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The Center for Nanoscience and Nanotechnology

Scientific Report 2008 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

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 Nano-center’s Dr. Yael Roichman (Chemistry) specializes in Holographic 2007-2008 annual scientific report. It highlights our scientific tweezers and manipulation of nano-objects. While and organizational progress over the last academic year. developing new methods in nano-manipulation, she will Before diving into the wealth of material which follows, contribute to a large number of cooperative research here is some brief information regarding our nano related projects in nanoscopy. activity. Dr. Oded Hod (Chemistry) specializes in computational Overall, last year, 158 nano-related papers, originating from methods for nano-objects, in particular carbon nanotubes 38 different research groups, have been published – many and Graphene. He adds a strong theoretical perspective to of them in highly ranked journals including Science, the the already existing experimental activity in these topics. Nature family, Physical Review Letters, PNAS, Nano Letters, Dr. Ella Sklan (Medicine) specializes in understanding the JACS, Angewandte Chemie International Edition, etc. 67 of life cycle of the Hepatitis C virus. Her work is aimed at these articles are the result of cooperation with researchers developing new antiviral strategies. A major element of her from other universities. research involves energy transfer using nanoparticles. We report on 61 various collaborative research projects 112 PhD and 108 MSc research students were involved in nationally and internationally with other academic nano-research at TAU over the course of 2008. The MSc institutions as well as 11 research projects with industrial program in Materials and Nanotechnology has already partners. passed all necessary internal (TAU) and external (Israeli Tel Aviv University (TAU) researchers applied for 49 nano Counsel of Higher Education) approvals. Budget has related patents - six of which have been approved during been allocated and the program is planned to begin in 2008. Four ties with industries have been signed – three of the following academic year. Our new weekly seminar which are related to renewable energy. Several others are program on materials and nanotechnology (23 seminars in the final stages of negotiations. in 2008) achieved an attendance of ~50 MSc and PhD students, as well as many faculty members, each week. We Continuing in our efforts to recruit new researchers, this have launched an exchange program of graduate students year we have successfully recruited several outstanding and senior scientists between Northwestern University and investigators currently engaged in nano related research. TAU. Five exchange scholarships have been granted.

Dr. Dan Peer (Life Sciences) specializes in selective “C” (TAU Micro and nano central characterization and targeting and reprogramming of leukocytes using fully fabrication facility) was inaugurated on October 2007. degradable nano-medications. Serving as a core member, It now encompasses the majority of micro and nano Dan is assigned to help develop the nano-biology general fabrication as well as most of the characterization research laboratory, which was established last year at the instrumentation on TAU’s campus. “C” is responsible for Nanocenter. providing service, training and consultation to costumers In addition, three new faculty members have joined the as well as maintaining and upgrading its facilities. The Nanocenter’s second circle: facility serves 25 TAU research groups as well as 16 external academic and industrial users.

3 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Major items that were purchased or installed in 2008 efforts and will focus on recruiting new core members in include: physics and medicine.

PPMS measurement station: an important research tool We will strengthen our fabrication capabilities by for transport measurement in low temperatures and strong purchasing a focused ion beam lithography system. We magnetic fields. are now in the final stages of the decision making and purchasing process. We will continue to develop the new Visualization and analytical characterization of laboratory dedicated to optical and electrical studies of biological nano system: the system serves researchers neural networks. We consider this laboratory as the starting from Biology and Medicine by helping them to visualize point for investigating the interface between biological and analytically characterize tissues at a cellular resolution. and physical systems. NIL – Nano imprinting lithography system: a tool for patterning nanostructures on hard and soft materials using Looking forward to a productive new year. stamps. TAU’s nano-imprinting system will be the first to be Sincerely yours, purchased and used in Israeli academia.

Next year we will continue in expanding the nano community, our resources and infrastructure. In the Prof. Ori Cheshnovsky upcoming academic year we will continue our recruiting Head of the Center for Nanoscience and Nanotechnology

4 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Table of Contents

TAU center for nanoscience and nanotechnology – overview 6 Research Infrastructure 8 Foci of research 9 Researchers 11 Progress reports 65 Publications 113 Patents 122 Collaborations 125 List of researchers 128 Scientific committee 131 Staff members 132

Cover picture in courtesy of: Dr. Shachar Richter and Ms. Netta Hendler. Graphic Design: Michal Semo-Kovetz and Yael Kfir, TAU Graphic Design Studio

5 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY TAU center for nanoscience and nanotechnology – overview

el Aviv University (TAU), recognizing the As a means of catalyzing nano activity, the Nano center’s emerging needs and opportunities in the central premises host the laboratories of the core faculty field of Nano Sciences and Nanotechnology members (so far, five were hired). These researchers (NST), established in 2000, the Center represent the diverse expertise necessary for developing for Nanoscience and Nanotechnology the new “nano-culture”. This core is extended and (TAU Nanocenter). The center which supported by additional “circle” of more than 50 research encompassesT activities across four faculties (Exact Sciences, groups distributed in the four relevant faculties. Researchers Engineering, Life Sciences and Medicine), provides the in this “circle,” to various degrees, contribute to, and benefit intellectual framework for interdisciplinary research, and from, the activities at the center. the technological infrastructure vital for nurturing leading- The policy and development plans of the center are edge research in NST. discussed and approved by a scientific committee which We believe that the mission of the Nanocenter can best be includes representatives from the four relevant faculties. achieved by implementing and maintaining the following: “C” (TAU Micro and nano central characterization Recruiting outstanding relevant researchers; developing and fabrication facility) was inaugurated in and organizing needed infrastructure; developing focused October 2007. The majority of the micro/ research areas; Developing training and educational nano fabrication and characterization programs; establishing ties and services with academia instrumentation on the TAU campus is managed by “C”. and industry; generating IP with good prospects of “C” is in charge of providing service, training and consultation commercialization; Promoting related academic activity to costumers as well as maintaining and upgrading its and topical laboratories. facilities. The facility serves 25 TAU research groups, as well as 16 external academic and industrial users. The TAU The TAU Nanocenter houses, within its approximately nanocenter, relies in its operation, also upon the facilities 1200 sq. meters, both public laboratories - operated and of the Wolfson Materials Center (Auger spectroscopy, X-ray maintained by technical and administrative staff – as well diffractometer, SIMS analysis, etc.). as private research laboratories. These laboratories maintain state of the art equipment for construction, realization and More information on the TAU Nanocenter can be found in general characterization of nano-structures. http://nano.tau.ac.il

6 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY B Tel Aviv University micro and nano central characterization and fabrication facility E quipment Electron microscopes  Environmental Scanning Electron Microscope (ESEM - FEI Quanta 200 FEG)

M issions  Field Emission High Resolution Scanning Electron  To provide Tel Aviv University Microscope (HRSEM - Jeol JSM-6700) users with access to state of the E-beam Lithography art micro and nano fabrication  E-beam lithography (Raith 150) and characterization equipment.  SEM with e-beam writing attachment (Jeol 6400 +  To train, consult and help users Elphy) to operate the equipment and to develop suitable protocols. AFM/STM  To provide services to external  AFM (Molecular Imaging PicoSPM II) academic users as well as  AFM (Veeco NanoScope IV MultiMode) industrial users.  Variable Temperature Ultra-High Vacuum STM/AFM System (Omicron)  AFM in a glove box (NT-MDT SMENA-A) Optical microscopy  Metallurgical Confocal microscope (Olympus LEXT) C ustomers  Measurement microscope (Hisomet II) Companies Photolithography  Al Cielo Ltd.  Contact lithography (Suss MA6, MJB3)  Applied Materials Israel  Direct laser writing & Photomask preparation  Cell Kinetics (Medisel) (Heidelberg Instruments DWL-66)  CI Systems  Compass Thin lm deposition/etching/characterization  El-Mul Technologies  E-beam deposition (VST, Edwards 306)  EL-OP Ltd.  Thermal evaporation (VST)  Flamingo Electronics  RF sputtering (MRC)  IAI  DC sputtering (Penta Vacuum)  Nova  RIE Etching (Unaxis)  NOVAMEDES  DRIE etching (Unaxis)  Orbotech  Wet etching  RAFAEL  Wet and dry Cleaning  TeraOP Measurements  Tessera Israel  Pro le/Step height (Tencor, Veeco)  TEVET  XRF (Jordan Valley) Academia  Spectroscopic Ellipsometer (Woollam M2000DUV) C ontact  Bar Ilan University  Spectroscopic Reectometer (Sentech FTP)  Ben Gurion University Mark Oksman Backend  Hebrew University Email: [email protected]  Dicing (K&S 982)  Technion Phone: 03-6407926  Wire Bonding (K&S)  Weizmann Institute

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

Flyer of the TAU micro and nano central characterization and fabrication facility

7 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY News in Research Infrastructure

ajor items that were purchased or Additional equipment which was promoted by the TAU installed in 2008 include: nanocenter includes:

PPMS – measurement station. „„The establishment of the Laboratory for Microscopy This system is an important research and Electrical measurements in biological systems. tool for transport measurement „„Support for ultracentrifuge analysis and sorting of in low temperatures and strong organic, inorganic, and biological nanoparticles as well magneticM fields. It supports research in nano-electronics as proteins. The ultracentrifuge is intended to serve in general and particularly in research focusing on nano- mainly the Faculties of Life-sciences and Medicine as magnetics and nano-ferroelectrics as well as nano- well as the Chemistry department. superconductivity. The system is installed in the new Laboratory for Nanosystems at Low Temperatures. „„Due to its prospects in nanoscopy, the center has supported the purchase of a University confocal Visualization and analytical characterization of microscopy lab (Faculty of Medicine) including a biological nano systems (600k$). 2-Photon confocal microscope system. This system serves a large group of researchers from the faculties of Life Sciences and Medicine. It is capable of „„We have upgraded our ability to manipulate and visualizing tissues at a cellular resolution for the purpose measure transport of individual nano objects in parallel of drug targeting. In particular, this system enables us to with observing them in our environmental SEM. monitor cells labeled with nanoparticles. The system is „„The nanocenter has also supported, through “C”, installed in the Faculty of Medicine equipment center. the refurbishing of several systems such as the NIL – Nano imprinting lithography (630k$). Pentha-Vacuum DC/RF sputtering system. The newly purchased PECVD system is in the final stages of This tool allows for patterning nanostructures on hard installation. and soft materials using stamps. TAU’s nano-imprinting system will be the first to be purchased and used in Israeli academia. The system will be installed in the clean rooms of the Nano-center.

8 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Foci of research

ver the past several years we have outlined of dielectric surfaces, developed by Prof. Rosenman four thematic topics to be the focus of (Engineering) is explored as a new tool to control cell- our scientific activity. The goal of the surface adhesion. Collaboration between Prof. Rosenman nanocenter is to promote and support and Prof. Gazit (Life Sciences) utilizes vacuum deposition these topics with the aim of achieving a techniques to deposit biological, polymer material onto critical mass of activity in these areas. surfaces with the aim to control surface wetting properties. Prof. Shacham-Diamand and Prof. Nathan from the school ORenewable energy of electrical engineering are interested in bio-chips. New battery technology and energy harvesting schemes Recent initiated collaboration between Dr. Hanein and as well as improved photovoltaic methodologies are Prof. Cheshnovsky (Chemistry) in collaboration with HUJI among the goals of the Nanocenter’s renewable energy researchers, Prof. Banin and Prof. Yitzchaik, aims to use research program. Prof. Peled and Prof. Golodnisky’s nano-approaches in order to realize an artificial retina. (Chemistry) research is at the forefront of battery and fuel cell technology. Dr. Richter (Chemistry) and Prof. Carmeli This year, in accordance with last year’s plan, we have (Life Sciences) innovated a unique solar cell. Dr. Scheuer, established a new laboratory for optical and electrical Prof. Boag and Dr. Hanein (all from Engineering) participate measurements on bio-nano systems. This lab will serve in a new nano-antenna project. Prof. Patolsky’s research has as a basis for a more comprehensive Bio-nano research produced new technologies in nano photovoltaics and fuel laboratory. cells. Dr. Selzer (Chemistry) and Prof. Patolsky (Chemistry) Magnetism, superconductivity and ferroelectricity are investigating nano-related thermoelectric power. This topic encompasses nano-magnetics, nano- The work is progressing well scientifically as is reflected ferroelectrics and nano-superconductivity. Research in this by three related industry contracts. We have invested in field is currently conducted at the School of Physics, School equipment infrastructure to further promote this activity. of Chemistry and the Faculty of Engineering with strong interfaculty collaborations. A few new notable activities Bio-Physical interfacing include: new methodologies of electrode-less deposition This topic encompasses the study of cell-substrate of magnetic alloys, a significant contribution to magnetics interaction at the nanoscale, utilization of nano-elements MEMS efforts, by Prof. Shacham-Diamand (Engineering) to interface with cells and the construction of novel bio- and Prof. Gileadi (Chemistry); Dr. Dagan’s (Physics) and chips and bio-sensors. This activity is marked by strong Dr. Richter’s (Chemistry) research toward modifying collaboration between researchers from the various the properties of superconductors, using self assembly faculties on campus. This is a prime example to the monolayers; Dr. Markovich (Chemistry) synthesizes impact of the nano-center in promoting and nurturing magnetic and ferroelectric nano-crystals, characterizes multidisciplinary activity. them and investigates various enhancement methods and applications; Prof. Cohen (Chemistry) and coworkers plan Currently, noted activity includes: Prof. Patolsky’s (Chemistry) to exploit these nano-crystals for imaging. nanowire based sensors; Dr. Hanein’s (Engineering) carbon nanotube interfaces; The newly developed method of The infrastructure for this activity has been dramatically surface wetting properties by electron bombardment enhanced by the establishment of a new lab. This

9 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY recently established Laboratory for Nanosystems at Low reached a critical mass in nanophotonics and nanoscopy. Temperatures includes the newly acquired PPMS system Dr. Yael Roichman (Chemistry) specializes in holographic and a SQUID magnetometer. It will serve as a public optical tweezers which serve as a strong tool in the field research laboratory in nano-magnetism, and nano- of nanoscopy. Ongoing activity includes the research superconductivity. conducted by Dr. Scheuer (Engineering) on nanophotonics, Prof. Cheshnovsky (Chemistry) on the spectroscopy of Nanoscopy nanoparticles and nano-junctions, and Prof. Mendelovic Recently, a new topic was added to the three outlined (Engineering) on photonic crystals. above. With the recruitment of Dr. Yael Roichman we have

10 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY ResearcherS

Researchers

Prof. David Andelman Physics

Polymeric Nano- templates and Nano-structures

n recent years an increasing number of physicists are focusing their attention on interesting physics found in biological and chemical systems in the nano scale. This branch of condensed matter physics is called "soft condensed matter" and aims at providing better understanding of biological and chemical systems, processes and materials. We study theoretically Iphysical properties of biomaterials and macromolecular materials such as proteins, DNA and other polymers. Most of these water soluble polymers and macromolecules are charged. Hence, special attention is paid to the inter-relation between their electrodynamical properties and their structural ones. We mention now several specific projects which are investigated in our group. Polymeric templating i) recent works involved new models to estimate the stiffness of charged macromolecules and its affect on the molecular References: conformation in aqueous solutions. 1. "Onset of DNA aggregation in presence of mono- ii) The adsorption of charged polymers onto oppositely charged and multivalent counterions". Burak, Y. ; Ariel, G. ; Andelman, D. Biophysical Journal, (2003), 85, 2100. surfaces is explored and results from a competition between 2. "Neutral and charged polymers at interfaces". Netz, electrostatic attraction to the charged surface and loss of R. R. ; Andelman, D. Physics Reports, (2003), 380, 1- entropy. 95. iii) We study heterogenous macromolecules such as polymer chains 3. "Structural changes in block copolymers: Coupling composed of several distinctive blocks (sub-units). Because of electric field and mobile ions". Tsori,Y . ; Tournilhac, the blocks have different physical properties, they induce F. ; Andelman, D. ; Leibler, L. Physical Review Letters,

(2003), 90, 145504. morphological changes and transitions. Recently, the response of such systems to electric fields was explored.

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

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

Prof. Eshel Ben Jacob Physics

Nanobio electronics

Fighting bacteria using man-made Nano Particles Today, there are an alarming increasing number of strains of disease- causing bacteria that can resist multiple drugs; bacteria are clearly capable of developing antibiotic resistance at a higher rate than scientists can develop new drugs [1]. To reverse this course of events, we have to develop novel strategies to fight them. We developed a new strategy of based on specially designed nano particles that have both hydrophobic and hydrophilic sites. These particles can both temper bacteria communication and even paralyze directly the individual bacteria as shown in the attached figures [2].

DNA based SET transistor Formation of networks of nano-bubbles in water using weak RF signals References: It is known that weak RF signals can have long time effect on water. 1. E. Ben Jacob, Y. Aharonov &Y. Shapira, Bacteria We have shown the effect on electrochemical deposition and on the harnessing complexity Biofilms. (2005) 1, 239–263. 2. N. Raichman, T. Gabay, Y. Katsir, Y. Shapira & E. Ben- growth of bacterial colonies [2]. Jacob. Engineered Self Organization in natural Understanding the mechanism of this phenomenon can serve the and man-made Systems. Continuum Models basis for many new applications. Together with Prof. Aharonov, we and Discrete Systems, Edited by Bergman D. et al investigate the idea that the effects are the outcome of the formation Kluwer Academic Publishers, Netherlands. p.187- of networks of nano bubbles (networks with long range orientation 205 (2004). correlations). 3. S. Caspi, E. Ben-Jacob. Conformation changes and folding of proteins mediated by Davydov's soliton. Physics Letters A, vol.272, no.1-2, pp.124-9 (2000) DNA-based Nano Electronics 4. S. Caspi and E. Ben-Jacob. Toy Model Studies of We perform theoretical studies of the propagation of both charge Soliton Mediated Protein Folding and Conformation and excitonic solitons along DNA molecules. These theoretical Changes. Europhys. Lett. 47, 522-527 (1999). investigations led to a patent of DNA-based single electron tunneling 5. Z. Hermon, S. Caspi, E. Ben-Jacob. Prediction of transistor. We emphasize that unlike other studies in which the DNA Charge and Dipole Solitons in DNA Molecules based on the behaviour of Phosphate Bridges as molecules are used as templates, in our approach the transistor “head” Tunnel Elements. Europhys. Lett. 43 (4) 482-487 is made of DNA molecules [3] as is shown in the figure below. (1998).

Tel: (972)-3-6407845, (972)-3-6407604, (972)-3-6425787 Fax: (972)-3-6422979 Email: [email protected] Personal Website: star.tau.ac.il/~eshel

14 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Dr. Yoram Dagan - Physics Strongly correlated electron systems

Research

Materials in which electrons are strongly interacting with each other exhibit variety of exotic properties such as: high temperature superconductivity, colossal magnetoresistance, ferroelectricity, magneto-electric effects in multiferroic materials. Examples for such materials are: cuprates, manganites, ruthenates, and many more. Generally speaking, small stimulus results in a large change in one or more physical property. In our laboratory we are studying the electronic structure and the nature of the phase transitions of such materials by tuning control parameters such as chemical doping, epitaxial strain, external fields etc. Of particular interest is the influence of sample dimensions and interfaces with other correlated systems on its physical properties. Current research topics are: Researchers i) Superconductivity on 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. ii) Interface effects between insulating perovskites. It has been found that when two insulating nonmagnetic perovskite form an epitaxial interface this interface can become highly conductive, Physics magnetic and even superconducting. Using our laser deposition facility we are trying to produce Dr. Yoram Dagan and study such interfaces. Strongly correlated electron systemsiii) 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 criticality and density waves. While the undoped material is antiferromagnetic upon adding charge carriers the material becomes superconducting. It is not clear whether these orders coexist and on what scale. We perform local and macroscopic tunneling study to clarify these issues that are eminent for understanding superconductivity in the cuprates.

