “green” energy storage devices- observation of QC effects is a direct evidence Supercapacitors. Deposition of PNT arrays on carbon electrodes of highly ordered sub-nano-crystalline areas strongly increase efficiency of these electrochemical units due to high embedded in the structures. The observed PL of density PNT coating. In the developed electrostatic supercapacitors the bio-nanotubes opens a new nanotechnology aromatic vertically oriented dipeptide nanotubes have been used field of bio-inspired materials for optical devices for modification of carbon electrodes of supercapacitors. The such as biosensors, LED, biolasers and more. conducted studies show that PNT-modified electrodes demonstrate pronounced rectangular shape voltammograms and possess a high double-layer capacitance exceeding that parameter for carbon nanotubes-coated electrodes.

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Prof. Yossi Rosenwaks

rof. Rosenwaks’ group is developing and implementing Nano Research projects new methods for measuring the electronic properties n Characterizing Si and III-V semiconductor of semiconductor materials and devices with nanowires nanometer spatial resolution. The various techniques n Studying AFM tip- Semiconductor electrostatic are based on scanning probe microscopy in general interaction and development of deconvolution and Kelvin probe microscopy (KPFM) in particular. algorithms for image reconstruction. P n Nanoscale electrical characterization of operating semiconductor devices. n Direct Measurement of Density of State and other Transport Properties of Organic Materials and Devices. n Photovoltaic Phenomena in photosynthetic proteins.

149 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY PROGRESS reports

Prof. Shlomo Ruschin

Photonic waveguide devices for sensing, was shown that the counter-directional wave telecommunications and signal processing suppression in unidirectional EDWRLs undergoes The main research activity of our group during this period focused on relaxation oscillations synchronously with developing novel devices for based on micron and nanometric size oscillating power. It was also shown that the structures for application in sensing, telecommunications and signal suppression in the first spike is maximal, so the processing and in addition, fundamental properties of waveguide gain switching technique provides the most structures containing metamaterials were investigated. favorable conditions for unidirectional lasing.

Devices for Signal Processing (With O. Amrani and Meta-material-based devices: Y. Ehrlichman) Waveguided devices were studied composed A digitally operated optical QAM Modulator based on a single by both, regular dielectrics and negative-index Multi-Electrode Mach Zehnder Modulator was investigated. It was materials disposed in an anti-symmetric way with demonstrated that a modulator with 13 electrodes and driving respect to the optical axis. Analysis showed that voltages of 0 and 1.68v is sufficient for generating a noise-immune paths were closed, hinting toward the possibility 64QAM constellation. With sufficient number of electrodes, close to of localized modes or light trapped with zero ray ideal error performance can be obtained for any constellation order velocity. A ray model shows also a quasi-perfect imaging effect for off-axis objects. Deviations Unidirectional Erbium-Doped Waveguide Ring Lasers from asymmetry allow, control of the group Relaxation oscillations and gain switching of erbium- doped velocity. waveguide ring lasers (EDWRLs) were studied using numerical Discovery of a critical sensitivity effect in an simulations based on time-dependent rate-propagation equations. interferometer sensor The counter-directional wave suppression was analyzed for different We reported the observation of anomalous waveguide ring cavity configurations and pumping schemes. It behavior in the spectral sensitivity response in a specially designed waveguided interferometer sensor. Approaching a definite critical point, the sensitivity increases nonlinearly.

Synthetic diffractive optics We demonstrated a physical implementation of the mathematical generating function for orthogonal modal functions by means of diffractive optical elements. It was shown theoretically and verified experimentally that the idea of generating function provides a natural way for generation of tailored complex light beams with balanced modal phases and powers and specified propagation directions. Computer simulation and experimental results were in a good agreement. Generic applications in fiber optical sensors and optical communications are foreseen.

Sensing Devices based on porous silicon Figure 1. Layout (upper) and Scanning Electron Microscope pictures (lower) of a Diffractive optical sensors with porous silicon Mach Zehnder interferometersensor displaying critical sensitivity

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layers were demonstrated in addition to an optical sensor for the detection of ammonia in gaseous phase under a changing humidity environment. The sensor was based on a sectioned nano- structured porous silicon (PSi) device in which the parts react distinctly to ammonia and water vapor. We presented also a method for analyte detection using an optical sensor array. The method was implemented in an ammonia gas detector, using a pH sensitive dye. The array is composed of four sensors, each coated with a different concentration of the dye. The resulting signal vector was collected by measuring the absorption at a single wavelength, at each sensor. Simple correlation of the signal vector with an expected gradient-like response enables detection of ammonia. Moreover, it improves immunity to false signals created by changes in Figure 2 SEM pictures of the binary PSi diffraction grating illumination intensity and the humidity of the environment. The method of detection is generic and applicable to sensor arrays where the probe concentration can be controlled.

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Prof. Arie Ruzin

he issue of contact scaling is vital in the overall framework of device and circuit miniaturization. Furthermore, even in fundamentally “large” devices, such as X- and Gamma-ray Tdetectors the nano-scale contacts are of great importance for material and interface studies. The understanding (and modeling) of the behavior of nanometer size contacts on low resistivity semiconductors is insufficient, and on high resistivity semiconductors it practically inexistent. In the last couple of years we made an emphasis on characterization and computer simulation Figure 1. (a) current and (d) topography STM image of a bare CdZnTe(110) surface, and after (b),(e) 2 sec and (c),(f) 5 sec of In evaporation. (a),(d) -4.2 V, (b),(e) -4.0 V of indium nano-contacts on semi-insulating and (c),(f) -5.0 V bias, respectively. (a)-(c) Current (I-images), (d)-(f) topography cadmium-zinc-telluride (CdZnTe). The nano- (z-images). Characteristic RHEED patterns along <001> and <110> directions are contacts were deposited in ultra-high vacuum shown in each inset. Black circle in (c) outlines dislocated region. [Ref. 2] Typical Conduction-AFM images of low indium coverage and high indium onto two-dimensional (atomically flat) surface coverage samples are shown in Fig.2. of (110) oriented CdZnTe substrates [Ref. 1]. The investigation was carried out in collaboration with Prof. Goldfarb from the School of Mechanical Engineering, and his team. The indium was shown to grow epitaxially on the 2D surface of CdTe creating an In-Te phase at the interface. The STM images of the surface at various experiment stages are shown in Fig.1. The nano-contact were characterized ex-situ by an atomic force microscope operated in the torsion TUNA mode. The contacts are not always detectable by topographic AFM characterization, but can be observed by Conduction-AFM measurement at negative tip bias.

References 1. A. Ruzin, “ Simulation of Schottky and Ohmic Contacts on CdTe”, J. Appl. Phys., 109, 1 (2011). Figure 2. (a) Topography and (b) TR-TUNA map of low indium coverage (LIC) 2. Gili Cohen-Taguri, Ori Sinkevich, Mario Levinshtein sample, (c) plot profile of LIC sample over the same line scan in the topography , Arie Ruzin, and Ilan Goldfarb, “ Atomic structure (red) and TR-TUNA (green) modes. (d) Topography and (e) TR-TUNA map of high and electrical properties of In(Te) nano-contacts on indium coverage (HIC) sample, and (f) plot profile of HIC sample over the same line scan in the topography (red) and TR-TUNA (green) modes. [Ref. 2] CdZnTe(110) by scanning probe microscopy”, Adv. In the Current-Voltage characterization (I-V) studies reveal clear rectifying Funct. Mater. 20(2), 215 (2010). behavior with exponential I-V dependence. In addition, exceptional uniformity 3. G. Cohen-Taguri, M. Levinshtein, A. Ruzin, I. among similar size contacts was observed. The polarity of the bias and the Goldfarb, “Real-space identification of the CZT(110) bias range at which the exponential current increase is observed indicate surface atomic structure by scanning tunneling possible tunneling mechanism. Computer simulation of nano-contacts is being microscopy”, Surface Sci. 602 (3), 712-723 (2008). performed in order to promote the understanding of this behavior. [Ref. 3]

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Prof. Ronit Sagi-Eisenberg

Functional phenotype driven screens of Mast Cell identification of the Rab network that controls Activation; Deciphering the role of Rab GTPases in Mast mast cell exocytosis should unveil the cellular Cell Function machineries involved in both the execution We developed a strategy that allows us to perform functional and and regulation of this process. We have already phenotype driven screens of mast cells. These cells are specialized identified 22 Rabs as significant modulators of secretory cells involved in innate and adaptive immune responses mast cell degranulation. To our knowledge the as well as in mediating allergic and inflammatory reactions. Mast involvement of 18 proteins, out of this list, was cells are packed with secretory granules (SGs), which contain allergic, heretofore not recognized. Rabs that serve as inflammatory and immunoregulatory mediators. When triggered, positive regulators might serve as cellular targets multiple signaling events are activated resulting in fusion of the for future developments of therapeutic agents to SGs with the plasma membrane (degranulation). Efforts are being treat allergic and inflammatory diseases. undertaken to develop novel therapies that will specifically target We are currently analyzing the pattern of mast cell activation. However, adopting screening approaches aiming individual cell responses by using a chip-based to unveil stimulus-secretion coupling networks in mast cells has nano-system. Responses of single cells to been limited due to their low transfection efficiency. Hence, genetic manipulations of the relevant Rabs under defined manipulations are unlikely to leave an impact on the actual readouts cellular settings are monitored and analyzed. of average secretion measured by conventional methodologies. Our We are combining multidisciplinary approaches strategy overcame this obstacle and allows us to investigating the including cell and molecular biology, genetics, and molecular networks that link mast cell signaling with degranulation. computational techniques aiming to elucidate Towards this goal, our first project was to screen the Rab family of the mechanisms by which these proteins affect small GTPases. mast cell degranulation thus deciphering the Rab Rab proteins localize to distinct membrane-bound compartments networks that regulate exocytosis. where they regulate transport and fusion events. Therefore,

Single cell analyses of mast cells double transfected with GFP andNeuropeptide Y (NPY)-mRFP, which we use as a reporter for exocytosis, cDNAs, indicate that the majority of cells (75-100%) co-express both GFP and NPY-mRFP. The lower paneldemonstratesthe applicability of this approach for functional and phenotype driven screens of mast cells.Visualized in this picture is a cell co-expressing a GFP tagged Rab 5 active mutant and NPY-mRFP and stained for serotonin, the endogenous marker of secretory granules.Bar 2micrometer. By Nurit Pereg.

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Dr. Ronit Satchi-Fainaro A Novel Nano-scaled Polymer Based Platform for Tumor Selective Targeting of Anticancer and Anti-angiogenic Agents

Polymer Therapeutics A novel combined targeted anticancer Polymer therapeutics is considered the first generation of and anti-angiogenic polymer “nanomedicines”. This family of drug-delivery systems is based on therapeutic for bone neoplasms: HPMA water-soluble polymeric carries of drugs. The therapeutic potential copolymer-ALN-TNP-470 conjugate of nano-constructs lies on the dramatic pharmacokinetic changes of Using multidisciplinary approaches involving the bound drugs that lead to improved efficacy and reduced toxicity. SPPS (solid phase peptide synthesis) and novel The multivalent properties of polymers allow the conjugation of “living polymerization” (RAFT: reversible addition- several compounds within the same polymeric carrier. Therefore, it fragmentation chain transfer), we synthesized and is possible to design multi-drug component therapy and combine characterized a polymer–drug nanoconjugate of targeting moieties. We designed, synthesized and characterized a HPMA copolymer-alendronate-TNP-470 designed polymeric platform for conjugation with different anticancer and to target bone neoplasms such as osteosarcoma anti-angiogenic agents. and bone metastases. We achieved a nano-scaled conjugate with a predetermined molecular Bone Neoplasms targeted conjugates weight, narrow polydispersity and high loading We designed and synthesized polymer conjugates composed of ALN and TNP-470 that were conjugated via of chemotherapeutic or anti-angiogenic agent and the Gly-Gly-Pro-Nle tetrapeptide. This cleavable aminobisphosphonate, alendronate (ALN). The drugs are conjugated linker allows liberation of the active agents in with a polymeric backbone. ALN facilitates the selective delivery the presence of cathepsin K, a cysteine protease to the bones. The conjugation with a polymer facilitates targeting secreted from osteoclasts into the resorption mostly to the tumor sites within the bones and scarcely to normal lacuna, mainly in bone-related diseases with healthy bones due to its passive extravasation through the leaky high absorption activity. The nanoconjugate tumor vessels. demonstrated synergistic anti-angiogenic and

(A) Intravital non-invasive fluorescence imaging of mCherry-labeled human osteosarcoma tumor-bearing mice treated with free or conjugated ALN and TNP-470. (B) Antitumor effect of free (red) or conjugated (green) ALN and TNP-470 on human osteosarcoma tumor growth compared to vehicle-treated group (blue) and images of resected tumors images. Scale bar represents 10 mm. On day 19 HPMA copolymer-ALN-TNP-470 conjugate inhibited tumor growth by 96% (P=0.001) compared with 45% (P=0.012) of free ALN and TNP-470. Data represent mean ± s.e.m.

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antitumor activity in vitro by inhibiting proliferation, migration and Treatment with the bone-targeted polymeric capillary-like tube formation of endothelial cells and proliferation conjugate demonstrated improved efficacy, was of human osteosarcoma cells. In addition, the nanoconjugate better tolerated, and more easily administered showed biocompatiblity in vitro and in vivo. Biodistribution studies intravenously than the clinically-used PTX revealed high localization of FITC-labeled conjugate at the tumors formulated in Cremophor/ethanol (4). in the bones or at osteoidic tumors. HPMA copolymer-ALN-TNP-470 nanoconjugate reduced VEGF-induced vascular hyperpermeability by PTX-PEG-ALN conjugate 92% and remarkably inhibited human osteosarcoma growth in mice We have investigated the role of the structure of by 96%. Toxicity and efficacy evaluation in syngeneic and xenogeneic the polymeric carrier on its targeting ability using osteosarcoma mice models revealed superior antitumor activity a different polymer, Poly(ethylene glycol) (PEG). and decreased organ-related toxicities of the conjugate compared Heterobifunctional PEG, that bears two different with the combination of free ALN plus TNP-470. Finally, comparative reactive groups at the polymer ends, offers the anti-angiogenic activity and specificity studies, using surrogate possibility to design precise and homogenous biomarkers of circulating endothelial cells (CEC), highlighted the polymer architecture with increased drug advantage of the conjugate over the free agents (1, 2). loading. Heterobifunctional BOC-NH-PEG-COOH was exploited to prepare a PEG-dendrimer, NH2- Targeting bone metastases with a novel bi-specific PEG-βGlu-(βGlu)2-(COOH)4, that presents a single anticancer and anti-angiogenic polymer-alendronate- amino group and four carboxylic groups for PTX taxane conjugate: HPMA copolymer-PTX-ALN conjugate and ALN coupling, respectively. PTX-PEG-ALN We designed and synthesized a polymer conjugate of paclitaxel (PTX) conjugate achieved better efficacy and safety and ALN. Both drugs were conjugated with N-(2-hydroxypropyl) profiles than free PTX plus ALN in both xenograft methacrylamide (HPMA) copolymer. and syngeneic mouse models of mammary cancer PTX was conjugated with HPMA copolymer-Gly-Phe-Leu-Gly-p- in the tibia. Biodistribution analysis using FITC- nitrophenol (HPMA copolymer-GFLG-ONp) through Phe-Lys-p- labeled conjugates demonstrated preferential aminobenzyl carbonate (FK-PABC) spacer. This dipeptide-PABC linker tumor accumulation of the conjugate. Finally, provided a stable conjugation chemistry of PTX with HPMA copolymer pharmacokinetic studies demonstrated longer by a carbonate linkage. Both GFLG and FK linkers are cleaved by the t1/2 of the conjugate than free PTX (6). lysosomal enzyme cathepsin B, which is overexpressed in epithelial and endothelial cells, and is secreted into the extracellular matrix. The Targeting avb3 integrin on physico-chemical properties of HPMA copolymer-PTX-ALN conjugate tumor vasculature using a novel were characterized (3). The hydrodynamic size of the conjugate is polyglutamic acid-paclitaxel ~100 nm, it has high affinity to the bone mineral hydroxyapatite and conjugate with the divalent PTX is released by cathepsin B. HPMA copolymer-PTX-ALN conjugate peptide E-[c(RGDfK)2]: PGA-PTX- exhibited cytotoxic effect on prostate and breast carcinoma cell lines E-[c(RGDfK)2] and demonstrated anti-angiogenic activity in vitro. The conjugate also We designed and synthesized a novel targeted exhibited an anti-angiogenic effect in vivo by decreasing microvessel conjugate of PTX, a biodegradable polymer density (MVD), and inducing apoptotic circulating endothelial cells and an integrin-targeted moiety resulting in (CEC) following treatment of the mice. Using intravital imaging a polyglutamic acid (PGA)-PTX-E-[c(RGDfK)2] system and mCherry-labeled breast cancer cell lines, we were able nano-conjugate. Polymer conjugation converted to monitor non-invasively the progression of orthotopic metastatic PTX to a water-soluble macromolecule, tumors injected into the tibia of the mice. HPMA copolymer- and the E-[c(RGDfK)2] enhanced the effects PTX-ALN conjugate showed the greatest antitumor efficacy on previously seen for PGA-PTX alone, utilizing the mCherry-labeled 4T1 mammary adenocarcinoma inoculated into additional active targeting to the αvβ3 integrin the tibia, as compared with PTX alone or in combination with ALN. overexpressed on tumor endothelial cells. PGA

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is enzymatically-degradable by cathepsin B, leading to PTX release 8. Scomparin A, Salmaso S, Bersani S, Satchi-Fainaro under lysosomal acidic pH. R, Caliceti P, Folate-targeted Pullulan bioconjugates PGA-PTX-E-[c(RGDfK)2] inhibited the growth of proliferating αvβ3- for anticancer drug delivery, European Journal of Pharmaceutical Sciences, 42(5), 547-558 (2011). expressing endothelial cells and several cancer cells. We showed that 9. Polyak D, Ryppa C, Ofek P, Licha K, Many A, Kratz F PGA-PTX-E-[c(RGDfK)2] blocked endothelial cells migration towards and Satchi-Fainaro R, Development of PEGylated vascular endothelial growth factor; blocked capillary-like tube doxorubicin-E-[c(RGDfK)2] conjugate for integrin- formation; and inhibited endothelial cells attachment to fibrinogen. targeted cancer therapy, Polymers for Advanced Orthotopic studies in mice demonstrated preferential tumor Technologies, 22, 103–113 (2011). accumulation of the RGD-bearing conjugate, leading to enhanced 10. Karton-Lifshin N, Segal E, Omer L, Portnoy M, Satchi- Fainaro R*, Shabat D*, Non-Invasive Intravital Optical antitumor efficacy and a marked decreased in toxicity as compared Imaging of Hydrogen Peroxide, Journal of the with free PTX-treated mice (7). American Chemical Society (JACS), in press (2011). Taken together, our conjugate alters the pharmacokinetics of both *Corresponding authors. the free drug and the conjugated PGA-PTX. Inclusion of an active 11. Fante C, Eldar-Boock A, Satchi-Fainaro R, Osborn targeting moiety to integrin expressing-cells, leads to a selective anti- H, Greco F, Synthesis and biological evaluation angiogenic therapeutic potential and an alternative manipulation of a polyglutamic acid-dopamine conjugate: a new antiangiogenic agent, Journal of Medicinal to overcome acquired multi-drug resistance, which warrants it as a Chemistry in press (2011). novel targeted, anti-angiogenic and anticancer therapy. 12. Weinstain R*, Segal E*, Satchi-Fainaro R and Shabat D, Reporting drug delivery system: A novel prodrug- References linker that signals active drug-release by generation 1. Segal, E., Pan, H., Benayoun, L., Kopeckova, P., Shaked, Y., Kopecek, J., and of fluorescence, Chemical Communications 46(4), Satchi-Fainaro, R. (2011) Enhanced anti-tumor activity and safety profile of 553-555 (2010). targeted nano-scaled HPMA copolymer-alendronate-TNP-470 conjugate 13. Ofek P, Fischer W, Calderon M, Haag R and Satchi- in the treatment of bone malignances. Biomaterials 32, 4450-4463. Fainaro R, In vivo delivery of siRNA to tumors and 2. Segal, E., Pan, H., Ofek, P., Udagawa, T., Kopeckova, P., Kopecek, J., and their vasculature by novel dendritic nanocarriers, Satchi-Fainaro, R. (2009) Targeting angiogenesis-dependent calcified FASEB Journal, 24(9), 3122-34 (2010). neoplasms using combined polymer therapeutics. PLoS One 4, e5233. 14. Ofek P, Miller K, Eldar-Boock A, Polyak D, Segal E and 3. Miller, K., Erez, R., Segal, E., Shabat, D., and Satchi-Fainaro, R. (2009) Targeting Satchi-Fainaro R, Rational design of multifunctional bone metastases with a bispecific anticancer and antiangiogenic polymer- polymer therapeutics for cancer theranostics, alendronate-taxane conjugate. Angew Chem Int Ed Engl 48, 2949-2954. Special Theme issue: Polymer Therapeutics as novel 4. Miller, K., Eldar-Boock, A., Polyak, D., Segal, E., Benayoun, L., Shaked, Y., nanomedicines, Israel Journal of Chemistry, 50 (2), and Satchi-Fainaro, R. (2011) Antiangiogenic Antitumor Activity of HPMA 185-203 (2010). (Cover feature). Copolymer-Paclitaxel-Alendronate Conjugate on Breast Cancer Bone 15. Marom H, Miller K, Bar Y, Tsarfaty G, Satchi-Fainaro Metastasis Mouse Model. Mol Pharm. R* and Gozin M*, Towards Development of Targeted 5. Clementi, C., Miller, K., Mero, A., Satchi-Fainaro, R., and Pasut, G. (2011) Non-Steroidal Antiandrogen-DOTA-Lantanoid Metal Dendritic Poly(ethylene glycol) Bearing Paclitaxel and Alendronate for Complexes for Prostate Cancer Diagnostics and Targeting Bone Neoplasms. Mol Pharm. Therapy, Journal of Medicinal Chemistry, 53(17), 6. Miller K, Clementi C., Polyak D, Eldar-Boock A, Benayoun L, Barshack I, 6316-25 (2010).* Corresponding authors. Shaked Y, Pasut G and Satchi-Fainaro R (2011) Anti-angiogenic activity of 16. David A and Satchi-Fainaro R, Special Theme issue: polyethyleneglycol-based paclitaxel and alendronate for the treatment of Polymer Therapeutics as novel nanomedicines, breast cancer bone metastases. Submitted. Editorial- Polymer Therapeutics- from bench to 7. Eldar-Boock, A., Miller, K., Sanchis, J., Lupu, R., Vicent, M. J., and Satchi- bedside, Israel Journal of Chemistry, 50 (2), 145-146 Fainaro, R. (2011) Integrin-assisted drug delivery of nano-scaled polymer (2010). therapeutics bearing paclitaxel. Biomaterials 32, 3862-3874.