6 Research Materials in which electrons are strongly interacting with each 5 other exhibit variety of exotic properties such as: high temperature 4 superconductivity, colossal magnetoresistance, ferroelectricity,

magneto-electric effects in multiferroic materials. Examples for such 3 materials are: cuprates, manganites, ruthenates, and many more. 2 Generally speaking, small stimulus results in a large change in one or 1 more physical property. Spinmagnetoresistance (%) In our laboratory we are studying the electronic structure and the 0 nature of the phase transitions of such materials by tuning control 0.12 0.14 0.16 0.18 parameters such as chemical doping, epitaxial strain, external fields Ce doping etc. Of particular interest is the influence of sample dimensions and Spin magnetoresistance resultingSpin magnetoresistance from scattering resulting from from magneticscattering from droplets in Pr Ce CuO as a interfaces with other correlated systems on its physical properties. magnetic droplets in Pr Ce CuO as a function of Ce 2-x x 4 function 2-xof Cex doping.4 Current research topics are: doping. i) Superconductivity on the nanoscale Superconductivity is a macroscopic quantum phenomenon. However, when the superconducting specimen is constituted becomes superconducting. It is not clear of weakly connected nano-grains many interesting physical whether these orders coexist and on what phenomena occur. In our laboratory we are able to probe scale. We perform local and macroscopic superconducting fluctuations and their dependence on the tunneling study to clarify these issues that are nanostructure of the sample. eminent for understanding superconductivity ii) Interface effects between insulating perovskites in the cuprates. It has been found that when two insulating nonmagnetic perovskite form an epitaxial interface this interface can become References: highly conductive, magnetic and even superconducting. Using 1. y. Dagan and R. L. Greene, “Hole superconductivity in electron-doped cuprates”, Phys. Rev. B, 76, 024506 our laser deposition facility we are trying to produce and study (2007). such interfaces. 2. y. Dagan, R. Beck and R. L. Greene, “Dirty iii) Local and macroscopic orders in electron-doped Superconductivity in the Electron-doped cuprate cuprates Pr2-xCexCuO4: Tunneling study”, Phys. Rev. Lett. 99, Electron-doped cuprates offer a unique laboratory for studying 147004 (2007). a variety of phenomena such as: superconductivity, quantum 3. y. Dagan, M. C. Barr, W. M. Fisher, T. Dhakal, A. Biswas, R. Beck, and R. L. Greene, “Origin of the anomalous criticality and density waves. While the undoped material is low temperature upturn in resistivity in the electron- antiferromagnetic upon adding charge carriers the material doped cuprates.” Phys. Rev. Lett., 94, 057005 (2005). 4. J. S. Higgins, Y. Dagan, M. C. Barr, R. L. Greene, and B. Weaver, “Role of oxygen in electron doped Tel: 972-3-6405554 cuprates”, Phys. Rev. B, 73, 104510 (2006). Fax: 972- 3-6429306 Email: [email protected]

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

Prof. Alexander Gerber Physics

Nano-scale magnetism and Hall effect spintronics

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

This magnetic field response of an ultra-thin Ni film with lateral dimensions 100 × 100 nm serves a prototype of the Hall effect - based magnetic memory bit.

Tel: (972)-3-6405405, (972)-3-6407023 Fax: (972)-3-6422979 Email: [email protected]

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

Two oppositely spin-polarized contacts with barriers Z1 and Z2, at a small distance l◀E. Crossed Andrew reflections (CARE) are represented. Perturbation of the superconducting gap occurs in the hatched regions.

Tel: (972)-3-6408205 Fax: (972)-3-6422979 Email: [email protected]

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

Prof. Ron Lifshitz Physics

Nanomechanics & Quasicrystals

ith recent advances in nanotechnology, Roukes and the theoretical group of Prof. Michael state of the art nanoelectromechanical Cross, both at Caltech, as well as the lab of Dr. systems (NEMS) can now be fabricated Eyal Buks at the Technion—is concerned with with lateral dimensions down to a few tens the theoretical study of nanomechanical systems, of nanometers and combined with self- covering a broad range of questions as listed assembled nanostructures such as nanowires below. Wand carbon nanotubes, achieving normal frequencies that exceed 1 GHz. As a consequence, NEMS are no longer simply smaller and Research projects in nanomechanics: improved versions of MEMS (microelectromechanical systems), but 1. Mesoscopic phonon transport — Transport of also offer great opportunities for the study of mechanics in physical mechanical energy (heat) through nanomechanical systems, with emphasis on the behavior of ballistic regimes that previously had been inaccessible experimentally. The phonons [1]. Lifshitz group—working in collaboration with the lab of Prof. Michael 2. dissipation of energy in nanomechanical resonators (beams, cantilevers, nanotubes, etc.) [2]. 3. Nonlinear dynamics of nanomechanical systems [3] — with emphasis on the response [4] and the synchronization [5] of coupled nanomechanical resonator arrays. 4. Quantum electromechanics — studying the possibility to observe quantum-mechanical behavior with nanomechanical devices [6].

The Lifshitz group is also involved in unrelated theoretical research in the field of quasicrystals. In collaboration with Prof. Ady Arie, of the Faculty of Engineering, Lifshitz is studying how to exploit nonlinear photonic quasicrystals for the These two phase-space diagrams demonstrate the parallel behavior of the so- purpose of optical frequency conversion [7,8]. called quantum Wigner function (left) and classical phase-space distribution (right), for a driven nonlinear resonator (blue is positive while red is negative). In collaboration with Prof. Mordechai Segev of The two distributions are similar in regions of high probability (dark blue), but the Technion, Lifshitz is studying the dynamical the quantum one is smeared due to quantum uncertainty, and is only zero- properties of optically-induced nonlinear on-average in regions where the classical probability of finding the resonator is photonic quasicrystals [9,10]. precisely zero. The diagrams were calculated by graduate student Itamar Katz with the aid of students Alex Retzker and Raphael Struab, working with Ron Selected References: Lifshitz. For detail, please read the Focus story at http://focus.aps.org/story/v20/ 1. M.C. Cross & R. Lifshitz, “Elastic wave transmission at st6 and see Ref. [6]. an abrupt junction in a thin plate with application to heat transport and vibrations in mesoscopic Tel: (972)-3-6405145 systems,” Phys. Rev. B 64 (2001) 085324. Fax: (972)-3-6406953 2. r. Lifshitz & M.L. Roukes, “Thermoelastic damping Email: [email protected] in micro- and nanomechanical systems,” Phys. Rev. Personal Website: www.tau.ac.il/~ronlif/ B 61 (2000) 5600-5609.

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

3. r. Lifshitz & M.C. Cross “Nonlinear dynamics of nanomechanical and micromechanical resonators,” Review of Nonlinear Dynamics and Complexity (2008). In press. 4. r. Lifshitz & M.C. Cross, “Response of parametrically-driven nonlinear coupled oscillators with application to micro- and nanomechanical systems,” Phys. Rev. B 67 (2003) 134302. 5. M.C. Cross, A. Zumdieck, R. Lifshitz, and J.L. Rogers, “Synchronization by nonlinear frequency pulling,” Phys. Rev. Lett. 93 (2004) 224101. 6. I. Katz, A. Retzker, R. Straub, and R. Lifshitz, “Signatures for a classical to quantum transition of a driven nonlinear nanomechanical resonator,” Phys. Rev. Lett. 99 (2007) 040404. 7. r. Lifshitz, A. Arie, and A. Bahabad, “Photonic quasicrystals for nonlinear optical frequency conversion,” Phys. Rev. Lett. 95 (2005) 133901. 8. A. Bahabad, N. Voloch, A. Arie, and R. Lifshitz, “Experimental confirmation of the general solution to the multiple phase matching problem,” J. Opt. Soc. Am. B 24 (2007) 1916-1921. 9. B. Freedman, G. Bartal, M. Segev, R. Lifshitz, D.N. Christodoulides, and J.W. Fleischer, “Observation of wave and defect dynamics in nonlinear photonic quasicrystals,” Nature 440 (2006) 1166- 1169. 10. B. Freedman, R. Lifshitz, J. W. Fleischer, and M. Segev, “Phason dynamics in nonlinear photonic quasicrystals,” Nature Materials 6 (2007) 776-781.

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

Prof. Alexander Palevski Physics

Quantum Transport in Nanostructures

One-dimensional quantum wires References: Electronic transport properties were studied at low temperatures 1. d. Kaufman, Yu. Berk, B. Dwir, A. Rudra, A. Palevski in V-grooved quantum wires. The quantization of the conductance and E. Kapon, Conductance quantization in V­groove quantum wires, Phys. Rev. B.59, R10433­R10436, as a result of one-dimensional band structure was observed. The (1999). role of the inter-subband scattering was elucidated. The value of 2. Tsukernik A, Palevski A, Goldman VJ, Luryi S, Kapon the interaction constant for GaAs was deduced from the Luttinger E, Rudra A. Quantum magnetotransport in periodic model. V-grooved heterojunctions. Phys. Rev. B, 63, 33151- 33154 (2001). Superconductor proximity effect in ferromagnetic 3. dwir B, Kaufman D, Kapon E, Palevski A Quantized conductance and intersubband scattering in junctions serially connected quantum wires, Europhys. Lett., The oscillations of the critical current were observed for the first time. 55, 80-85, (2001). The theory based on the formation of the π-junction in Josephson 4. y. Blum, A. Tsukernik, M. Karpovski and A. Palevski, coupled structures containing ferromagnetic layers was verified. Oscillations of the critical current in Nb-Cu-Ni- Cu-Nb junctions, Phys. Rev. Lett.89, 187004-(1-4), Neuronal Networks (in collaboration with the group of (2002). 5. y. Blum, A. Tsukernik, M. Karpovski, V.Shelukhin Prof. E. Ben Jacob) and A. Palevski, Critical current in Nb-Cu- We have lithographically fabricated and studied in vitro neuronal Nb junctions with non-ideal interfaces networks. Phys.Rev.B 70, 214501 (2004) The networks exhibit scale invariant Levy distribution and long-range 6. I. Sternfeld, V. Shelukhin, A. Tsukernik, M. correlations. Karpovski, A. Gerber and A.Palevski, Proximity effect in granular superconductor-normal metal structures, Phys. Rev. B 71, 64515-1-5 (2005) 7. E. Levy, A. Tsukernik, M. Karpovski, A. Palevski, B. Dwir, E. Pelucchi, A. Rudra, E. Kapon, Y. Oreg. Luttinger liquid behavior in weakly disordered quantum wires cond-mat/0509027 (2005)

The above figure shows quantum nano- wire device: (a) SEM micrograph of the wire grown on prefabricated V-grove substrate of GaAs with the gates. (b) schematic drawing explaining the special separation between 2-dimensional and 1-dimensional regions

Tel: (972)-3-6409456, (972)-3-6408193 Email: [email protected]

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

Prof. Ori Cheshnovsky Chemistry

Nanoscale Optics in STM Junctions. Electronic Properties of Clusters

Light, tunneling junctions and nanoparticles: Clusters and photoelectrons: In this project, we study the correlation between the electrical The long controversial problem, of a critical size in properties and the optical properties of isolated nanocrystals or which clusters of bivalent metals approach band- polymeric films. The sample, deposited on a surface, will be studied gap closure (metallic behavior), was addressed by using scanning Tunneling Microscope (STM). The transport properties us. By using PES of negatively charged clusters we of the sample will be measured using I-V spectroscopy. In parallel, on showed that the band gap closes at the cluster-size the same particle, light emission induce by inelastic tunneling will of ~400 atoms. At smaller sizes mercury clusters be monitored. A dedicated STM head is coupled to a high collection behave as semiconductors with band gap varying efficiency mirror was developed for this project. A major virtue of for 3 eV (Hg4) to 0.2 eV (Hg28O). Electron-hole pairs the project is that the optical and electrical measurements will be could be efficiently excited in semiconductor performed on the same single isolated nanoparticle. In case in which mercury clusters. Their thermalization and the particle is inhomogeneous, it different light emitting parts are recombination via Auger electron ejection is the differentiated. The same methods will serve in studying the relation focus of our current research. The understanding between the morphology segregation and light emission in multi- of the dynamics of these processes may offer ways chromophor polymeric films. to improve the performance of semiconductor based nano-devices.

References: 1. E. Flaxer, O. Sneh and O. Cheshnovsky. Molecular Light Emission Induced by Inelastic Electron Tunneling.Science 262, 1993, 2012-2014. 2. r. Busani, R. Giniger, T. Hippler and 0. Cheshnovsky. Auger Recombination and Charge Carrier

Thermalization in Hg-n Clusters-Photoelectron studies.Phys. Rev. Lett. 90, 2003, 83401-83405. 3. J. R.R. Verlet, A. E. Bragg, A. Kammrath, O. STM measurement of a single CdSe nanocrystal on Au substrate. Cheshnovsky and D. M. Neumark. Observation of I.) Surface topography II.) Photon emission map revealing high emission intensity Large Water-Cluster Anions with Surface-Bound at the apparent location of the nanocrystal. Excess Electrons. Science 307, 2005, 93-96.

Tel: (972)-3-6408325, (972)-3-6409293 Fax: (972)-3-6406997 Email: [email protected] Personal Website: www.tau.ac.il/chemistry/cheshn

21 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. M. Marcovitch and H. Diamant. Enhanced neither molecular liquids nor atomic or molecular dispersion interaction in confined geometry. Phys. Rev. Lett. 95, 223203 (2005). crystals. Examples include surfactant solutions, 2. A. Gopal, V. A. Belyi, H. Diamant, T. A. Witten, and K. polymer solutions, interfacial monolayers, Y. C. Lee. Microscopic folds and macroscopic jerks membranes, suspensions, and liquid crystals. The rich in compressed lipid monolayers. J. Phys. Chem. B phaseC behavior and dynamic response of such materials stem from 110, 10220 (2006). the existence of inner structures on an intermediate, nanometer-to- 3. R. Hadgiivanova and H. Diamant. Premicellar micron scale between the molecular and the macroscopic scales aggregation of amphiphilic molecules. J. Phys. Chem. B 111, 8854 (2007). (e.g., micelles, colloid particles, polymeric structures). The theoretical 4. H. Diamant. Long-range hydrodynamic response challenge is to account for the emergence of these structures, their of particulate liquids and liquid-laden solids. Isr. J. effect on material properties, and their various instabilities. Chem. 47, 225 (2007). In the past several years we have been focusing on the dynamics and 5. E. Haleva and H. Diamant. Critical swelling of flow properties of complex fluids, and on various effects caused by particle-encapsulating vesicles. Phys. Rev. Lett. micro- and nano-scale confinement. Recently studied systems have 101, 078104 (2008). included: (a) colloid suspensions in narrow channels; (b) particle- encapsulating vesicles; (c) fluid membranes with embedded proteins; (d) compressed surfactant monolayers; (e) surfactant aggregates (micelles); (f) membrane stacks (lamellar phases).

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

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

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

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

Dr. Oded Hod Chemistry

Computational Nano-Materials Science: towards electronic, spintronic, and electro-mechanical devices at the nanoscale

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 and commercial computational chemistry packages, operating on a highly parallelizable high-performance computer cluster, allows us to address the properties and functionality of a variety of systems ranging from carefully tailored molecular structures up to bulk systems. On top of basic science questions, the design of technologically applicable nanoscale material properties for future applications in fields such as nano-electronics, nano-spintronics, accurate and sensitive chemical References: sensing, and nano-mechanical devices, is being pursued. 1. V. Barone, O. Hod, and G. E. Scuseria, “Electronic Structure and Stability of Semiconducting Graphene Nanoribbons”, Nano Letters 6, 2748-2754 (2006). 2. 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). 3. O. Hod and G. E. Scuseria, “Half-metallic zigzag carbon nanotube dots”, ACS Nano 2, 2243-2249 (2008). 4. O. Hod, J. E. Peralta, and G. E. Scuseria, “Edge effects in finite elongated graphene nanoribbons”, Phys. Rev. B 76, 233401 (2007). 5. 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). 6. O. Hod, E. Rabani, and R. Baer, “Magneto-resistance of nanoscale molecular devices”, Acc. Chem. Res. 39, 109-117 (2006). 7. O. Hod, R. Baer, and E. Rabani, “Inelastic effects in Tel: (972)-3-6405850 Aharonov-Bohm molecular interferometers”, Phys. Email: [email protected] Rev. Lett. 97, 266803 (2006). Personal Website: http://www.tau.ac.il/~odedhod/

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

Prof. Joseph 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. Klafter Temporal 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 Molecules Proc. 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 Schryver Single Enzyme single enzyme reaction for extended periods of time (hours), using Kinetics of CALB Catalyzed Hydrolysis Angewandte 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. Szabo What 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 Trajectories Biophys. 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: www.tau.ac.il/~klafter

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

Prof. Gil Markovich Chemistry

Synthesis and Physical Studies of Colloidal Nanocrystals and Nanowires and their Assemblies

he group uses various colloidal chemistry methods to prepare inorganic nanocrystals, mostly of functional oxides or noble metals, and study their magnetic, optical, magneto-optical and magneto-resistive properties. The Langmuir-Blodgett technique is used by the group to prepare ordered close-packed monolayersT of magnetic nanocrystals. Spin polarized transport is studied in Fe3O4 nanocrystal films in various types of nanoscale devices and by scanning tunneling spectroscopy. The magnetic properties of these monolayers as well as multi-layer films were studied to learn about various physical aspects of such arrangements of strongly interacting superparamagnetic particles, especially with respect to the magnetization freezing transition. Another study on magnetic nanocrystals focuses on defect induced ferromagnetism in non-magnetic oxide nanocrystals, such as HfO2. Nanocrystals made of ferroelectric materials such as BaTiO3 are also currently being References: studied using electron holography, which is capable of imaging the 1. T. Fried, G. Shemer, and G. Markovich, “Ordered internal polarization fields in the nanocrystals and by this open a new Two-Dimensional Arrays of Ferrite Nanoparticles”, Advanced Materials 13, 1158-61 (2001). window into the largely unknown world of nano-ferroelectrics. 2. P. Poddar, T. Fried and G. Markovich, “First-Order Metal-Insulator Transition and Spin-Polarized Another field of research is the combination of chirality and surface Tunneling in Fe3O4 Nanocrystals”, Phys. Rev. B 65, plasmons of colloidal noble metal nanoparticles. The group has 172405 (2002). recently demonstrated the resonant enhancement of absorption 3. N. Taub, O. Krichevski, G. Markovich, “Growth of and circular dichroism in chiral molecules attached to silver Gold Nanorods on Surfaces”, J. Phys. Chem. B 107, 11579 (2003). nanoparticles. 4. O. Krichevski, E. Tirosh, G. Markovich, “Formation of silver-gold nanowires in thin surfactant solution In another project, wet colloidal chemistry techniques for the growth films”, Langmuir 22, 867 (2006). of metallic nanowire arrays on surfaces are being developed. A recent 5. G. Shemer, O. Krichevski, G. Markovich, T. development of a preparation of mixed gold-silver nanowires in a Molotsky, I. Lubitz, A. B. Kotlyar, “Chirality of Silver thin surfactant solution film on a substrate led to the formation of Nanoparticles Synthesized on DNA”, J. Am. Chem Soc. 128, 11006 (2006). very thin (3-5 nm thick) and micrometer long nanowire networks 6. I. Lieberman, G. Shemer, T. Fried, E. M. Kosower, which posses metallic conductivity and are highly transparent. G. Markovich, “Plasmon Resonance Enhanced Absorption and Circular Dichroism”, Angew. Chem. Int. Ed. 47, 4855-4857 (2008). Tel: (972)-3-6406985 7. E. Tirosh, N. Taub, S. A. Majetich, G. Markovich, “Scanning Tunneling Spectroscopy study of Fax: (972)-3-6405911 Temperature Dependent Magnetization Switching Email: [email protected] Dynamics in Magnetic Nanoparticle Arrays”, Isr. J. Personal Website: www.tau.ac.il/chemistry/markovich Chem. (in press).

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 recent series of papers that focus on the electron focused on particular types of interfacial transmission properties of water, arguably the systems and processes - those encountered in most important electron transmitting medium, the evolving field of Molecular Electronics. The has demonstrated a new resonance effect that possibility that molecules and small molecular explains the observed high efficiency of electron assemblies can replace conventional transmission through this medium. More recent Mconductors and semiconductors in nano-scale electronic devices has work has focused on analyzing the crucial issue become a subject of intense discussion. The new fundamental issues of thermal relaxation and heating effects as well associated with such systems - the electronic structure, the charge as heat conduction in molecular conductors transfer properties, energy transfer and relaxation and the capacitive that bear on the question of thermal stability of properties (to name just a few), of molecules connected to conducting such systems, and on developing a theoretical leads, present new theoretical and experimental challenges. Recent framework for understanding inelastic tunneling studies in our group aim at developing theoretical and numerical features and phonon induced non-linear response tools to study electron transmission through such interfaces. A of molecular conduction junctions. Our current studies aim at analyzing the possibility to probe and control of molecular junctions by light.