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PGA-PTX-E-[c(RGDfK)2] conjugate inhibits the growth of mammary tumors in mice and is not toxic. (A) PGA-PTX-E-[c(RGDfK)2] conjugate accumulates in tumors. PGA-E-[c(RGDfK)2]-Cy5.5 conjugate selectively accumulate in 4T1 tumors in vivo. Images show accumulation 7 h after treatment. Tumor area indicated by T, Urine remnant on the mouse fur represented by U and was not calculated. T= counts/sec/tumor area. (B) PTX-treated mice showed signs of toxicity after 5 days of treatment, indicated by death of 2 mice and decrease in body weight. Data represents mean ± s.e.m. (C) PGA-PTX-E-[c(RGDfK)2] conjugate inhibits tumor growth. T/C for PGA-PTX-E-[c(RGDfK)2] was 0.59, 16 days after the end of treatment, but was ~ 0.83 for PTX or PGA-PTX.

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Prof. Koby Scheuer

he research directions during the last year were focused on optical nano-antennas for imaging and solar power harvesting. The results of our work on the subject have shown that metallic nano-antennas can operate with high efficiency in telecom wavelengths. Figure 1 shows an SEM image of one of the fabricated Tnano-antennas. Figure 2 shows the spectral response of optical nano- antennas in the telecom wavelengths band and figure 3 depicts the emitted beam from the array.

Figure 1 – SEM image of a nano-antenna

Figure 2 – Experimentally measured spectral response of nano-antennas

Figure 3 – The beam emitted from the nano-antennas array

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Prof. Daniel Segal

isfolding of proteins can lead to recessive loss of their normal function which could in turn be very detrimental. In addition, certain misfolded proteins tend to self assemble into toxic nano-scale aggregates and fibrils. This dominant gain-of-function is exemplified in Mthe so-called ‘amyloidogenic proteins, whose aggregates and fibrils are associated with diseases such as Alzheimer’ Disease, Parkinson Disease, Huntington’s, Type 2 diabetes and prion disease. Drug development and screening for inhibitors of protein misfolding and inhibitors of amyloidogenic aggregation is a major endeavor of biomedical research in the academia and industry. While in vitro and cell culture-based screenings are amenable to high throughput technology, further verification in the context of the intact organism is traditionally done in rodents. This entails very lengthy and costly assays and involves considerable animal suffering. The fruit fly Drosophila offers a useful intermediate in preclinical studies, between cell culture and mammals. Over the past couple of decades it has proven to be a highly successful model for studying many human diseases in the context of the intact organism, including drug screening. This is thanks to the relative low cost of its rearing in large numbers, its short Segal, D. (2010). Complete Phenotypic Recovery of life cycle, and its remarkable amenabiliy to genetic manipulations. Alzheimer’s Disease Model by a Quinone-Tryptophan Hybrid Aggregation Inhibitor. PLoS One 5: e11101. We use it as a model for studying protein misfolding diseases and for development of novel therapeutics for theses maladies. These studies In another work we aimed at using a natural are conducted in collaboration with the team of Prof. Ehud Gazit. product for inhibiting the toxic Aβ oligomers. We Alzheimer Disease identify a natural substance, based on cinnamon extract (CEppt), which markedly inhibits the In vitro studies by the Gazit lab indicated that certain small molecules formation of toxic Aβ oligomers and prevents the are effective inhibitors of assembly of amyloid-beta (Aβ) into soluble toxicity of Aβ on neuronal PC12 cells. When fed nano-oligomers and fibrils which are the major cause of brain damage to the AD fly model, CEppt rectified their reduced in Alzheimer Disease (AD). Following this we rationally designed longevity, fully recovered their locomotion Tryptophan-modified naphthoquinones and demonstrated their defects and totally abolished tetrameric species of efficacy as Aβ inhibitors in vitro, in cultured cells. Furthermore, when Aβ in their brain. Furthermore, oral administration fed to transgenic Alzheimer’s disease Drosophila model it prolonged of CEppt to an aggressive-AD transgenic mice their life span and completely abolished their defective locomotion model led to marked decrease in Aβ load in their (Fig. 1). This was accompanied by dramatic reduction in Aβ levels and brains along with improvement in cognitive aggregates in extracts and histological examinations of their brains behavior. (Frydman-Marom et al., 2011) (Scherzer-Attali, et al., 2010). More recently we began to examine their effects when injected IP into aggressive-AD model mice. As in Frydman-Marom, A., Levin, A., Farfara, D., Benromano, T., flies, we observed marked amelioration of the cognitive deficits and Scherzer-Attali, R., Peled, S., Vassar, R., Segal, D., Gazit, E., Aβ brain load in these mice (submitted for publication). Frenkel, D., and Ovadia, M. (2011). Orally administrated cinnamon extract reduces b-amyloid oligomerization Scherzer-Attali, R, Pellarin, R., Marino Convertino, M., Frydman-Marom, A., and corrects cognitive impairment in Alzheimer’s Egoz-Matia, N., Peled, S., Levy-Sakin, M., Shalev, DE., Caflisch, A., Gazit, E., and disease animal models. PLoS One, 6(1): e16564.

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Parkinson Disease Type 2 Diabetes The intracellular oligomerization of α-synuclein is associated with Nano-scale deposites of the islet amyloid Parkinson’s disease and appears to be an important target for disease- polypeptide (IAPP) is a characteristic feature of modifying treatment. Yet, to date, there is no specific inhibitor for the pancreas islets failure in type 2 diabetes. We this nano-aggregation process. Using unbiased systematic peptide are in the process of using a bacterial-based (BiFC) array analysis, we indentified molecular interaction domains within screening system for small molecules as inhibitors the β-synuclein polypeptide that specifically binds α-synuclein. of IAPP aggregation. We have also generated Adding various versions of peptide fragments of β-synuclein to transgenic fly strains containing inducible IAPP, α-synuclein significantly reduced both amyloid fibrils and soluble aiming at developing it into a model of type 2 oligomer formation in vitro. A retro-inverso version showed to eb diabetes that would also allow screening for small highly metaboliccally stable and when fed to Drosophila model IAPP-inhibitory molecules in the context of the expressing mutant A53T α-synuclein in the nervous system, resulted whole organism. in a significant recovery of the behavioral abnormalities of the treated flies and in a significant reduction in α-synuclein accumulation in the Cancer brains of the flies (Shaltiel-Karyo et al., 2010) Misfolding of key proteins is characteristic also of various types of cancer. Focusing on two Shaltiel-Karyo, R., Frenkel-Pinter, M., Frydman-Marom, A., Shalev, D.E., Segal, such proteins, the transcription factor p53 and D. and Gazit, E. (2010). Inhibition of a-synuclein oligomerization by stable the von-Hippel-Lindau (vhl)-associated proteins cell-penetrating b-synuclein fragments results in phenotypic recovery of we are in the process of developing assays for Parkinson’s disease model flies. PLoS One 5(11):e13863. in vitro, bacterial and p53 (or vhl) transgenic Drosophila for examining the effect of various Glaucoma stabilizing small molecules on the folding and Mutations in the myocilin (myoc) gene are found in adult onset primary toxic aggregation of p53 and vhl with the hope open-angle glaucoma and in families with juvenile onset. Myoc that these could be developed in the future as mutations appear to cause glaucoma not due to haploinsufficiency anti-cancer drugs. or overexpression. Rather, many myoc glaucoma-causing mutations were found to generate a misfolded Myoc protein that forms secretion-incompetent nano-aggregates. These aggregates are retained in the endoplasmic reticulum (ER), leading to ER stress which is believed to result in apoptosis. No disease modifying treatment is available for glaucoma. We are in the process of developing assays for in vitro, cell culture and Myoc-transgenic Drosophila for examining the effect of various stabilizing small molecules on the folding and toxic aggregation of Myoc.

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Prof. Doron Shabat

uring the course of our work at Tel-Aviv University, we have developed novel molecular systems with self-immolative capabilities. The ability of a molecule to undergo spontaneous domino-like disassembly upon a stimulus event is referred as self-immolative feature. Initially, we developed Da chemical adaptor system for targeted prodrug approach. The prodrug is disassembled of the targeting moiety to release the active drug upon a triggering event. Next, we developed dendrimers with self-immolative capabilities and later, we extended this approach to linear polymers and comb polymers. We also introduced a novel technique for exponential amplification of diagnostic signals. This technique is based on a distinctive dendritic chain reaction (DCR) and has the potential to detect a single molecule activity. Recently, we become interested in the field of Near-Infrared imaging. We developed a novel paradigm for obtaining a Turn-ON mechanism in cyanine dyes and demonstrate this concept for noninvasive optical imaging of inflammation in animal-model.

Chemical Adaptor systems We have developed a drug delivery system based on a chemical adaptor that provides a generic linkage of a drug with a targeting Figure 1: General design of the chemical adaptor device in a manner set to be triggered by defined enzymatic activity system. Cleavage of the enzyme substrate generates an (Figure 1). The system is generic and allows using a variety of drugs, intermediate that spontaneously rearranges to release the targeting devices, and enzymes by introducing the corresponding drug from the targeting device. substrate as a trigger for drug release in the chemical adaptor. The chemical adaptor system was designed with stable chemical biosensor molecules, which are used to detect/ linkages, in order to avoid nonspecific drug release in vivo. Proof of amplify enzymatic activity. The development and concept was demonstrated using etoposide as the drug, an HPMA- evaluation of self-immolative dendrimers so far, copolymer as the targeting device and catalytic antibody 38C2 as the generate seventeen publications. The concept triggering enzyme (Figure 2). was also highlighted in Nature and in Chemical & Engeenering News. Self-immolative dendrimers Self-immolative dendrimers are unique structural molecules Self-immolative Polymers that can release all of their tail units, through a domino-like chain Smart polymers are special kinds of polymeric fragmentation, which is initiated by a single cleavage at the molecules that respond to external stimuli. We dendrimer’s core (Figure 3). Incorporation of drug molecules as the have developed a novel smart polymer designed tail units and an enzyme substrate as the trigger, can generate a to sequentially disassemble into its building multi-prodrug unit that is activated with a single enzymatic cleavage. blocks upon initiation by a triggering event Dendritic prodrugs, activated through a single catalytic reaction by at the polymer head (Figure 4). The polymer a specific enzyme, were shown to present significant advantages in structure is based on a polycarbamate backbone the inhibition of tumor growth, especially if the targeted or secreted that disassembles through a domino-like, enzyme exists at relatively low levels in the malignant tissue. Self- 1,6-elimination and decarboxylation reactions. To immolative dendrimers were also applied as a general platform for demonstrate the concept, we synthesized a self-

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immolative polymer that amplifies a single cleavage reaction into performed in water environment. The technique multiple-release of fluorogenic molecules and confirmed the head is based on a distinctive dendritic chain reaction to tail disassembly concept. These polymers can be used to prepare (DCR); the diagnostic signal was generated upon highly sensitive molecular sensors with large signal-to-noise ratios. disassembly of a self-immolative dendrimer that The sensors should be useful for the detection of a wide range of released chromogenic molecules (Figure 7). Under biological and chemical activities through use of the appropriate ideal conditions, a single analyte molecule initiates trigger at the polymer-head. a dendritic chain reaction that generates a strong Insertion of additional substituents at a specific position of each diagnostic signal. When coupled with a protease monomer generates self-immolative comb-polymers with side- diagnostic probe, the DCR technique detected releasable groups that could be used as a drug delivery system (Figure the activity of penicillin-G-amidase with high 5). Upon activation of the head group, the comb-polymer undergoes sensitivity. This is the first example of exponential complete disassembly to release multiple copies of side-reporter signal amplification performed under aqueous group. The polymer was prepared by simple polymerization of a conditions that is not based on PCR. monomer, followed by capping of the polymer head with a trigger. This technique allowed rapid synthesis of the polymeric molecule A Unique Paradigm for a Turn-ON Near- containing a large number of reporter units. We demonstrate that a Infrared Cyanine-Based Probe: Non- water-soluble version of the comb-polymer can be activated by an Invasive Intravital Optical Imaging of enzyme and thus has potential as selctive drug delivery system. Hydrogen Peroxide The development of highly sensitive fluorescent Chemotherapeutic Bone-Targeted Bisphosphonate probes in combination with innovative optical Prodrugs with Hydrolytic Mode of Activation techniques is a promising strategy for intravital Our group is also developing prodrugs for selective chemotherapy a non-invasive quantitative imaging. Cyanine representative example is described below: fluorochromes belong to a super-family of dyes that Osseous tissues are considered to be limited as therapeutic target have attracted substantial attention in probe design sites due to their biological properties. We have designed and for molecular imaging. We have developed a novel synthesized two kinds of hydrolytically-activated chemotherapeutic paradigm to introduce a Turn-ON mechanism in prodrugs containing bisphosphonate, a bone-targeting moiety. cyanine molecules, based on a distinctive change The first can be conjugated to drug molecules with an available in their π-electrons system. Our new cyanine hydroxy group; the drug is attached to the bisphosphonate fluorochrome is synthesized through a simple component through an ester-labile linkage. The second is for use two-step procedure and has an unprecedented with drug molecules with amine functional group. In this case, a self- high quantum yield of 16% and large extinction immolative linker is used to attach the drug to the bisphosphonate coefficient of 52,000-1 M cm-1. The synthetic strategy component through a carbonate-labile linkage. The concept was allows one to prepare probes for various analytes demonstrated using the drugs camptothecin, which has a hydroxy by introducing a specific triggering group on the functional group, and tryptophan, which is a model molecule for probe molecule. The probe was equipped with a a drug with amine functionality. Both prodrugs showed significant corresponding trigger and demonstrated efficient binding capability to hydroxyapatite, the major component of bone, imaging of endogenous hydrogen peroxide, and were hydrolytically activated under physiological conditions. produced in an acute LPS-induced inflammation model in mice. This approach provides, for the first Dendritic Chain Reaction time, an available methodology to prepare modular Signal amplification techniques are broadly used to improve the molecular Turn-ON probes that can release an detection sensitivity of various analytes for diagnostic purposes. We active cyanine fluorophore upon reaction with have developed a novel, non-PCR-based, modular technique for specific analyte. exponential amplification of diagnostic signal that is conveniently

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Figure 3: Self-immolative dendrimers, as shown in the picture, spontaneously release all the end-group molecules following a single activation event. This triggering event induces a cascade of self-eliminations, which leads to complete dissociation of the dendrimer into its separate building blocks.

References 1. Miller, K., Erez, R., Segal, E., Shabat, D., Satchi-Fainaro, R., “A Novel Bispecific Targeting Agent Based on a Polymer-Alendronate-Taxane Conjugate to Target Prostate Cancer Bone Metastases” Angew. Chem. Int. Ed. Engl., 2009, 48, 2949-54. 2. Stern, L., Perry, R., Ofek, P., R., Many, A., Shabat, D., Satchi-Fainaro, R. “A Figure 6: Camdronate – A chemotherapeutic Bone- Targeted Bisphosphonate Prodrug with Hydrolytic Mode novel antitumor prodrug designed to be cleaved by the endoprotease of Activation legumain” Bioconjug. Chem., 2009, 20, 500-10. 3. Erez, R., Segal, E., Miller, K., Satchi-Fainaro, R., Shabat, D., “Enhanced Cytotoxicity of a Polymer-Drug Conjugate with Triple Payload of Paclitaxel”, Bioorg. Med. Chem., 2009, 17, 4327-35. 4. Avital-Shmilovici, M., Shabat, D., “Enzymatic Activation of Hydrophobic Self-Immolative Dendrimers: The Effect of Reporters with Ionizable Functional Groups”, Bioorg. Med. Chem. Lett., 2009, 19, 3959-62. 5. Sella, E., Shabat, D., “Dendritic Chain Reaction”, J. Am. Chem. Soc. 2009, 131, 9934-6. 6. Weinstein, R., Baran, S. P., Shabat, D., “Activity-Linked Labelling of Enzymes by Self-Immolative Polymers”, Bioconjug. Chem., 2009, 20, 1783–1791. 7. Perry-Feigenbaum, R., Baran, S. P., Shabat, D., “The Pyridinone-Methide Elimination”, Org. Biomol. Chem., 2009, 7, 4825-4828. 8. Weinstain, R., Segal, E., Satchi-Fainaro, R., Shabat, D., “Real-Time Monitoring of Drug Release”, 2010, Chem. Commun., 46, 553-5. Figure 8: Upper image: Photograph of a masked-probe 9. Avital-Shmilovici, M., Shabat, D., “Self-Immolative Dendrimers: A Distinctive and an active one in PBS 7.4 [50 μM] solutions. Lower Approach to Molecular Amplification”, Soft Matter, 2010, 6, 1073–1080. image: Photograph of a masked-probe and an active one 10. Sella, E., Lubelski, A., Klafter, J., Shabat, D., “Two-Component Dendritic in PBS 7.4 [50 μM] solutions by NIR camera (excitation at Chain Reactions: Experiment and Theory”, J. Am. Chem. Soc., 2010, 132, wavelength 595 nm, cutting filter of >635 nm). 3945-52. 11. Avital-Shmilovici, M., Shabat, D., “Dendritic Chain Reaction: Responsive Release of Hydrogen Peroxide upon Generation and Enzymatic Oxidation of Methanol”, Bioorg. Med. Chem., 2010, 18, 3643-7. 12. Sella, E., Weinstain, R., Erez, R., Burns, Z. N., Baran, S. P., Shabat, D., “Sulfhydryl- Based Dendritic Chain Reaction”, Chem. Commun., 2010, 21, 6575-7. 13. Karton-Lifshin, N., Segal, E., Omer, L., Portnoy, M., Satchi-Fainaro, R., Shabat, D., “A Unique Paradigm for a Turn-ON Near-Infrared Cyanine-Based Probe: Non-Invasive Intravital Optical Imaging of Hydrogen Peroxide”, J. Am. Chem. Soc., 2011, In Press.

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Prof. Yosi Shacham-Diamand Microelectronics for Biosensing Applications

Introduction The microelectronic-biomedical research Detection of cancer in early stages is known to have a dramatic effect includes a combined biosensor based on the on mortality rates and broad social and economical implications. integration of three different approaches, Diagnostic devices converging biology and microelectronics are each covers a different aspect of cancer: The becoming a major factor in the emerging fields of biomedicine and first approach, Electrochemical detection of cancer diagnostics. Diagnostic biochip devices have an enormous enzymatic activity: when the biomarker is an potential, mainly due to their high sensitivity and accuracy and enzyme, a special substrate may be found or moreover, ease of operation along with low cost. Electrochemical ‘tailored’ which upon biocatalysis yields an and electrical biosensors offer exciting opportunities for numerous electroactive product. Example: The Enzyme decentralized clinical applications. Although progress made in this Alkaline Phosphatase is abundant in the human field was rapid, these methods had no impact on neither incidence body in few subtypes appearing at different nor mortality rates and few of the technologies or biomarkers have organs. Few of these subtypes correlates transitioned into the clinical arena. strongly with certain malignancies whereby It is anticipated that “multi target strategies” will enable a more the expression level of these enzymes may rapid detection and facilitate a more accurate high confident early increase or decrease dramatically as a response diagnostics. Therefore, the current trend is to “probe the tumor” to cell transformation and tumor growth. Our from a few angles, gathering information which represents various biosensor can accurately detect levels of alkaline pathways in a high throughput manner with increased integration phosphatase by employing a substrate catalyzed and miniaturization. Since different cancer cell characteristics are to a product which is electroactive. That way, manifested both extracellularly and membranaly, checking one and when the enzyme is present in a sample, a current not the other might lead to false (negative or positive) results. signal is observed upon addition of the substrate and application of electric potential. Nanovolume Results biopsies are measured electrochemically As the expression of unique functional biomarkers is the hallmark immediately upon their removal, yielding results of every malignancy, pathology and infection these miniature within few minutes, in what could be considered diagnostic devices were planned to detect ultra low levels of various as ‘direct diagnostics’. The second approach, biomarkers in a simultaneous fashion thus providing a more accurate is the electrochemical immuno-detection of detection with high confidence. specific cancer secreted biomarkers. Biomarker

Figure 1. A scheme of the integrated multi method biosensing system

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molecules are “captured” and consequently lead to electrochemical References detection by a modified enzyme-linked immunosorbent assay 1. Vernick, S., Freeman, A., Rishpon, J., Niv, Y., Vilkin, A., (ELISA) performed on a microelectrode within a miniature and Shacham-Diamand, Y. (2011). “Electrochemical Biosensing for Direct Biopsy Slices Screening electrochemical cell. Antibodies against the different biomarkers for Colorectal Cancer Detection”, Journal of The are immobilized on different electrodes as an array. To ensure stable Electrochemical Society, 158(1), P1-P4. oriented immobilization of the antibodies they are first thiolated 1. Vernick, S., Freeman, A., Rishpon, J., and Shacham- enabling oriented covalent bonding to a gold working electrode. Diamand, Y. (2009). “Direct Biopsy Screening The screened cancer cell culture is subsequently incubated with the of Colorectal Cancer by Electrochemical immobilized antibodies in the electrochemical chamber. Following Biosensor”, ECS Transactions 19 (33), 61. 1. Einati, H., Mottel, A., Inberg, A., Shacham-Diamand, Y. the capture of the biomarkers by the immobilized antibodies and (2009). “Electrochemical Studies of Self-Assembled washing of nonbound markers, an antibody–Enzyme (HRP, horse- Monolayers Using Impedance Spectroscopy”, radish peroxidase) immunoconjugate is added. Following washing Electrochimica Acta 54(25), 6063-6069. of unbound reagent, the conjugated HRP enables electrochemical 1. Ben-Yoav, H., Biran, A., Pedahzur, R., Belkin, S., detection upon the addition of an appropriate substrate. Buchinger, S., Reifferscheid, G., and Shacham- The third approach is a MEMS based detection of cancerous cell Diamand, Y. (2009). “Whole Cell Electrochemical Biosensor for Water Genotoxicity Bio-Detection”. by sensing membrane bound biomarkers. Electro-mechanical Electrochimica Acta 54 (25), 6113-6118. measurement of the dissociation (unbinding force) of the biologically modified micro actuator from its recognized cell-embedded biomarker will be achieved by a disposable innovative MEMS actuator with a vertical motion driven by electrostatic forces. Furthermore, an innovative work is being conducted in the development and characterization of specialized ISFET (Ion-sensitive field effect transistors) modified by self-assembled monolayers and used for the ultra sensitive detection of biomarkers.

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Dr. Ella Sklan

Viral-Host interactions of positive strand RNA viruses Major Achievements Positive-strand RNA viruses encompass over one-third of all virus We have managed to identify HCV non-structural genera and include numerous pathogens. Our long term goal is to protein 5A (NS5A) as a key lipid droplet binding identify and characterize the interactions of viral proteins with their protein (Fig. 1). NS5A was tightly and irreversibly host cell. Our current model systems include Hepatitis C virus (HCV) bound to lipid droplets which are major site of and Dengue virus. HCV assembly. Our data supports a model where NS5A’s interaction with core on the lipid droplet During the last year projects in the laboratory focused on initiates assembly. Our data further emphasizes 1. Development of a unique mammalian system for the identification the role of LDs in the HCV life cycle. and characterization of new interactions between viral non- structural proteins and host cell proteins. Reference 2. Identification and characterization of miRNAs involved in the HCV Hirschberg K., Asher M., Nahmias Y., Sklan EH. The life cycle and HCV induced Hepatocellular carcinoma. hepatitis C virus NS5A is a major lipid droplets binding protein. 2011. Submitted to J. Virol. 3. Characterization of the membrane association mechanisms of Dengue virus non-structural proteins. 4. Using live cell imaging to study HCV assembly.

Figure 1: NS5A is a major lipid droplet binding protein. Shown is an image of a region of interest within a living cell transfected with NS5A-GFP captured using a confocal microscope. Identification of lipid droplets using BODIPY558/568 dodecanoic acid. Cells expressing NS5A-GFP (green) were treated with oleic acid and 4 h later labeled with the bodipy dye (red). Bar 1 µm.

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Dr. Inna Slutsky

ince the early time of Descartes at the turn of the Regulation of synaptic transfer function 17th century, scientists and philosophers have been by amyloid-β peptides searching for the physical correlate of thoughts We discovered that amyloid-β peptide, previously and memories. During the past 60 years, mounting thought to be a “synaptotoxic” molecule leading evidence indicates that experience-dependent to memory impairments in Alzheimer’s disease, changes in synaptic transmission and neuronal critically regulates release probability of single wiring,S phenomena collectively termed synaptic plasticity, underlie hippocampal synapses in a history-dependent the cellular basis of neural computation, learning and memory. manner (Abramov et al., 2009). Against the Individual synapses – the elementary units of information transfer – prevailing dogma, we demonstrated that both encode and store new information in response to the environmental elevation and reduction in amyloid-β levels changes through structural and functional reorganization. However, attenuated short-term synaptic dynamics, the key mechanisms that normally maintain plasticity of synapses findings which implied a physiological role for during adulthood or initiate synapse dysfunction and loss in endogenous amyloid-β peptides in synaptic neurodegenerative diseases remain unknown. function. Moreover, our study shed light on the early pathological events initiating synapse GABA nanosensor for studying molecular mechanisms loss in Alzheimer’s disease, and provided a new of synaptic variability conceptual framework for future research into We uncovered a molecular mechanism of presynaptic heterogeneity the initiation of the disease and potential drug along axons (Laviv et al., 2010). This study integrated, for the first development. time, measurements of inter-molecular interactions, synaptic vesicle recycling and calcium transients at the level of single synapses in live Magnesium as a positive regulator of cultured neurons. Utilizing FRET spectroscopy and FM-based imaging, synaptic and cognitive function we demonstrated that release probabilities along axons are largely As a continuation of our in-vitro study (Slutsky et determined by variability in the local GABA concentration in the al., 2004), we found that physiological fluctuations vicinity of presynaptic boutons acting on GABAB-type receptors, the in the CSF magnesium concentration profoundly activity of which is regulated by ongoing neuronal activity. In addition impact synaptic and cognitive functions in to the theoretical importance of the findings, the work opened new rats (Slutsky et al., 2010). We demonstrated technical venues for studying structure-function relationship at the that supplementation to rat’s diet with newly single synapse level to be used for a wide spectrum of questions in synthesized magnesium-threonate resulted neuroscience (Lewis, 2010). in enhanced learning, associative and spatial FRET measurements at the single synapse level in hippocampal memory, increase in the number of synapses, and neurons (from Laviv et al., 2010). enhanced synaptic plasticity in ageing and young

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rats. Given a profound deficiency in magnesium intake in humans, 3. Slutsky, I., Abumaria, N., Wu, L. J., Huang, C., Zhang, L., this study suggest that decreasing ongoing background Ca2+ flux in Li, B., Zhao, X., Govindarajan, A., Zhao, M. G., Zhuo, M., spines may be a promising therapeutic approach for prevention or et al. (2010). Enhancement of Learning and Memory by Elevating Brain Magnesium. Neuron 65, 165-177. reversal of age-dependent memory decline. 4. Abramov, E., Dolev, I., Fogel, H., Ciccotosto, G. D., Ruff, E., and Slutsky, I. (2009). Amyloid-[beta] as a positive References endogenous regulator of release probability at 1. Laviv, T., Riven, I., Dolev, I., Vertkin, I., Balana, B., Slesinger, P. A., and Slutsky, hippocampal synapses. Nat Neurosci 12, 1567-1576. I. (2010). Basal GABA regulates GABA(B)R conformation and release 5. Slutsky, I., Sadeghpour, S., Li, B., and Liu, G. (2004). probability at single hippocampal synapses. Neuron 67, 253-267. Enhancement of synaptic plasticity through 2. Lewis, S. (2010). Synaptic transmission: A closer look at presynaptic GABAB chronically reduced Ca2+ flux during uncorrelated receptors. Nat Rev Neurosci 11, 664-665. activity. Neuron 44, 835-849.

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Prof. Michael Urbakh

Electrovariable nanoplasmonics at the interface: the thermally activated formation We introduced a new approach for as well as rupturing of an ensemble of atomic electrically tunable reflection of light at contacts. a liquid-liquid interface. Its operation principle relies on voltage controlled Single molecular force spectroscopy localization of metal nanoparticles To both explore the results of force spectroscopy at the interface. For appropriate sizes experiments and to reveal a molecular scale and charges of the nanoparticles, and energy landscapes, we established relationships concentration of the electrolytes, about between equilibrium properties of the nanoscale 0.5 V potential variation is required systems and the characteristic features measured to reversibly convert the interface of two immiscible electrolytic under non-equilibrium conditions. We found that solutions from a transparent window to a mirror. dynamics of conformational degrees of freedom may lead to nonexponential kinetics for single Nanotribology proteins unfolding under force. The focus is on a molecular level description of processes occurring between and close to interacting surfaces which is needed to References first understand, and later manipulate friction. Novel methods for 1. Barel I., Urbakh M., Jansen L. and Schirmeisen A., controlling friction using mechanical and chemical approaches have Multibond Dynamics of Nanoscale Friction: The Role of Temperature, Phys. Rev. Lett., 104, 066104 (2010). been introduced. We proposed a novel mechanism of temperature 2. Filippov A.E., Vanossi A., Urbakh M., Origin of Friction dependence of friction at the nanoscale that explains the experimentally Anisotropy on a Quasicrystal Surface, Phys. Rev. observed nonmonotonic enhancement of dry nanoscale friction at Lett., 104, (2010). cryogenic temperatures for different material classes. Our simulations 3. Urbakh M. and Meyer E., The renaissance of friction, show that this effect emerges from two competing processes acting Nature Materials, 9, 8-10 (2010). 4. Flatte M.E., Kornyshev A.A., Urbakh M., Electrovariable Nanoplasmonics and Self-Assembling Smart Mirrors, J. Phys. Chem. C, 114, 1735-1747 (2010). 5. T.-L. Kuo, S. Garcia-Manyes, J. Li, I. Barel, H. Lu, B. Berne, M. Urbakh, J. Klafter, J. Fernandez, Probing static disorder in Arrhenius kinetics by single-molecule force spectroscopy, PNAS, 107, 11336-11340 (2010). 6. Berkovich R., Garcia-Manyes S., Urbakh M., Klafter J., Fernandez J.M., Collapse dynamics of single proteins extended by force, Biophys. J. 98 2692–2701 (2010). 7. Barel I., Urbakh M., Jansen L. and Schirmeisen A., Temperature Dependence of Friction at the Nanoscale: When the Unexpected Turns Normal, Tribology Lett., 39, 311-319 (2010). 8. Berkovich R., Garcia-Manyes S., Urbakh M., Klafter J., Fernandez J.M., Hopping around an entropic barrier created by force, Biochem. Biophys. Research Commun., Biochem Biophys Res Commun, vol 403, 1 133-7 (2010). 9. Flatte M., Kornyshev A.A., Urbakh M. Nanoparticles at electrified liquid-liquid interfaces: new options for electro-optics, Faraday Discussions, 143, 109-115 (2009).

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Publications

1. Electronic structure of single 9. Anisotropic magneto-transport 16. Three dimensional DNA molecules resolved by effects at SrTiO3/LaAlO3 characterization of drug- transverse scanning tunneling interfaces encapsulating particles using spectroscopy Ben Shalom M, Tai C W, Lereah Y, STEM detector in FEG-SEM Shapir E, Cohen H, Calzolari A, Sachs M, Levy E, Rakhmilevitch D, Barkay Z, Rivkin I, Margalit R. Micron Cavazzoni C, Ryndyk D A, Cuniberti Palevski A and Dagan Y. Phys. Rev. B Jun. 2009; 40: 480-485 G, Kotlyar A, Di Felice R, Porath D. 2009; 80: 140403 17. Secondary Electron Emission Nature Mat. 2008; 7: 68-74 10. Polar Kerr effect as probe Contrast of Quantum Wells in 2. Efficient procedure of for time-reversal symmetry GaAs p-i-n junctions preparation and properties of breaking in unconventional Grunbaum E, Barkay Z, Shapira Y, long uniform G4-DNA nanowires superconductors Barnham K W J, Bushnell D B, Ekins- Borovok N, Molotsky T, Ghabboun J, Kapitulnik A, Xia J, Schemm E, Daukes N J, Mazzer M and Wilshaw Porath D, Kotlyar A. Anal Biochem. Palevski A. New Jour. Phys. 2009; 11: P. Microsc. Microanal. Apr. 2009; 15: 2008; 374: 71-78 055060 125-129 3. Formation of polyaniline layer 11. Inverse proximity effect in 18. On the Mechanism of Floating on DNA by electrochemical superconductor-ferromagnet and Sliding of Liquid Marbles polymerization bilayer structures Bormashenko E, Bormashenko Y, Bardavid Y, Ghabboun J, Porath Xia J, Shelukhin V, Karpovski M, Musin A, Barkay Z. Chemphyschem. D, Kotlyar A B, Yitzchaik S. Polymer Kapitulnik A, Palevski A. Phys. Rev. 2009; 10, 654-656 2008; 49: 2217–2222 Lett. 2009; 102: 087004 19. Shape, vibrations, and effective 4. High-resolution STM imaging of 12. ATM deficiency leads to surface tension of water marbles novel single G4 DNA molecules destabilization of phase Bormashenko E, Pogreb R, Whyman Shapir E, Sagiv L, Borovok N, synchronization in dissociated G, Musin A, Bormashenko Y, Barkay Molotski T, Kotlyar A B, Porath D. J. and homogeneous cortical Z. Langmuir 2009; 25: 1893-1896 Phys. Chem. 2008; 112: 9267-9269 neurons 20. Micromorphology and Levin-Small1 Noah, Yekutieli Ziv, 5. Assembling of G-strands into Maturation of the Yellow Shein Mark, Shiloh Yosef, Ben Jacob novel tetra-molecular parallel Granules in the Hornet Gastral Eshel and Barzilai Ari. In printing G4-DNA nanostructures using Cuticle avidin-biotin recognition 13. X-ray initiation of nonthermal Plotkin M, Volynchik S, Barkay Z, Borovok N, Iram N, Zikich D, growth of single crystal pyramids Bergman D J, Ishay J S. Zoological Ghabboun J, Livshits G, Porath D, in amorphous barium titanate Research 2009; 30: 65-73 Kotlyar A. Nucl. Acid Res. 2008; 36: Feldman Y, Lyahovitskaya V, Leitus 21. Preparation and analysis of a 5050-5060 G, Lubomirsky I, Wachtel E, Bushuev two-components breath figure at V A, Vaughan G, Barkay Z and 6. Radiationless Transitions of G4 the nanoscale Rosenberg Yu. APL Aug. 2009; 95: Wires and dGMP Kofman R, Allione M, Celestini 051919 Gepshtein R, Huppert D, Lubitz I, F, Barkay Z and Lereah Y. Eur. Phys. J. Amdursky N & Kotlyar A B. J. Phys. 14. Robust method of D 2008; 50: 279-284 Chem. A 2008; 112: 12249-12258 manufacturing rubber waste- 22. Free-standing, thermostable, based water repellent surfaces 7. Molecular analysis of micrometer-scale honeycomb Bormashenko E, Goldshtein V, recombinase-mediated cassette polymer films and their Barayev R, Stein T, Whyman G, exchange reactions catalyzed by properties Pogreb R, Barkay Z and Aurbach integrase of coliphage HK022 Bormashenko E, Schechter A, D. Polym. Adv. Technol. 2009; 20: Malchin N, Molotsky T, Yagil E, Stanevsky O, Stein T, Balter S, Musin 650-653 Kotlyar A, Kolot M. Res. Microbiol. A, Bormashenko Y, Pogreb R, Barkay 2008; 159, 663-670. 15. Enhanced osseointegration Z, Aurbach D. Macromol. Mater. Eng. of grit-blasted, NaOH-treated 2008; 293: 872-877 8. Separation of 1-23-kb and electrochemically complementary DNA strands by hydroxyapatite-coated Ti-6Al-4V urea-agarose gel electrophoresis implants in rabbits Hegedüs E, Kókai E, Kotlyar A, Lakstein D, Kopelovitch W, Barkay Dombrádi V, Szabó G. Nucleic Acids Z, Bahaa M, Hendel D, Eliaz N. Acta Res. 2009; 37: e112 Biomaterialia 2009; 5: 2258-2269

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23. Modification of Protein Crystal 31. Integrin-targeted nanoparticles 37. Controlling the Optical Packing by Systematic Mutations Ben-Arie N, Kedmi R and Peer D. Transparency of Meta-Materials of Surface Residues: Implications Methods in Molecular Biology 2009; with a Strong DC Magnetic Field, on Biotemplating and Crystal In press in Plasmonics Porosity Strelniker Y M and Bergman DJ. 32. Surface plasmon amplification Wine Yariv, Cohen-Hadar Noa, Satoshi Kawata, Vladimir M. Shalaev by stimulated emission of Lamed Raphael, Freeman Amihay, and Din Ping Tsai, Proc. SPIE radiation: Quantum generation Frolow Felix. Biotechnology and Nanoimaging, Nanofabrication and of coherent surface plasmons in Bioengineering 2009; 104: 444-457 their Applications IV 2008; 7033: Nanosystems 70331D 24. Directed Metallization of Bergman D J and Stockman M I. Single-Enzyme Molecules With Phys. Rev. Letters 2003; 90: 027402- 38. Manipulating the optical Preserved Enzymatic Activity 1–027402-4 transparency of anisotropic Vernick Sefi, Moscovich-Dagan Hila, meta-materials with magnetic 33. Electromagnetic Eigenstates of Porat-Ophir Carmit, Rishpon Judith, field and liquid crystals: Influence Finite Cylinders and Cylinder- Freeman Amihay and Shacham- of the nano-structures shape Clusters: Application to Diamand Yosi. IEEE transactions on Strelniker Y M, Bergman D J, Fleger Macroscopic Response of Meta- nanotechnology 2009; 8 95 Y, Rosenbluh M, Stroud D and Materials, in Plasmonics: Metallic Voznesenskaya A O. To appear 25. Protein Crystal-Mediated Nanostructures and their Optical in Proc. of the SPIE Conference Biotemplating Properties VI entitled Plasmonics: Nanoimaging, Cohen-Hadar Noa, Wine Yariv, Bergman D J, Ed. Mark I. Stockman, Nanofabrication and their Lagziel-Simis Shira, Moscovich- Proc. SPIE 7032, 70321A (2008) Applications, in the SPIE Meeting Dagan Hila, Dror Yael, Frolow Felix 34. Electromagnetic Eigenstates on Optics and Photonics, The San and Freeman Amihay. Journal of Applied to the Theoretical Diego Convention Center, San Porous Media 2009; 12: 213-220 Discussion of Meta-Materials Diego, CA, 2-6 August 2009 26. Systemic siRNA delivery to with Negative Refraction 39. Manipulating the transmittance leukocye-implicated diseases Bergman D J and Ben-Yakar Y. of a nano-perforated conducting Peer D and Shimaoka M. Cell Cycle To appear in Proc. of the SPIE film by a magnetic field 2009; 8: 853-9 Conference entitled Plasmonics: Y.M. Strelniker and D.J. Metallic Nanostructures and their 27. Nanocarriers delivering RNAi to Bergman, Proceedings of the Optical Properties, in the SPIE cancer cells: from challenge to 2nd International Congress on Meeting on Optics and Photonics, cautious optimism Advanced Electromagnetic The San Diego Convention Center, Peer D. Therapy 2009; 6: 293-296 Materials in Microwaves and Optics San Diego, CA, 2–6 August 2009 (Metamaterials 2008), Pamplona, 28. Immune Targeting Nanoparticles 35. Critical point in the strong-field Spain, September 23-26. Containing siRNAs to Curtail magnetotransport of a three- Leukocyte-Implicated Diseases 40. Gravity orientation in social dimensional binary disordered Peer D. Human Gene Therapy 2009; wasp comb cells (Vespinae) and composite medium 20: 532-533 thepossible role of embedded Magier R and Bergman D J. Phys. minerals 29. RNAi nanomedicines as novel Rev. B 2008; 77: 144406 Ishay J S, Barkay Z, Eliaz N, Plotkin platform for personalized 36. Transmittance and transparency M, Volynchik S and Bergman D J. medicine of subwavelength-perforated Naturwissenschaften. 2008; 95: Kemdi R and Peer D. Nanomedicine conducting films in the presence 333-42 2009; In press of a magnetic field 41. Xanthopterin in the Oriental 30. Targeted Stabilized Strelniker Y M and Bergman D J. Hornet (Vespa orientalis): Light Nanoparticles for an Efficient Phys. Rev. B 2008; 77: 205113 absorptance is increased with Delivery of siRNAs in vitro and maturation of yellow pigment in vivo granules Srinivasan C, Peer D and Shimaoka Plotkin M, Volynchik S, Ermakov N M. In Cytokine protocols. Methods Y, Benyamini A, Bergman D J and in Molecular Biology 2009; In press Ishay J S. Photochem Photobiol. 2009; 85: 955-61

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65. Phage therapy as a solution for 74. Nanoscale oxygen octahedral 82. Dissipative two-electron transfer: antibiotic resistance of bacteria tilting in 0.90(Bi12/Na12/)TiO3- A numerical renormalization Yacoby I, Vaks L and Benhar I. Afr. J. 0.05(Bi12/K12/)TiO30.05-BaTiO3 group study Biotech; In press lead free perovskite piezoelectric Tornow S, Bulla R, Anders F B and ceramics Nitzan A. Phys. Rev. B 2008; 78: 66. An Electrochemical Tai Cheuk W and Lereah Y. Applied 035434 Immunosensor for C-Reactive Physics Letters 2009; 95: 062901 Protein Based on Multi-Walled 83. Chiral control of electron Carbon Nanotube-Modified 75. Amplification from Nd3+ doped transmission through molecules Electrodes Si-Ti sol-gel channel waveguides Skourtis S S, Beratan D N, Naaman Buch M, Rishpon J. Electroanalysis Peled Asher, Nathan Menachem, R, Nitzan A and Waldeck D H. Phys. 2008; 20: 2592-2594 Arie Ady, Tsukernik Alexander and Rev. Let. 2008; 101: 238103 Ruschin Shlomo. Optical Materials 67. Fiber microciol optical gyroscope 84. Decaying Rabi oscillations 2009; 31: 1284-1287 Scheuer J. Opt. Lett. 2009; 34: 1630 in quantum-dot tunnelling 76. Nonequilibrium steady state junctions 68. Side coupled adjacent resonators transport via the reduced density Fainberg B and Nitzan A. Phys. CROW - formation of Mid-Band matrix operator Status Solidi A. 2009; 206: 948-951 Zero Group Velocity Subotnik J E, Hansen T, Ratner M A Weiss O and Scheuer J. Opt. Express 85. The non-linear response of and Nitzan A. J. Chem. Phys. 2009; 2009; 17: 14817 molecular junctions: the polaron 130: 144105 model revisited 69. Dynamical Slowing and Galperin M, Nitzan A and Ratner M trapping of light in coupled 77. Nanotechnology: Applications, A. J. Phys.: Condens. Matter. 2008; semiconductor laser arrays customer products and Benefits 20: 374107 Yifat Y and Scheuer J. Opt. Express Adlakha-Hutcheon G, Khaydarov 2009; 17: 17530 86. Inelastic transport in the R, Korenstein R. Nanomaterials: Coulomb blockade regime within 70. Spectral Properties of Active Risks and Benefits, Nato Science a nonequilibrium atomic limit Racetrack Semiconductor for Peace and Security Series – C: Galperin M, Nitzan A and Ratner M Structures with Intracavity Environmental Security (Edit. A. Phys. Rev. B. 2008; 78: 125320 Reflections Igor Linkov and Jeffery Steevens) Alexandropoulos D, Scheuer J Springer 87. Multibody Scattering, and Vainos N A. IEEE J. Select. Top. Correlation, Molecular 78. Cooperative effects in Quantum. Electron. 2009; 15: 1420 Conduction and the 0.7 Anomaly molecular conduction II: The Subotnik J E, Nitzan A. J. Chem. 71. Size effects on melting and Semiconductor−Metal Molecular Phys. 2008; 129: 144107 wetting in the Ga-Pb nano-alloys Junction Allione M, Kofman R, Celestini F and Landau A, Kronik L and Nitzan A. J. 88. Nuclear Coupling and Lereah Y. The European Physical Phys. Chem. A 2009; 113: 7451-7460 Polarization in Molecular Journal D 2009; 52: 207 Transport Junctions: Beyond 79. Transport in State Space: Tunneling to Function 72. Discrete angle rotations of Bi Voltage-Dependent Galperin M, Ratner M A, Nitzan A nanoparticles embedded in a Ga Conductance Calculations of and Troisi A. Science 2008; 319: 1056 Matrix Benzene-1,4-dithiol Be›er A, Kofman R and Lereah Y. Yeganeh S, Ratner M, Galperin M 89. Inelastic effects in molecular Central European Journal of Physics and Nitzan A. Nano Let. 2009; 9: junction transport: Scattering 2009; 11534-00634-3 1770-74 and self-consistent calculations for the Seebeck coefficient 73. Quantitative strain-field 80. Raman scattering in current Galperin M, Ratner MA, Nitzan A. measurements of 1:1 B-site carrying molecular junctions Molecular Physics 2008; 106: 397- cation ordered domains and Galperin M, Ratner M A and Nitzan 404 antiphase boundaries in A. J. Chem. Phys. 2009; 130: 144109 Pb(Sc12/Ta12/)O3 ceamics by 90. Cooperative effects in molecular 81. Raman scattering from high-resolution transmission conduction non-equilibrium molecular electron microscopy Landau A, Kronik L and Nitzan A. J. conduction junctions Tai Cheuk W and Lereah Y. Applied Comp. Theor. Nanoscience 2008; 5: Galperin M, Ratner M A and Nitzan Physics Letters 2009; 94: 051908 535-544 A. Nano Lett. 2009; 9: 758-762