References: 1. A. Nitzan and Mark Ratner, Electron transport in molecular wire functions: Models and Mechanisms Science, 300, 1384-1389 (2003) 2. d. Segal, A. Nitzan and P. Hänggi, Thermal conductance through molecular wires J. Chem. Phys. 119, 6840-6855 (2003) 3. M. Galperin and A. Nitzan, Current-Induced Light Emission and Light-Induced Current in Molecular- Tunneling Junctions Phys. Rev. Letters 95, 206802 (2005)

Tel: (972)-3-6408904 Fax: (972)-3-6423765 Email: [email protected] Personal Website: 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. ofN reduced dimensionality, and their applications for addressing Lieber. Multiplexed, electrical detection of cancer important chemical, biochemical, physical and technological markers using nanowire sensor arrays. Nat. problems. Specifically, the research will focus on the synthesis, Biotechnol., 23, 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 combine (2006). tuneable optical, electrical and magnetic properties, as well as the 5. f. Patolsky and C. M. Lieber. Nanosensors and study and understanding of the mutual interactions between light, Future Medicine Nanomedicine, 1, 51-65 (2006). electricity, and magnetism at the nanometer scale. A major goal of 6. f. Patolsky, G. Zheng and C. M. Lieber. Nanosensors this research is to address the "structure-function" relationship, as and Future Medicine Nature 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-density biological and chemical detection area, with the aim to explore and nanowire transistor arrays. Science, 313, 1100-1104 exploit the nano-scale potential advantages in answering ‘open (2006). questions’ in biology.

Tel: (972)-3-6408437 Email: [email protected]

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

SEM images of cross-section of the LiI-P(EO) 9% γ–F 2O (8nm) electrolyte 3 2 3 Τ typically cast (a) and cast under a magnetic field gradient (b)

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

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

Dr. Moshe Portnoy Chemistry

Design and investigation of nanoscale dendritic composite materials for catalysis and biomedical applications

endrimers are branched, highly ordered few dendrimers have been prepared on solid macromolecules that are assembled in a modular, support. We developed an efficient synthesis of iterative fashion from polyfunctional building new poly(arylbenzylether) dendrons on solid blocks. The results of the process are not only polymer support, functionalized their termini aesthetically appealing but offer chemists three- with catalytic units and explored their properties. dimensional structures of nanometer-range size An unprecedented positive dendritic effect on Dwith a variety of interesting architecture-dictated properties for the Pauson-Khand intramolecular annulation a wide spectrum of applications. The modular mode of assembly was discovered when cobalt complexes of this and highly ordered nature of dendrimers make them especially dendrimer were used as reaction catalysts. An suitable for the building of nanoscale devices. During the past even more dramatic effect was demonstrated few years, my group actively pursued the preparation of dendritic with poly(arylbenzyl-ether)-dendrons for Pd- molecules on insoluble support as a platform for the generation of catalyzed Heck and Suzuki processes. Recently, highly active and selective heterogeneous catalysts. To date, very we began exploring dendrimers as platforms for diagnostic agents for molecular imaging.

References: 1. A. Dahan and M. Portnoy,Synthesis of poly(aryl- benzyl ether) dendrimers on solid support. Macromolecules 36, 2003, 1034-1038. 2. A. Dahan and M. Portnoy,A remarkable dendritic effect in the polymer-supported catalysis of the Heck arylation of olefins,Org. Lett. 5, 2003, 1197- 1200. 3. A. Dahan, A. Weissberg and M. Portnoy,Preparation of novel polythioether dendrons on solid support, Chem. Commun. 2003, 1206-1207. 4. A. Dahan and M. Portnoy, Dendrons and dendritic catalysts immobilized on solid support: synthesis and dendritic effects in catalysis, J. Polym. Sci.

Tel: (972)-3-6406517, (972)-3-6406518

Fax: (972)-3-6409293

Email: [email protected] Postal Address: School of chemistry, Tel Aviv University, Tel Aviv 69978

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

Prof. Eran Rabani Chemistry

Theory of nano-materials

Structure of nanomaterials structure. Our focus was mainly devoted to The development of atomistic models to study structural properties understand the role of the environment on these of semiconductor nanocrystals and carbon nanotubes is one of physical properties. We have been involved in the the major subjects of my research. We were the first to develop an development of novel algorithms to solve the atomistic force-field model for semiconductor nanocrystals. Our electronic structure of such large systems. model was used to explain the coverage of the different facets of the nanocrystal and the preferential growth of nanocrystals to Conductance and magnetoresistance in nanorods. 1D structures Using analytic continuum models and atomistic Self-assembly of nanoparticles empirical calculations we have shown that We developed an integral equation theory to study the interactions relatively small magnetic fields are required to between nanoparticles in solutions and more recently we developed control the current through a nanoring, despite a lattice-gas model to study drying mediated self-assembly of the fact that a ring at the nanoscale captures only nanoparticles. Our approach lays down the theoretical foundation of a small fraction of the magnetic flux. dynamical assembly of nanoparticles in 2D and 3D. References: Optical and electronic properties of nanomaterials 1. E. Rabani, Structure and Electrostatic Properties of Another focus includes the study of electronic and optical properties Passivated CdSe Nanocrystals, J. Chem. Phys. 115, 1493-1497 (2001). of semiconductor nanocrystals and other low dimensional quantum 2. E. Rabani, D.R. Reichman, P.L. Geissler, and L.E. Brus, Drying-Mediated Self-Assembly of Nanoparticles, Nature 426, 271-274 (2003). 3. o. Hod and E. Rabani, A Coarse-Grained Model for Nanometer Scale Molecular Pumps Proc. Natl. Acad. Sci. USA 100, 14661-14665 (2003). 4. o. Hod, R. Baer, and E. Rabani, A Parallel Electromagnetic Molecular Logic Gate, J. Am. Chem. Soc. 127, 1648-1649 (2005). 5. C.G. Sztrum and E. Rabani, Out-of-equilibrium self- assembly of binary mixtures of nanoparticles, Adv. Mater., in press (2005).

Simulations of the formation of out-of-equlibrium self-assembled superstructures

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

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

Dr. Shachar Richter Chemistry

The Bio and Molecular Electronics Group

he Bio and Molecular electronics group was founded in resistance properties at room temperature. 2003. Our main focus is on construction and electrical (ii) Film Formation From Dipeptide Nanotubes characterization of novel organic and bio-molecular In this research project we present a novel thin films and monolayers. On going projects: method to produce a new family of films based (i) Construction and characterization of molecular and on the controlled organization of diphenylalanine bio-photonic based devices Recently we constructed dipeptide nanotubes. Peptide-based nanotubes Ta working electronic device based on a vertical configuration, provide a new building block for bio- which consists of organic molecules and Photo-System I based nanotechnology, via self-assembly processes. nanoparticles adsorbed in a self assembled fashion between a Such nano-templates can be controlled to bottom gold electrode and a top palladium or ITO layer (Figure 1). Our produce films that present well-ordered self- prototype molecular device which was synthesized by Dr. M. Gozin aligned properties, and well-defined geometrical from TAU showed unique coulomb staircase and negative differential structure with nucleation centers and grain boundaries. This new family of films has been produced via control over the inter-molecular interactions between the nanotubes, and control over the polymerization process that is responsible for the construction of the film.

References: 1. g. Meshulam, N. Rosenberg, A. Caster, L. Burstein, M. Gozin, S. Richter ,Construction of dithiol-based nanostructures by a layer-exchange process, Small 1 (8-9): 848-851 2005. 2. N. Verleger, N. Rosenberg, M. Gozin, S. Richter, Influence of Junction-containing Alkanethiols on Molecular-based electronic devices and novel bio-organic thin films. Top (from Schottky Barrier Height at the Hg/WSe2 Interface”, left ro right): (i) A molecular-based device based on vertical configuration in which submitted for publication. the molecular layer is encapsulated between top and bottom electrodes. (ii) SEM 3. A. Caster, M. Meshulam, N. Rosenberg, H. Marom, A. image of the molecular device (iii) Differential conductivity data of molecular Holtzman, M. Gozin, S. Richter Fabrication of Vertical device based on ferrocene moiety. The coulomb blockade and the negative Ferrocene-based Molecular Devices. , submitted differential resistance properties of the molecule are clearly exhibited. Bottom for publication. (i) biophotonic device: a molecular device composed of nano-bio-photonic 4. N. Hendler, N. Seldelman E Gazit and S. Richter. particles is showing photo-conductivity properties. (ii) Thin films composed of From single peptide nanotubes to ordered thin dipeptide nanotubes (iii) thin films composed of dipeptide with embedded inside films. In preparation (dark cylindrical feature) 5. fabrication of molecular electronic device for measuring the electrical properties of organic molecules, A Caster and S. Richter U.S. provisional Tel: (972)-3-6405711 patent filed (2005)

Fax: (972)-3-6405612 Email: [email protected] Personal Website: www.tau.ac.il/~srichter

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

Dr. Yael Roichman Chemistry

Optical assembly of new materials and devices

ur group uses holographic optical tweezers in two deferent modes: we study interactions between microscopic objects that lead to organization, and we construct prototype materials and devices to address the technological issue of which materials and devices should be built. HOolographic optical tweezers (HOTs) use computer generated sequences of holograms which create dynamic arrays of optical traps. One direct application of HOTs is the manipulation of colloidal particle and their organization into interesting structures. We use the HOTs to construct new complex materials with optical properties such as metamaterials and photonic bandgap materials. Using several traps to manipulate a single particle enables us to trap, transport, fuse and cut non-spherical objects such as nanowires. A more sophisticated approach uses the holograms to change the mode of the laser light, generating potential landscapes which both trap and drive colloidal particles. These potential landscapes serve to create simple model systems in which organization in far-from-equilibrium conditions can be studied.

References: 1. Anomalous collective dynamics in optically driven colloidal rings, Y. Roichman, G. M. Zaslavsky and D. G. Grier, Physical Review E 75, 020401(R) CdS nanowires manipulated by HOTs: (2007). (a) trapping and transporting, (b) rotating, 2. Manipulation and assembly of nanowires with holographic optical traps, (c) rotation using an optical vortex, R. Agarwal, K. Ladavac, Y. Roichman, G. Yu, C. M. Lieber and D. G. Grier, (d) cutting, and (e) fusing. Optics Express 13, 8906-8912 (2005). (cond-mat/0509297) 3. optimized holographic optical traps, M. Polin, K. Ladavac, S. Lee, Y. Roichman and D. G. Grier, Optics Express 13, 5831-5845 (2005). (cond- mat/0504203) 4. 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 Email: [email protected]

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

Dr. Yoram Selzer Chemistry

Molecular Electronics Understanding the Physics and Chemistry of Single Molecule Junctions

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

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

Tel: (972)-3-6407361 Email: [email protected]

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

Prof. Yoram Shapira Engineering

Self assembly of organic and bio-molecules at semiconductor surfaces

rofessor Yoram Shapira aims at redirecting microelectronics to integrating new functions into the conventional microprocessor chip. Integrating mechanical, optical, chemical and biological technologies unto multi-functional chips will enable them not just to “think” but also to sense, see, act and communicateP with their operators, possibly within our bodies. There they can be utilized as micro-laboratories and biosensors as well as interact with bio-systems diagnostically, therapeutically and perhaps surgically.

Other fields of interest aim at getting complete understanding of carrier transfer via a molecule or a molecular film at the semiconductor/ organic interface implies understanding of: (1) the nature of the Surface electronic properties of semiconductors modified molecular levels relevant to charge transfer into the semiconductor by organic layers in nanometric dimensions are investigated using Surface Photovoltage Spectroscopy and transport through the molecular film, (2) the nature of the (SPS). SPS is a well-established contactless technique for chemical and electronic interactions between the molecule and the the characterization of semiconductors, which relies on surface and (3) the impact of molecular structure, i.e., of molecular analyzing illumination-induced changes in the surface orientation and order, and of neighboring molecules on the electronic voltage. structure of the semiconductor surface. This research is aimed at addressing these problems by conducting a parallel experimental References: and computational effort. Current activity is directed towards 1. A. Merson, Th. Dittrich, Y. Zidon, J. Rappich, Y. Shapira, studies of nanometer scale high-K oxide layers for 65-nm-design- “Charge transfer from TiO2 into adsorbed benzene rule transistors. The physical properties and reliability implications diazonium compounds”, Appl. Phys. Letters, 85, 1075, 2004. of these layers and their semiconductor interfaces are investigated. 2. J. Yang, K. C. Gordon, A. J. McQuillan, Y. Zidon, Y. The results of the preceding projects will be implemented in applied Shapira, “Photoexcited carriers in organic light programs for in-vivo drug delivery systems as well as distributed emitting materials and blended films observed by information-gathering micro-arrays. surface photovoltage spectroscopy”, Phys. Rev. , B 71, 155209, 2005. 3. 1. M. Gurfinkel, M. Borenstein, A. Margulis, S. Sade, Y. Fefer, Y. Weizman, Y. Shapira, “Study of hot-carrier- induced photon emission from 90 nm Si MOSFETs”, Appl. Surf. Sci., 248, 62, 2005 4. M. Gensch, K. Roodenko, K. Hinrichs, R. Hunger, A.G. Güell, A. Merson, U. Schade, Y. Shapira, Th. Dittrich, J. Rappich, N. Esser, “Molecule-solid Tel: (972)-3-6409452 interfaces studied with infrared ellipsometry: ultra- Fax: (972)-3-6405315 thin nitrobenzene films”, J. Vac. Sci. Technol., B 23, Email: [email protected] 1838, 2005. Personal Website: www.eng.tau.ac.il/~shapira/

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

Prof. R. L. Boxman, Prof. S. Goldsmith, Dr. N. Parkansky, Dr. V. Zhitomirsky 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, properties L. 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 of nano- and micro-particles in ethanol and their characterization” Powder Technology Vol. 150 "Forest" of erect multi-wall carbon nano-tubes desposited on a Ni-coated glass (2005) pp. 36-41. substrate at room temperature in open air, by a single 20 µs arc discharge.

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

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

Dr. Noam Eliaz Engineering

From Biomaterials to Space, from Hydrogen to Hydroxyapatite

r. Noam Eliaz has been involved in several projects related to Nano Science & Technology. These projects are consisted of both experimental and modeling work. Firstly, an MSc student (M. Eliyahu) used electrochemical atomic force microscopy to study in situ and ex situ the processes of nucleation and growthD as well as the microstructure of hydroxyapatite electrodeposited on titanium for biomedical applications. Electrodeposition of (a) (b) hydroxyapatite was shown to result from precipitation in solution, AFM deflection images acquired ex situ after: (a) 2 and (b) following two stages: (1) instantaneous nucleation, two-dimensional 60 min electrodeposition of hydroxyapatite on pure Ti at growth; (2) progressive nucleation, three-dimensional growth. Secondly, 85°C. The transition from a two-dimensional growth to a in a joint work with Soreq NRC, a model was developed to describe the three-dimensional growth is evident. processes involved in the irradiation of solid targets by femtosecond laser pulses and to predict the optimal target and laser parameters for References: efficient nanoparticles synthesis. Aluminum and carbon nanoparticles/ 1. N. Eliaz and M. Eliyahu, “Electrochemical Processes nanotubes were then successfully synthesized and characterized by of Nucleation and Growth of Hydroxyapatite on several analytical techniques. Thirdly, also in collaboration with Soreq Titanium Supported by Real Time Electrochemical NRC, an MSc student (R. Verker) constructed a laser-driven flyer ground Atomic Force Microscopy,” submitted. simulation system and used it to accelerate aluminum flyers to impact 2. S. Eliezer, N. Eliaz, E. Grossman, D. Fisher, I. Gouzman, velocities as high as 2.9 km/s against Kapton films with different Z. Henis, S. Pecker, Y. Horovitz, M. Fraenkel, S. Maman and Y. Lereah, “Synthesis of Nanoparticles thicknesses, thus simulation hypervelocity space debris impacts at low- with Femtosecond Laser Pulses,” Physical Review B, Earth orbits. Impact effects on the internal structure of the polymer 69(14) (2004), 144119-1 – 144119-6; Virtual Journal were studied by means of X-ray microtomography. Currently, the work of Nanoscale Science & Technology, 9(17) (2004); is being extended as a PhD work in which synergistic effects of space Virtual Journal of Ultrafast Science, 3(5) (2004). environment on durability of hybrid nano-composites will be studied. 3. S. Eliezer, N. Eliaz, E. Grossman, D. Fisher, I. Gouzman, Z. Henis, S. Pecker, Y. Horovitz, M. Fraenkel, S. Fourthly, an MSc student (V. Kalmanovitch) modeled the diffusion of Maman, V. Ezersky and D. Eliezer, “Nanoparticles hydrogen in various metallic glasses under different conditions of short and Nanotubes Induced by Femtosecond Lasers,” range order and diffusion paths. Both curvature of the Arrhenius plot Laser and Particle Beams, 23(1) (2005), 15-19. and an inverse Arrhenius law were observed. The effect of alloying 4. r. Verker, N. Eliaz, I. Gouzman, S. Eliezer, M. Fraenkel, elements on the activation energy of hydrogen diffusion was evaluated S. Maman, F. Beckmann, K. Pranzas and E. Grossman, in terms of their electronic structure and mean volume per atom. “The Effect of Simulated Hypervelocity Space Debris on Polymers,” Acta Materialia, 52(19) (2004), 5539-5549. 5. N. Eliaz, D. Ashkenazi and V. Kalmanovich, “Hydrogen Diffusion in Metallic Glasses: FCC-Like Short Range Tel: (972)-3-6407384, (972)-3-6407384 Order and the Non-Arrhenius Behavior,” submitted. Fax: (972)-3-6407617 Email: [email protected] Personal Website: www.eng.tau.ac.il/~neliaz/

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

Prof. Ilan Goldfarb Engineering

Surface Science and Nanostructures Laboratory

r. Goldfarb is mainly interested in self-assembled growth) can provide the means to control them and self-organized growth of epitaxial and perhaps even tailor-on-demand. Therefore, nanostructures inside STM. One way to self- the projects carried out in the laboratory are assemble nanostructures is to introduce strain aimed at exploring epitaxial materials systems into the growing layer by carefully controlling the with varying mismatch, such as Ge/Si [1] (see the mismatch between the crystalline lattices of the figure below), Ti/Si[2], Fe/Si [3], Co/Si [4], etc., in Dlayer and the substrate (heteroepitaxy). In other words, relaxation order to produce some generalized model(s), and of this strain drives the self-assembled formation of nanocrystal the ability to achieve degree of understanding arrays, which can be used in quantum-dot and -wire devices, and control sufficient for implementation in real provided the size and shape distribution of the nanocrystals in the devices. One of the strengths of the laboratory array is sufficiently narrow, and their degree of crystalline perfection is the rare ability to observe the evolution of the is high. Since these characteristics in self-assembled nanocrystals growing epilayers in real-space and -time by STM, are thermodynamically and/or kinetically determined, only deep due to state-of-the-art UHV SPM Microlab where understanding of these tendencies (that occur naturally during the deposition flux is incident upon the sample while it is being scanned and continuously imaged during growth.

References: 1. I. Goldfarb, Effect of strain on the appearance of subcritical nuclei of Ge nanohuts on Si(001), Phys. Rev. Lett. 95, 025501 (2005). 2. I. Goldfarb, G. Cohen-Taguri, S. Grossman, M. Levinshtein, Equilibrium shape of titanium silicide nanocrystals on Si(111), Phys. Rev. B 72, 075430 (2005). 3. I. Goldfarb, Synthesis of ultrathin semiconducting iron silicide epilayers on Si(111) by high-temperature flash, Surf. Sci. (Lett) 554, L87 (2004). 4. I. Goldfarb and G.A.D. Briggs, Reactive deposition epitaxy of CoSi2 nanostructures on Si(001): Nucleation and growth, and evolution of dots during anneal, Phys. Rev. B. 60, 4800 (1999).