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91. Electromechanical properties 99. Polaronic Molecular transistors 107. The Regulative Role of Neurite of suspended Graphene Mentovich E, Belgorodsky B, Gozin Mechanical Tension in Network Nanoribbons M and Richter S. Adv. Mat. Accepted Development Hod O and Scuseria G E. Nano for publication (after minor Anava S, Greenbaum A, Jacob E Letters. 2009; 9: 2619-2622 revisions) B, Hanein Y, Ayali A. Biophysical Journal 2009; 96:1661-1670 92. Classical to quantum 100. Controlled patterning of peptide transition of a driven nonlinear nanotubes and nanospheres 108. Integration of suspended carbon nanomechanical resonator using inkjet printing technology nanotubes into micro-fabricated Katz I, Lifshitz R, Retzker A and Adler-Abramovich L. Gazit E. J. Pep. devices Straub R. New J. Phys. 2008; 10: Sci. 2008; 14: 217-223 Karp G A, Ya’akobovitz A, David-Pur 125023 M, Ioffe Z, Cheshnovsky O, Krylov 101. Patterned arrays of ordered S and Hanein Y. J. Micromech. 93. Pattern selection in peptide nanostructures Microeng. 2009; 19: 085021 parametrically-driven arrays of Adler-Abramovich L, Aronov D, nonlinear resonators Rosenman G, Gazit E. J. Nanosci. 109. Investigation of the Dynamic Kenig E, Lifshitz R and Cross M C. Nanotechnol. 2009; 9: 1701-1708 Behavior of Bridged Nanotube Phys. Rev. E 2009; 79: 026203 Resonators by Dissipative 102. Design of metal binding sites Particle Dynamics Simulation 94. Intrinsic localized modes in onto self-assembling peptide Liba O, Hanein Y, Kauzlari´c parametrically-driven arrays of fibril scaffolds D, Greiner A, Korvink J G. nonlinear resonators Kasotakis E, Mossou E, Adler- International Journal for Multiscale Kenig E, Malomed B A, Cross M C Abramovich L, Forsyth T, Gazit E, Computational Engineering 2008; and Lifshitz R. Phys. Rev. E 2009; 80: Mitraki A. Biopolymers. 2009; 92: 6: 549-562 046202 164-172 110. Carbon nanotube electrodes for 95. Nanotechnology and 103. Self-assembly of phenylalanine effective interfacing with retinal Quasicrystals: From self assembly oligopeptides: Insights from tissue to photonic applications experiments and molecular Shoval A, Adams C, David-Pur M, Lifshitz R. In Silicon Versus Carbon dynamics simulations in implicit Shein M, Hanein Y, Sernagor E. (NATO Science for Peace and solvent Frontiers in Neuroengineering 2009; Security Series B: Physics and Tamamis P, Adler-Abramovich L, 2: 4 Biophysics), Eds. Y Magarshak, Reches M, Marshall K, Sikorski S Kozyrev and A K. Vaseashta. P, Serpell L, Gazit E, Archontis G. 111. One-to-one neuron–electrode Springer, Dordrecht, 2009; 119-136 Biophys. J. 2009; 96: 5020-9 interfacing Greenbaum A, Anava S, Ayali A, 96. Asymmetric field dependence of 104. Self-assembled Bio-Inspired Shein M, David-Pur M, Ben Jacob E, magnetoresistance in magnetic Quantum Dots: Optical Hanein Y. Journal of Neuroscience films Properties Methods 2009; 182: 219-224 Segal A, Shaya O, Karpovski M and Amdursky N, Molotskii M, Gazit E Gerber A. Phys. Rev. B 2009; 79: and Rosenman G. App. Phys. Lett. 112. Process entanglement as a 144434 2009; 94: 261907 neuronalanchorage mechanism to rough surfaces 97. Magnetization driven metal – 105. Rasosomes spread Ras signals Sorkin R, Greenbaum A, David-Pur insulator transition in strongly from plasma membrane M, Anava S, Ayali A, Ben Jacob E, disordered Ge:Mn magnetic ‘hotspots’ Hanein Y. Nanotechnology 2009; 20: semiconductors Kofer-Geles M, Gottfried I, Haklai R, 015101 Riss O, Gerber A, Korenblit I Ya, Elad-Zefadia G, Kloog Y, Ashery U. Suslov A, Passacantando M and Biochim. Biophys. Acta. Mol. Cell 113. Single superconducting energy Ottaviano L. Phys. Rev. B 2009; 79: Res. 2009; 1793: 1691-702 scale in electron-doped cuprate 241202 superconductor Pr2-xCexCuO4- 106. Engineered neuronal circuits Δi 98. Large-scale fabrication of shaped and interfaced with Diamant H, Greene R L, Dagan Y. 4-nm-channel vertical -proteins carbon nanotube microelectrode Phys. Rev. B 2009; 80: 012508 ambipolar transistor arrays Mentovich E, Belgorodsky B, Khalifa Shein M, Greenbaum A, Gabay T, I, Richter S. Nano Lett. 2009; 9: 1296- Sorkin R, David-Pur M, Ben Jacob 1300 E, Hanein Y. Biomed Microdevices 2009; 11: 495-501

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114. The magnetic contribution to the 121. Detection of non-uniform 130. Detection of Heating in Current specific heat of Pb1−xGdxTe doping distribution along Silicon Carrying Molecular Junctions by Łusakowski A, Górska M, Anderson nanowires using Kelvin Probe Raman Scattering J R, Dagan Y and Gołacki Z. J. Phys.: Force Microscopy and Scanning Ioffe Z, Shamai T, Ophir A, Noy G, Condens. Matter 2009; 21: 265802 Photocurrent Microscopy Yutsis I, Kfir K, Cheshnovsky O, Selzer Koren E, Berkovich N, Allen J E, Y. Nature Nanotechnology 2008; 115. Electrical Depth Profiling in Thin Lauhon L, Rosenwaks Y. Appl. Phys. 3: 727 SiON Layers Lett. 2009; 95: 92105-7 Rozenblat A, Rosenwaks Y, Segev L 131. Fabrication of highly stable and Cohen H. Appl. Phys. Lett. 2009; 122. Electrostatic Properties of Silane configurable metal quantum 94: 1 Monolayers in an Electrolytic point contacts Environment Itach N, Yutsis I, Selzer Y. Nano Lett. 116. Tracing the Mechanism of Halpren E, Khamaisi B, Shaya O, 2008; 8: 3922 Molecular Gated Transistors Shalev G, Doron A, Levy I and Shaya O, Shaked M, Usherenko Y, 132. Measurement of electronic Rosenwaks Y. J. Phys. Chem. C 2009; Halpern E, Doron A, Cohen A, Levy transport through 1G0 gold 113: 16802-6 I and Rosenwaks Y. J. Phys. Chem. C contacts under laser irradiation 2009; 113: 6163-8 123. Two Dimensional Imaging of Ittah N, Noy G, Yutsis I, Selzer Y. Strain and Composition Induced Nano Lett. 2009; 9: 1615 117. Three-Dimensional Atom-Probe Confinement Potential in III-V Tomographic Studies of Nickel 133. In vitro and in vivo evaluation of Quantum Dots Monosilicide/Silicon Interfaces a paclitaxel conjugate with the Shusterman S, Reizman A, Sher A, on a Subnanometer Scale divalent peptide E-[c(RGDfK)2] Paltiel Y, Schwarzman A, Azriel O, Adusumilli P, Murray C E, Lauhon L J, that targets integrin αvβ3 Boag A, Rosenwaks Y, Galindo P L. Seidman N D, Avayu O, Rosenwaks Ryppa C, Mann-Steinberg H, Europhysics Lett; In press Y. ECS Transactions 2009; 19: 303- Biniossek M, Satchi-Fainaro R, 314 124. A unified theory of dipolophoresis Kratz F. International Journal of for nano particles Pharmaceutics 2009; 368: 89-97 118. Tomographic study of atomic- Miloh T. Phys. Fluids 2008; 20: scale redistribution of platinum 134. A novel antitumor prodrug 107105 during the silicidation of Ni platform designed to be cleaved 0.95Pt0.05/Si (100) thin films 125. Nonlinear alternating electric by the endopeptidase legumain Adusumilli Praneet, Lauhon Lincoln field dipolophoresis of spherical Stern L, Perry R, Ofek P, Many J, Seidman David N, Murray Conal nanoparticles A, Shabat D, Satchi-Fainaro R. E, Avayu Ori and Rosenwaks Yossi. Miloh T. Phys. Fluids 2009; 21: Bioconjugate Chemistry 2009; 20: Appl. Phys. Lett. 2009; 94: 113103-5 072002 500-510 119. Hot-Electron Characteristics in 126. Electro-convection about 135. Targeting bone metastases Chemically Resolved Electrical conducting particles with bi-specific anticancer Measurements of Thin Silica and Yariv E, Miloh T. J. Fluid Mech. 2008; and anti-angiogenic polymer- SiON Layers 595: 163-172 alendronate-taxane conjugate Rozenblat A, Rosenwaks Y and Miller K, Erez R, Segal E, Shabat 127. Macro-scale description of Cohen H. Appl. Phys. Lett. 2009; 94: D, Satchi-Fainaro R, Angewandte transient electro-kinetic 213501-3 R. Chemie-International Edition phenomena over polarizable English. 2009; 48: 2949-2954 120. Surface chemical modification dielectric solids induces nanometer scale Yossifon G, Frankel I, Miloh T. J. Fluid 136. Targeting angiogenesis- electron confinement in field Mech. 2009; 620: 241-262 dependent calcified neoplasms effect device using combined polymer 128. Boundary effects on electro- Shalev G, Halpern E, Doron A, therapeutics magneto-phoresis Virobnik U, Cohen A, Sanhedrai Y, Segal E, Pan H Z, Ofek P, Udagawa T, Yariv E, Miloh T. J. Fluid Mech. 2009; Rosenwaks Y and Levy I. J. Chem. Kopeckova P, Kopecek J and Satchi- 622: 195-207 Phys. 2009; 131: 024702-6 Fainaro R. PLoS ONE 2009; 4: e5233 129. Nonlinear electrokinetic phenomena around nearly sharp tips in microflows Eckstein Y, Yossifon G, Seifert A, Miloh T. J. Colloid & Interface Sci. 2009; 338: 243-249

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137. Design and Development 143. Insights into modeling 150. Atomic structure and electrical of polymer conjugates as Streptozotocin-induced diabetes properties of In(Te) nano- anti-angiogenic agents, in ICR mice contacts on CdZnTe(110) by Special Theme issue: Polymer Dekel Y, Glucksam Y, Elron-Gross I scanning probe microscopy Therapeutics: Clinical and Margalit R. Lab Animal 2009; Cohen-Taguri G, Sinkevich O, Applications and Challenges for 38: 55-60 Levinshtein M , Ruzin A, Goldfarb I. Development Adv. Funct. Mater. 2009; In press 144. Control and prevention of Segal E and Satchi-Fainaro R. bacterial infections in burns by 151. Scanning Tunneling Advanced Drug Delivery Reviews. new formulations based on drug/ Spectroscopy study of 2009; 61: 1159-1176 carrier systems Temperature Dependent 138. Polymer Therapeutics: From Glucksam Y, Gross-Elron I, Raskin Magnetization Switching novel concepts to clinical A, Gornbein P, Keller N, Margalit R, Dynamics in Magnetic applications Schumacher I. J Israeli Military Med. Nanoparticle Arrays Miller K and Satchi-Fainaro R. Wiley 2009; 5: 66-70 Tirosh E, Taub N, Majetich S A, Encyclopedia of Chemical Biology, Markovich G. Isr. J. Chem. 2008; 48: 145. A novel Diclofenac-carrier for Ed. N R Civjan, John Wiley & Sons, 81-86 local treatment of Osteoarthritis Inc. 2009; 3: 783-799 applying live-animal MRI 152. Inter-particle Spin Polarized 139. In vitro and in vivo evaluation of Elron-Gross I, Glucksam Y, Biton I E, Tunneling in Arrays of Magnetite doxorubicin conjugates with the Margalit R. J. Cont. Rel. 2009; 135: Nanocrystals divalent peptide E-[c(RGDfK)2] 65-70 Taub N, Tsukernik A, Markovich G. J. that target integrin αvβ3 Mag. Mag. Mater. 2009; 321: 1933- 146. Liposomal dexamethasone- Ryppa C, Mann-Steinberg H, 1938 diclofenac combinations for Fichtner I, Weber H, Satchi- local Osteoarthritis treatment 153. Float and Compress: A Fainaro R, Biniossek M and Kratz F. Elron-Gross I, Glucksam Y, Margalit R. Honeycomb like Array of a Highly Bioconjugate Chemistry 2008; 19: Intl. J. Pharma. 2009; 376: 84-91 Stable Protein Scaffold 1414-22 Heyman A, Medalsy I, Dgany O, 147. Elucidation of architectural 140. TNP-470: The resurrection of Porath D, Markovich G, Shoseyov O. requirements from a spacer the first synthetic angiogenesis Langmuir. 2009; 25: 5226 in supported proline-based inhibitor, In: Angiogenesis: An catalysts of enantioselective 154. Silver nanoparticle–E. coli integrative approach from aldol reaction colloidal interaction in water and science to medicine Goren K, Kehat T, Portnoy M. Adv. effect on E. coli survival Satchi-Fainaro R and Mann- Synth. Catal. 2009; 351: 59-65 Dror-Here A, Mamane H, Belenkova Steinberg H. Editors William Figg T, Markovich G, Adin A. J. Colloid and Judah Folkman, Springer- 148. Cyclic 2:1 and 1:2 aldehyde- Interface Sci.2009; 339: 521-526 Verlag, Heidelberg, Germany. 2008; to-acetone byproduct adducts 35: 387-406 in aldol reaction promoted by 155. Magnetoresistive telegraph supported proline-incorporated noise in Langmuir-Blodgett 141. Enhanced cytotoxicity of a catalysts films of colloidal magnetite polymer-drug conjugate with Tuchman-Shukron L, Kehat T, Portnoy nanocrystals probed by Scanning triple payload of paclitaxel M. Eur. J. Org. Chem. 2009; 992-996 tunneling microscopy Erez R, Segal E, Miller K, Satchi- Tirosh E, Tsukerman B, Taub N, Fainaro R and Shabat D. Bioorganic 149. Polymer-supported highly Majetich S A, Markovich G. Phys. and Medicinal Chemistry. 2009; 17: enantioselective catalyst for Rev. B; In press 4327-4335 nitro-Michael addition: tuning through variation of the number 156. Shape and Dimension-Controlled 142. Targeting the folate receptor of H-bond donors and spacer Single-Crystalline Silicon and with polymer therapeutics length SiGe Nanotubes: Towards Gabizon A and Satchi-Fainaro Tuchman-Shukron L and Portnoy M. NanoFluidic FET Devices R. Springer-Verlag, Heidelberg, Adv. Synth. Catal. 2009; 351: 541-546 Ben Ishai M, Patolsky F. J. Am. Germany. 2009; In press Chem. Soc. 2009; 131: 3679-3689 Bioelectrochemistry. 2009; 75: 95–103

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157. The structure of genetically 164. Novel Approach to Space- 171. Spin screening of magnetization modified iron-sulfur cluster F-X in Survivable Polyimides: Liquid due to inverse proximity effect in photosystem I as determined by Phase Deposition of Titania superconducting/ ferromagnetic X-ray absorption spectroscopy Coating on Kapton bilayers Gong X M, Hochman Y, Lev T, Bunker Gouzman I, Gershevitz O, Shelukhin V, Karpovski M, Palevski G, Carmeli C. C. Biochim. Biophy. Grossman E, Eliaz N and Sukenik A, Xia J, Kapitulnik A, Tsukernik A. Acta-Bioener. 2009; 1787: 97-104 C N. In Proc. of the 9th Int. Space Future Trends in Microelectronics: Conf.: Protection of Materials From Nanophotonics to Sensors 158. Spatial analysis of erythrocyte and Structures from the Space and Energy, Ed. S Luryi, J Xu, A membrane fluctuations by digital Environment, AIP (Toronto, Canada, Zaslavski, John Wiley & Sons Inc. holographic microscopy May 19 - 23, 2008), Ames Institute of 2010 Rappaz B, Barbul A, Hoffmann A, Physics, NY, USA . 2009; 391-404 Boss D, Korenstein R, Depeursinge 172. Resonant tunneling of electrons C, Magistretti P J, Marquet P. Blood 165. Erosion of POSS-Polyimide Films in quantum wires (Review) Cells Molecules and Diseases 2009; under Hypervelocity Impact Krive I V, Palevski A, Shekhter R 42: 228-232 and Atomic Oxygen: The Role I, Jonson M. Low Temp. Phys. of Mechanical Properties at 2010; 36: 119-141 159. Emerging methods and tools for Elevated Temperatures environmental risk assessment, 173. Tuning Spin-Orbit Coupling Verker R, Grossman E and Eliaz N. decision-making, and policy and Superconductivity at the Acta Materialia 2009; 57: 1112-1119 for nanomaterials: summary SrTiO3/LaAlO3 Interface: A of NATO Advanced Research 166. Corrosion Behavior of Magnetotransport Study Workshop Composition Modulated Ben Shalom M, Sachs M, Linkov I, Steevens J, Adlakha- Multilayer Zn-Co Electrodeposits Rakhmilevitch D, Palevski A and Hutcheon G, Korenstein R. J. Produced Using a Single-Bath Dagan Y. Phys. Rev. Lett. 2010; 104: Nanoparticle Res. 2009; 11: 513-527 Technique 126802 Thangaraj V, Eliaz N and Hegde A C. 160. Human health riskd of 174. Bioinspired peptide nanotubes: Journal of Applied Electrochemistry engineered nanomaterials Deposition technology and 2009; 39: 339-345 Elder A, Lynch I, Grieger K, physical properties Korenstein R. Nanomaterials: 167. Synthesis and AFM Shklovsky J, Beker P, Amdursky N, Risks and Benefits, Nato Science characterization of poly(dG)- Gazit E and Rosenman G. Materials for Peace and Security Series – C: poly(dC)-gold nanoparticle Science and Engineering B 2010; Environmental Security (Edit. conjugates Bioconjug 169: 62–66 Igor Linkov and Jeffery Steevens) Zikich D, Borovok N, Molotsky T, 175. Transparent metal nanowire thin Springer Kotlyar A. Chem. 2010; 21: 544-547 films prepared in mesostructured 161. Electrocrystallization of 168. Specific high-affinity binding of templates Hydroxyapatite and its Thiazole Orange to Triplex and Azulai D, Belenkova T, Gilon H, Dependence on Solution G-quadruplex DNA Barkay Z, Markovich G. Nano Lett. Conditions Lubitz I, Zikich D, Kotlyar A. 2009; 9: 4246-4249 Eliaz N and Sridhar T M. Crystal Biochemistry 2010; 49: 3567-3574 176. Control of biofilm formation in Growth & Design 2008; 8: 3965-3977 169. Synthesis of chiral silver clusters water using molecularly capped 162. Electrocrystallization of Calcium on a DNA template silver nanoparticles Phosphates Molotsky T, Tamarin T, Ben Moshe Dror-Ehre A, Adin A, Markovich G, Eliaz N. Israel Journal of Chemistry A, Markovich G, Kotlyar A B. J. Phys. Mamane H. Water Res. 2010; 44: 2008; 48: 159-168. Chem. 2010; edited and published 2601-2609 online ahead of print - http://pubs. 163. Electrochemical Processes 177. Ferroelectric and related acs.org/doi/abs/10.1021/jp911968x of Nucleation and Growth of phenomena in biological and Calcium Phosphate on Titanium 170. Anisotropic magnetotransport at bioinspired nanostructures Supported by Real-Time the SrTiO3/LaAlO3 interface Amdursky N, Beker P, Shklovsky Quartz Crystal Microbalance Ben Shalom M, Tai C W, Lereah Y, J, Gazit E and Rosenman G. Measurements and XPS Analysis Sachs M, Levy E, Rakhmilevitch D, Ferroelectrics 2010; 399: 107 Eliaz N, Kopelovitch W, Burstein L, Palevski A and Dagan Y. Phys. Rev. B Kobayashi E and Hanawa T. Journal 2009; 80: 140403 of Biomedical Materials Research: Part A 2009; 89: 270-280

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178. Bioinspired Peptide Nanotubes 187. Correlated dynamics of 195. Whole Cell Sensing Systems I: as Supercapacitor Electrodes inclusions in a supported Reporter Cells and Devices Beker P, Koren I, Amdursky N, membrane Ron E & Rishpon J. Electrochemical Gazit E and Rosenman G. Journal Oppenheimer N and Diamant H, Cell-Based Sensors 2010; 117: 77-84 of Materials Science 2009; DOI Phys. Rev. E 2010; 82: 041912 196. Carbon nanotubes based 10.1007/s10853-010-4624-z 188. Nanoscale displacement electrochemical biosensor for 179. Bioinspired Supercapacitor measurement of electrostatically detection of formaldehyde Electrodes with Peptide actuated Micro-devices using released from a cancer cell line Nanotubes optical microscopy and digital treated with formaldehyde- Beker P and Rosenman G. J. of image correlation releasing anticancer prodrugs Material Research 2010 Ya›akobovitz Assaf, Krylov Slava, Bareket L, Rephaeli A, Berkovitch Hanein Yael. Elsevier, Sensors and G, Nudelman A & Rishpon J. 180. Quantum Confinement in Self- Actuators A Physical 2010 Bioelectrochemistry 2010; 77: 94-99 Assembled Bio-Inspired Peptide Hydrogels 189. Carbon nanotube integration 197. Characterization of Peptide- Amdursky N, Gazit E and Rosenman into MEMS devices Nanostructure-Modified G. Advanced Materials 2010; 22: Hanein Yael. Physica Status Solida Electrodes and Their Application 2311 2010 for Ultrasensitive Environmental Monitoring 181. Elementary building blocks 190. Dynamic single-cell imaging of Adler-Abramovich L, Badihi- of self-assembled peptide direct reprogramming reveals an Mossberg M, Gazit E & Rishpon J. nanotubes early specifying event Small 2010; 6: 825-83 Amdursky N, Gazit E, Molotskii M Smith Z D, Nachman I, Regev A & and Rosenman G. J. of Amer. Chem. Meissner A. Nature Biotechnol 2010; 198. Band splitting and modal Soc. 2010 28: 521-6 dispersion induced by symmetry breaking in coupled-resonator 182. Broad Band Enhancement of 191. Self-organizational tendencies of slowlight waveguide structures Light Absorption in Photosystem heteroepitaxial transition-metal Scheuer J and Shtaif M. Opt. Express I by Metal Nanoparticle Antennas silicide nanoislands 2010; 18: 1762 Carmeli I, Lieberman I, Kraversky L, Goldfarb I, Roizin E, Manor S, Fan Z Y, Govorov A O, Markovich G, Levinshtein M. Mat. Sci. Semicon. 199. Noise in the wire: the real Richter S. Nano Lett. 2010; 10: 2069- Proc. 2009; 12: 6 impact of wire resistance for 2074 the Johnson (-like) noise based 192. Atomic structure and electrical secure communicator 183. Probing magnetization properties of In(Te) nanocontacts Kish L B, Scheuer J. Phys. Lett. A dynamics of strongly interacting on CdZnTe(110) by scanning 2010; 374: 2140 magnetic nanoparticles through probe microscopy magnetoresistive current noise Cohen-Taguri G, Sinkevich O, 200. Photoconductance and measurements Levinshtein M, Ruzin A, Goldfarb I, inverse photoconductance in Taub N, Markovich G. J. Phys. D: Adv. Funct. Mater. 2010; 20: 215 films of functionalized metal Appl. Phys. 2010; Accepted nanoparticles 193. Evidence of electronic growth Nakanishi H, Bishop K J M, 184. Localized Rayleigh instability in in titanium and cobalt silicide Kowalczyk B, Nitzan A, Weiss E A, evaporation fronts islands Tretiakov K V, Apodaca M M, Klajn Diamant H and Agam O. Phys. Rev. Manor S, Tripathi J K, Goldfarb I, R, Stoddart J F and Grzybowski B A. Lett. 2010; 104: 047801 Mater J. Sci. 2010, published online: Nature 2009; 460: 371-375 DOI 10.1007/s10853-010-4393-8 185. Long-range dynamic correlations 201. Nonlinear hopping transport in in confined suspensions 194. Optical and Electrical Interfacing ring systems and open channels Frydel D and Diamant H. Phys. Rev. Technologies for Living Cell Bio- Einax M, Körner M, Maass P and Lett. 2010; 104: 248302 Chips Nitzan A. Phys. Chem. Chem. Phys. Shacham-Diamand Y, Belkin 186. Hydrodynamic interactions in 2010; 12: 645-654 S, Rishpon J et al. Current ribbon channels: from quasi- Pharmaceutical Biotechnology one-dimensional to quasi-two- 2010; 11: 376-383 dimensional behavior Novikov S, Rice S A, Cui B, Diamant H, Lin B, Phys. Rev. E 2010; 82: 031403

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202. Coherent charge transport 211. POSS-Polyimide Nanocomposite 217. Novel fibrillar insulin through molecular wires: Exciton Structure and its Effect of formulations for oral blocking and current from Mechanical Properties administration: Formulation and electronic excitations in the wire Verker R, Grossman E, Gouzman I in vivo studies in diabetic mice Li G, Fainberg B D, Nitzan A, Kohler and Eliaz N. The 14th Israel Mater. Dekel Y, Glucksam Y, Margalit R. J. S and Hänggi P. Phys. Rev. B 2010; Eng. Conf. — IMEC-14, Tel-Aviv Cont. Rel. 2010; 143: 128-135 81: 165310 University, Israel, December 13-14, 218. Paclitaxel-clusters coated with 2009 203. Steady-state theory of current hyaluronan as selective tumor- transfer 212. Thin Film Oxide Barrier Layers: targeted nanovectors Ben Moshe V, Nitzan A, Skourtis S Protection of Kapton from Space Rivkin I, Cohen K, Koffler J, S and Beratan D. J. Phys. Chem. C Environment by Liquid Phase Melikhov D, Peer D and Margalit R. 2010; 114: 8005–8013 Deposition of Titanium Oxide Biomaterials 2010; 31: 7106-7114 Gouzman I, Gershevitz O, Grossman 204. Steady state current transfer and 219. Novel steroid carbamates E, Eliaz N and Sukenik C N. ACS scattering theory reverse multidrug-resistance Applied Materials & Interfaces 2010; Ben-Moshe V, Rai D, Skourtis S S and in cancer therapy and show 2: 1835-43 Nitzan A. J. Chem. Phys 2010; 133: linkage among efficacy, loci of 054105 213. Space-Survivable Polyimides: drug action and P-glycoprotein›s Liquid Phase Deposition of cellular localization 205. Kramers barrier crossing as a Titania Thin Films on Kapton and Argov Mirit, Bod Tal, Batra Satish and cooling machine POSS-Polyimide Margalit Rimona. Eur. J. Pharm. Sci. Schiff P and Nitzan A. Chemical Gouzman I, Verker R, Grossman E, 2010; 41: 53-59 Physics, in press Girshevitz O, Malevsky V, Sukenik C 220. Evaluation of leakage currents 206. Unidirectional hopping transport N and Eliaz N. The 14th Israel Mater. and the gate oxide in vertical of interacting particles on a finite Eng. Conf. — IMEC-14, Tel-Aviv molecular transistors chain University, Israel, December 13-14, Mentovich E and Richter S. Jpn. J. of Einax M, Solomon G, Dieterich W 2009 Appl. Phys. 2010; 49: 01AB04 and Nitzan A. J. Chem. Phys 2010; 214. Space Durable Nanocomposite 133: 054102 221. High-yield fabrication of Films Based on POSS-Polyimide/ molecular vertical junctions 207. Circular Currents in Molecular Multi-Wall Carbon Nanotubes Mentovich E, Rosenberg-Shraga Wires Azulai D, Verker R, Gouzman I, Eliaz N, Kalifa I, Tsukernik A, Hendler N, Rai D, Hod O and Nitzan A. J. Phys. N and Grossman E, The 14th Israel Gozin M and Richter S. J. Nanosci. Chem., in press Mater. Eng. Conf. — IMEC-14, Tel- Nanotec; In press Aviv University, Israel, December 208. Molecular conduction junctions: 13-14, 2009 222. Peptide-based Spherulitic Films- Intermolecular effects formation and properties Landau A, Kronik L and Nitzan A. In 215. Nanoparticle Plasma Ejected Sidelman N, Rosenberg Y and Perspectives of Mesoscopic Physics, Directly from Solid Copper by Richter S . J.Coloid. Interf. Sci. 2010; (World Scientific, Singapore, 2010), Localized Microwaves 387-391 CB28 Jerby E, Golts A, Shamir Y, Wonde S, Mitchell J B A, LeGarrec J L, 223. Nanometer-Sized Active- 209. Chiral control of current transfer Narayanan T, Sztucki M, Ashkenazi Channel Molecular Quantum-Dot in molecules D, Barkay Z and Eliaz N, Applied Transistor Ben-Moshe V, Beratan D N, Nitzan Physics Letters 2009; 95: 191501-1-3 Mentovich E, Belgorodsky B, Gozin A and Skourtis S S. In Perspectives M and Richter S. Adv. Mater. 2010; of Mesoscopic Physics, (World 216. Material Processing by Localized 22: 1-5 (Including cover page) Scientific, Singapore, 2010), CB29 Microwaves Jerby E, Meir Y, Golts A, Shamir Y, 224. Polarizability of DNA Block 210. TriSilanolPhenyl POSS-Polyimide Wonde S, Mitchell J B A, KeGarrec Copolymer Nanoparticles Nanocomposites: Structure- J L, Narayanan T, Sztucki M, Eliaz N, Observed by Electrostatic Force Properties Relationship Ashkenazi D and Barkay Z. The 14th Microscopy Verker R, Grossman E, Gouzman I Israel Mater. Eng. Conf. — IMEC-14, Sowann M, Faroum M, Mentovich and Eliaz N. Composites Science Tel-Aviv University, Israel, December E, Ibrahim I, Alemdaroglu F E, Kwak and Technology 2009; 69: 2178-84 13-14, 2009 M, Richter S, Herrmann. Macromol. Rapid Comm. 2010; 31: 1242-1246 (Including Cover page)

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225. Three Dimensional 232. Measurements of Strains in 239. Transistor Gating by Polar multifunctional molecular Core-Shell Heteroepitaxial Molecular Monolayers circuits Semiconductor Nanowires Shaya O, Einati H, Fishelson Mentovich E, Kalif I, Shraga N, Lereah Yossi, Larbony–Ben Ishay N, Shacham-Diamand Y and Arvushenko G and Richter S. J.Phys. Moshit, Popovitz-Biro Ronit and Rosenwaks Y. Appl. Phys. Lett 2010; Chem. Lett 2010; 1574–1579 Shtrikman Hadas. The proceeding 97: 053501-3 of ICM 17 (International Conference 226. Plasmon enhancement of the 240. Wettability study using for Microscopy) Rio de Janeiro, Sept photosystem I assisted by metal transmitted electrons in 2010, M1-34 nanoparticle antennas environmental scanning electron Carmeli I, Lieberman I, Kraversky L, 233. Morphological study of soot microscope Govorov A, Markovich G and Richter particles by off-axis electron Barkay Z. APL 2010; 96: 183109 S. Nano. Lett. 2010; 10: 1374-1382 holography 241. Secondary electron doping Tai C W, Pawlyta M and Lereah Y. The 227. Construction and operation of contrast: Theory based on proceeding of ICM 17 (International sub-10 nm vertical molecular scanning electron microscope Conference for Microscopy) Rio de transistors and Kelvin probe force Janeiro, Sept 2010, M2-22 Mentovich E and Richter microscopy measurements S. Proceedeings of the 3rd 234. Secondary electron doping Volotsenko I, Molotskii M, Barkay Z, International Nanoelectronics contrast: Theory based on Marczewski J, Grabiec P, Jaroszewicz Conference (INEC) 2010; 646-647 HRSEM and KPFM Measurements B, Meshulam G, Grunbaum E, Volotsenko I, Molotskii M, Barkay Rosenwaks Y. JAP 2010; 107: 014510 228. Resistivity at low temperatures Z, Marczewski J, Grabiec P, in electron-doped cuprate 242. Study of fracture evolution in Jaroszewicz B, Meshulam G, superconductors copper sheets by in situ tensile Grunbaum E and Rosenwaks Y. J. Finkelman S, Sachs M, Droulers G, test and EBSD analysis Appl. Phys. 2010; 107: 014510-7 Butch N P, Paglione J, Bach P, Greene Ifergane S, Barkay Z, Beeri O and R L and Dagan Y Phys. Rev. B 2010; 235. Measuring the active dopant Eliaz N. J. Mat. Sci. 2010; 45: 6345 82: 094508 distribution and diffusion 243. Cerenkov-type second-harmonic constant in Silicon nanowires 229. Femtosecond Response of generation in two-dimensional Koren E, Berkovich N and Quasiparticles and Phonons in nonlinear photonic structures Rosenwaks Y. Nanoletters 2010; 10: Superconducting YBa Cu O Saltiel S M, Sheng Y, Voloch-Bloch 2 3 7-δ 1163-1167 Studied by Wideband Terahertz N, Neshev D N, Krolikowski1 W, Arie Spectroscopy 236. Self-assembeled monolayers on A, Koynov K and Kivshar Y S. IEEE Pashkin A, Porer M, Beyer M, Kim K molecular gated transistors Journal of Quantum Electronics W, Dubroka A, Bernhard C, Yao X, Shaya O, Halpren E, Khamaisi B, 2009; 45: 1465-1472 Dagan Y, Hackl R, Erb A, Demsar J, Shaked M, Usherenko Y, Shalev G, 244. Control of Free Space Huber R and Leitenstorfer A. Phys. Doron A, Levy I and Rosenwaks Y. Propagation of Airy Beams Rev. Lett. 2010; 105: 067001 Appl. Surf. Sci. 2010; 256: 5789-95 generated by Quadratic 230. Size effects on melting and 237. Response to comment on “Direct Nonlinear Photonic Crystals wetting in the Ga–Pb nano-alloy measurement of minority Dolev Ido, Ellenbogen Tal, Voloch- Allione M, Kofman R, Celestini F and carriers diffusion length using Bloch Noa and Arie Ady. Applied Lereah Y. The European Physical Kelvin probe force microscopy” Physics Letters 2009; 95: 201112 Journal D 2009; 52: 207 Shikler R and Rosenwaks Y. Appl. 245. Quasi-phase-matched Phys. Let. 2010; 96: 216102 231. Correlation of Quasi-Liquid State concurrent nonlinearities in in Nano-Particles with Surface 238. Electrostatic effects of real periodically poled KTiOPO4 for Diffusion (non-ideal) polar self-assembled quantum computing over the Jarby S, Marchak D and Lereah monolayers optical frequency comb Y. The proceeding of ICM 17 Shaya O, Amit I and Rosenwaks Y. Pysher Matthew, Bahabad Alon, (International Conference for Applied Materials & Interfaces. Peng Peng, Arie Ady and Pfister Microscopy) Rio de Janeiro, Sept Olivier. Optics Letters 2010; 35: 565- 2010, M1-51 567

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246. Nonlinear diffraction from a 254. Omni-directional phase 261. Non-thermal magnetization virtual beam matching of arbitrary processes reversal assisted by unpolarized Saltiel S M, Neshev D N, by radial quasiperiodic nonlinear current Krolikowski1 W, Voloch-Bloch N, Arie photonic crystal Riss O, Gerber A, Korenblit I Y, A, Bang O and Kivshar Y S. Physical Voloch-Bloch Noa, Davidovich Karpovsky M, Hacohen-Gourgy S, Review Letters 2010; 104: 083902 Tomer, Ellenbogen Tal, Ganany- Tsukernik A, Tuaillon-Combes J, Padowicz Ayelet and Arie Ady. Melinon P and Perez A. Phys. Rev. B 247. Magnetic Modulation Biosensing Optics Letters 2010; 35: 2499-2501 2010; 82: 144417 for Rapid and Homogeneous Detection of Biological Targets at 255. Rapid Homogeneous Detection 262. Photoelectric Junctions between Low Concentrations of Biological Assays Using GaAs and Photosynthetic Danielli A, Porat N, Ehrilch M and Magnetic Modulation Biosensing Reaction Center Protein Arie A. Current Pharmaceutical System Frolov L, Rosenwaks Y, Richter S, Biotechnology 2010; 11: 128-137 Danielli A, Porat N, Ehrilch M Carmeli C and Carmeli I. J. Phys. and Arie A. Journal of Visualized Chem. C. 2008; 112: 13426-13430 248. Periodic, quasi-periodic, and Experiments 2010; 40 http://www. random quadratic nonlinear 263. The Structure of Ggenetocally jove.com/index/details.stp?id=1935, photonic crystals Modified Iron-Sulfur Cluster F IN doi: 10.3791/1935 X Arie Ady and Voloch Noa. Laser and Photosystem I As Determined By Photonics Reviews 2010; 4: 355–373 256. Three dimensional ferroelectric X-Ray Absorption Spectroscopy domain visualization by Gong Xiao-Min, Hochman 249. Simultaneous parametric Cerenkov-type second harmonic Yehoshua, Lev Tal, Bunker Grant and oscillation and signal-to-idler generation Carmeli Chanoch. Biochim. Biophys. conversion for efficient down- Sheng Y, Best A, Butt H J, Krolikowski Acta 2009; 1787: 97–104 conversion W, Arie A and Koynov K. Optics Porat Gil, Gayer Ofer and Arie Ady. 264. Picosecond Electron Transfer Express 2010; 18: 16539-16545 Optics Letters 2010; 35: 1401-1403 From Photosysnthetic Reaction 257. Broadband nonlinear frequency Center Protein to GaAs 250. Cerenkov-type second harmonic conversion Sepunaru L, Tsimberov I, Forolov L, generation with fundamental Suchowski Haim, Bruner Barry D, Carmeli C, Carmeli I and Rosenwaks beams of different polarizations Arie Ady and Silberberg Yaron. Y, Nano Lett. 2009; 9: 2751-2755 Sheng Y, Saltiel S M, Krolikowski Optics and Photonics News 2010; W, Arie A, Koynov K and Kivshar Y. 265. Theoretical examination of 21: 36-41 Optics Letters 2010; 35: 1317-1319 aggregation effect on the 258. Three-wave mixing of Airy beams dielectric characteristics of 251. Tunable upconverted optical in quadratic nonlinear photonic spherical cellular suspension parametric oscillator with crystal Ron A, Fishelson N, Croitoriu N, intracavity adiabatic sum- Dolev Ido and Arie Ady. Applied Benayahu D, Shacham-Diamand Y. frequency generation Physics Letters 2010; 97: 171102 Biophys. Chem 2009; 140: 39-50 Porat Gil, Suchowski Haim, Silberberg Yaron and Arie Ady. 259. Reversal of the Extraordinary 266. Dielectric dispersion of Optics Letters 2010; 35: 1590-1592 Hall Effect polarity in thin Co-Pd suspended cells using 3D multilayers reconstructed morphology 252. Switching the acceleration Rosenblatt D, Karpovski M and model direction of Airy beams by a Gerber A. Appl. Phys. Lett. 2010; 96: Ron A, Singh R R, Fishelson N, nonlinear optical processes 022512 Shur I, Socher R, Croitoriu N, Dolev Ido, Ellenbogen Tal and Arie Benayahu D, Shacham-Diamand Ady. Optics Letters 2010; 35: 1581- 260. Monitoring magnetization Y. Bioelectrochemistry 2009; 75: 1583 reversal and perpendicular 95-103 anisotropy of ferromagnetic 253. Improving the efficiency of an films by the extraordinary optical parametric oscillator by Hall effect and anisotropic tailoring the pump pulse shape magnetoresistance Sacks Zachary, Gayer Ofer, Tal Eran Rosenblatt D, Karpovski M and and Arie Ady. Optics Express 2010; Gerber A. Jour. Appl. Phys. 2010; 18: 12669-12674 108: 043924

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267. The effect of surface 273. Self-assembly of Paclitaxel 280. Adjustment of Protein Crystal treatment on the surface with lipidated hyaluronan acts Porosity for Biotemplating: texture and contact angle of as selective tumor-targeting Chemical and Protein electrochemically deposited nanovehicle with robust anti- Engineering Tools hydroxyapatite coating and on tumor activities Wine Yariv, Cohen-Hadar Noa, its interaction with bone-forming Rivkin I, Koffler J, Cohen K, Lagziel-Simis Shira, Dror Yael, Frolow cells Melichov D, Peer D and Margalit R. and Freeman Amihay AIP Conf. Eliaz N, Shmueli S, Shur I, Benayahu Biomaterials 2010; 31: 7106-7114 Proc. 2010; 1254: 198-203. Porous D, Aronov D, Rosenman G. Acta. Media and its Applications in 274. Systemic siRNA delivery: A Biomater. 2009; 5: 3178-91 Science, Engineering, and Industry: progress report 3rd International Conference; 268. The effect of irregularity Weinstein S and Peer D. doi:10.1063/1.3453810 on the dielectric dispersion Nanotechnology Law and Business characteristics of spherical 2010; 6: 454-466 281. Self-Assembly of Phenylalanine cellular suspension Oligopeptides: Insights from 275. RNAi Nanomedicines: challenges Ron A, Fishelson N, Shur I, Croitoriu Experiments and Simulations and opportunities within the N, Benayahu D, Shacham-Diamand Tamamis P, Adler-Abramovich, L, immune system Y. Colloids Surf B Biointerfaces 2009; Reches M, Marchakk K, Sikorski P, Weinstein S and Peer D. 74: 127-35 Serpell L, Gazit E and Archontis G. Nanotechnology 2010; 21: 232001, Biophys J. 2009; 96 269. Dielectric screening of early 1-13 differentiation patterns in 282. Blue luminescence based on 276. Overcoming RNAi transduction mesenchymal stem cells induced quantum confinement at peptide in leukocytes using targeted and by steroid hormones nanotubes stabilized nanoparticles Ron A, Shur I, Daniel R, Singh Amdursky N, Molotskii M, Aronov Elfakess R and Peer D. IDrugs 2010; R R, Fishelson N, Croitoriu N, D, Adler-Abramovich L, Gazit E and 13: 626-31 Benayahu D, Shachm-Diamand Y. Rosenman G. Nano. Lett. 2009; 9 Bioelectrochemistry 2010;78: 161-72 277. Induction of therapeutic gene 283. Self-Assembled Fmoc-Peptides silencing in leukocyte-implicated 270. RNAi-mediated CCR5 silencing as a Platform for the Formation diseases by targeted and by LFA-1-targeted nanoparticles of Nanostructures and Hydrogels stabilized nanoparticles: an prevents HIV infection in BLT Orbach R, Adler-Abramovich L, overview of RNAi delivery to mice Zigerson S, Mironi-Harpaz I, Seliktar leukocytes Kim S S, Peer D, Kumar P, D and Gazit E. Biomacromolecules Peer D. Journal of Controlled Subramanya S, Wu H, Asthana D, 2009; 10: 2646-2651 Release 2010; In press Habiro K, Yang Y G, Manjunath 284. Self-assembled arrays of peptide N, Shimaoka M and Shankar P. 278. Polysaccharides as building nanotubes by vapour deposition Molecular Therapy 2010; 18: 370- blocks for nanotherapeutics Adler-Abramovich L, Aronov D, 376 Mizrahy S and Peer D. In Handbook Beker P, Yevnin M, Stempler S, of harnessing biomaterials for 271. The systemic toxicity of Buzhansky L, Rosenman G and nanomedicine 2011. Peer D. (Editor). positively charged lipid- Gazit E. Nature Nanotech. 2009; 4: Pan Stanford publishing; In press nanoparticles and the role of 849-854 Toll-like receptor 4 in immune 279. Demonstration of a spaser-based 285. Probing the Inner Cavities of activation nanolaser Hydrogels by Proton Diffusion Ben-Arie N, Kedmi R and Peer D. Noginov M A, Zhu G, Belgrave A M, Amdursky N, Orbach R, Gazit E & Biomaterials 2010; 31: 6867-6875 Bakker R, Shalaev V M, Narimanov Huppert D. J. Phys. Chem. 2009; 45: E E, Stout S, Herz E, Suteewong T 272. Objective Detection of Colitis 19500-19505 and Wiesner U. Nature Letters 2009; by PET Imaging Using a 64Cu- 08318 286. Self-assembled bioinspired Labeled Anti-β7 Integrin quantum dots: Optical properties Antibody Amdursky N, Molotskii M, Gazit E, Dearling J J, Park E J, Voss S, Rosenman G. Appl. Phys lett. 2009; Dunning P, Fahey F, Treves T, 94: 261907 Solapino S, Shimaoka M, Packard A B, and Peer D. Inflammatory Bowel Disease 2010; 16:1458-66