Scanning tunneling microscopy (STM) micrograph of pyramidal Ge/Si(001) nanohuts

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

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

Dr. Yael Hanein Engineering

Microfluidics for self-assembly, nanotubes – neuron interfaces

ur research is focused on developing novel micro A third theme of our research is geared towards and nanofabrication techniques and systems. the realization of devices consisting of well Our main interest is in systems for biological ordered single walled carbon nanotubes. A newly applications. In the last several years we have developed method, we recently demonstrated, developed a novel class of carbon nanotube (CNT) establish the means to achieve precise positioning based micro electrodes, specifically designed of these tiny elements in a manner suited for the toO interface with neuronal systems. The enhanced electrochemical production of useful, commercial devices. properties of the electrodes, their flexible and simple micro-fabrication preparation procedure as well as their bio-compatibility and durability References: suggest that carbon nanotube electrodes are a promising platform 1. J. Clemmens, H. Hess, R. Lipscomb, Y. Hanein, Karl F. for high resolution capacitive electrochemical applications. Böhringer, Mechanisms of microtubule guiding on Microfabricated Kinesin coated surfaces: Chemical and Topographic Surface Patterns, Carolyn M. A second theme of our research concerns with a novel approach of Matzke, George D. Bachand, Bruce C. Bunker, Viola patterning cultured neural networks in which a particular geometry Vogel, Langmuir, 19, 10967-10974, 2004. is achieved via anchoring of cell clusters (tens of cells/each) at 2. Xuanhong Cheng, Yanbing Wang, Yael Hanein, specific positions. Compact connections among pairs of clusters Karl F. Böhringer and Buddy D. Ratner, Novel occur spontaneously through a single non-adherent straight bundle Cell Patterning Using Microheater Controlled Thermoresponsive Plasma Films, Journal of composed of axons and dendrites. The approach can be used to Biomedical Materials Research, 70A, 159-168, 2004. build advanced Neuro-chips for bio-sensing applications (e.g drug 3. Tamir Gabay, Eyal Jakobs, Eshel Ben-Jacob, and and toxin detection) where the structure, stability and reproducibility Yael Hanein, Engineered self-organization of neural of the networks are of great relevance. networks using CNT clusters, Physica A, 350, 611- 621, 2005. 4. 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, 7, 2666 -2671, 2007.

Neuronal cells on a small, high density CNT island and CNT based chip for recording and stimulation of neuronal systems.

Email: [email protected] Personal Website: www.eng.tau.ac.il/~hanein

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

Tel: (972)-3-6408245, (972)-3-6408139 Fax: (972)-3-6423508 Email: [email protected]

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

Prof. Gil Rosenman Engineering

Ferroelectric nanodomain polarization reversal and development of new generation of nonlinear photonic devices

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 Wettability engineering of Hydroxyapatite bionano- structures. Atomic Force Microscopy and Kelvin Probe Microscopy ceramics by surface potential modulation method. The variation of contact angle is in the range 10-100˚. Such a studies of ferroelectric domains, electronic properties of domains and wettability modification allows effective immobilization domain boundaries. Investigation of pyroelectric, piezoelectric and of various biological cells photovoltaic properties of ferroelectric with nanometer resolution. Hydroxyapatite. Semiconductor properties of Hydroxyapatite, electronic structure and optical properties. New method of wettability modification and bioactivation of bones implants. Wettability engineering for biocells adhesion. Wettability patterning and arrayed Hydroxyapatite in micro- and nanometer scale.

References: 1. g. Rosenman, P. Urenski, A. Agronin, Y. Rosenwaks, M. Molotskii, Submicron Ferroelectric Domain Structures Tailored by High Voltage Scanning Probe Microscopy, Appl. Phys. Lett., 82, 103 (2003) Fig. 1 (Top): Nanometer scale domain structures tailored using HVAFM for (a) 2. M. Molotskii, A. Agronin, P. Urenski, M. Shvebelman, nonlinear 2-D nonlinear optical converter (domains 1x1 mm); (b) domain grating G. Rosenman, and Y. Rosenwaks, Ferroelectric with period 410 nm for optical coupler (c) domain grating with period 500 nm for domain breakdown, Phys. Rev. Lett, 90, 107601 UV laser (2003) Fig. 2 (Bottom): 2D nanometer scale domain structures of tailored different 3. g. Rosenman, Y. Rosenwaks, P. Urenski, "Tailoring symmetry using IEB method in LiNbO for nonlinear photonic devices Domain Engineered Structures in Ferroelectric 3 Materials, US Patent No. 6,653,630, Nov. 25, 2003 Studies of physical properties of biological and 4. g. Rosenman, E.Weinbrand, "Ferroelectric domain reversal by indirect charged particle beam", biomimetic materials in nanometer scale Provisional Patent, November, 2004 Bones: Collagen and Hydroxyapatite. Nanoscale piezoelectric studies 5. C. Halperin, S. Mutchnik, A. Agronin, M. Molotskii, of bones. Nanoscale imaging of ferroelectric properties in bones. 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: www.eng.tau.ac.il/~gilr/

41 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 concentrating on: 1. M. Molotskii, P. Urenski, A. Agronin, M. Shvebelman, nanoscale electrical measurements, Kelvin probe G. Rosenman, and Y. Rosenwaks “Ferroelectric Domain breakdown”, Phys. Rev. Lett., 90, 107601-4, force microscopy (KPFM), nanodomain engineering in (2003). ferroelectrics, and local measurement of surface density 2. S. Saraf, M. Molotskii, and Y. Rosenwaks “Local of states in organic and inorganic semiconductors. Measurement of Surface States Energy Distribution TheP laboratory includes 5 KPFM systems operating in air, controlled in Semiconductors Using Kelvin Probe Force humidity, and ultra-high vacuum environments. Microscope”, Appl. Phys. Lett., 86, 172104-6 (2005). 3. o. Tal, N. Tessler, C. K. Chan, A. Kahn, and Y. Rosenwaks, “Direct determination of the hole density of states in undoped and doped amorphous organic films with high lateral resolution”, Phys. Rev. Lett., 95 256405-8.

Micrometer size organic thin film (10 nm thick) field effect transistor (OFET) measured by KPFM to extract the electronic density of states, charge carrier mobility, and Einstein relation in molecular amorphous materials.

Current Research Projects: • Nanoscale Potential Distribution in Organic Materials and Devices. • Nanoscale characterization of semiconductor surface states. • Nanostructured Ferroelectrics: a new technology for optical devices. • High Voltage AF M for various applications. • AFM tip– Semiconductor electrostatic interaction.

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

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

Prof. Arie Ruzin Engineering solid state detectors and devices laboratory

Activities related to atomic force microscopy and nano (Oxide/Nitride/Oxide) memory devices. We are scale characterization also involved in sub-micron device simulations, The activity in the laboratory is divided into macroscopic, microscopic using commercial TCAD software. and nano-scale electrical characterization, as well as simulation of solid state devices and radiation detectors in particular. The emphasis References: of the research is on radiation-induced defects as well as on as-grown 1. Inberg, A. Ruzin, I. Torchinsky, V. Bogush, Nathan defects. The radiation-induced defects are divided into point defects Croitoru, Y. Shacham-Diamand, "Annealing influence on electrical transport mechanism of and defect clusters. Many of the defects and defect complexes are electroless deposited very thin Ag(W) films", to be unstable near room temperature, and thus evolve with time changing published in Thin Solid Films. the material properties. We attempt to observe the electrical activity 2. Iris Visoly-Fisher, Sidney R. Cohen, Arie Ruzin, David of defect clusters by atomic force microscopy. Another aspect of the Cahen, "How polycrystalline devices outperform research is to study the electrical activity of chemically etched surface single crystal ones: The case of thin film compound of CdZnTe semi-insulating crystals. We were able to observe large solar cells", J. Adv. Mater., Vol. 16, No. 11, pp. 879-883 (2004). scale linear faults on the surface penetrating deep into the bulk, as 3. ruzin, I. Torchinski, I. Goldfarb, "Electrical shown in Fig. 1. measurements of structural defects in Cd0.9Zn0.1Te by Atomic Force Microscopy based methods", We are also involved in studies of thin films (<100 nm) for future Semicond. Sci. Technol. Vol. 19, pp. 644-647 (2004). microelectronic applications, etc. A relatively new activity starting these days involves study of trapped charge in sub-micron ONO

Fig. 1: Extended faults on the surface of etched CdZnTe. (a) Topography image with 5 nm height variations. (b) Surface potential difference image with 100 mV dynamic range

Tel: 972-3-640 5214 Personal Page: http://www.eng.tau.ac.il/~aruzin/

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

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

44 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

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

45 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 doing so. We further hypothesize that removal blind as a result of devastating disease or of the non-permissive cures and supplement the trauma. In the Western world, the main factors RGCs with axonal growth promoting substances leading to blindness are diseases such as will lead to axonal functional regeneration. Based diabetes, age related macular degeneration on these hypotheses we intend to use holistic (AMD) and glaucoma, or traumas such as car approach that combines nanotechnological Mand work accidents, terrorism and wars. In the third world, malnutrition methodologies that will supplement the neurons as well as infective and toxic alimentation are the leading factors of with the necessary cues that will accelerate their blindness. Our work is based on our hypothesis that retinal ganglion growth. Our specific aims are: (i) Implantation of cells (RGC) are capable of growing their axons following injury; biodegradable three-dimensional scaffold in the however, the non-permissive environment prevents them from optic nerve and assessing its ability to promote RGC survival and axonal regeneration. (i) Spatial and temporal controlled secretion from specially designed nano-structures that will implanted in the optic nerve. (iii) Implantation of nano- chips and electrodes in the optic nerve in order to generate biofeedback necessary to maintain homeostatic conditions.

References: 1. Shirvan, A., Ziv, I., Fleminger, G., Shina, R., He, Z., Brudo, I., Melamed, E., and Barzilai, A., Semaphorins as mediators of neuronal death. J. Neurochem. 73 961-971 (1999). 2. Shirvan, A., Melamed, E., and Barzilai, A., Induction of neuronal apoptosis by semaphorin 3A derived peptide. Brain Res. Mol. Brain Res. 83 81-93 (2000). 3. Shirvan, A., Kimron, M., Holdengreber, V., Ziv, I., Melamed, S., Melamed, E., Barzilai, A., and Solomon, A.S., Anti sema3A antibodies resuce retinal ganglion cells from cell death induced by optic nerve axotomy. J. Biol. Chem. 277 49799-49807 (2002).

Tel: (972)-3-6409782, (972)-3-6407129 Fax: (972)-3-6407643 Email: [email protected]

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

References: We have no publications, yet, that resulted from our Nano acitivity. We do have a patent application: Yacobi, Y., Ron, E.Z., Shabat, D., Shamis, M., Benhar, I. (2005). Targeted drug-carrying viruses. US Provisioinal Targeted drug-carrying phage nanoparticle: general scheme application submitted.

Tel: (972)-3-6407511, (972)-3-6407510 Fax: (972)-3-6409407 Email: [email protected] Personal Website: www.tau.ac.il/lifesci/biotechnology/benhar

47 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 conversion efficiency of 58%. It was found that the highly efficient photosynthetic reaction center the self assembled dry PS I retained its activity protein in solid state scaffolds. The assembly of the as it generated a reversible photovoltage of 1 soft protein-made photosystem I (PS I) into a solid V as measured by KPFM1,2. A photocurrent of state scaffold without damaging the activity is very 0.35A/cm2 was measured when the oriented self challenging therefore the robust chlorophyll-protein assembled monolayer of PS I on metal electrode PSP I reaction center from cyanobacteria was selected. Induction was capsulated in a nitride micro cell and toped of cysteine mutants in the outer loops of this membrane protein with the transparent indium tin oxide electrode. enabled fabrication of oriented self assembled monolayer by These photovoltaic devices are being used for formation of sulfide bonds to metal electrodes as determined by development of cost effective solar cells. It can be AFM. In the biological membranes the efficient PS I generates light- applied in the development of bio-nano-photo- induced vectorial charge transfer across nano size protein creating sensors, in artificial vision and as photo-switches a potential of 1 V in 200 ns at quantum efficiency of 1 and energy in molecular electronics.

References: 1. Frolov, L.; Rosenwaks, Y.; Carmeli, C.; Carmeli, I. Fabrication of Photo-Electronic Device by Direct Chemical Binding of the Photosynthetic Reaction Center Protein to Metal Surfaces. Adv. Mater. 2005, 17, 2434-2437. 2. Pending # 60/654,502, (2005) Fabrication of nano- photoelectrical devise from photosystem I

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]

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

Prof. Amihay Freeman Life Sciences

Biotemplating by stabilized protein crystals; Directed metallization of biologically active proteins and cells

iotemplating of synthetic gels and metals by stabilized protein crystals for the fabrication of novel composite materials: [1,2]. The project involves design, preparation and characterization of protein crystals used as biotemplates [3] and studies on factors affecting the voids array formed within protein crystals. This project involvedB 4 PhD programs : two submitted and approved and two ongoing. These projects are carried out in collaboration with Prof Frolow from our department and served as basis for its extension to collaboration with Prof Gurevitch from Plant Sciences.

Directed metallization of biologically active proteins and cells for the fabrication of nanosized biosensors and biochips: [ref 4 & two patent applications]. The feasibility of new methods for the fabrication of active protein-metal hybrids was demonstrated. Adaptation of these methods for the metallization of microbial cells is ongoing. Stabilized lysozyme crystal template This project is carried out in collaboration with Prof. Shacham from Physical Electronics and Prof. Rishpon from our department.

References: 1. Cohen-Hadar N, Wine Y, Nachliel E, Huppert D, Gutman M, Frolow F & Freeman A (2005) Biotemplating of synthetic gels by stabilized protein crystals. Submitted to Biotechnol & Bioengineer. 2. dotan N, Cohen N, Kalid O & Freeman A (2001) Supramolecular assemblies made of biological macromolecules. In Nanosurface chemistry (Rosoff N.,Ed) pp 461-471, Marcel Dekker. 3. dotan N, Arad D, Frolow F & Freeman A (1999) Self–assembly of a tetrahedral lectin into predesigned diamond-like protein crystals. Angewandte Chemie Int Ed 38:2363-6. Shacham-Diamand Y, Inberg A, Sverdlov Y, Croitoru N, Moskovich H & Freeman A (2003) Electroless processes for micro and nano-electronics.

Electrochim Acta 48:2987-96.

Glucose oxidase silver hybrid

Tel: (972)-3-6409054 Fax: (972)-3-6405147 Email: [email protected]

49 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 needed for efficient assembly into well-ordered, the hallmark of several diseases of unrelated origin, stiff, and elongated nanotubes with a remarkable including Alzheimer’s disease, Type II diabetes, persistence length, that could serve as a mold for and Parkinson’s disease. We suggested, based on the fabrication of nanoscale inorganic material. experimental and bioinformatical analysis, that We later reveal that diphenylglycine, a highly aromatic stacking interactions may provide energetic similar analogue and the simplest aromatic contributionT as well as order and directionality in the self-assembly dipeptide, forms spherical nanometric assemblies. process. Our model recently gained experimental and theoretical These properties of the peptide nanostructures, support from leading groups and it serves as the basis for the taken together with their biological compatibility development of novel therapeutic agents to treat the disorders. and remarkable mechanical, and chemical In the path of our reductionist approach toward the identification stability, may provide very important tools for of the shortest motifs that mediate the assembly of the fibrils, we future nanotechnology applications. We recently demonstrated that the diphenylalanine core-recognition motif of demonstrated the ability of the nanotubes to the Alzheimer’s b-amyloid contains all the molecular information serve in advanced electrochemical sensing.

References: 1. reches, M., & Gazit, E. (2003) Casting Metal Nanowires within Discrete Self-Assembled Peptide Nanotubes. Science 300, 625-627. 2. reches, M., & Gazit, E. (2004) Formation of Closed- Cage Nanostructures by Self-Assembly of Aromatic Dipeptides. Nano Lett. 4, 581-585. 3. yemini, M., Reches, M., Rishpon, J., & Gazit, E. (2005) Novel Electrochemical Biosensing Platform Using Self-Assembled Peptide Nanotubes. Nano Lett. 5, 183-186. 4. Kol, N., Abramovich, L., Barlam, D., Shneck, R. Z., Gazit E. , & Rousso, I. (2005) Self-Assembled Peptide Nanotubes Exhibit Unique Mechanical Stiffness. 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: www.tau.ac.il/~ehudg

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

Prof. Yoav I. Henis Life Sciences

Nano-Scale Lipid Domains and Their Role in Ras Signaling

e study the dynamics of the interactions References: of proteins with cholesterol-enriched 1. Niv, H., Gutman, O., Kloog, Y. and Henis, Y.I. (2002) nanoscale lipid domains (lipid rafts) in the Activated K-Ras and H-Ras display different interactions with saturable nonraft sites at the membranes of live cells. Such domains surface of live cells. J. Cell Biol. 157, 865-872. are believed to play important roles in 2. Shvartsman, D.E., Kotler, M., Tall, R.D., Roth, M.G. cellular signaling. Although extensively and Henis, Y.I. (2003) Differently anchored influenza characterizedW in artificial membranes and in detergent-resistant hemagglutinin mutants display distinct interaction membrane fractions, their existence in live cells is under debate. We dynamics with mutual rafts. J. Cell Biol. 163, developed biophysical methods based on fluorescence recovery 879-888. 3. rotblat, B., Prior, I.A., Muncke, C., Parton, R.G., Kloog, after photobleaching (FRAP) to study rafts in live cells. By changing Y., Henis, Y.I. and Hancock, J.F. (2004) Three separable the area illuminated by a submicron laser beam, in combination with domains regulate GTP-dependent association of cholesterol depletion treatments, we can differentiate between lateral H-ras with the plasma membrane. Mol. Cell Biol. 24, diffusion and membrane-cytoplasm exchange, and investigate the 6799-6810. role of nanoscale rafts in controlling the membrane interactions and 4. Roy, S., Plowman, S., Rotblat, B., Prior, I.A., Muncke, signaling of Ras proteins. These proteins regulate cell growth, and C., Grainger, S., Parton, R.G., Henis, Y.I., Kloog, Y. and Hancock, J.F. (2005) Individual palmitoyl constitutively active Ras mutations contribute to the development of residues serve distinct roles in H-Ras trafficking, many human tumors. These studies can pave the way to understand microlocalization, and signaling. Mol. Cell Biol. 25, the regulation of differentR as signaling pathways and to find ways to 6722-6733. disrupt Ras signaling.

Tel: (972)-3-6409053, (972)-3-6423766 Fax: (972)-3-6407643 Email: [email protected] Personal Website: www.tau.ac.il/lifesci/neurobiochemistry/fac

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

G4-DNA molecular wire. Left panel - Schematic presentation of 4G-wire; right panel - AFM image of 4G wire.

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

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

Prof. Rimona Margalit Life Sciences

Drug delivery by nano-particles based on biomaterials: biophysical properties, cell-particle interactions and therapeutic responses

ur efforts in the drug delivery arena focus on two and human xenograft mouse tumor models. drug delivery technologies that are inventions Neoplasia 6, 343-353. of our group. Both are based on biomaterials, 3. Peer D, Margalit R. Tumor-targeted hyaluronan nano-liposomes increase the antitumor activity and can form vesicular nano-sized particles. of liposomal doxorubicin in syngeneic and human The particles of one technology are named xenograft mouse tumor models. Neoplasia 6 (2004), Bioadhesive Liposomes (BALs), consisting of 343-353. regular liposomes - hence their shell is a lipid bilayer membrane. 4. Margalit R., Peer D. Lipidated glycosaminoglycan O particles and their use in drug and gene delivery Surface-modification by covalent binding of target-recognition agents such as hyaluronan, collagen, EGF or gelatin to the liposomal for diagnosis and therapy. Published patent application US2004241248 (2004). surface, renders them bioadhesive. The particles of the second technology are named gagomers (GAGs), their shell is made of hyaluronan, and their interior contains water and lipids. The goal is to apply such nano particles as drug carriers for the treatment of pathologies such as tumors, infectious diseases and inflammations, that require systemic administration, in order to improve deficiencies of treatment with free drugs, as the latter lead to poor therapeutic responses and to treatment failures. Our conceptual approach, for any project, is to start at the molecular level and proceed systematically to studies in cell cultures, and then to animal studies. At the molecular level we investigate structural, physicochemical and biochemical properties of these nanoparticles. In cell cultures we explore cell–carrier interactions with particular emphasis on: kinetics and thermodynamics of cell-carrier binding, cellular localizations of carrier and drug, the mechanisms by which carrier-mediation affects drug entry into cells, and therapeutic activity. The in vivo studies focus on pharmacokinetics, drug and carrier biodistributions, adverse effects, and therapeutic responses.

References: 1. Peer D, Florentin A, Margalit R. (2003) Hyaluronan is a key component in cryoprotection and formulation of targeted unilamellar liposomes. Biochim. Biophys. Acta 1612, 76-82. 2. Peer D, Margalit R. (2004) Tumor-targeted hyaluronan nano-liposomes Drug delivery to tumor cells mediated by targeted increase the antitumor activity of liposomal doxorubicin in syngeneic nano carriers. Left-hand side: Bioadhesive Liposomes bound to mouse melanoma cells. Drug load (fluorescein, green fluorescence) is localized at Tel: (972)-3-6409822 the cell membrane. Right-hand side: Gagomers (red Fax: (972)-3-6406834 fluorescence) bound to mouse leukemia cells. Drug Email: [email protected] load (doxorubicin, red fluorescence) is localized inside the cell.

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

Dr. Dan Peer Life Sciences

Selective targeting and reprogramming of leukocytes using fully degradable nanomedicines

ur lab is studying how to manipulate cells’ designing highly selective targeting moieties functions in order to generate novel therapeutic and novel nanocarriers, with an ultimate goal strategies to treat inflammatory diseases and to translate some of our findings into clinical cancers. We are combining a multidisciplinary settings. approach including immunology, cell and molecular biology, genetics, protein engineering, We are particularly interested in materialO sciences, nanotechnology and computational techniques 1. Identifying key genes responsible for to develop innovative therapeutics to target specific cells within the pluripotent hematopoietic stem cells self- immune system. In addition, we are developing nanomedicines by renewal properties. 2. Studying the role of cell cycle regulators in proliferation, migration, and cytokine production in lymphocytes, macrophages and dendritic cells during inflammatory bowel diseases and rheumatoid arthritis . 3. developing and studying novel approaches to target cancer stem cells. 4. harnessing siRNAs and miRNAs as novel tools for drug discovery and for therapeutic applications.

References: 1. Peer D , Zhu P, Carman CV, Lieberman J and Shimaoka M. (2007). Selective gene silencing in activated leukocytes by targeting siRNAs to the integrin lymphocyte function- associated antigen-1. Proc. Natl. Acad. Sci. USA , 104, 4095-4100 . 2. Peer D, Karp JM, Hong S, Farokhzad O, Margalit R, and Langer R (2007). Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnology. 2,751-760. 3. Peer D , Park EJ, Morishita Y, Carman CV, and Shimaoka M (2008). Systemic Leukocyte-Directed Selective targeting of siRNAs (red) into activated lymphocytes (green)using fusion siRNA Delivery Revealing Cyclin D1 as an Anti- protein that target conformation-selective integrin LFA-1. Naive cells (not stained) Inflammation Target. Science . 319, 627-630 . do not uptake siRNAs.

Tel: (972)-3-6407925 Fax: (972)-3-6407925 Email: [email protected] Personal Website: http://www.tau.ac.il/lifesci/departments/cell_r/members/peer/peer.html

54 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 [1]. Voltammetric and time based amperometric We have effectively exploited the unique electronic properties of techniques were applied to demonstrate the carbon nanotubes (CNT) in electrochemistry as a means of promoting significantly improvement electrochemical the electron transfer reaction for the development of enzyme based parameters by the PNT. These findings clearly sensors. CNT were attached to gold or carbon electrodes and applied show that this novel class of peptide nanotubes in a sensitive detection of hydrogen peroxide employing the enzyme provides an attractive component for future horse reddish peroxidase immobilized on a CNT modified electrode. electroanalytical biosensors. This sensor was capable to measure enzymatic activity released from Lipid nanolayer on gold electrode the mycobacteria smegmatis (a model system for mycobacteria We have investigated interactions between tuberculosis). CNT attached to electrodes were also exploited in a receptors and hormone by following the highly sensitive electrochemical enzyme immunosrnsors. impedance changes in 5-7nm thick lipid Peptide nanotubes on amperometric electrodes bilayers on gold electrodes. The system respond In addition, we have examined the possibility of employing peptide to estrogen or testosterone at physiological nanotubes (PNT) as catalytic elements in amperometric biosensors concentrations. Moreover, it enables the detection of xenohormones like xenoestrogens that are a health risk in the environment [2]. Lab on a Chip We developed an innovative electrochemical ‘lab on a chip’ system that integrates the applicability of physiological reactions to serve as biosensors with the advantages of micro electro mechanical systems (MEMS). The novel specific design and process of the nano-biochip adjusted to an exclusive biochemical process enables highly accurate, sensitive and rapid diagnosis of physiological reactions by a hand held miniaturize device [3]. This system was used in the detection the response of microorganisms to acute toxicity in water. References: 1. M. Yemini, M. Reches, J. Rishpon and E. Gazit, Nano letters 5: 83-186 (2005) 2. V Sacks-Granek and J. Rishpon, Environ. Sci Tech., 36, 1574-1578 (2002) Tel: (972)-3-6409366, (972)-3-6407525 3. r. Popovtzer, T. Neufeld, D. Biran, EZ. Ron, J. Rishpon, Fax: (972)-3-6409407 and Y. Shacham-Diamand Nano Letters 5, 1023 – Email: [email protected] 1027 (2005).

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

Ionic channels in the myocardium

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

56 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 single molecules or molecular assemblies that pro- vide structure, control, signaling, homeostasis, and motility in cells, i.e., at the “nano” scale of about 100 mm or less. There have been many scientific and tech- nological advances in both physical and biological sciencesN over the past several years that make nano medicine research particularly attractive at this time. New tools are being developed that permit imaging of structure at this scale, high-speed measurement of Stem cells differentiation, Cell on Chip, Surface functionalisation and nanopatterning, Nanotechnology applied to living cells, In- the dynamic behavior of these molecular assemblies, and the forces pro- vivo imaging, Molecular regulation, Nanotechnologies & cancer, duced by molecular machines as well as the forces needed to disrupt Converging technologies them. These advances are complemented, on the biological side, by the develop molecular and biochemical platform that dramatically expanded knowledge of the human genome, a greater un- enables the isolation and manipulation of the stem derstanding of the pathophysiology of specific diseases at the molecular and progenitor cells to differentiation. The regulato- scale, the need to develop more specific treatments of disease, and the ry circuit will be applied and will enable the knowl- desire to understand the dynamic behavior of dysfunctional cellular ma- edge to set up the conditions for cells expansion and chinery in the context of the total cell machinery. The need for more pre- maintaining their phenotype and control the stem cise measurements of the behavior of the nanomachinery within cells cells differentiation to utilize the cells as biomedical combined with the expanding array of tools capable of making these devices. This approach will lead to explore the en- measurements led to the identification of Nanomedicine theme of “New coded information relevant to cells differentiation in Pathways to Discovery”. specific contacts that will enable to produce well- Stem cell has a broad use in cell therapy and tissue engineering. Mesen- defined populations of programmed cells. It will lead chymal stem cells derived from the bone marrow are able to differenti- to numerous applications in the fields of molecular ate to various lineages: osteogenic, chondrogenic and muscle cells or medicine and cellular Nano-biotechnology that can behaves more plastic and differentiates to other tissues. Before stem cells apply to a new approach to bioengineering. can be used for cell therapy, the definition of their identity and cultur- ing conditiones needs to be explored. The research conducted at the References: laboratory is to answer the question of mesenchymal stem cells (MSC) 1. Luboshits G., Benayahu D. 2005. MS-KIF18A, new kine- identity. We are using animal models of to retrieve mesechymal tissues sin; structure and cellular expression. Gene 351, 19-28. and to culture MSCs to analyze their gene profiling. Micro array used to 2. Shur I., Benayahu D. 2005. Characterization and Func- explore the gene expression and analysis of growth factor, hormone, and tional Analysis of CReMM, a Novel Chromodomain genes of signaling pathway involved in cell activation and differentiation Helicase-DNA-binding Protein. J Mol Biol. 352(3): 646- according to tissue source and profiling. This knowledge will enable to 655. 3. Benayahu D., Akavia U. D., Socher R., Shur I. Gene Ex- pression in Skeletal Tissues: Application of Laser Cap- ture microdissection. J of Microscopy 220 (Pt 1):1-8. Tel: (972)-3-6406187 4. Shur I, Socher R, Hameiri M, Fried A, Benayahu D. 2005. Fax: (972)-3-6407432 Molecular and cellular characterization of SEL-OB/ Email: [email protected] SVEP1 in osteogenic cells in vivo and in vitro J Cell Physiology (In Press).

57 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 effectiveT therapies while eliminating the potential for both under- and blood cell membrane mechanical fluctuations overdosing, we have developed a novel methodological platform to in non-proliferative and proliferate diabetic induce highly efficient transfer of specifically designed nanoparticles retinopathy. Graefes Arch Clin Exp Ophthalmol. 242: 937-43. carrying drugs into cells. The method is based on exposure of cells to 3. Antov, Y. Barbul, A.Mantsur H.and Korenstein, R trains of low unipolar electric fields which leads to an efficient uptake (2005) Electroendocytosis: Exposure of cells to of macromolecules and nanoparticles into cells. One application of pulsed low electric fields enhances adsorption and this methodology is the treatment and cure of solid tumors in mice uptake of macromolecules. Biophys J. 88: 2206-23. 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)-3-6406042, (972)-3-6406042 Fax: (972)-3-6408982 Email: [email protected]

58 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 development of new drug delivery systems that cells, tumor vasculature and non-endothelial tumor mediate drug release selectively at the tumor site. stroma. The ability of cancers to grow is dependent on Multimodality targeted nanomedicines offer the the formation and maintenance of new blood vessels potential for improved efficacy and diminished from pre-existing vasculature in a complex process toxicity. One way to achieve such selectivity is referred to as Angiogenesis (Figure 1). Tumors may to activate a prodrug specifically by a confined remainT small and dormant if unable to elicit functional angiogenesis. enzymatic activity. In this concept, the enzyme is Consequently, the microvascular endothelial cell, recruited by a tumor, either expressed by the tumor cells or the tumor has become a paramount factor in tumor progression and metastases endothelial cells, or is brought to the tumor by formation making both the tumor cells and their surrounding stroma a targeting moiety. The prodrug is converted to a target for combined anticancer and anti-angiogenic therapy. an active drug by the local or localized enzyme at the tumor site. Alternatively, the lower pH in the tumor microenvironment can be utilized for selectively activating a prodrug. Our strategy for advancing the field of vascular biology and the development of vascular targeting nanomedicines is by: 1. Characterization of tumor vasculature for tailored-made therapy. Identifying new molecular markers on tumor endothelial cells in order to develop better drugs and better targeting moieties. 2. Design of novel nanocarriers as strategies Figure 1. The angiogenic switch and the use of nanomedicines, such as Polymer to target angiogenesis inhibitors to Therapeutics (A), to treat angiogenic tumors (B-C). The enhanced permeability tumor vasculature. To improve the and retention (EPR) effect allows nanoconjugates to extravasate through the therapeutic index of chemotherapeutic and tumor leaky vessels (D-E), accumulate in the tumor bed selectively and internalize into the tumor epithelial and tumor endothelial cells via endocytosis (F). antiangiogenic agents by conjugation to polymeric nanocarriers. Selective therapy remains a key issue for successful treatment in 3. Investigation of the mechanism of action cancer therapy. Prolonged administration of effective concentrations of angiogenesis inhibitors (endogenous of chemotherapeutic or anti-angiogenic agents is usually not and pharmacological inhibitors). possible because of dose-limiting systemic toxicities involving 4. Intravital non-invasive molecular non-malignant tissues. Therefore, a constant effort has been the imaging of treated tumor-bearing mice to follow tumor progression, pharmacodinamics and pharmacokinetics of the synthesized Tel: (972)-3-6407427 nanomedicines. Fax: (972)-3-6409113 Our lab has recently designed some novel anti- Email: [email protected] angiogenic and antitumor polymer-drug nano-

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

conjugates (Figure 2). Our results point at our polymer therapeutics 5. Satchi-Fainaro R and Barnés CM, Drug delivery as novel bi-specific nano-conjugates targeting both the tumor systems to target the tumor vasculature and the epithelial and endothelial compartments warranting their use on a tumor cell, Drug Delivery Companies Report, Spring /Summer, 43-49 (2004). wide spectrum of primary tumors and metastatic ones. 6. Satchi-Fainaro R, Mamluk R, Wang L, Short S, Puder M, Nagy J, Feng D, Dvorak AM, Dvorak HF, Mukhopadhyay D and Folkman J, Inhibition of vascular leakiness and angiogenesis by TNP-470 and its polymer conjugate, caplostatin, Cancer Cell, 7(3), 251-261 (2005). 7. duncan R, Ringsdorf H and Satchi-Fainaro R, Polymer therapeutics--polymers as drugs, drug and protein conjugates and gene delivery systems: past, present and future opportunities. Journal of Drug Targeting, 14(6):337-41 (2006). 8. Sagi A, Segal E, Satchi-Fainaro R* and Shabat D*, Dramatic drug-release enhancement with an

elimination-based AB3 self-immolative dendritic amplifier, Bioorganic and Medicinal Chemistry, 15, 3720–3727 (2007). * Corresponding authors. 9. Segal E and Satchi-Fainaro R, Design and Development of polymer conjugates as anti-angiogenic agents, Special Theme issue: Polymer Therapeutics: Clinical Applications and Challenges for Development, Advanced Drug Delivery Reviews, in press (2008). Figure 2. Intravenous administration of a FITC-labelled polymer-drug nano- 10. Ryppa C, Mann-Steinberg H, Biniossek M, Satchi- conjugate with a diameter size of 100 nm into: (a) Normal vasculature adjacent Fainaro R* and Kratz F*, In vitro evaluation of to (b) tumor blood vessels in a subcutaneous implanted osteosarcoma. paclitaxel conjugates with the divalent peptide Tumor vessels demonstrate exaggerated size, tortuosity, and permeability. (c) E-[c(RGDfK)2] that target integrin αvβ3, International Internalization of a FITC-labelled (green) nano-conjugate (d) into a human Journal of Pharmaceutics, in press (2008). umbilical vein endothelial cell (HUVEC). *Corresponding authors. 11. Satchi-Fainaro R, Duncan R and Barnes CM, In References: Advances in Polymer Science, Polymer Therapeutics: 1. Satchi R, Connors TA and Duncan R, PDEPT: Polymer-directed enzyme current status and future challenges, 193, Springer- prodrug therapy. HPMA copolymer-cathepsin B and PK1 as a model Verlag, Germany, 1-65 (2006). combination, British Journal of Cancer, 85 (7) 1070-1076 (2001). 12. Satchi-Fainaro R and Mann-Steinberg H, TNP-470: 2. Satchi-Fainaro R, Targeting tumour vasculature: reality or a dream?, Journal The resurrection of the first synthetic angiogenesis of Drug Targeting, 10 (7) 529-533 (2002). inhibitor, In: Angiogenesis: An integrative approach 3. Satchi-Fainaro R, Hailu H, Davies JW, Summerford C and Duncan R, PDEPT: from science to medicine. Editors: William Figg and Polymer directed enzyme prodrug therapy. II. HPMA copolymer- Judah Folkman, Springer-Verlag, Germany, 387-406 β-lactamase and HPMA-Cephalosporin-Doxorubicin as a model (2008). combination, Bioconjugate Chemistry, 14 (4), 797-804 (2003). 13. Miller K and Satchi-Fainaro R, Polymer Therapeutics: 4. Satchi-Fainaro R, Puder M, Davies J, Tran H, Greene AK, Corfas G and Folkman From novel concepts to clinical applications, In J, Targeting angiogenesis with a conjugate of HPMA copolymer and TNP- Wiley Encyclopedia of Chemical Biology, John 470, Nat. Med., 10(3), 255 (2004). Wiley & Sons, Inc. in press (2008).

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

Dr. Ella Sklan Medicine

Interactions of positive strand RNA viruses with the host cell

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

Tel: (972)-3-6409872 Fax: Email: [email protected]

61 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 Email: [email protected]

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

Dr. Ilan Tsarfaty Medicine

Nanoparticles Based Met-HGF/SF Molecular Imaging

rowth factors and their receptors that play HGF/SF coupled to biotin was used important roles in normal development have in scatter assay to demonstrate that HGF/SF retained its biological often been implicated in tumorigenicity and activity. Biotnylated HGF/SF was metastasis. In the past years, attention has incubated with Met expressing focused on the role of the tyrosine kinase growth DA3 cells, the cells were fixed and factor receptor Met and its ligand, hepatocyte stained with Quantum Dot Avidin nanoparticles (Red) and subjected Ggrowth factor/scatter factor (HGF/SF), in metastasis. HGF/SF to confocal laser microscopy. The Red staining demonstrates the is a paracrine factor produced primarily by mesenchymal cells internalization of the ligand into the cells that induces mitogenic, motogenic, and morphogenic effects on a wide variety of cells. Met-HGF/SF signaling can increase receptor and their ligand in vitro and in vivo. We production of proteases and urokinase, which are important for utilize confocal based intravital molecular and high metastasis and induce angiogenic activity. HGF/SF transgenic resolution MRI imaging to visualize the expression mice develop a broad array of histologically distinct tumors. of the receptor and its interaction with the ligand Mutations in the Met tyrosine kinase domain have been identified in vivo and in vitro. in both hereditary and sporadic forms of human papillary renal References: carcinoma. Furthermore, Met and HGF/SF have been implicated 1. Shaharabany, M., Abramovitch, R., Kushnir T, Tsarfaty in breast cancer. G, Ravid-Megido M, Horev J, Ron R, Itzchak Y, Tsarfaty We are developing Met-HGF/SF nanoparticles based direct molecular I. In vivo molecular imaging of Met tyrosine kinase growth factor receptor activity in normal organs imaging modalities for in vivo imaging of tumors, lymph nodes, and distal and breast tumors. Cancer Res. 15;61(12):4873-8. metastasis. Fluorescent gold- and gadolinium-based nanoparticles are 2001 coupled to antibodies against Met or coupled to HGF/SF. The labeled 2. yerushalmi G. M., Leibowitz-Amit R., Shaharabany proteins retained their biological activities. Cellular molecular imaging M. and Tsarfaty, I. Met-HGF/SF Signal Transduction techniques are used to study the interaction between the Ab/ligand Induces Mimp, a Novel Mitochondrial Carrier to the receptor. We are also developing high-resolution functional Homologue Which Leads to Mitochondrial Depolarization. Neoplasia 4(6): 510-22, 2002. molecular optical and MRI techniques to image Met and HGF/SF 3. S. Moshitch - Moshkovitz, G. Tsarfaty, D.W. Kaufman, overexpression in tumors and metastasis. HGF/SF induce dramatic G. Y. Stein, K. Shichrur J.H. Resau, G.F. Vande Woude, increase of blood flow in the tumor. Using optical imaging modalities and I. Tsarfaty, High-Resolution In Vivo Direct and nanoparticles we imaged HGF/SF increase in blood flow in a Molecular Imaging of Early Tumorigensis and single blood vessel. Our recent studies also show that Met functional Malignant Progression Induced by Transgenic molecular imaging improves mapping of local and distant metastasis. Expression of GFP-Met (In press, Neoplasia) 4. Tsarfaty, G. Y. Stien, S. Moshitch - Moshkovitz, D.W. The primary aim of our work is to develop novel transgenic mice and Kaufman, B. Cao, J. H. Resau, G.F. Vande Woude, nanoparticles-based molecular imaging methodologies to visualize and and I. Tsarfaty. HGF/SF-Induced Alteration of Blood measure the expression and activity of tyrosine kinase growth factor Flow and Volume in Mammary Tumors HGF/SF Increases Tumor Blood Volume: A Novel Tool for in Vivo Functional Molecular Imaging of Met (In press, Tel: (972)-3-6407015 Neoplasia) Fax: (972)-3-6409160 This work is part of a collaboration between Tel Aviv University, Email: [email protected] Sheba Medical Center the Van Andel Research Institute (Grand Rapids MI) and Michigan University, Ann Arbor MI.

63 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY

Progress Reports

PROGRESS reports

Prof. Ari Barzilai

Introduction Millions of people throughout the world become blind as a result of devastating disease or trauma. In the Western world, the main factors leading to blindness are diseases such as diabetes, age related macular degeneration (AMD) and glaucoma, or traumas such as car and work accidents, terrorism and wars. In the third world, malnutrition as well as infective and toxic alimentation are the leading factors of blindness.

Hypothesis Our work is based on our hypothesis that retinal ganglion cells (RGC) are capable of growing their axons following injury; however, the non-permissive environment prevents them from doing so. We further hypothesize that removal of the non-permissive cures and supplement the RGCs with axonal growth promoting substances will lead to axonal functional regeneration.

Objectives Figure 1. Representation of optic nerve axotomy. As shown Based on these hypotheses we intend to use an integrative in these pictures the integrity of the menings and the approach that combines nanotechnological methodologies vascularization is not affected by the surgical procedure. that will supplement the neurons with the necessary cues that will accelerate their growth. Our specific aims are: Implantation of biodegradable three-dimensional scaffold intact. It is now fully operational and all the in the optic nerve and assessing its ability to promote RGC experiments are conducted using this model survival and axonal regeneration. (i) Spatial and temporal system. controlled secretion from specially designed nano-structures To measure the extent of the axonal growth that will implanted in the optic nerve. (iii) Implantation of nano- process, we have adopted a unique method chips and electrodes in the optic nerve in order to generate of MRI that enables us to visualize the growth biofeedback necessary to maintain homeostatic conditions. process in vivo. The rats were injected intra- ocularly with Mn2+ 24 hours prior to MRI Results analysis. In addition, we dissected out the Unique model of axotomy: optic nerves and assess the growth process This model of axotomy is unique in its design. The complete using specific markers of neuronal growth. cut of the axons is done by using special designed tools made The axotomized optic nerves were injected from micro glass pipettes and used to generate a complete cut with 3 types of self-assembling peptides and of the optic nerve axons without affecting the vascular supply bio-gels made out of hyaluronic acid and to either the retina or the nerve and leaves the neural scaffold laminin (HA). The results are very encouraging.