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287. Genetic Engineering of 295. Electrolytes: Single Lithium Ion 303. The Influence of Doping on Biomolecular Scaffolds for the Conducting Polymers the Chemical Composition, Fabrication of Organic and Golodnitsky D. In: J Garche, C Dyer, Morphology and Electrical Metalic Nano-Wires P Moseley, Z Ogumi, D Rand and Properties of Si(1-x)Gex Ostrov N and Gazit E. Angew. Chem. B Scrosati (Editors) Encyclopedia Nanowires Int. Ed. Engl. 2010; 17 of Electrochemical Power Sources Givan U and Patolsky F. J. Phys. 2009; 5: 112–128. Amsterdam: Chem. C 2010; 114: 4331-4335 288. Charachterization if Peptide Elsevier. Nanostructures Modified 304. Electrochemical Synthesis Electrodes and their Application 296. Hydrogen–Bromine Fuel Cells of Morphology-Controlled for Ultra- Sensitive Enviromental Peled E, Blum A and Goor M. Segmented CdSe Nanowires Monitoring Encyclopedia of Electrochemical Shpaisman N, Givan U and Patolsky Adler-Abramovich L, Badihi- Power Sources 2009; 5. Amsterdam: F. ACS Nano. 2010; 4: 1901-1906 Mossberg M, Gazit E, Rishpon J. Elsevier 305. A Route to High-Quality Small 2010; 7: 825-831 297. Shape and Dimension-Controlled Crystalline Coaxial Core/ 289. Strong Piezoelectricity in Single-Crystalline Silicon and Multishell Ge@Si(GeSi)(n) Bioinspired Peptide Nanotubes SiGe Nanotubes: Towards Nano and Si@(GeSi)(n) Nanowire Kholkin A, Amdursky N, Bdikin I, Fluidic FET Devices Heterostructures Gazit E & Rosenman G. ACS Nano. Ben Ishai M and Patolsky F. J .Am Ben Ishai M and Patolsky F. 2010; 2: 610-614 .Chem. Soc. 2009; 131: 3679–3689 Advanced Materials 2010; 8: 902-906 290. Artificial solid-electrolyte 298. Pressure-Modulated Alloy 306. Knocking Down Highly-Ordered

interphase (SEI) for improved Composition in Si(1-x)Gex Large-Scale Nanowire Arrays cycleability and safety of Nanowires Pevzner A, Engel Y, Elnathan R, lithium–ion cells for EV Givan U and Patolsky F. NanoLetters Ducobni T, Ben-Ishai M, Reddy N K, applications 2009; 9: 1775–1779 Shpaisman N, Tsukernik A, Oksman Menkin S, Golodnitsky D, Peled E. M and Patolsky F. NanoLetters 2010; 299. Tube-in-Tube and Wire-in- Electrochemistry Communications 10: 1202-1208 Tube NanoBuilding Blocks: 2009; 11: 1789–1791 Towards the Realization of 307. Heteroepitaxial Si/ZnO 291. High-Power Copper Sulfide Multifunctional Nanoelectronic Hierarchical Nanostructures for Cathodes for Thin-film Devices Future Optoelectronic Devices Microbatteries Ben Ishai M and Patolsky F. Angew. Devika M, Reddy N K, Pevzner A and Mazor H, Golodnitsky D and Peled Chem. Int. Ed. 2009; 46: 8699-8702, Patolsky F. Chem. Phys. Chem. 2010; E Electrochemical and Solid-State Accepted as Hot Paper 11: 809-814 Letters 2009; 12: A232-A235 300. Weak rectifying behaviour of 308. Supersensitive Explosives 292. Electroless Nickel Current p-SnS/n-ITO heterojunctions Detection by NanoNose Arrays Collector for 3d-Microbatteries Reddy D M, Reddy N K, Ramesh Engel Y, Elnathan R, Davidi G, Flexer Ripenbein T, Golodnitsky D, Nathan K, Patolsky F and Gunasekhar K R. E and Patolsky F. Angew. Chem. Int. M, Peled E. Journal of Applied Solid State Electronics 2009; 53: Ed. 2010; 49: 6830-6835. Accepted Electrochemistry 2010; 40: 435–444 630-634 as Hot Paper with Cover Page 293. Stochastic Model of Lithium Ion 301. Nanomaterials for Neural 309. Controlled and Wall-Selective Conduction in Poly(ethylene Interfaces Chemical Alteration of Silicon Oxide Kotov N A, Winter J O, Clements I P, Nanotubes Gitelman L, Averbuch A, Nathan Jan E, Timko B P, Campidelli S, Pathak Ben-Ishai M and Patolsky F. J. Am. M, Schuss Z, Golodnitsky D. J. Appl. S, Mazzatenta A, Lieber C M, Prato M, Chem. Soc. 2010; accepted Phys. 2010; 107: 064318 Bellamkonda R V, Silva G A, Shi Kam 310. Nanotextured Copper Substrates N W, Patolsky F, Ballerini L. Advanced 294. Stochastic Model of Lithium Ion as Highly Effective and Long- Materials 2009; 21: 3970-4004 Conduction in Poly(ethylene) Lasting Fuel Cell Anodes Oxide 302. Temperature dependent Granot E, Filanovsky B, Dirawi R and Gitelman L, Averbuch A, Nathan structural properties of Patolsky F. Angew. Chem. Int. Ed. M, Schuss Z, Golodnitsky D. J. Appl. nanocrystalline SnS structures 2010; Provisionally Accepted for Phys. 2010; 107: 064318 Reddy D M, Reddy N K, Ramesh Publication K, Patolsky F and Gunasekhar K R. Appl. Phys. Lett. 2009; 95: 261907

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311. CdSe-ZnO Hierarchal 318. Some liver functions in the 324. Exact asymptotics for the heterostructures Oriental Hornet (Vespa strongfield macroscopic Devika M, Reddy N K, Pevzner A, orientalis) are performed in the magnetotransport of a Ben-Ishai M and Patolsky F. J. Mater. cuticle: Exposure to UV light composite medium Chem. 2010; In Revision influences these activities Bergman D J and Strelniker Y M. Plotkin M, Volynchik S, Itzhaky D, Phys. Rev B 2010; 82: 174422 312. Amyloid-[beta] as a positive Lis M, Bergman D J and Ishay J S. endogenous regulator of release 325. Controlling the optical spectra of Comparative Biochemistry and probability at hippocampal Gold nano-islands by changing Physiology part A: Molecular & synapses the aspect ratio and the inter- Integrative Physiology 2009; 153: Abramov E, Dolev I, Fogel H, islands distance: Theory and 131-135 Ciccotosto G D, Ruff E and Slutsky I. experiment Nat Neurosci A 2009; 12, 1567-1576 319. Xanthopterin in the Oriental Strelniker Y M, Fleger Y, Hornet (Vespa 3 orientalis): Light Rosenbluh M and Bergman D J. 313. Basal GABA regulates absorptance is increased with Appeared in the SPIE Conference GABA(B)R conformation and maturation of yellow pigment entitled “Plasmonics: Metallic release probability at single granules Nanostructures and their Optical hippocampal synapses Plotkin M, Volynchik S, Ermakov N Properties”, in the SPIE Meeting Laviv T, Riven I, Dolev I, Vertkin I, Y, Benyamini A, Bergman D J and on Optics and Photonics, The San Balana B, Slesinger P A and Slutsky I. Ishay J S. To appear in J. Photochem. Diego Convention Center, San Neuron 2010; 67: 253-267 Photobiol. Diego, CA, 1-5 August 2010 314. Enhancement of Learning and 320. Strong-field magnetotransport in 326. The Oriental hornet Vespa Memory by Elevating Brain a composite electrical conductor: Orientalis (Hymenoptera: Magnesium Exact asymptotic results Vespinae) cuticular yellow Slutsky I, Abumaria N, Wu L J, Bergman D J, Strelniker Y M and stripe as an organic solar cell: a Huang C, Zhang L, Li B, Zhao X, Magier R. Physica B 2010; 405: 3037- hypothesis Govindarajan A, Zhao M G, Zhuo M, 3041 Plotkin M, Volynchik S, Hiller et al. Neuron 2010; 65: 165-177 R, Bergman D J and Ishay J S. 321. Manipulating the transparency 315. Supported N-alkylimidazole- In Photobiology: Principles, and other optical properties of decorated dendrons as Applications and Effects 2009; Lon metamaterials by applying a heterogeneous catalysts for the N. Collignon and Claud B. Normand magnetic field Baylis-Hillman reaction (Editors), Nova Science Publishers, Strelniker Y M and Bergman Goren K and Portnoy M. Chem. Inc. D J, Fleger Y, Rosenbluh M, Commun. 2010; 46: 1965-1967 Voznesenskaya A O, Vinogradov A P 327. Solar Energy Harvesting in the 316. Solid-phase synthesis of uniform and Lagarkov A N. Physica B 2010; Epicuticle of the Oriental Hornet linear oligoethers with repeating 405: 2938–2942 (Vespa orientalis) functional arms as multivalent Plotkin M, Hod I, Zaban A, Boden 322. Numerical and analytic results spacers S A, Bagnall D M, Galushko D and for the macroscopic magneto- Spasser L and Portnoy M. J. Polym. Bergman D J. Naturwissenschaften transport of three-dimensional Sci. Part A: Polym. Chem. 2010; in 2010; 97: 1067-76. periodic composites press Strelniker Y M and Bergman D J. J. 328. A Role for ADP-ribosylation 317. Micromorphology and Magnetism and Magnetic Materials factor 1 in the Regulation if maturation of the yellow 2009; 321: 814-817 hepatitis C virus replication granules in Hornet cuticle Matto Meirav, Sklan Ella, David 323. Peculiarities of Tamm states Plotkin M, Volynchik S, Barkay Z, Naama, Melamed-Book Naomi, formed in degenerate photonic Bergman D J and Ishay J S. Zool. Res. Casanova James E, Glenn Jeffrey band gaps 2009; 30: 65-73 S and Aroeti Benjamin. J. Virology Merzlikin A M, Vinogradov A P, 2010; doi:10.1128/JVI.00753-10 Lagarkov A N, Levy M, Bergman D J and Strelniker Y M. Physica B 2010; 405: 2986–2989

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329. Six RNA viruses and forty- 336. X-ray photoelectron 343. Special Theme issue: Polymer one hosts: viral small RNAs spectroscopy of nano- Therapeutics as novel and modulation of small RNA multilayered Zr-O/Al-O coatings nanomedicines, Editorial- repertoires in vertebrate and deposited by cathodic vacuum Polymer Therapeutics- from invertebrate systems arc plasma bench to bedside Parameswaran P, Sklan E, Wilkins C, Zhitomirsky V N, Kim S K, Burstein L David A and Satchi-Fainaro R. Israel Burgon T, Samuel M A, Lu R, Ansel and Boxman R L. Appl. Surface Sci. Journal of Chemistry 2010; 50: 145- K M, Heissmeyer V, Einav S, Jackson 2010; In press 146 W, Doukas T, Paranjape S, Polacek 337. Real-time monitoring of drug 344. Targeting the folate receptor C, dos Santos F B, Jalili R, Babrzadeh release with liposomes and polymer F, Gharizadeh B, Grimm D, Kay M, Weinstain R, Segal E, Satchi- therapeutics Koike S, Sarnow P, Ronaghi M, Ding Fainaro R and Shabat D. Chemical Gabizon A, Shmeeda H, Baabur H S W, Harris E, Chow M, Diamond M Communications 2010; 46: 553-555 and Satchi-Fainaro R. In Targeted S, Kirkegaard K, Glenn J S, Fire A Z. Drug Strategies for Cancer and PLoS Pathog. 2010; 6: e1000764 338. Development of PEGylated Inflammation, C Leamon and doxorubicin-E-[c(RGDfK) ] 330. Electrostatic Force Microscopy 2 A Jackman (Eds.) 2010; In press. conjugate for integrin-targeted study of Single Au-CdSe Hybrid Springer-Verlag, Heidelberg, cancer therapy Nanodumbbells: Evidence for Germany Polyak D, Ryppa C, Ofek P, Leicha Light Induced Charge Separation K, Many A, Kratz F and Satchi- 345. Ligand-assisted vascular Costi Ronny, Cohen Guy, Salant Asaf, Fainaro R. Polymers for Advanced targeting, In Drug Delivery Rabani Eran and Banin Uri. Nano. Technology 2010; In press Eldar-Boock A, Polyak D and Satchi- Lett. 2009; 9: 2031-2039 Fainaro R. In Oncology - From Basic 339. In Vivo delivery of small 331. Can impact excitation explain Research to Cancer Therapy, F Kratz interfering RNA to tumors efficient carrier multiplication in and P Senter (Eds.) 2010; In press. and their vasculature by novel carbon nanotube photodiodes? Wiley-VCH Verlag GmbH & Co. dendritic nanocarriers Baer Roi and Rabani Eran. Nano Lett. KGaA, Weinheim, Germany Ofek P, Fischer W, Calderon M, 2010; 10: 3277-3282 Haag R and Satchi-Fainaro R. FASEB 346. Recent progress in polymer 332. Lattice gas model for the drying- Journal 2010; 24: 3122-34 therapeutics as nanomedicines mediated self-assembly of Omer L, Baabur H and Satchi- 340. Towards Development of nanorods Fainaro R. In Handbook for Targeted Non-Steroidal Sztrum-Vartash Claudia G and Harnessing biomaterials for Antiandrogen-DOTA-Lantanoid Rabani Eran. J. Phys. Chem. C 2010; Nanomedicine: Preparation, toxicity Metal Complexes for Prostate 114: 11040-11049 and applications, D. Peed (Ed.) 2010; Cancer Diagnostics and Therapy In press. Pan Stanford Publishing, 333. Theory of multiexciton Marom H, Miller K, Bar Y, Tsarfaty Hackensack, NJ, USA generation in semiconductor G, Satchi-Fainaro R and Gozin M. nanocrystals Journal of Medicinal Chemistry 347. Novel Farnesylthiosalicylate (FTS) Rabani Eran and Baer Roi. Chem. 2010; 53, 6316-25 – Eluting Composite Structures Phys. Lett. 2010; 496: 227-235 Kraitzer Amir, Kloog Yoel and 341. Design and Development Zilberman Meital. European Journal 334. Simulating lattice spin models of polymer conjugates as of Pharmaceutical Sciences 2009; on GPUs antiangiogenic agents, 37: 351-362 Levy Tal, Cohen Guy and Rabani Special Theme issue: Polymer Eran. J. Chem. Theory Comput. Therapeutics: Clinical Applications 348. Antibiotic-Eluting Bioresorbable 2010; 6: 3293–3301 and Challenges for Development Composite Fibers for Wound Segal E and Satchi-Fainaro R. Healing Applications: 335. Cathodic arc plasma deposition Advanced Drug Delivery Reviews Microstructure, Drug Delivery of nano-multilayered Zr-O/Al-O 2009; 61: 1159-1176 and Mechanical Properties thin films Elsner Jonathan J and Zilberman Kim Sun Kyu, Le Vinh Van, Boxman 342. Special Theme issue: Polymer Meital. Acta Biomaterialia 2009; 5: R L, Zhitomirsky Z N, Lee Jeong Therapeutics as novel 2872-2883 Yong. Surf. Coat. Technol. 2010; 204: nanomedicines 1697-1701 Ofek P, Miller K, Eldar-Boock A, Polyak D, Segal E and Satchi-Fainaro R. Israel Journal of Chemistry 2010; 50, 185-203

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349. Highly Porous Nano and Micro- 355. Composite alginate hydrogels: 363. Down-Regulating Protein Kinase Structured Films Loaded with An innovative approach for C alpha: Functional Cooperation Bioactive Agents for Biomedical the controlled release of between the Proteasome and the Applications: Structure – Release hydrophobic drugs Endocytic System Profile Effects Josef Elinor, Zilberman Meital Melnikov S and Sagi-Eisenberg R. Rachelson Adi and Zilberman and Bianco-Peled Havazelet. Acta Cell Signal. 2009; 21: 1607-1619 Meital. Advanced Engineering Biomaterialia 2010; In press 364. Activation of mast cells by Materials (Advanced Biomaterials) 356. Vertically stacked molecular trimeric G protein Gi3; Coupling 2009; 11: B122-128 junctions, toward a 3D to A3 adenosine receptor directly 350. Highly Porous Bioresorbable multifunctional molecular circuit and upon T cell contact Scaffolds with Controlled Release comprising proteins and redox Baram D, Dekel O, Mekori Y and of Bioactive Agents for Tissue molecules Sagi-Eisenberg R. J Immunol. 2010; Regeneration Applications Mentovich E D, Kalifa I, Shraga N, 184: 3677-3688 Grinberg Orly, Binderman Itzhak, Avrushchenko G, Gozin M, Richter 365. Theoretical and Experimental Bahar Hila and Zilberman Meital. S. J. Phys. Chem. Lett. 2010; 1 1574- Investigation of Optically Acta Biomaterialia 2010; 6: 1278- 1579 Driven Nanoelectromechanical 1287 357. Mucin Complexes of Oscillators 351. Novel Antibiotic-Eluting Wound Nanomaterials: First Biochemical Ilic B, Krylov S and Craighead H G. Dressings: An In-Vitro Study Encounter Journal of Applied Physics 2010; and Engineering Aspects in the Belgorodsky B, Drug E, Fadeev L, 107: 034311 Dressing›s Design Hendler N, Mentovich E, Gozin M. 366. Real-Time Synchronous Imaging Elsner Jonathan J and Zilberman Small 2010; 6: 262-269 of Electromechanical Resonator Meital. Journal of Tissue Viability 358. Organic Reactions Promoted by Mode and Equilibrium Profiles 2010; 19: 54-66 Mucin Glycoproteins Linzon Y, Krylov S, Ilic B, Southworth 352. Novel Biodegradable Composite Shraga N, Belgorodsky B, Gozin M. D, Barton R, Cipriany B, Cross J, Wound Dressings with J. Am. Chem. Soc. 2009; 131: 12074- Parpia J, Craighead H. Optics Letters Controlled Release of Antibiotics: 12075 2010; 35 Microstructure, Mechanical and 359. Quantifying the Stacking 367. Young’s Modulus and Density Physical Properties Registry Matching in Layered Measurements of Thin Atomic Elsner Jonathan J, Shefy-Peleg Materials Layer Deposited Films using Adaya and Zilberman Meital. Hod O. Israel Journal of Chemistry Resonant Nanomechanics Journal of Biomedical Materials 2010; 50, 506-514. arXiv:1009.5639 Ilic B, Krylov S and Craighead H G. Research Part B: Applied Journal of Applied Physics 2010; Biomaterials 2010; 93: 425-435 360. Stacking and Registry Effects in 108: paper 044317. Published also Layered Materials: The Case of 353. Composite Fiber Structures with in the Virtual Journal of Nanoscale Hexagonal Boron Nitride Antiproliferative Agents Exhibit Science & Technology (a weekly Marom N, Bernstein J, Garel J, Advantageous Drug Delivery and multijournal compilation of the Tkatchenko A, Joselevich E, Kronik Cell Growth Inhibition in-vitro latest research on nanoscale L and Hod O. Phys. Rev. Lett. 2010; Kraitzer Amir, Kloog Yoel, Haklai systems) 2010; 22 105: 046801. arXiv:1002.1728 Roni and Zilberman Meital. Journal 368. Examination of the induced of Pharmaceutical Sciences 2010; 361. Analytic Treatment of the Black- potential gradients across inner accepted Hole Bomb and outer cellular interfaces Hod S and Hod O. Phys. Rev. D 354. In-vitro Microbial Inhibition in a realistic 3D cytoplasmic- (Rapid Communication) 2010; 81: and Cellular Response to Novel embedded mitochondrion model 061502(R). arXiv:0910.0734 Biodegradable Composite Ron A, Fishelson N, Croitoru N, Shur Wound Dressings with 362. Nonlinear dynamics of I, Benayahu D, Shacham-Diamand Controlled Release of Antibiotics nanomechanical resonators Y, J. Electroanal. Chem. 2010; 638: Elsner Jonathan J, Berdicevsky Lifshitz Ron and Cross M 59-69 Israela and Ziloberman Meital. Acta C. In Nonlinear Dynamics of Biomaterialia 2010; In press Nanosystems 2010; Ch. 8. G Radons, B Rumpf and H G Schuster (Eds.) Wiley-VCH, Weinheim.