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

Control Axotomy Only Axotomy+HA gel We have analyzed the results of one self- assembling peptide AM-1-3 (received from Prof. Mitraki, WP-1) and the HA. In both cases the biogel scaffolds enhanced the growth process as assessed by the MRI analyses, and confocal microscopy (cholera toxin and the GAP-43). The biogels provided a substrate that enabled the growing axons to cross the lesion site and to grow their axons beyond that point. No such phenomenon was observed in axotomized non-treated optic nerves. Surprisingly, the MRI analysis has shown that injured axons concomitantly injected with HA have reached the area of the optic chiasm 28 days post injury. In addition to the injection of biogel scaffolds we have found that injection of activated mononuclear cells into the injured optic nerve prevented the Wallerian degeneration of the axotomized optic nerve.

Figure 2. MRI of the Mn2+-enhanced visual pathway obtained from a control group rat 24 hours after injection of 150 nmol Mn2+ into the right corpus vitreous. The optic nerve is labelled with yellow arrows. While in control untreated rats the Mn2+ induces signal enhancement, no traces of signal enhancement are observed in axotomized animals. Marked degree of axonal regeneration is detected in axotomized optic nerve treated with gels made out of hyaluronic acid (HA). The Mn2+ label reached the optic chiasm but not the superiour colliculus. The MRI was performed one month after injury.

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

Prof. Itai Benhar

he key nano activity our group was engaged in is the and have a prolonged circulation time. In yet ongoing project of evaluating targeted drug-carrying unpublished experiments we could apply bacteriophages and potential nanomedicines. targeted chloramphenicol-carrying phages Bacteriophages (phages) have been used previously for in a lethal infection model of Staphylococcus therapy of bacterial infections, for genetic research, for aureus bacteria in BALB/c mice. We found that discovery of specific target-binding proteins, as tools we can protect the mice from a lethal bacterial forT vaccination or as potential gene delivery vehicles. In the ongoing challenge. project we are evaluating the possibility of applying filamentous bacteriophages as targeted drug carriers for two modalities: 1) the References: eradication of pathogenic bacteria as a means to meet the challenge 1 yacoby I, Bar H, and Benhar I. (2007) Targeted of spreading antibiotic resistance among pathogenic bacteria. 2) drug-carrying bacteriophages as anti bacterial nanomedicines. Antimicrob Agents Chemother. Application of the phages as anti tumor agents. Having provided 51(6):2156-63. proof-of principle of the potential of both the anti-bacterial and 2 yacoby, I. and Benhar I. (2007) Targeted anti bacterial the anti-cancer phages in cell culture systems (published 2006 and therapy. Infect Disord Drug Targets. 7(3):221-9. 2007), we have now progressed to next level towards preclinical 3 yacoby, I. and Benhar, I. (2008) Targeted development: testing our platform in animal models. These targeted Bacteriophages as Therapeutic Agents. Expert Opin drug-carrying phages, due to genetic and chemical modifications Drug Targets. 5(3):321-329. 4 Bar, H., Yacoby, I. and Benhar, I. (2008) Killing represent a modular targeted drug-carrying platform of nanometric cancer cells by targeted drug-carrying phage dimensions where targeting moieties and conjugated drugs may be nanomedicines. BMC Biotech. 8:37. exchanged at will. 5 yacoby, I. and Benhar, I. (2008) Potential of Specifically, the study is based on our ability to genetically engineer Antibacterial Nanomedicines. Nanomedicine and chemically modify filamentous phages that display or form 3(3):329-41. a stable complex with a target-specific antibody on their coat and 6 yacoby, I., Vaks, L. and Benhar, I. (2008) Phage therapy as a solution for antibiotic resistance of are used to deliver cytotoxic drugs to target cells. The antibodies are bacteria. Afr. J. Biotech. In Press. specific for binding pathogenic bacteria, or an anti-tumor-associated- antigen antibody. The genetic modification endows the phages with binding specificity towards the target cells and also modifies the drug carrying capacity as well as the pharmacokinetic properties of the phages. The drugs are linked to the phages by means of chemical conjugation through labile linkers subject to controlled release at or inside the target cell. We have demonstrated the feasibility of using this platform against pathogenic bacteria. In a related study we demonstrated growth inhibition of tumor cells by hygromycin and by doxorubicin-conjugated phages targeted via chimeric anti ErbB2 and EGFR antibodies. We also found that targeted drug-carrying phages are not toxic to mice (up to 1011 phages IV or IP). We further found that phages that carry chloramphenicol connected through an aminoglycoside linker are greatly reduced in immunogenicity,

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

Prof. Reuven Boxman

Introduction as a micro-reservoir for lubricant, which may be a The Electrical Discharge and Plasma Laboratory at Tel Aviv University conventional material such as the solid lubricant in an inter-faculty facility in which the science of electrical discharges Stearin, or nano-fullerenes of MoS2 suspended and the plasma which they produce are investigated, and applications in mineral oil. The micro-hardness of treated of these phenomena are developed. Much of the applications are in steel surface increased by factor of 10-40%, due the realm of plasma processing of materials, and include deposition to formation of fine grain structure and ferrite- of nano-structured thin films and coatings, nano-texturing of austenite transformation. Lifetime of the lubricant tribological surfaces, and production of nano-particles. film increased more then order of magnitude.

Vacuum Arc Deposition of Nano-structured Thin Films Nano-particle Production and and Coatings Characterization Vacuum arc deposition exploits the high velocity fully ionized metal Pulse submerged arcs are high current electrical vapor plasma jet produced by high current electrical discharges discharges sustained between electrodes in a vacuum environment to produce thin films and coatings. The submerged in a liquid. The discharge produces a laboratory designed and built and unique triple-cathode vacuum plasma bubble within the liquid, characterized by arc plasma source. The cathodes can be operated simultaneously to extreme temperature gradients. These discharges produce multi-component “designer alloy” films, or alternatively to are investigated in the lab for producing nano- produce multi-layer films. In a completed project, nano-layered films particles based on the electrode materials, and/ of TiN, NbN, and ZrN, and well as multi-component films comprised or the liquid in which they are submerged. of these components were rapidly deposited (at ~1 µm/min) and Pulsed arc production of WC powders in deionized characterized. “Superhard” TiN/Nb films were produced. water and analytical ethanol was studied. The arc The lab participated in an European Union sponsored coordination was ignited between a 99.99% graphite (C) and a action entitled “Deposition of super-hard nanocomposite films by 99.5% W electrode. The pulse energy and duration plasma processing”, and in this framework hosted the International were in the ranges of 7.7-192 mJ and 25-65 ms,

Conference on Super-hard coatings. Currently the lab is studying respectively. The highest quantity of WC1-x was jointly with Ulsan University hard coatings based on nano-layered produced by arcing a C anode with W cathode and nano-composite Al2O3/ZrO2, sponsored by the ministries of in both liquids and for different discharge energy science of Israel and Korea, and the deposition of ceramic/fullerene and capacitors. Arcing in ethanol increased the composite films jointly with the Technion. production of the WC1-x phase. The number ~10 nm particles was by two orders greater Nano-structuring of Tribological Surfaces when using a W anode and a C cathode pair than The lab is investigating nano-structuring of wear surfaces using a by using the opposite polarity while arcing in pulsed arc in air. In this method, the texturing is preformed in open ethanol. Arcing with a W anode and C cathode air on samples at room temperature, in cooperation with the Holon in water produced bigger particles, uniformly Institute of Technology. Discharges are produced between a steel distributed in the range of 0.5-2.5 μm. sample and a high voltage counter-electrode. The counter-electrode was 3 mm diam steel rod with a 28° cone tip. Each discharge produces a small nano-textured dimple on the sample surface, which serves

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

Prof. Ori Cheshnovsky

Detection of Heating in Current Carrying Molecular Junctions by Raman Scattering

n important consequence of electron-vibration modes show similar heating as a function of bias interaction in molecular-junction-transport is heat at room temperature, suggesting fast internal generation, i.e., energy transfer to the underlying vibrational relaxation processes. These results nuclear motions. In balance with heat dissipation, this demonstrate the power of direct spectroscopic has important implications on the issue of junction probing of heating and cooling processes in stability. Advancement in molecular electronics nanostructures. necessitatesA thorough understanding of these processes in molecular junctions. Such an understanding depends on the ability to monitor Reference: non-equilibrium occupancy of vibrational levels at current carrying 1. Ioffe Z. Shamai T., Ophir A., Noy G., Yutsis I., Kfir K., junctions as a function of bias. We report (in cooperation with the Cheshnovsky O., Selzer Y. Detection of Heating in Current Carrying Molecular Junctions by Raman group of Y. Selzer) on the realization of such a capability by utilizing Scattering. Nature Nanotechnology 3, 727-732 the Stokes (S) and AntiStokes (AS) components of Surface Enhanced (2008). LINK: http://www.nature.com/nnano/ Raman Spectroscopy (SERS) to probe the effective temperature of journal/vaop/ncurrent/pdf/nnano.2008.304.pdf current carrying junctions. In our specific junction, all Raman active

Figure 1: Raman spectra and maps of a junction. (a) Raman spectrum in the Stokes regime using the 671nm laser, of BPDT molecules in a junction (black) and as a monolayer at an arbitrary spot on the Ag electrode (red). (b) The corresponding anti- Stokes spectrum. (c) An optical picture showing a top view of a junction. (d) A Raman map of a junction based on the 1585cm-1 Stokes line. The enhancement of signal at the junction is shown as brighter pixels. The points at which the spectra at (a) were taken are indicated by arrows. (e) A Raman map of the 1585cm-1 AS line of the same junction.

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

Dr. Yoram Dagan

Superconductivity and magnetism at interfaces Superconductivity and Magnetism on between insulating perovskites 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 (2DEG). over a coherence length-scale, ξ. However, when It has also been demonstrated that in some samples this interface the superconducting specimen is constituted exhibits superconductivity with transition temperature Tc ≈ 200mK, of weakly connected nano-grains whose size is and in others ferromagnetism. The main parameter responsible for smaller than ξ, or when the coherence length the 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 trying to navigate through the phase diagram of interesting physical phenomena occur. The first this interface by varying the number of charge carriers using gate case is realized in granular superconductors (GSC), voltage and via proximity to other superconductors. and High Tc cuprate superconductors (HTCS) fit to the second. Tuning Superconductivity in Perovskites Using Organic We study the magneto-transport properties and monolayers in particular the vortex Nernst effect in granular

In a material undergoing a superconducting transition, the superconductors Al-Ge and Al-Al2O3 where phase electrons condense into a macroscopic ground state below a critical fluctuations can be tuned using the grain size and temperature Tc. We use organic molecular and bio-inspired thin films inter-grain resistance as control parameters and in order to control the properties of high Tc cuprate superconductors in the electron-doped HTCS Pr2-xCexCuO4-δ (PCCO) and other perovskite superconductors. This will be done by chemical near a possible superconductor to insulator and and opto-electrical tuning of the electronic properties of the antiferromagnetic to paramagnetic quantum superconductor surface using bio-optical active proteins and polar phase transitions. self assembled monolayers.

Layer by layer deposition of LaAlO3 as (LHS) AFM images of 20uc LaAlO3 terraces on Magnetoresistance at low temperatures detected in-situ by RHEED oscillations SrTiO3 (RHS) height profile. may be explained by weak localization

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

Prof. Guy Deutscher

Nano-scale planar superconductor/ferromagnetic K in a compound having a maximum critical contact temperature of 40 K (LaSrCuO), and with the We have produced nano-scale In (S)/Ni(F) contacts in a planar recent observation of domain formation by geometry by producing cross junctions, first depositing a thin Ni layer, Scanning Tunneling Microscopy in underdoped letting it oxidize briefly, and then depositing an In layer. The junction cuprates. size range studied was from a few microns down to about 100 nm. It was found that for certain oxidation conditions and junction sizes, G. Deutscher and P. G. de Gennes, C. R. Physique 8, 937 (2007). the conductance of the junction was dominated by a few pinholes in the Ni oxide layer, effectively making it a point-contact junction. Broken symmetry near the pseudo-gap Below the superconducting critical temperature of the In layer the temperature of the High Tc Cuprate conductance of the junction was found to vary as a function of bias YBaCuO in the underdoped phase and temperature in a way consistent with the occurrence of electron- Polar Kerr effect measurements performed on hole reflections (Andreev – Saint-James or ASJ reflections) at the YBaCuO single crystals and epitaxial films have interface. This has opened the possibility of fabricating devices were revealed the apparition of a magnetic moment at two neighboring such junctions crossed ASJ reflections could take below a temperature which is higher than the place. In such a device the two members of a Cooper pair could be critical temperature in underdoped samples. on separate ferromagnetic legs, which would open several intriguing The Kerr angle appears below a well defined applications (1). temperature in a way that suggests a second order phase transition. A very strong field is S. Hacohen-Gourgy, B. Almog and G. Deutscher, Appl. Phys. Lett. 92, 152502 (2008). necessary to reverse the moment obtained when cooling the sample in a weak field, suggesting Nano-scale emerging superconductivity in the High Tc the existence of magnetic domains . oxides It remains to be established if the observed transition is related to the formation of domains A new mechanism for high temperature superconductivity has been seen in STM, and if they are consistent with the proposed (1). It is based on properties of the Cu-O-Cu bonds, in which bond contraction model of Deutscher and de the d-electrons on neighboring Copper atoms are coupled via the Gennes. p-orbital of the Oxygen. It is in fact this coupling that leads to anti- ferromagnetism in the Copper oxides. But what is envisioned here Jing Xia, E. Schemm , G. Deutscher et al., Phys. Rev. Lett. is that holes introduced in the pristine anti-ferromagnet can under 100, 127002 (2008). certain conditions gain energy if they get localized on neighboring Cu atoms, if the Cu-O bonds will contract sufficiently. This model predicts the formation of domains consisting of columns of hole rich contracted Cu-O-Cu bonds separated by hole poor columns of stretched Cu-O-Cu bonds. These domains are predicted to form at a temperature that is higher than the transition to superconductivity. This prediction is consistent with the increasing disorder observed in the distance of Cu-O bonds below a temperature of about 150

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

Prof. Haim Diamant

Statistical thermodynamics of fluctuating capsules Premicellar aggregation of amphiphilic Sub-micron membrane vesicles (or liposomes) are commonly used to molecules encapsulate and deliver biochemical agents in various biological and The formation of nano-sized aggregates (micelles) industrial systems. Those semipermeable capsules are osmotically in dilute solutions of amphiphilic molecules is a swollen by a fixed number of trapped molecules, while their volume ubiquitous and useful phenomenon. Using a new and inner pressure are not prescribed. We have been studying the model of micellization, we showed earlier that, statistical thermodynamics of this special class of finite-size systems. under certain realistic conditions, a significant We have shown that, under rather general conditions, as the number amount of metastable aggregates exist well below of encapsulated particles is increased, or the outer concentration the critical micelle concentration – a phenomenon is decreased, the swelling toward maximum volume exhibits a that has been reported also experimentally. (See continuous phase transition. This newly discovered criticality implies Activity Report for 2006-2007.) We have extended a universal behavior of strongly swollen capsules as they approach the theory in two directions pertaining to the osmotic lysis. In addition, a unifying scaling analysis has been devised experimental and technological relevance of for pressurized and particle-encapsulating random manifolds, such premicellar aggregates – their lifetime and encompassing a wide range of systems. We have confirmed the polydispersity. We have demonstrated that, over predictions of this analysis in several specific models. most of the metastable concentration range, the The work has been done by Emir Haleva (PhD student). It is supported premicellar aggregates should have macroscopic by the American Chemical Society Petroleum Research Fund. lifetimes and small polydispersity. The work has been done by Radina Hadgiivanova (PhD student).

Correlated motion of membrane inclusions Proteins embedded in bilayer membranes, or particles embedded in fluid monolayers, move in a correlated way due to flows that their motions induce within the sheet and in the surrounding liquid. In addition, their presence in the layer modifies its response to stresses – its effective viscosity – much like the way colloid particles modify the viscosity of a 3D suspension. We have derived the coupling diffusion coefficients of pairs of such inclusions, along with their dependence on the concentration of inclusions and the effect How does a vesicular capsule swell? As the number of molecules making the of that concentration on the response of the membrane increases (curves from bottom to top), the swelling with the number of embedding membrane. encapsulated particles approaches criticality (top black curve). These theoretical curves are highly universal – i.e., they can be made to fit a large variety of vesicles and encapsulated solutions.

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The work has been done by Naomi Oppenheimer (PhD student). It is supported by the Israel Science Foundation.

References: 1. E. Haleva and H. Diamant, Critical swelling of particle-encapsulating vesicles, Phys. Rev. Lett. 101, 078104 (2008). 2. E. Haleva and H. Diamant, Swelling of particle-encapsulating random manifolds, Phys. Rev. E 75, 021132 (2008). 3. r. Hadgiivanova and H. Diamant, Premicellar aggregation of amphiphilic molecules: aggregate lifetime and polydispersity, submitted. 4. N. Oppenheimer and H. Diamant, Correlated diffusion of membrane proteins and their effect on membrane viscosity, submitted.

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

Prof. Amihay Freeman

Protein Mediated Nano-Scale Biotemplating

Our research is focused on the development of new methodologies for the preparation of nanostructured novel composite materials by protein mediated biotemplating The research program is divided into two arms: The first is focused on the use of single, soluble protein molecules 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 [1, 2]). The resulting enzymatically active soluble hybrids were successfully nano-wired to platinum electrode allowing glucose determination in the absence of oxygen (a study Figure 1: High Resolution Electron Microscope (Philips Tecnai F20) micrographs, obtained without staining for carried out in collaboration with Prof. Y. Shacham-Diamand from silver-glucose oxidase hybrid. The chemical identity of the the Faculty of Engineering and Prof. J. Rishpon from our faculty. The silver deposit was confirmed by EDX (inserts). silver-glucose oxidase hybrid was also used as a new antibacterial agent to combat biofilms by enzymatically attenuated in situ silver release [3]. The methodology developed for the production of silver- enzyme hybrids was recently successfully applied for the preparation of avidin-silver hybrid (Mor et al (2008), manuscript in preparation). In the second arm we continued our study aiming at the establishment of methodologies for the monitoring of the ‘filling’ process of a protein crystal biotemplate [4] with elucidation of the mechanism of chemical crosslinking of protein crystal by glutaraldehyde – a prerequisite for biotemplating without distortion – and resolution of its end products by x-ray analysis [5], a study carried out in collaboration with Prof. F. Frolow] and demonstrated the construction of a 3D metal nanoparticles array formation within the crystals voids array (see figure3 and [6]). To gain control on the voids array of the protein crystal biotemplate we have recently concluded three projects: in the first the capability to alter the geometry of the crystal’s voids array by chemical Figure 2: High Resolution Electron Microscope (Philips modification of the protein ‘building block’ with purification of Tecnai F20) micrographs, obtained without staining for the modified protein prior to crystallization (Cohen-Hadar et al, palladium-glucose oxidase hybrid. The chemical identity of the palladium deposit was confirmed by EDX (inserts). manuscript in preparation); in the second the use of co-addition of modifying agents into the crystallization medium was demonstrated

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(Lagziel-Simis et al, manuscripts in preparation) and in the last, the use of site directed point mutations (Wine et al, Submitted).

References: 1. dagan-Moscovich H, Cohen-Hadar N, Porat C, Rishpon J, Shacham- Diamant Y, Freeman a (2007) Nanowiring of the catalytic site of novel molecular enzyme-metal hybrids to electrodes. J Phys Chem C, 111:5766- 5769. 2. S. Vernik , H. Moscovich-Dagan , C. Porat-Ophir , J. Rishpon , A. Freeman, Shacham-Diamand Y. (2008) Directed metallization of single enzyme molecules with preserved enzymatic activity. IEEE Transactions on Nanotechnology . In press. 3. 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. 4. Cohen-Hadar N, Wine Y, Nachliel E, Huppert D, Gutman M, Frolow F, Freeman A (2006) Monitoring the stability of crosslinked protein crystals biotemplates: a feasibility study. Biotechnol Bioeng 94:1005-1011. 5. Wine Y, Cohen-Hadar N, Freeman A, Frolow F (2007) Elucidation of the mechanism and end products of glutaraldehyde crosslinking reactions by X-ray structure analysis. Biotechnol Bioeng 98:711-718. 6. Cohen-Hadar N, Wine Y, Lagziel-Simis S, Dror Y, Frolow F and Freeman A. (2008) J Porous

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.

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

Prof. Ehud Gazit

Cancer diagnostics, by nanotechnology based nanotubes at the micro-, nano-electronics biosensor that profiles tissues acoustically. industry, such as in the field of diagnostics and Dr. Ludmila Buzhansky biosensing, field effect transisrors (FET), micro- electro-mechanical system (MEMS), solar cells Malignant tissue characterized in its unique viscoelastic and and more. The performance of such devices can metabolic properties, as well as express on its surface characterized be improved by unraveling the electronic and molecular markers, which varied in their type and quantity due to the energetic structure of the nanotubes. By knowing tumor type and phase. These viscoelastic, metabolic and molecular the work function of the nanotubes we can go cancerous transformations, affect the acoustic profile of the tissue. half way and design in a more intelligent and Amendis had designed and patented the Bio-SoNaR (biological logical way devices which involve electrons or acoustic nano resonator), an innovative nanofabricated bio-sensor holes movement from or to the nanotube. that enables the sensing of tissue’s acoustic profile. In our lab we tested With the described techniques we were able to the device and proved that the Amendis’s Bio-SoNaR can acoustically conclude about the electrostatic polarizability profile a live, intact, malignant tissue. In the future, Amendis will and the high dielectric constant the nanotubes combine the Bio-SoNaR along with advanced algorithmic code. possess. Moreover, a new understanding of the This combination will save the need for biopsy and will enable non- energy levels of the nanotubes was obtained by invasive, irradiation free and accurate diagnosis of cancer, in real-time discovering their work function. and in a harmless manner to humans and their environment. In our future plans we will continue to research the physical properties of several self assembly Electronic Characterization of self assembled peptide peptide nanostructures (such as peptide nanotubes via atomic force microscopy based hydrogels and nanospheres). The physical methodologies properties include photoluminescence, excitonic Nadav Amdursky, PhD student states, piezoelectric and paraelectryc properties of the peptide nanostructures. The use of atomic force microscopy (AFM) based methodologies enable us to explore the electronic characterization of material Peptide-Based Hydrogels in nanometric resolution and in non invasive way, unlike other Ron Orbach MSc Student techniques which cannot yield high resolution results such as photoemission techniques. In this work we focus on two main Hydrogels are frequently used as 3D scaffolds techniques; electrostatic force microscopy (EFM) and Kelvin probe to support the growth of cultured cells for force microscopy (KFM) to characterize the electronic properties of tissue engineering and regeneration. A variety peptide nanotubes (PNT). The researched PNT are well ordered, long of natural polymers may be used as hydrogel- forming materials. These polymers are appealing and hollow nanotube made by self assembly of COOH-Phe-Phe-NH2 (FF) building blocks. for medical use owing to their similarity to the Where as the EFM scans can tell us about the capacity and the natural extracellular matrix (ECM), which allows dielectric constant of the nanotubes, the KFM provide us important cell adhesion while maintaining very good information about the energy levels of the nanotubes. At recent biocompatible and biodegradable properties. years, a great effort has been invested in the corporation of peptide Peptide-based hydrogels exhibit the advantages

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

of both synthetic and naturally derived hydrogel forming materials. reinforced materials. Since peptide nanotubes They are easy to manufacture in large quantities and can also be are biocompatible, they can be used to reinforce easily decorated chemically and biologically. materials and implants in medical use such as Our group has previously reported the efficient self-assembly of dental material and bone grafting substitutes. The the Fmoc-Phe-Phe (Fmoc-FF) into a rigid hydrogel with remarkable initial tests will examine the reinforcement effect physical properties. In order to gain a better insight and identification of peptide nanotubes on epoxy. The tension of novel materials for biomedical use we (in collaboration with Dr. and compression properties of the epoxy and Dror Seliktar – Technion) characterized the self-assembly of eight nanotube/epoxy composites will be measured new different Fmoc-peptides into various structures with distinctive using standard tests (American Society for Testing molecular and physical properties. Each of these novel nanostructured and Materials D638-99) and dogbone models. materials are formed under mild conditions in an aqueous solution using low-molecular weight building blocks. In most cases, their The use of self assembled peptide properties enable utilization in different biomedical applications nanostructures to encapsulate including drug delivery, tissue engineering and tissue regeneration, magnetic nano-particles due to their biocompatibility and assembly into 3D networks. Inbal Yanai MSc Student Following in-vitro studies we recently began to study the peptide- based hydrogels in-vivo (in collaboration with Prof. Ari Barzilai and Dr. Lose of cerebral neural cells is observed in Arie Solomon – TAU and Prof. Smadar Cohen - BGU). Moreover, using several age-associated disorders such as this Fmoc-peptide library we study the role of aromatic groups in Alzheimer’s disease, Parkinson’s disease and regulating the self-assembly process, and consequently influencing other neurodegenerative disorders. Currently, the the structural and physical properties of the resulting hydrogels. medical procedures for the diagnosis of those Self-assembly is a promising technique in the formation of nano- diseases are not very conclusive. The need for new materials. By using bio-physical techniques we intend to investigate methods is relevant now more than ever with more deeply the aromatic effect on this process and to further explore the hydrogels potential at in-vivo systems.

Diphenylalanine Peptide Nanotubes as a reinforcement agent Even Nitzan MSc student, Adler-Abramovich Lihi PhD student

Indentation type experiments using an atomic force microscopy revealed impressive mechanical properties of the diphenylalanine peptide nanotubes. It was found that they maintain high averaged point stiffness of 160 N/m, and correspondingly highY oung’s modulus of approximately 19 GPa, which places these peptide nanotubes among the stiffest bio-inspired materials presently known. Inspired by these findings we have decided to create composite material Transmitting electron microscope micrograph of the integrated with the peptide nanotubes in order to create new nanospheres decorated with gold particles.

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

longer life expectancy and the increase of the elderly population. Furthermore, we studied the peptide nanotubes The work at our laboratory of the mechanism of self-assembly had mechanical properties, which were directly led to the discovery of aromatic dipeptides that self assemble into measured by indentation type experiments using various structures such as nanotubes, nanospheres and others. These an atomic force microscopy. structures are well-ordered and discrete. Moreover, we explored the potential of a self- The ongoing research is directed towards the development of novel immolative dendritic system to serve as a contrast agents to produce magnetic resonance imaging (MRI) based transporter platform for control assembly of on peptide nanostructures loaded with ferromagnetic nano-particles. the peptide nanostructures. Self- immolative The experimental model includes short peptides which self assemble dendrimers are a novel class of molecules that into closed caged nanospheres under certain reaction conditions and can amplify a single cleavage event, which is encapsulate the magnetite nano-particles during the self-assembling received at a focal point, into multiple releases of process. In order to develop efficient diagnostic tool the nanospheres tail groups at the periphery. will be decorated with recognition motifs that could specifically bind Additionally, we used the inkjet technology for antigens that are associated with various degenerative diseases. the application of peptide nanostructures on The formation and stability of the nanospheres was investigated in non-biological surfaces. The ADNT which self various tests at different conditions. The nanospheres have been assemble readily in solution were used as an „ink“ successfully decorated with amyloid beta recognition motif and with and patterned on transparency foil and ITO plastic biotin- streptavidin gold in order to show that the chemistry didn’t surfaces using a commercial inkjet printer. affect the spheres and to visualize the attachment of the gold particle In summary, the remarkable thermal, chemical and on the nanospheres surface. mechanical durability and the ability to pattern and control the assembly of the peptide nanotubes Characterization, controlled assembly and patterning suggests their application in conventional of aromatic dipeptides nanostructures microelectronic and microelectromechanics Adler-Abramovich Lihi PhD student processes, as well as fabrication into functional nanotechnological devices. Organic and inorganic self-assembled tubular nanostructures were suggested to have key potential in nanotechnological devices and applications. Several studies have shown the possible use of bionanometric material for applications ranging from molecular electronic to drug delivery. The diphenylalanine peptide, the core recognition motif of the Alzheimer‘s Beta-amyloid polypeptide, efficiently self-assembles into discrete, well-ordered peptide nanotubes. In the current research, using different microscopy and spectroscopy tools we describe a remarkable thermal stability of aromatic dipeptide nanotubes (ADNT) both in aqueous solution and under dry conditions. In addition, the peptide nanotubes exhibit substantial chemical stability in various organic solvents as acetone or acetonitrile.

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

Prof. Ilan Goldfarb

he main research direction in this period focused on only the miscut angle, but also by choosing an self-organization of silicide nanocrystals on vicinal Si azimuthal miscut direction, and varying the surfaces. Results of our work (two papers in press) magnitude and the polarity of the flash current, have indicated, that under certain conditions, self- (b) the self-organization phenomenon itself,

assembled heteroepitaxial CoSi2 nanocrystals not on such self-patterned substrates, by varying only preferentially decorate the step-bunch edges on the deposition methods and parameters, as aT vicinal Si(111) surface, which by itself is not a new phenomenon, well as the heterosystem (e.g., Co/Si, Ti/Si, etc.), but their mean size and separation distance along the ledges is also and (c) electronic properties of the self-ordered dictated by the parent step-bunch height. Such a self-organization nanostructures themselves, such as the local produces one-dimensionally ordered nanostructure arrays, and density of states (LDOS) by scanning tunneling locally, where the terrace width is comparable with the nanocrystal- spectroscopy (STS). Up until now, these projects nanocrystal separation distance – even two-dimensionally ordered have been at the M.Sc. level and have been partly patterns result (see Figure below). These results imply that functional funded by short-term grant schemes (such as by self-assembled and self-ordered nanostructure arrays can be non- the US Air Force). However now, due to winning lithographically fabricated bottom-up on the properly miscut and a 4-year ISF personal grant on this topic, this prepared vicinal substrates (e.g. 4°-5°), by carefully choosing the research is going to be significantly boosted, deposit materials (and hence the heterosystem, e.g. Co/Si) and both in terms of funding and duration, as well as selecting the desired deposition method (e.g. solid-phase epitaxy) in terms of manpower and quality (collaboration and parameters. with another experimental (Kaplan, Technion) Hence, currently three topics are being investigated, at the M.Sc. and theoretical (Rabani, TAU) groups, and raising level, in this respect: (a) substrate self-patterning by controlling not the level to doctoral or even post-doctoral level). On top of this achievement, continuation of the work on the Ge/Si nanocrystals has lead to an additional publication in Physical Review Letters, second in two years. There are two additional topics studied in the lab, namely the investigation of surface effects in contact formation to CZT crystals, at the Ph.D. level (funded by the ISF), and a newly contemplated X-sectional STM/STS studies of multilayered compound-semiconductor superlattices (funded by the industry). Finally, two more topics begin to materialize in the laboratory: “Spintronics & magnetic nanostructures” in collaboration with G. Markovich, at a post-doc level, and “Characterizations of multilayered structures by STM and KPFM “ at a Scanning tunneling microscopy (STM) micrograph of self-ordered CoSi2 nanocrystals on Si(111) Ph.D. level (in collaboration with Y. Rosenwaks).

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Dr. Michael Gozin

Mucins’ Complexes with PAHs and Nanomaterials

Bogdan Belgorodsky, Eyal Drug, Ludmila Fadeev, Netta Hendler, Elad Mentovich, Michael Gozin

ncreasing exposure of biological systems to hydrophobic carbon nanotubes (MWNT) ligands. UV-vis and pollutants, such as polycyclic aromatic hydrocarbons and fluorescence spectra that were measured for various nanomaterials, is of great public concern. Organisms each of the separated BSM-ligand complexes have an array of biological defense mechanisms and it is revealed unprecedented capabilities of a salivary believed that mucosal gel (which covers the respiratory system, glycoprotein to bring into aqueous solution the gastrointestinal tract, etc.) provides an effective chemical various organic and inorganic water-insoluble Ishield against a range of toxic materials. However, the mechanisms materials. All UV-vis spectra of the obtained and portals of entry of water-insoluble materials into various complexes demonstrated superimposition of biological systems are yet to be fully understood. In the present work, characteristic BSM peaks with absorbance peaks we demonstrate that a representative mucin glycoprotein, Bovine clearly belonging to chromophores of the bound Submaxillary Mucin (BSM), has impressive and unprecedented ligands. We found that the BSM-complexed capabilities for binding and solubilizing of water-insoluble materials Ant, Bap, Cor and C60 chromophores exhibited and nanoparticles in physiological solution. Our results provide line-broadening and bathochromic shifts when a unique example to a route of how hydrophobic materials could compared to spectra of the non-complexed be solubilized in a biological system and what could be the first ligands in chloroform. The UV-vis spectrum of biochemical interface between such materials and living organisms. the BSM-complexed Ant essentially preserved its Combustion of wood, coal, liquid fuels and domestic and industrial well-resolved features, strongly suggesting that waste results in emission of enormous amounts of polyaromatic the protein is bound to a monomer of this PAH. hydrocarbons (PAHs) and carbon nanoparticles into the atmosphere. In contrast, lost of fine structure in spectra of the In contrast to PAHs, which are well known as powerful mutagens and BSM-complexed Bap and Cor chromophores may carcinogens, the biological effects (transport, bio-accumulation and indicate that these larger ligands are bound to toxicity) of various nanomaterials have only begun to be explored. BSM in a form of π-π stacked dimers or even larger It is expected that an array of biological defenses should protect the aggregates. The spectrum of BSM-complexed organisms from these materials. For example, it is believed that the C60, characterized by broad absorbance bands, mucosal gel that covers the respiratory and gastrointestinal tracts unambiguously showed that this ligand is bound should provide an effective physical and chemical shield against in a form of clusters. To the best of our knowledge, a range of toxic materials. The primary components of mucus are this is the first demonstration of a IF-WS2 complex high-molecular weight mucin glycol-proteins that form numerous with any host and the first stable dispersion of this covalent and non-covalent bonds with other mucin molecules. nanomaterial in solution. The UV-vis spectrum of The condensed and complex microstructure of the mucus network the BSM-complexed MWNT closely resembled gives rise to a highly visco-elastic gel that significantly impedes the reported spectra for the nanomaterial dispersion transport rates of large macromolecules and nanoparticles. The in aqueous solutions. Complexation modes of fast rate of mucosal exchange offers an effective natural protective the evaluated ligands were further investigated and disposal mechanism for various potentially toxic exogenous using three-dimensional excitation-emission materials. fluorescence spectroscopy. No fluorescence

Our study was focused on preparation of a series of BSM complexes was detected for BSM complexes with C60, IF- with anthracene (Ant), benzo[a]pyrene (Bap), coronene (Cor), WS2 and MWNT. We found that BSM-complexed

C60-fullerene (C60), fullerene-like WS2 (IF-WS2) and multi-walled Ant, Bap and Cor exhibited significant decreases

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in fluorescence intensity. We observed bathochromic shifts in SEC analysis of Ant-BSM complexation products maximum emission wavelengths from 15 nm (for Ant and Bap) to 55 showed formation of larger aggregates not nm (for Cor) as compared to fluorescence spectra of non-complexed found in the native BSM protein chromatogram. ligands in chloroform solutions. Despite the shift, the fluorescent A fraction of the population had retention times spectrum of BSM-complexed Ant had most of the well-resolved similar to those observed in the chromatogram features of the free ligand. In contrast, significant changes were of BSM; however, most of the material observed in the shapes of the fluorescence spectra of the bound eluted at retention times of 11.3 and 8.4 min, Bap and Cor relative to the spectra of the chloroform solutions of the corresponding to higher molecular weight free ligands. We believe that in the case of Cor ligand, the large red species. The chromatogram monitored at 390 nm, shift in the maximum emission of the complexed Cor could not be a wavelength at which only the Ant chromophore attributed only to solvatochromism. Supporting our interpretation is observed, revealed that most of the Ant ligand of the UV-vis spectroscopy results that Cor binds as an aggregate, was located in these new products and only a fluorescence data strongly indicate that discotic Cor ligands are small amount of the ligand was bound by species bound to BSM glycoprotein in the form of π-π stacked clusters. corresponding in size to the native BSM. DLS Further characterization and evaluation of overall sizes of the BSM analysis of the Ant-BSM complexation products complexes were performed using dynamic light scattering (DLS) and showed two; relatively narrow populations of high performance size-exclusion liquid chromatography (SEC). We species. The smaller sized species with Rh of 10 found that in phosphate buffer solution the native BSM glycoprotein nm are presumably BSM dimers, whereas the was present in two populations. The SEC chromatogram of the BSM larger species with Rh of 120 nm correspond to was characterized by two partially overlapping peaks at 18.5 and oligomers of BSM and to Ant-BSM complexation 15.8 min. DLS measurements indicated that the one population was products. SEC analysis of Bap-BSM complexation comprised of species with a median hydrodynamic radius (Rh) of 4 products also showed formation of large size nm, a size that corresponds to the monomeric unit of the BSM protein products. The chromatogram monitored at with reported molecular weight of 170 KDa. The second population 280 nm showed that although a considerable was comprised of larger species with a broader range of sizes (Rh of population of species had the same elution time 70 nm), indicating presence of BSM in a form of oligomers. as the BSM protein, a significant portion of the material eluted at retention times of 13.5 and 8.4 min. The SEC chromatogram monitored at 390 nm (wavelength at which only the Bap chromophore is observed) revealed that although the Bap ligand was present in all species, the host-to-ligand ratio in larger entities was substantially higher than in species that eluted at 15.6 min. The DLS analysis of Bap-BSM complexation products indicated the Figure 1. BSM complexes with water-insoluble materials are soluble in presence of two major and one minor population physiological buffer. A, C -fullerene in sodium phosphate buffer (left) and C - 60 60 of species. The lower molecular weight species, fullerene in complex with BSM in sodium phosphate buffer (right). B, IF-WS2 with R of 4 nm, were attributed to monomers of in sodium phosphate buffer (left) and IF-WS2 in complex with BSM in sodium h phosphate buffer. C, MWNT in sodium phosphate buffer (left) and MWNT in BSM and the larger species, with Rh values of 21 complex with BSM in sodium phosphate buffer (right).

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and 179 nm, correspond to Bap-BSM complexation products. revealed that majority of the MWNT ligand

The Cor and C60 complexes with BSM gave similar results. SEC analyses was in the complex with the larger radius. The of these complexes showed practically complete transformation of DLS measurements showed presence of two the starting BSM protein into larger, ligand-loaded entities. The DLS populations of species: a smaller sized species analysis of Cor- and C60-BSM complexation products also showed a (Rh of 10 nm) and larger species (Rh values in presence of one major population with Rh values of 140 and 180 for range of 180-290 nm and higher); these species

Cor and C60, respectively. The DLS and SEC results for Ant, Bap, Cor are presumably various length MWNTs and their and C60 ligands provided very important and complementary data bundles coated with a layer of BSM. to supplement our UV-vis and fluorescence spectroscopy findings. We have demonstrated that a representative Although there are various modes by which smaller hydrophobic mucin protein, bovine submaxillary mucin, ligands such as Ant and Bap can be bound inside small hydrophobic has impressive capabilities for binding and cavities formed by BSM protein, larger cluster-forming compounds solubilizing water-insoluble materials and nano- such as Cor and C60 have large hydrophobic surfaces that require a particles in physiological solution. Different different mode of binding for their solubilization. In the latter mode, modes of binding were observed for the several BSM oligomers are recruited for “coating”, creating submicron- hydrophobic compounds tested. The larger C60- size nanostructures. It should be mentioned that practically all fullerene and coronene molecules bound to BSM available BSM is participating in the dissolution process. In contrast in a form of clusters, whereas smaller anthracene to that of C60-fullerene, SEC analysis of IF-WS2-BSM complexation and benzo[a]pyrene exhibited significantly lower showed formation of two products. The chromatogram, monitored degrees of aggregation. Interestingly, the BSM at 280 nm, shows that although the major species eluted at the same glycoprotein was also capable of unbundling time as BSM protein, a certain population eluted at retention time of carbon nanotube aggregates. The ability of 8.5 min. The chromatogram monitored at 550 nm revealed that the mucins to solubilize otherwise water-insoluble

WS2 ligand was present in both products. The host-to-ligand ratio in materials in a physiological solution suggests species that eluted at 8.4 min was substantially higher than in species that these proteins may function as the first that eluted at 16.2 min. The DLS analysis also showed the presence biochemical interface between living organisms of two populations of species. The species with Rh of 10 nm was and polyaromatic hydrocarbons and various attributed to BSM dimers and the larger species, with Rh of 180 nm, nano-materials. probably corresponds to nanoparticles comprised of a hydrophobic

IF-WS2 cluster core coated by several BSM oligomers.