187 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY PUBLICATIONS

369. Optical modeling of 375. Temperature dependence of 382. Multibond Dynamics of bioluminescence in whole cell buried channel ion sensitive field Nanoscale Friction: The Role of biosensors effect transistors Temperature Ben-Yoav H, Elad T, Shlomovits O, Novitski R, Einati H, Shacham- Barel I, Urbakh M, Jansen L and Belkin S and Shacham-Diamand Y. Diamand Y. J. Appl. Phys. 2009; 106: Schirmeisen A. Phys. Rev. Lett. 2010; Biosensors and Bioelectronics 2009; 094501 104: 066104 24: 1969-1973 376. Interface states formation in 383. Origin of Friction Anisotropy on a 370. Evaluation of chrono- a localized charge trapping Quasicrystal Surface amperometric signal detection nonvolatile memory device Filippov A E, Vanossi A, Urbakh for the analysis of genotoxicity Shapira A, Shur Y, Shacham- M.Phys. Rev. Lett. 2010; 104 by a whole cell biosensor Diamand Y, Shappir A and Eitan 384. The renaissance of friction Buchinger S, Grill P, Morosow V, B. J. Vac. Sci. Technol. B 2009; 27: Urbakh M and Meyer E. Nature Ben-Yoav H, Shacham-Diamand Y, 508-511 Materials 2010; 9: 8-10 Biran A, Pedahzur R, Belkin S and 377. Electrochemical studies of Self Reifferscheid G. Analytica Chimica 385. Electrovariable Nanoplasmonics Assembled Monolayers using Acta 2009; 659: 122-128 and Self-Assembling Smart Impedance spectroscopy Mirrors 371. Time Effects in the Einati H, Mottel A, Inberg A, Flatte M E, Kornyshev A A, Urbakh Electrodeposition of CoPt Shacham-Diamand Y. Electrochim. M. J. Phys. Chem. C 2010; 114: 1735- magnetic Alloys Acta, 2009; 54: 6063-6069 1747 Gileadi E, Berkh O, Shacham- 378. Formation and Characterization Diamand Y, Electrochem. and Solid- 386. Probing static disorder in of Low Resistivity sub -100 nm State Lett. 2009; 12: D53-D56 Arrhenius kinetics by single- Copper Films Deposited by molecule force spectroscopy 372. Metallization Technologies and Electroless on SAM Kuo T L, Garcia-Manyes S, Li J, Barel Strategies for Plastic Based Asher T, Glickman E, Inberg A, I, Lu H, Berne B, Urbakh M, Klafter Biochips, Sensors and Actuators Fishelson N, Shacham-Diamand Y, J, Fernandez J. PNAS 2010; 107: for Health Care and Medical Electrochim. Acta 2009; 54: 6053- 11336-11340 Applications 6057 Shacham-Diamand Y, Krylov 387. Temperature Dependence of 379. Electrical properties of sub- S, Shmilovich T, Ofek Almog R, Friction at the Nanoscale: When 100 nm Cu films deposited Fishelson N, Sverdlov Y, Torchinsky I, the Unexpected Turns Normal by electroless plating on Rosenman G, Inberg A and Berkh O. Barel I, Urbakh M, Jansen L and amino-terminated silicon oxide ECS Transactions 2009; 23: 243-254 Schirmeisen A. Tribology Lett. 2010; activated with Au nano-particles 39: 311-319 373. Direct Biopsy Screening Inberg A, Glickman E, Asher T, of Colorectal Cancer by Fishelson N, Shacham-Diamand 388. Block Copolymers at Nano- Electrochemical Biosensor Y. Surface & Coatings Technology Patterned Surfaces Vernick Sefi, Freeman Amihay, 2009; 204: 520-524 Man X K, Andelman D and Orland H. Rishpon Judith and Shacham- Macromolecules 2010; 43: 7261-7268 380. Electrochemical studies of self- Diamand Yosi. ECS Trans 2009; 19: assembled monolayers using 389. Ionic Effects on the Electric Field 61 impedance spectroscopy Needed to Orient Dielectric 374. Electroless deposition of NiWB Einati H, Mottel A, Inberg A, Lamellae alloy on p-type Si(1 0 0) for NiSi Shacham-Diamand Y. Electrochimica Putzel G G, Andelman D, Tsori Y and contact metallization Acta 2009; 54: 6063-6069 Schick M. J. Chem. Phys. 2010; 132: Duhin A, Sverdlov Y, Feldman Y, 164903.1-10 381. Nanoparticles at electrified Shacham Y. Electrochimica Acta liquid-liquid interfaces: new DOI: 10.1063/1.3383243; [arXiv: 2009; 54: 6036-6041 options for electro-optics Uhttp://arxiv.org/abs/1004.5158U] Flatte M, Kornyshev A A, Urbakh M. Faraday Discussions 2009; 143: 109-115

188 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Patents Accepted

1. System for and method 9. Peptide nanostructures 17. Optical sensor and modulator, of positioning cells and encapsulating a foreign material 7,613,367 determining cellular activity and method of manufacturing Ilan Goldfarb-Engineering, Oren thereof, 7,684,844 same, 238445 Levy-Engineering, Ben Zion Eshel Ben Jacob-Exact Sciences, Ehud Gazit-Life Sciences, Meital Steinberg-Engineering, Amir Boag- Ronen Segev-Exact Sciences, Reches-Life Sciences Engineering, Viacheslav Krylov- Itay Baruchi-Exact Sciences, Engineering Eyal Hulata-Exact Sciences, Yael 10. Magnetic thin film sensor based Hanein-Engineering, Tamir Gabay- on the extraordinary hall effect, 18. Micro-electrochemical energy Engineering, Yoash Shapira 7,463,447 storage cells, RE41578 Alexander Gerber-Exact Sciences Menachem Nathan-Engineering, 2. Human synthetic single-chain Emanuel Peled-Exact Sciences, Dan antibodies directed against the 11. An apparatus for treating an Haronian-Engineering common epitope of mutant p53 individual, 229679 and their uses, 1863846 Yona Keisari Medicine Sackler 19. Displacement sensor based on Beka Solomon-Life Sciences, Sara Faculty, Rafi Korenstein-Medicine- photonic crystal waveguides, Orgad-Life Sciences, Itai Benhar- Faculty, Igor Entin-Medicine Faculty, 7,738,110 Life Sciences, Ronit Rosenfeld-Life Yosef Rosemberg Menachem Nathan-Engineering, Sciences Ben Zion Steinberg-Engineering, 12. Novel fuels/fuels for non-alkaline Oren Levy-Engineering, Amir Boag- 3. Surface plasmon amplification by fuel cells, 1249052 Engineering stimulated emission of radiation, Emanuel Peled-Exact Sciences, 7,569,188 Tair Duvdevani-Exact Sciences, 20. Three-dimensional microbattery, David Jonathan Bergman-Exact Avi Melman-Exact Sciences, Adi 4555378 Sciences, Mark Stockman Aharon-Exact Sciences Menachem Nathan-Engineering, Emanuel Peled-Exact Sciences, 4. Optoelectronic device and 13. Fuel cell with proton conductive Diana Golodnitsky-Exact Sciences, method of fabricating the same, membrane and with improved Ela Strauss-Exact Sciences, Vladimir 7524929 water and fuel management, Yufit-Engineering, Tania Ripenbein- Chanoch Carmeli-Life Sciences, 7,727,663 Engineering, Inna Shechtman, Shachar Richter-Exact Sciences, Emanuel Peled-Exact Sciences, Tair Svetlana Menkin-Exact Sciences Itai Carmeli-Life Sciences, Ludmila Duvdevani-Exact Sciences, Arnon Frolov-Life Sciences Blum-Exact Sciences, Vladimir 21. Planar-resonator based Livshits-Exact Sciences, Adi Aharon- optical chemo-and biosensors, 5. Lipidated glycosaminoglycan Exact Sciences 7,447,391 particles and their use in drug Menachem Nathan-Engineering, and gene delivery for diagnosis 14. Three-dimensional micorbattery, Asher Peled-Engineering, Shlomo and therapy, 7544374, 231126 7,618,748 Ruschin-Engineering, Tali Zohar- Rimona Margalit-Life Sciences, Dan Menachem Nathan-Engineering, Engineering Peer-Life Sciences Emanuel Peled-Exact Sciences, Diana Golodnitsky-Exact Sciences, 22. Displacement sensor based on 6. Peptide comprising less than 10 Ela Strauss-Exact Sciences, Vladimir photonic crystal waveguides, aminoacids and capable of self- Yufit-Engineering, Tania Ripenbein- 7,466,424 aggregating under physiological Engineering, Inna Shechtman, Menachem Nathan-Engineering, conditions, 227987 Svetlana Menkin-Exact Sciences Ben Zion Steinberg-Engineering, Ehud Gazit-Life Sciences] Oren Levy-Engineering, Amir Boag- 15. Fuel cell with proton conducting Engineering 7. Peptide nanostructures membrane, 2,397,536 containing end-capping Emanuel Peled-Exact Sciences, 23. Apparatus and methods modified peptides and methods Tair Duvdevani-Exact Sciences, for optical amplifications in of generating and using the Avi Melman-Exact Sciences, Adi semiconductors, 7,724,425 same, 7,786,086 Aharon-Exact Sciences Shlomo Ruschin-Engineering, Ehud Gazit-Life Sciences, Meital Stanislav Stepanov-Engineering Reches-Life Sciences 16. Ion conductive matrixes and their use, 2,320,696 24. Embeded channels, embedded 8. Peptide nanostructures and Emanuel Peled-Exact Sciences, waveguides and methods of methods of generating and using Tair Duvdevani-Exact Sciences, Avi manufacturing and using the the same, 7491699 Melman-Exact Sciences same, 7,653,281 Ehud Gazit-Life Sciences, Meital Shlomo Ruschin-Engineering, Reches-Life Sciences Stanislav Stepanov-Engineering 25. Novel anti-allergic agents, 1191943 Ronit Sagi-Eisenberg-Medicine- Sackler Faculty, Tamar Raz

189 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Collaborations with Industrial Institutes

Ady Arie Ilan Goldfarb Gil Rosenman 1. ElOp – “Efficient generation of mid- 1. SemiConductor Devices – “Cross- 1. Supercapacitors, Magneton Program infrared light” Sectional Scanning Tunneling supported by Ministry of Israel – 2. VGEN – “Efficient frequency doubling Microscopy of Superlattices” “Development peptide nanotubes- and tripling of fiber lasers” 2. Hewlett-Packard Laboratories. This based new energy storage devices” 3. Raicol – “Development of nonlinear research is to be conducted at HP photonic crystals” Labs (Palo Alto, Ca, USA), in course of a 2010-2011 sabbatical leave Yossi Rosenwaks from TAU – “Materials Science of Memristive Switches” 1. HMI, Germany – “Grain boundaries in Zahava Barkay polycrystalline solar cells” 1. Bypass – “medical devices” 2. Chiba University, Japan – “Grain 2. Medinol – “heart stents” boundaries in Pentacene transistors” 3. Orbotech – “devices also by laser Yael Hanein 3. SCD, Israel – “KPFM of infrared treatments” 1. ElOp – “Development of conductive detectors” 4. Vishay – “small scale capacitors” transparent coating using 5. Soreq NRC, Israel – “Failure analysis microfabrication” of electronic, optical and mechanical 2. RAFAEL – “Sensitivity Enhancement Ronit Satchi-Fainaro devices” of Micro-electromechanical Sensors Using Carbon Nanotubes” 1. María Jesús Vicent, Centro de 3. Nano Retina – “Validation of novel Investigación Príncipe Felipe, retinal implant device prototypes” Medicinal Chemistry Unit, Polymer Ari Barzilai Therapeutics Laboratory, Valencia, 1. Dr. Solomzi Makohiso from Spain AYANDA, Lausanne, Switzerland 2. Felix Kratz, Tumor Biology Center, – “The generation of implanted Gil Markovich Freiburg, Germany microelectrode to enhance optic 1. PV NanoCell, Migdal Ha›Emek, 3. Ruth Lupu, Division of Experimental nerve regeneration following “Metal nanowire films as transparent Pathology and Laboratory Medicine, axotomy” conductors for solar cells” Mayo Clinic, Mayo Medical Laboratories, Rochester, MN, USA Dafna Benayahu Dan Peer 1. EU – FP7, Cooperation 7 – SM-STREP 1. Quark Pharmaceuticals, Ness Ziona, Yosi Shacham-Diamand – “Exploring Cellular Dynamics at Israel – “Novel targeting strategies for 1. GTEC, Austria – “Project rean chip” Nanoscale” sarcomas” 2. ÖSSUR, Iceland – “Project smart Hand” 2. Segev Laboratories, Ness Ziona, Israel – “Nanopolymers for RNAi delivery” Reuven Boxman 3. Scigen, Singapore – “Structural Ella Sklan characterization of nanodiamonds” 1. ISCAR, Ltd., Israel – “Nano-structured 4. Alnylam Pharmaceuticals, Cambridge, 1. Dr. Philppe Hlaphon Alfabio Marseille, Zr-Al-O coatings” MA, USA – “Targeting Mantle cell France 2. EU FP7 NATIOMEM Consortium lymphoma with RNAi-Nanomedicines” (DHI – Denmark, SKJOLSTRUP & 5. Roche, Nutly, NJ, USA – GRONBORG ApS - Denmark, Umgeni “Development of novel nanocarriers Water – South Africa, Kawar Energy against solid tumors” LTD CO LLC – Jordan) – “Nano- 6. GSK, Cambridge, MA, US. – “Evaluation structured TiON Photo-Catalytic of novel therapeutic RNAi in Membranes for Water Treatment” inflammation using nanotechnology”

190 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Collaborations with other Academic Institutes

Ady Arie Dept. of Analytical Biochemistry, Photo-Catalytic Membranes for Water University of Potsdam (UP), Germany; Treatment” 1. Australian National University, Dimiri Papkovski, LUXCEL, Ireland; Australia and Max Planck Institute, Marco Sampietro, Polytechnic Mainz, Germany – “Cerenkov-type University of Milano (PUM), Italy; Ori Cheshnovsky second-harmonic generation in Elisabeth Csöregi, SciTech Link HB two-dimensional nonlinear photonic (STL), Sweden 1. Prof. Yael Hanein, TAU, Prof. Uri structures” Banin and Prof. Shlomo Yitchaik, the 2. Australian National University, Hebrew University of Jerusalem – Australia and Max Planck Institute, Itai Benhar “Artificial Retina” Mainz, Germany – “Three dimensional ferroelectric domain visualization 1. Uri Sivan and Yoram Reiter, Technion, by Cerenkov-type second harmonic Israel Institute of Technology, Haifa, Yoram Dagan generation” Israel – “Antibody-based electronic 1. Prof. R. L. Greene, University of 3. Australian National University, switches” Maryland, USA – “Probing Local and Australia – “Nonlinear diffraction from macroscopic orders in electron- a virtual beam” doped cuprates” 4. University of Virginia, USA – “Quasi- David Bergman 2. Dr. Zaher Salman, PSI, Switzerland phase-matched concurrent 1. Prof. Mark I Stockman, Physics – “Incipient magnetism in SrTiO / nonlinearities in periodically poled 3 Department, Georgia State University, LaAlO ” KTiOPO4 for quantum computing 3 Atlanta, GA, USA – “Electromagnetic 3. Prof. Misha Reznikov, Technion over the optical frequency comb” Properties of Nanosystems in Switzerland – “Incipient magnetism in 5. Weizmann Institute of Science, Coherent, Strong, and Ultrafast Fields” SrTiO /LaAlO ” Rehovot, Israel – “Tunable 3 3 2. Dr. Yakov M Strelniker, Physics 4. University of Maryland, USA – upconverted optical parametric Department and Minerva Center, “Resistivity at low temperatures oscillator with intracavity adiabatic Bar Ilan University, Ramat Gan, in electron-doped cuprate sum-frequency generation”. Israel, Andrey N. Lagarkov and superconductors” 6. Weizmann Institute of Science, Alexei P. Vinogradov of the Institute 5. University of Maryland, USA and Rehovot, Israel – “Broadband for Theoretical and Applied University of Illinois, Urbana, USA nonlinear frequency conversion” Electromagnetics in Moscow, Russia – “Anomalous Enhancement of – “Optics and Magnetooptics of the Superconducting Transition Nanostructures Made of Magnetic Temperature in Electron-Doped Ari Barzilai (Gyrotropic) Anisotropic and Meta- Cuprate Heterostructures” 1. Prof. Anna Mitraki, University of Crete, Materials” 6. University of Konstanz, Germany, Vassilika Vouton, Heraklion, Crete, 3. Dr. Yakov M Strelniker, Physics University of Fribourg, Switzerland, Greece Department and Minerva Center, Shanghai Jiao Tong University, Bar Ilan University, Ramat Gan, Israel Shanghai, China, Walther-Meissner- – “Strong-Field Magneto-Resistance Institut, Garching, Germany and Dafna Benayahu in Disordered Composite Media Jozef Stefan Institute, Ljubljana, and New Types of Percolation Slovenia – “Femtosecond Response 1. European consortium EXCELL, Nano Phenomena” of Quasiparticles and Phonons technology on biological scale in Superconducting YBa2Cu3O7-δ Jenny Emnéus, Dept. of Micro and Studied by Wideband Terahertz Nanotechnology, Danish Technical Reuven Boxman Spectroscopy” University, Denmark; Merab Kokaia, Wallenberg Neurocenter, University 1. The University of Ulsan, Korea – of Lund (ULUND), Sweden; Alberto “Nano-composite and nano-layered Guy Deutscher Martínez Serrano, Center of Molecular coatings of Al-O/Zr-O” Biology “Severo Ochoa”, University 2. Weizmann Institute of Science, 1. Amit Goyal, Oak Ridge National Autonomous of Madrid (UAM), Spain; Rehovot, Israel – “Synthesis of nano- laboratory Erika Kálmán, Hungarian Academy of particles using a pulsed submerged 2. Xavier Obradors, University of Sciences Chemical Research Center discharge” Barcelona (CRC), Hungary; Roberto Raiteri, 3. Universita Degli Studi Dell›aquila, Dept. of Biophysical and Electronic Italy; University of Surrey, UK; Engineering (DIBE), University of Universite Pierre et Marie Curie - Paris Genova, Italy; Ulla Wollenberger, 6, France – “Nano-structured TiON

191 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY COLLABORATIONS

Haim Diamant Israel Institute of Technology, Haifa, 2. Prof. Oren Negev, Ben Gurion Israel University, “Carectization of bio-nano 1. G Haran, Weizmann Institute, 4. Prof. Georgios Archontis, Department materials” Rehovot, Israel. “Protein dynamics in of Physics, University of Cyprus, 3. Prof. Howard L. Weiner, Brigham membranes” Nicosia, Cyprus & Women’s Hospital, Center for 2. TA Witten and KYC Lee, James Franck 5. Prof. Anna Mitraki, Department of Neurologic Diseases, Harvard Institute, University of Chicago, Materials Science and Technology, University, Boston, MA, USA USA Supported by the US–Israel University of Crete, Vassilika Vouton, 4. Prof. Sanjiv Sam Gambhir, Molecular Binational Science Foundation – Heraklion, Crete, Greece Imaging Center, Department of “Microrheology and instability of 6. Prof. Trevor Forsyth, EPSAM/ISTM, Radiology, Stanford University, compressed surfactant monolayers” Keele University, United Kingdom, Stanford, California, USA 3. A Schmidt, University of Köln, M Partnership for Structural Biology, 5. Dr. Hagai Cohen, Weizmann Institute Gottlieb, Ben-Gurion University, Institut Laue Langevin, Grenoble of Science, Rehovot, Israel Be›er Sheva, Israel and B Feringa, Cedex9, France Rijksuniversiteit, Groningen. 7. Prof. Louise Serpell, Department of Supported by NanoScience Europe – Biochemistry, School of Life Sciences, Yael Hanein “Directed and autonomous motion of University of Sussex, Falmer, Brighton, hybrid magnetic nano-objects” United Kingdom 1. Andreas Greiner & Jan G Korvink, 4. B Lin and SA Rice, Department of Laboratory for Microsystems Chemistry, University of Chicago, USA Simulation, Department of – “Dynamics of confined suspensions” Alexander Gerber Microsystems Engineering, University 5. O Agam, the Hebrew University of of Freiburg, Germany Jerusalem, Jerusalem, Israel – “Curved 1. University of L’Aquilla, Italy – 2. Dr. Evelyne Sernagor, Institute of liquid strips” “Magnetic semiconductors” Neuroscience, Medical School, 2. Université Claude Bernard, Lyon 1, Newcastle University, Newcastle, UK France 3. Prof. Uri Banin, the Hebrew University Noam Eliaz 3. University of Lyon, France of Jerusalem, Jerusalem, Israel 4. University of York, Great Britain 4. Prof. Shlomo Yitchaik, the Hebrew 1. I Gouzman and E Grossman, Bar Ilan University of Jerusalem, Jerusalem, University – “Thin Film Oxide Barrier Israel Layers” Ilan Goldfarb 1. W D Kaplan, Technion, Israel Institute Oded Hod Amihay Freeman of Technology, Haifa, Israel and E Rabani, TAU – “Pushing the Limits 1. Prof. Leeor Kronik, Weizmann institute 1. Dr. Ayelet Fishman, Biotechnology, of the ‹Bottom-Up› Approach: of Science, Rehovot, Israel – “Real Technion, Israel Institute of Self-Organized Growth of Silicide space and real time modeling of Technology, Haifa, Israel – “Cyt P450 nanostructures on Si Surfaces” electronic transport in molecular metal hybrids for electrobiochemical junctions” production of chemicals” 2. Prof. Ernesto Joselevich, Weizmann Michael Gozin Institute of Science, Rehovot, Israel – “Electromechanical properties of Ehud Gazit 1. Dr. Syed F. Ali, Senior Biomedical boron nitride nanotubes” Research Scientist; Head of 3. Prof. Ron Naaman, Weizmann 1. Prof. Yuri Feldman, the Hebrew Neurochemistry Laboratory, Division Institute of Science, Rehovot, Israel University of Jerusalem, Jerusalem, of Neurotoxicology, National Center – “Electronic properties of organic Israel – “dielectric spectroscopy of for Toxicological Research/FDA, monolayers adsorbed on GaAs” nanotubes” Jefferson, AR; Adjunct Prof., Depts. of 2. Prof. Hanna Dodiuk, Plastics Biochemistry and Molecular Biology, Engineering & Polymers Department, Neurology and Pharmacology & Shenkar College of Engineering Toxicology, University of Arkansas Alexander Kotlyar & Design, Ramat Gan, Israel – for Medical Sciences, Little Rock, AR 1. Prof. Danny Porath, the Hebrew “Reinforcement of epoxy system and Dept. of Pharmacology, Duke University of Jerusalem, Jerusalem, using self assembling peptide University Medical Center, Durham, Israel – “DNA-nanoelectronics” nanostructures as nano-filler” NC 2. Prof. Leonid Gurevich, Aalborg 3. Prof. Dror Seliktar, Faculty of University, Denmark – “Conductivity Biomedical Engineering, Technion, of G4-DNA nanowires”

192 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY COLLABORATIONS

Slava Krylov Gil Markovich Ruth Nussinov 1. Prof. Harold Craighead, Dr. Rob Ilic, 1. Prof. Sara Majetich, Carnegie-Mellon 1. Center for Cancer Research, Cornell University, Ithaca, New York, University, “Strongly Interacting Nanobiology Program, National USA Magnetic Dipole Arrays _ Magnetic Cancer Institute, National Institutes of Phases and Phase Transitions” Health, Frederick, MD, USA 2. Prof. Hennes Lichte, Dresden 2. Laboratory of Computational Biology, Yossi Lereah University, “Exploring nanoscale National Heart, Lung and Blood ferroelectricity in isolated and Institute, National Institutes of Health, 1. Group of Prof. R Kofman, Nice interacting ferroelectric nanocrystals Bethesda, MD, USA University, France – “Quasi-melted using electron holography” state of Nano-particles” 3. Prof. Oded Shoseyov and Dr. Danny 2. Prof. Richard Kofman, University of Porath, the Hebrew University of Alexander Palevski Nice-Antipolis, France – “Size effects Jerusalem, Jerusalem, Israel – “Float on melting and wetting in the Ga–Pb and Compress: A Honeycomb like 1. Prof. A. Kapitulnik, Stanford University, nano-alloy” Array of a Highly Stable Protein School of Medicine, Palo Alto, 3. Group of Prof. H. Lichte from Dresden Scaffold” California, USA – “Proximity effect in University, Germany (EC Grant) 4. Prof. Avner Adin, the Hebrew S/F systems (US-Israel BSF)” – “Electron Holography of Nano- University of Jerusalem, Jerusalem, 2. Dr. Hadas Strikman, Weizmann Particles” Israel; Dr. Hadas Mamane, TAU – Institute of Science, Rehovot, Israel – “Preventing biofilm formation in “Quantum Phase Transitions” filtration membranes using silver Ron Lifshitz nanoparticles” 1. Prof. Michael Cross, the California Dan Peer Institute of Technology, California, 1. Prof. Ronen Alon ,Weizmann USA – “Nonlinear dynamics of Abraham Nitzan Institute, Rehovot, Israel – “Evaluating nanomechanical resonators” 1. Prof. Mark Ratner and Prof. Tamar the affinity upregulation of ICAM-1 2. Dr. Yuriy Tsarin, the Institute Seideman, Molecular electronics using bio-nanotechnology” of Radio Astronomy, National Northwestern University, USA 2. Prof. Jeff Karp, MIT, Cambridge, MA, Academy of Sciences of Ukraine – 2. Prof. Wolfgang Dieterich and Prof. USA – “Targeting Mesenchymal stem “Homoclinic orbits and chaos in a Wolfgang Belzig, University of cells using targeted nanoparticles” pair of parametrically-driven coupled Konstanz, Germany – “Unidirectional 3. Prof. Judy Lieberman; Prof. Alan nonlinear resonators hopping transport of interacting Packard; Prof. Motomu Shimaoka, particles on a finite chain” Harvard University; Medical School, 3. Rigoberto Hernandez, Georgia Boston, MA, USA – “Targeting breast Rimona Margalit Institute of Technology cancer stem cells using RNAi- 4. Spiros Skortis, University Spiros nanomedicines” 1. Prof. Satish Batra, Department 4. Prof. Priti Kumar, Yale, New havean, of Obstetrics and Gynecology, Skortis of Cyprus, Georgia Tech – “Steady state current transfer and CT, USA and Prof. Prema Shankar, University Hospital, Lund, Sweden – Texas Tech, El Paso, TX, USA – “LFA-1 “Novel steroid carbamates reverse scattering theory” 5. Ron Naaman & David Cahen, nanoparticles entrapping CCR5- multidrug-resistance in cancer siRNAs for suppression of HIV therapy and show linkage among Weizmann Institute, Rehovot, Israel 6. Boris Feinberg, Holon Institute of infection” efficacy, loci of drug action and 5. Prof. Derek Dexyhoorn, University P-glycoprotein›s cellular localization” Technology and Peter Hänggi, University of Augsburg, Germany – of Miami, Miami, FL, USA – “LFA- 2. Jonathan Leor, TAU and Ron Apta, 1 targeted nanoparticles as HIV Ben Gurion University of the Negev, “Coherent charge transport through molecular wires: Exciton blocking and microbicide” Be›er Sheva, Israel – “Targeting 6. Prof. Carmelo Carlo-Stella, University inflammation to improve healing, current from electronic excitations in the wire” of Milan, Italy – “Targeting blood repair and regeneration of the cancers using nanotechnology” infracted heart” 7. M. Körner , University of Ilmenau, Germany – “Nonlinear hopping 7. Harvard University, Boston, MA, USA, transport in ring systems and open Yale University, New havean, CT, USA, channels” Texas Tech, El Paso, TX, USA – “RNAi- mediated CCR5 silencing by LFA-1- targeted nanoparticles prevents HIV infection in BLT mice”

193 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY COLLABORATIONS

8. Harvard University, Boston, MA, USA – 3. H Cohen, Weizmann Institute of and Auto mation, Moscow, “Objective Detection of Colitis by PET science, Rehovot, Israel – “Molecular Russia – “Nonlinear optical effects Imaging Using a Cu-Labeled Anti-b7 doping” phenomena in amyloid fibrils and Integrin Antibody” 4. Hagai Cohen, Weizmann Institute peptide nanotubes” of Science, Rehovot – “Chemically 4. University of Nebraska-Lincoln controlled doping of gated molecular – “Ferroelectric phenomena in Emanuel Peled junctions” biological and bioinspired materials” 5. Andreas Herrmann, University 1. W Wieczorek, University of Warsaw of Groningen, Netherlands and 2. B Scrosati, University of Rome Mukhles Sowwan, Alquds University, Yossi Rosenwaks 3. S Greenbaum, Hunter College Palestinian Authority – “Polarizability of DNA Block Copolymer 1. HMI, Germany – “Grain boundaries in Nanoparticles Observed by polycrystalline solar cells” Moshe Portnoy Electrostatic Force Microscopy” 2. Chiba University, Japan and University of Michigan, USA – “Grain 1. Prof. Scott J Miller, Yale University, 6. Sasha Govorov, Ohio State University, USA – “Plasmon enhancement of boundaries in Pentacene transistors” New havean, CT, USA – “Synthesis 3. Soreq research center, Israel – “UHV- and study of organocatalysts the photosystem I assisted by metal nanoparticle antennas” KPFM of Quantum dots and KPFM of tethered to dendronized polymer InSb” support” 7. Chad Mirkin, Notrhwestern University, Chicago, USA 4. SCD, Israel – “KPFM of infrared detectors” 5. D Cahen, Weizmann Institute of Eran Rabani Yael Roichman Science, Rehovot, Israel – “Self- 1. Prof. Uri Banin and Prof. Oded Miloh, assembled monolayers on Si” the Hebrew University of Jerusalem, 1. Dov Levine, Technion, Israel Institute 6. Northwestern University, USA and Jerusalem, Israel – “Self-organization of Technology, Haifa, Israel, David Max Planck, Halle, Germany – “Si of nano-crystals and nano-rods” & G. Grier & Paul Chaikin, Department Nanowires” “Nanoscale particle pollution” of Physics, New York University, 7. Basel University, Switzerland – 2. Prof. Roey Baer, the Hebrew New York, USA – “Faceting and “Reconstruction of KPFM images” University of Jerusalem, Jerusalem, Roughening: The Effects of Disorder Israel – “Multiaxons in half conductor and Quasicrystallinity” nanocrystals” & “Nanotubes” 2. Anne Bernhaim, Ben Gurion Ronit Sagi-Eisenberg 3. Peter Rossky, The center for University, Be›er Sheva, Israel – “Active microheology of actin myosin gels 1. Tohoku University, Aobayama, computational materials science, Aoba-ku, Sendai, Miyagi, Japan – University of Texas, Austin, USA using holographic tweezing and imaging” “Synaptotagmin IX internalizes – “excitons in semiconducting through an Arf6-dependent pathway nanocrystals by electron-phonon 3. Ronen Rapaport, the Hebrew University of Jerusalem, Jerusalem, and upregulates cell surface couplings” expression of β1 integrin” 4. Irene Burghardt and Erick Bittner, Israel and Efrat Lifshitz, Technion, University of Houston, USA – “The Israel Institute of Technology, Haifa, dynamics of excitons in organic light Israel – “Nano-Precision incorporation harvesting materials” of Single and clustered Quantum Ronit Satchi-Fainaro 5. Prof. Louis Bruce & Prof. Tony Hanes, Dots into nano-optical Devices” 1. Jindřich Kopeček, Department of Heads of EFRC Center, Colombia Pharmaceutics and Pharmaceutical University, New York, USA Chemistry, Center for Controlled Gil Rosenman Chemical Delivery, University of Utah, 1. University Aveiro, Portugal – Salt Lake City, Utah, USA Shachar Richter “Piezoelectricity in nanostructured 2. Paolo Caliceti, Department of Pharmaceutical Sciences, Faculty of 1. A Hermann, RUG University, The bioinspired materials” 2. Radboud University, Institute for Pharmacy, University of Padua, Padua, Netherlands and M Sowann, Italy Al-Quds University, Palestinian Molecules and Materials, Nijmegen, the Netherlands – “Physical properties 3. Dr. Maria J. Vicent, CIPF, Valencia, Authority – “hybride-bio-polymeric Spain nanoparticles” of bioinspired materials” 3. Moscow State Institute of 4. Prof. Felix Kratz, Freiburg University, 2. S Govorov, Ohio University, USA – Freiburg, Germany – “Development of “plasmonics” Radioengineering, Electronics PEGylated doxorubicin-E-[c(RGDfK)2]

194 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY COLLABORATIONS

conjugate for integrin-targeted Ella Sklan Inna Slutsky cancer therapy” 5. Prof. Rainer Haag, Organic and 1. Dr. Leslie Lobel, Ben-Gurion 1. Prof. Minke, the Hebrew University of Macromolecular Chemistry, University, Be›er Sheva, Israel Jerusalem, Jerusalem, Israel Department of Chemistry and 2. Dr. Benjanim Aroeti, Institute of Life 2. Prof. Bernhard Bettler, University of Biochemistry Freie Universitaet Berlin, Sciences, the Hebrew University of Bazel, Switzerland Berlin, Germany – “In Vivo delivery of Jerusalem, Jerusalem, Israel 3. Prof. Ciccotosto, the University of small interfering RNA to tumors and 3. Dr. Philppe Hlaphon Alfabio Marseille, Melbourne, Australia – “Amyloid- their vasculature by novel dendritic France [beta] as a positive endogenous nanocarriers” 4. Meirav Matto, Institute of Life regulator of release probability at Sciences, the Hebrew University of hippocampal synapses” Jerusalem, Jerusalem, Israel 4. Prof. Paul Slesinger, Salk Institute, USA Jacob (Koby) Scheuer 5. James E. Casanova, University – “Basal GABA regulates GABA(B)R of Virginia Health System, conformation and release probability 1. E Kapon, EPEL – “Coupled laser arrays” Charlottesville, VA, USA at single hippocampal synapses” 2. University of Aston, UK – “Long laser 6. Jeffrey S. Glenn, Stanford University, 5. Prof. Liu & Prof. Tonegawa, MIT, encrypted communication” School of Medicine, Palo Alto, Cambridge, MA, USA, Prof. Zhuo, California, USA University of Toronto, Canada 7. Parameswaran P, Wilkins C, Burgon – “Enhancement of Learning Yosi Shacham-Diamand T, Samuel MA, Lu R, Ansel KM, and Memory by Elevating Brain Heissmeyer V, Einav S, Jackson W, Magnesium” 1. Division of Qualitative Hydrology, Doukas T, Paranjape S, Polacek C, German Federal Institute of dos Santos FB, Jalili R, Babrzadeh Hydrology (BfG), Koblenz, Germany F, Gharizadeh B, Grimm D, Kay M, 2. Institute of Life Sciences, the Hebrew Meital Zilberman Koike S, Sarnow P, Ronaghi M, Ding University of Jerusalem, Jerusalem, SW, Harris E, Chow M, Diamond 1. Prof. Israela Berdicevsky, Faculty of Israel MS, Kirkegaard K, Glenn JS and Fire Medicine, Technion, Israel Institute of 3. Department of Electrical AZ, Stanford University, School of Technology, Haifa, Israel Measurements, Lund University, Medicine, Stanford, California, USA 2. Prof. Havazelet Bianco-Peled, Lund, Sweden Chemical Engineering, Technion, 4. ARTS Lab and CRIM Lab, Scuola Israel Institute of Technology, Haifa, Superiore Sant’Anna, Pisa, Italy Israel 5. Aalborg University, Aalborg, Denmark 6. Tyndall Institute, Cork, Ireland 7. The laboratory for Synthetic Perceptive, Emotive and Cognitive Systems – SPECS, Institute of Audiovisual Studies, Universitat Pompeu Fabra, Barcelona, Spain 8. Department of Technology and Health, Istituto Superiore di Sanità, Roma, Italy 9. Newcastle University, England

195 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Scientific Groups

Physics Dr. Michael Gozin Dr. Yael Roichman Preparation, characterization and Optical assembly of new materials and Prof. David Andelman biomedical applications of fullerene/ devices Polymeric nano-templates and nano- nanotube protein complexes; novel [email protected] structures (theory) fullerene-derived amino acids and Dr. Yoram Selzer [email protected] peptides (with Prof. A. Kotlyar) The physics and chemistry of singles [email protected] Dr. Roy Beck-Barkai molecule junctions Biomolecules Supramolecular Dr. Oded Hod [email protected] Assemblies, Supramolecular Forces Computational Nano-Materials Science: Prof. Doron Shabat within Intermediate Filaments, towards electronic, spintronic, and Theranostic drug delivery systems, Signal Small Angle X-ray Scattering electro-mechanical devices at the Amplification, Turn-ON optical imaging [email protected] nanoscale probes for cancer diagnosis [email protected] Prof. Eshel Ben Jacob [email protected] Nano Bio Electronics Prof. Joseph Klafter Prof. Michael Urbakh [email protected] Single molecule dynamics, nanomotors Theoretical studies and modeling in and nanofriction (theory) Prof. David Bergman fields of nanomechanics’ frictions at the [email protected] Nano-plasmonics and Nano-photonics; nanoscale, single molecular spectroscopy Magneto-transport in Nano-composites Prof. Gil Markovich and molecular motors [email protected] Synthesis and physical studies of colloidal [email protected] Prof. Yoram Dagan nanoparticles and their assemblies Superconductivity and ferro-magnetism [email protected] in the nanoscale Prof. Abraham Nitzan Engineering [email protected] Electronic processes at molecular Prof. Ady Arie Prof. Guy Deutscher interfaces (theory) [email protected] Nonlinear photonic crystals, nonlinear Melting of nano-grains, plasmonics superconductivity in nano-grain Prof. Fernando Patolsky [email protected] composites The synthesis and characterization [email protected] of new nanoscale materials for the Dr. Alon Bahabad development of nanoelectronic, electro- General topics: Nonlinear optics, extreme Prof. Alexander Gerber nonlinear optics, nanophotonics, Giant magneto-resistance in nano- optic and electro-magneto-optical devices and their applications in biology, quantum optics composites [email protected] [email protected] chemistry and technology [email protected] Dr. Zahava Barkay Prof. Ron Lifshitz Surface characterization methods based Electro-mechanical properties of Prof. Emanuel Peled and Prof. Diana Golodnitsky on scanning electron microscopy nanostructures (theory) [email protected] [email protected] Nano materials and thin films for electrochemical energy storage and Prof. Amir Boag Prof. Alexander Palevski conversion Photonic crystals E-transport in low-dimensional [email protected] [email protected] semiconductor nanostructures [email protected] Prof. Moshe Portnoy Prof. Reuven L. Boxman , Dr. Nanoscale composite materials for Nahum Parkansky and Dr. Vladimir catalysis and biomedicine Zhitomirsky [email protected] Electrical discharge and plasma lab Chemistry Prof. Eran Rabani [email protected] Prof. Ori Cheshnovsky Theory of nano-materials (theory) Prof. Shmuel Einav Nanoscale optics in STM junctions, [email protected] Bio-chips Electronic properties of clusters Dr. Shachar Richter [email protected] [email protected] Molecular electronics of self assembly Prof. Haim Diamant layers Theory of Complex Fluids [email protected] [email protected]

196 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Scientific Groups

Prof. Noam Eliaz Prof. Yosi Shacham-Diamand Dr. Avigdor Eldar Design, synthesis and characterization Nano-chemical processes for micro- Sub-micron light-guided protein of new osteoconductive functionally electronics and integration of biological localization and super-resolution graded hydroxyapatite coatings; material on chip for acute toxicity microscopy for studying division and biomaterials, electrochemistry, SPM detection signaling in bacteria [email protected] [email protected] [email protected] Prof. Ilan Goldfarb Dr. Natan Shaked Prof. Amihay Freeman Growth of epitaxial nanostructures, STM Interferometry, microscopy and Biotemplating of stabilized protein [email protected] nanoscopy in biological cells and tisues crystals; directed metallization of [email protected] biologically active proteins and cells Prof. Yael Hanein [email protected] Microfluidics for self-assembly, Prof. Ben Steinberg nanotubes-neurons interfaces Electromagnetics of nano-scale systems. Prof. Ehud Gazit [email protected] Nano-photonics. Optical properties of Self-assembly of short aromatic peptides: complex media made of nano-scale from amyloid disease to nanotechnology Prof. Slava Krylov inclusions. Optical Gyroscopes [email protected] Micro- and Nanoelectromechanical [email protected] Systems (MEMS/NEMS), micro- and nano Prof. Jonathan M. Gershoni sensors and actuators Prof. Meital Zilberman Nano-optical sensing of protein: Protein [email protected] Polymeric biomaterials and implants, interactions controlled drug release, tissue [email protected] Prof. David Mendlovic engineering Silicon nano-photonic dynamic devices Prof. Alexander Kotlyar [email protected] [email protected] DNA-based organic nano wires [email protected] Prof. Touvia Miloh Nano-mechanics, fluid dynamics in nano- Prof. Rimona Margalit channels; elastic nano-fibers (theory) Life Sciences Drug delivery by nano-particles based [email protected] Prof. Azem Abdussalam on biomaterials: biophysical properties, cell-particle interactions and therapeutic Dr. Nahum Parkansky Protein folding and Unfolding by responses Nanoparticles production, Molecular Chaperones [email protected] characterization and application. [email protected] [email protected] Prof. Uri Ashery Dr. Iftach Nachman Microfluidic approaches to study cell Prof. Gil Rosenman From Neuron to Network: The Roles of developmental decisions. Ferroelectric nanodomain polarization Synaptic Proteins in Neuronal Network [email protected] reversal and development of a new Activity generation of nonlinear photonic devices [email protected] Dr. Dan Peer [email protected] Prof. Ari Barzilai Selective targeting and reprogramming of leukocytes using fully degradable Prof. Yossi Rosenwaks The molecular mechanism of optic nerve nanomedicines Nano-probing, scanning probe degeneration and regeneration [email protected] microscopy [email protected] [email protected] Prof. Itai Benhar Prof. Judith Rishpon Application of nano technologies in Prof. Shlomo Ruschin Targeted drug-carrying phage electrochemical biosensors Micro-electrooptics nanoparticles [email protected] [email protected] [email protected] Dr. David Sprinzak Prof. Arie Ruzin Prof. Chanoch Carmeli Probing intercellular signaling at the Solid state detectors and devices Application of the photosynthetic nano scale level laboratory reaction center proteins, PS I in [email protected] [email protected] the fabrication of novel nanobio- photovoltaic devices Prof. Jacob Scheuer [email protected] Integrated nano-photonics, slow light and polymer optics [email protected]

197 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Scientific Groups

Mathematics Prof. Rafi Korenstein Dr. Ronit Satchi-Fainaro Electrical enhancement of drug nano- Targeting tumor vasculature with Prof. Zeev Schuss carrier, nanoscale cell membrane polymer conjugates of angiogenesis Ionic permeation in protein channels of dynamics inhibitors biological membranes and applications [email protected] [email protected] to models of neurons and cardiac myocytes Prof. Ruth Nussinov Dr. Ella Sklan [email protected] Nanostructure design based on naturally- Interactions of positive strand RNA occurring protein building blocks viruses with the host cell [email protected] [email protected] Dr. Eran Perlson Dr. Inna Slutsky Medicine Nanomotors and microfluidic platforms Information processing: From nano-scale Prof. Dafna Benayahu reveal neurodegeneration mechanisms single synapse to memory function Nano manipulation of stem cells [email protected] [email protected] differentiation to become biomedical Prof. Ronit Sagi-Eisenberg Dr. Ilan Tsarfaty devices Nano scale functional genomics and Nanoparticles based Met-HGF/SF [email protected] proteomics analyses of mast cell molecular imaging activation. [email protected] [email protected]

198 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Head of the Center for Nanoscience and Nanotechnology

Prof. Ori Cheshnovsky

Scientific committee

Prof. Guy Deutscher, Chairman Prof. Ori Cheshnovsky, Head of the Center Prof. Rimona Margalit, Faculty of Life Sciences Prof. Alexander Palevski, School of Physics and Astronomy Prof. Yael Hanein, Faculty of Engineering Prof. Gil Markovich, School of Chemistry Prof. Yossi Rosenwaks, Faculty of Engineering Prof. Koby Scheuer, Faculty of Engineering Dr. Inna Slutsky, Faculty of Medicine Dr. Dan Peer, Faculty of Life Sciences

199 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Staff Members

Name Function Dr. Moshe Evenor Administrative manger Ms. Lauren Itzhak Secretary Ms. Ruth Bernstein-Peretz Internet Dr. Artium Khatchatouriants Bio-AFM, RAMAN Dr. Zahava Barkay ESEM lab Director Dr. Yossi Lereah HRTEM instructor and researcher

TAU micro and nano central characterization & fabrication facility – personnel

Name Position Directors Prof. Ori Cheshnovsky Academic co-director Prof. Yael Hanein Academic co-director Administration Ms. Inna Veksler Processing Mr. Mark Oksman Chief Engineer Mr. Maurice Saidian Clean Rooms Engineer (Engineering Faculty) Mr. Assaf Hazzan Clean Rooms Engineer (Nano center) Mr. Alexander Gurevitch Process Engineering Mr. David Shreiber Process Engineering SEMs, EBEM, FIB Dr. Alexander Tsukernik E-Beam microscopy and lithography Ms. Michal Eitan-Wiener Electron & Ion Beam Lithography & Microscopy Mr. Denis Glozman, Ms. Netta Hendler Training (Student) Glove boxes Mr. Gregory Avrushchenko Lab Engineer Mr. Yoni Engel FTIR

200 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY http://nano.tau.ac.il Studio Design Graphic TAU Michal Semo-Kovetz, & Production: Design Graphic