We expected that, like C60-fullerene, MWNT would form relatively large aggregates, binding all available BSM protein. However, results of both DLS and SEC analyses clearly demonstrated that only a fraction of the available BSM protein participated in complexation. The SEC chromatogram, monitored at 280 nm, showed that although a considerable fraction of the species elute at times equivalent to those observed for BSM protein alone, a significant portion of the material eluted at a retention time of 8.4 min. The SEC chromatogram monitored at 550 nm, at which only the MWNT was observed,

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Dr. Yael Hanein

n the past several years we have developed new methods for neuronal cell patterning and recording using nano topography realized by islands of high density fabrics made of carbon nanotubes (CNT). Carbon nanotube coated surfaces are biocompatible, and are excellent surfaces for cell growth and thus are excellent candidates to be used to interface man- Imade substrates with biological systems. In the past year we focused on improving our understanding on the surface-cell interaction and the understanding of mechanical mechanisms taking place during the organization of the cells. The bio-physical aspects were explored using staining and microscopy methods. By investigating cell-CNT interaction we were able to revisit issues related to network patterning. Figure 3: CNT integrated with silicon structures. The In particular we recently described the role of tension as an important integration intails both mechanical anchoring and parameter in setting neuronal networks (NNs) structure. electrical interfacing. We are currently engaged in new collaborations exploring the benefits of CNT neuro-electrodes for retinal interfacing applications. We also explore chemical approaches to further enhance the performances of these electrodes. Preliminary data show markedly high S/N recordings from whole mount retina, with conspicuous increase in recorded signal suggesting improved coupling. Additional activity of our lab concerns the integration of CNT with silicon based MEMS devices. We have recently been able to work out a scheme how to achieve such integration using simple, scalable means.

Figure 1: Neuronal circuit on CNT electrodes and electrical recording and References: stimulation data. 1. Z. R. Abrams and Y. Hanein, Radial deformation measurements of isolated pairs of single-walled carbon nanotubes, Carbon, Vol. 45, pp. 738-743, 2007. 2. Tamir Gabay, Moti Ben-David, Itshak Kalifa, Raya Sorkin, Ze’ev R. Abrams, Eshel Ben-Jacob and Yael Hanein, Electro-chemical and biological properties of carbon nanotube based multi-electrode arrays, Nanotechnology, Vol. 18, pp. 035201-035206, 2007. 3. Ze’ev R. Abrams, Zvi Ioffe, Alexander Tsukernik, Figure 2: Very S/N ration data recorded from a whole mount retina using a CNT Ori Cheshnovsky, and Yael Hanein, A Complete MEA. Scheme for Creating Large Scale Networks of

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Carbon Nanotubes, Nano Letters, Vol. 7, pp. 2666-2671, 2007. 4. Orly Levy, David Kauzlari´c, Ze´ev R. Abrams, Yael Hanein, Andreas Greiner and Jan G. Korvink, Dissipative particle dynamics model of carbon nanotubes, Molecular Simulation, Vol. 34, pp. 737- 748, 2008. 5. E. Ben-Jacob and Y. Hanein, Carbon nanotube micro-electrodes for neuronal interfacing, Journal of Materials Chemistry, 10.1039/b805878b, 2008. 6. Sarit Anava, Alon Greenbaum, Eshel Ben Jacob, Yael Hanein and Amir Ayali, The regulative role of neurite mechanical tension in network development (Submitted, 2008). 7. Raya Sorkin, Alon Greenbaum, Moshe David-Pur, Sarit Anava, Amir Ayali, Eshel Ben-Jacob, and Yael Hanein, Process entanglement as a neuronal adhesion mechanism (Submitted, 2008). 8. Y. Hanein, M. David-Pur, S. Ben-Valid, S. Yitzchaik, Very low impedance mico/nano electrodes, Eurosensors XXII, Dresden, Germany, 7-10 September 2008. 9. M. David-Pur M, C. Adams C, E. Sernagor, R. Sorkin, A. Greenbaum, M. Shein, E. Ben-Jacob E, and Y. Hanein, Carbon Nanotube Based MEA for Retinal Interfacing Applications, MEA-Meeting 2008, July 8-11, Reutlingen, Germany.

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Prof. Yoav I. Henis

e study the dynamics of the interactions largely unknown. We conducted interdisciplinary of proteins with nanoscale lipid domains studies combining biophysics (FRAP studies on live in the membranes of live cells, and with cells), mathematical modeling (in silico simulation specialized nanostructures (focal adhesions) studies) and cell biology studies to show that four that function in cell motility and signaling. dynamic states of focal adhesion proteins (paxillin We developed biophysical methods based and vinculin) exist: an immobile fraction bound Won fluorescence recovery after photobleaching (FRAP) to study the to focal adhesions, a fraction associated with interactions of signaling proteins (e.g., Ras oncogenic proteins) with these nanostructures that undergoes exchange, a the plasma membrane and of focal adhesion plaque proteins with juxtamembrane fraction experiencing attenuated the focal adhesions in live cells. diffusion, and a fast-diffusing cytoplasmic pool. The juxtamembrane region surrounding FAs The two main nano-related research directions during this period displays a gradient of focal adhesion plaque have focused on: proteins with respect to both concentration and dynamics. We propose that this juxtamembrane (1) The membrane anchorage of Ras proteins, especially the domain can act as an intermediary layer, enabling highly oncogenic constitutively active K-Ras(G12V) mutant, and its fast regulation of focal adhesion formation and modulation by the cationic amphiphilic drug chlorpromazine (CPZ) reorganization. (one paper in press). These studies have revealed the mechanism by which this drug is able to selectively detach from the plasma membrane oncogenic proteins such as K-Ras, by interfering with their attachment to the membrane via interactions of polybasic cluster of amino acids in their tails. This results in alteration of the localization of K-Ras within nanodomains, reduces its affinity to the plasma membrane, and leads to redistribution to internal organelles such as mitochondria or endosomes. Depending on the organelle that the activated K-Ras is translocated to, the cells are either induced to undergo apoptosis (when K-Ras is in the mitochondria) or are growth-arrested (endosomal localization) by CPZ. These findings have a potential for the future development of therapeutic approaches to counteract oncogenic K-Ras activity.

(2) Factors regulating the molecular dynamics of focal adhesions (a manuscript is now in preparation). These studies are conducted in collaboration with Prof. Benjamin Geiger (Weizmann Institute) and Prof. Joseph Klafter (School of Chemistry, Tel Aviv University). Focal adhesions are specialized membrane-associated multi-protein complexes that link the cell to the extracellular matrix and play crucial roles in cell-matrix sensing. However, the regulation of FA dynamics is

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Dr. Yossi Lereah

Solid Nano-Particles in Liquid Nano-Containers The movement of the solid nano-particle in the Solid/liquid two-components Ga-Pb structures in isolated liquid nano-container, seen in fig. 1, was analyzed nanometer sized particles have been produced and studied by quantitatively and was found as non random electron microscopy. The production, based on the breath figure movement. The influence of temperature on the technique, was obtained at Nice University (Prof. R. Kofman’s group), interaction (wetting) with the container’s walls while Transmission Electron Microscopy was obtained at Tel-Aviv was studied. University. Characterization of Materials at Nanometer Scale by Electron holography Characterization of ferro-electric domains was obtained by Dr. Cheuk-wai TAI (a post doc from Hong-Kong). Characterization of electric-fields in ferro-electric nano-particles was obtained by Daniel Szwazmann (a student, supervised in collaboration with Gil Markovich). Characterization of Carbon soot was obtained in collaboration with Dr. M. Pawlyta (a visitor from Poland). Fig. 2, taken from Daniel Swarzmann’s work, shows the Fig.1: The movement of solid nano-particle, 8nm (diameter) Pb, in liquid nano- dependence of ferro-electric electric field on the container, 20nm (diameter) Ga. Preferred seats are found. particle’s size.

Obtaining corrected atomic scale images Due to lens aberrations the conventional high resolution images are limited to indicate the spacing between atomic planes, however the exact location of atoms are difficult to be interpreted. Overcoming this problem is obtained by acquisition series of images at different defocus conditions and reconstruction of “True Image”. The relevant software was purchased and is the procedure is being studied being studied by applying the method into two relevant problems: 3.1. Defect analysis in nano particles of HfO . In Fig. 2: Size-dependent Electric Field calculated from the gradient observed in the 2 previous study, Gil markovich and Einat Tirosh phase images within the BTO NCs. The electric field region from Bulk BaTiO3 single crystal is shown for comparison. proposed that in these crystals, magnetic

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properties are correlated with crystallographic defects. Accordingly, the method of “True Image” is being used (by Dr. Check-wai TAI) for quantitative analysis the defects including strain mapping in their surround. Conductivity in Granular Al:Ge System. During the 80’s an intensive study on various aspects of conductivity in granular Al:Ge was obtained by Guy Deutscher’s group. In view of the advanced electron microscopy methods available nowdays, the system is re-examined. Fig. 3 demonstrates a case of “soft contact” between two Al grains.

Fig. 3: A “soft contact” between Al nano-crystals embedded in amorphous Ge

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Prof. Rimona Margalit

Carrier-mediated drug delivery in cancer, diabetics and inflammatory diseases

Cancer targeted nano-liposomes (denoted ULV-RL). This (1) The novel formulation of paclitaxel in tumor-targeted carriers was determined qualitatively (figure 1B, C) and (gagomers), denoted TX/GAG. The achievements of building these quantitatively – an affinity ratio of 16/1 was found novel formulations and investigating their structural properties for the tumor-targeted vs. the non-targeted, and in vitro activities were summarized in the 2006-2007 report. liposomes. During 2008 this novel formulation was tested in vivo against the conventional formulation of detergent-solubilized free drug denoted Diabetes TX/Cre, in mice bearing solid tumors. The major achievements are: A therapeutically-effective oral insulin formulation (a) TX/GAG as well as the carrier itself (i.e., drug free gagomer) are is a not-yet-achieved primary goal in diabetes safe in vivo (b) TX/GAG, unlike TX/Cre is long-circulating and provides treatment. In this project nano-sized insulin fibrils active drug targeting to the tumor and (c) Treatment with TX/ were formed inside the muco-adhesive gagomer GAG slows down tumor progression significantly with indications particles (figure 2). The major findings are: (a) The of trend-turn to tumor regression, whereas upon treatment with novel insulin formulation, denoted gagomeric- TX/Cre tumor progression increases exponentially. This novel insulin, was stable in media simulating the formulation merits further development towards clinical studies. environments within the Gastrointestinal tract (2) Hyaluronan bioadhesive liposomes as tumor-targeted (b) In an in vitro bioassay it was verified that carriers for diagnostics and treatment of brain tumors. This the gagomeric-insulin formulation can release project was initiated in 2008, in vitro, utilizing the 9L and the C6 cell active insulin monomers. (c) Selecting a well- lines (both originating from rat brain tumors). The major findings are: known diabetes mouse model (Streptozotocin- (a) Unique to these brain-tumor cell cultures, CD44 receptors to which induced) to test the novel insulin formulation, the carriers are targeted, are present not only on the cell membranes critical needs was found to further develop this but also on the fibrillar connections between cells (figure 1A). (b) model and the experimental protocols for testing The targeted nano-liposomes (denoted ULV-HA-BAL) bind with high novel diabetes treatments and controls. These affinity to the tumor cells and the intercellular fibers, significantly needs were successfully addressed and can now better than the non-specific adherence of the conventional non- be of assistance to others in the field (d) under conditions that mimic human eating habits, a single dose of the novel formulation given orally reduced blood glucose levels significantly, quite equivalent to the conventional treatment of subcutaneous injection, with a later onset but significantly longer duration. Oral administration of free insulin had no effect. These results indicate the novel insulin formulation has high potential to perform as long-acting insulin, meriting further investigation. Moreover, forming nano fibrils Figure 1: Confocal micrographs of rat brain tumor cells (9L). A: identification inside gagomers may emerge to be a general and localization of CD44 receptors by a mAb against CD44 carrying a green- approach for oral administration of therapeutic fluorescing tag (FITC). B: Bound ULV-RL. C: Bound ULV-HA-BAL. Both liposome proteins. types are labeled by a red-fluorescing lipid (Rhodamine-PE).

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Inflammatory diseases Macrophages, phagocytic cells that are major constituents of defense mechanisms, stimulate the immune system to secrete both pro- and anti-inflammatory cytokines. Unregulated release of pro-inflammatory cytokines may lead to chronic auto-immune inflammatory diseases. Hyaluronan (HA), and its receptors (CD44) when expressed on macrophage membranes, may have key roles in macrophage activities and may also be used for anti-inflammatory therapeutic approaches utilizing targeted hyaluronan-nanocarriers. Figure 2: Electron micrographs of the novel gagomer- insulin formulation. A. Nano insulin fibrils B. A view of a The relationships among CD44, HA and macrophage activities in the gagomer particle (left-hand particle) and a view inside an inflammation arena still need molecular elucidation. Macrophages are insulin-gagomer revealing the intra-particle nano insulin also known to endocytose particles such as liposomes and spheres, fibrils (right hand particle). which is detrimental for drug carriers designated to deliver drugs to receptors on cell membranes. Current findings are: (a) Expression of CD44 receptors on macrophage membranes was verified for the macrophage cell line RAW264.7. Extending such studies, CD44 was also found in membranes of primary macrophages, and on both young and mature RAW264.7 cells. (b) Macrophages bound, with high affinity, both regular (RL) and hyaluronan (HA-BAL) liposomes, but with a distinct critical difference: TheR L were endocytosed (figure 3A), while the HA-BAL remained bound to their receptors at the cell surface (figure 3B). This is clear experimental support that the latter, Figure 3: Confocal micrographs of liposome interactions with macrophages (RAW264.7 cells). The green but not former, are eminently suitable to perform their designated fluorescence marks the cell membrane, and the red dots role as carriers of drugs that stimulate secretion of anti-inflammatory are the liposomes A: regular liposomes (RL) inside the cell. cytokines. B: hyaluronan bioadhesive liposomes (HA-BAL) localized at the cell surface.

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Prof. Gil Markovich

he Markovich group focuses on studies of various types of physical phenomena related to inorganic nanocrystals. In the last year the group has been T working on several nanocrystal systems: Preparation of two-dimensional magnetic nanocrystal arrays and studies of their magnetic and spin-polarized electron transport properties with emphasis on their magnetization dynamics

Magnetite (Fe3O4) nanocrystal monolayers were produced using the Langmuir-Blodgett technique and deposited on various substrates. In one study, the films were deposited in small gaps between two electrodes defined by electron beam lithography. Magneto- transport measurements revealed relatively large magnetoresistance Studies of the interactions of values (10-25%) at temperatures >200K and their magnetic field and chiral molecules with surface temperature dependence indicated the dominance of inter-particle plasmon excitations of noble metal tunneling in the contribution to the measured magnetoresistance. nanoparticles In a second study, a multilayer film was deposited on a gold film We have used colloidal silver nanoparticles, in the and studied by a variable-temperature, ultra-high vacuum scanning size range of 10-50 nm to enhance the absorption tunneling microscope. In this project, temperature dependent noise of chromophore molecules, attached through a in the tunneling current was observed and correlated to the dynamics short tri-peptide (glutathione) to the particles’ of magnwtic moment switching of the nanocrystals. surfaces. The absorption of the chromophores, in resonance with the surface plasmon excitation Studies of defect induced ferromagnetism in oxide of the silver particles, was enhanced by about nanocrystals, such as HfO2 two orders of magnitude. In addition, we have

In this project, colloidal HfO2 nanocrystals were produced using studied the circular dichroism induced at the thermal decomposition of organometallic precursors in a high achiral chromophore molecules by attachment boiling point organic solvent. It was found that by tuning synthesis to the chiral peptide. This weak circular dichroism conditions, i.e., type of solvent and surfactants, temperature, the response was also enhanced by two orders of concentration of defects in the nanocrystals could be controlled, magnitude on binding to the silver particles. turning a small part of the nanocrystals into ferromagnetic for the higher defect concentrations. Currently, a high-resolution electron Studies of nanoscale ferroelectricity in microscopy study, performed in collaboration with Cheuk-Wai Tai BaTiO3 nanocubes and Yossi Lereah is aimed at identifying the exact nature of these Ferroelectric BaTiO3 nanocubes in the size range of defects and defective nanocrystals. 20-100 nm were synthesized and studied by x-ray diffraction,R aman spectroscopy and transmission

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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.

Deposition of metal nanowire films on surfaces using colloidal chemistry A technique for the deposition of very thin films containing networks of high aspect ratio gold/silver nanowires has been developed. The technique involves the preparation of a growth solution containing a mixture of gold and silver salts and a reducing agent in the presence of high concentrations of surfactant molecules. After its preparation the solution is spread on various surfaces with a controlled thickness and then let dry. While drying the surfactant molecules form tubular template structures in which the metal nanowires grow. These nanowire network films are highly conductive, as well as transparent due to the low volume filling of the nanowires.

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Prof. Alexander Palevski

Quantum electronic transport in nanostructures

n our research laboratory at the Department of Condensed Achievements: Matter we currently conduct experimental research related to The theory based on the formation of the nanoscience in the following three directions: π-junction in Josephson coupled structures containing ferromagnetic layers was verified and Superconductor proximity effect in ferromagnetic the oscillations of the critical current versus the and normal junctions thickness of F-layer were observed. IWe investigate the superconductor critical current through nano- The predictions of Luttinger liquid theory were size ferromagnetic layers. The theoretically predicted spin screening verified and the value of the interaction constant effects in S/F nanostructures are studied by both transport and for GaAs was deduced from the Luttinger model. optical methods. Little-Parks oscillations were observed in 100 nm One-dimensional quantum wires and mesoscopic Nb cylinders. effects Electronic transport properties are studied at low temperatures in Three invited lectures on the above subjects were V-grooved quantum wires. The quantization of the conductance as a presented at the in the international scientific result of one-dimensional band structure is observed. The dephasing meetings and conferences in Leiden (Holland), in 1D is studied. Kharkov (Ukraine), Crete (Greece). Metal-superconductor quantum phase transition in nanocylinders Reference: Our experimental groups in collaboration with the collegues in I. Sternfeld, R. Koret, H. Shtrikman, A. Tsukernik, M. WIS developed a new technology to fabricate superconducting Karpovski and A. Palevski, Quantum phase transition in ultra small hollow superconducting cylinders, nanocylinders with the diameters as small as 50 nm. The quantum submitted to publication (2007). phase transition is investigated in these structures.

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 Nb nanocylinder with Au contacts (right).

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Prof. Fernando Patolsky

uring the years 2007-2008 my group worked on Dthe following direction: 1. New approaches for the synthesis of multicomponent nanoparticles and the applications. 2. The synthesis and characterization of a new family of Si and Si/Ge highly controlled nanotubular structures. We are currently applying this nanotubular structures in biosensing and nanofluidic studies. 3. The development of photovoltaic future devices based on nanoscale light collectors arrays. 4. The development of highly efficient fuel cells of ultra-low cost based on cheap nanocatalyst elements. 5. Biosensing of a broad range of diseases based on large scale nanowires-based FET arrays. 6. The development of novel approaches for the assembly of ultra- large arrays of nanowires elements.

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

Prof. Emanuel Peled and Prof. Diana Golodnitsky

he major research efforts have been focused on the of new mobile electronic and implantable medical development of nanomaterials for 3D-lithium-ion devices: high energy and peak power, fast charge, microbatteries (3DMB) and fuel cells. long cycle life and safe behavior. 3D-interlaced (3D-IMB) and 3D-concentric micro- Within the frame of the current research batteries (3D-CMB) consist of tens of thousands of nanoporous silicon membranes have been multi microcells connected in parallel within a half prepared by DRIE and metal assisted anisotropic mmT thick non-conducting perforated high-aspect-ratio silicon etching. It was found that increase of the HF or glass substrate. TAU research group has recently developed concentration is followed by the decrease of and demonstrated the first working prototype of a rechargeable pore size; hydrogen peroxide increases pores

3D-concentric lithium ion microbattery with amorphous MoOxSy dimensions; addition of ethanol promotes cathode*. A semi-3DMB-on-Si cell demonstrated less than 0.1% uniformity of the porous silicon layer. The capacity loss over 100 successive cycles with 100% DOD. A semi- nanoporous membranes (Fig.1) demonstrate 3DMB-on-MCP cell with a composite cathode (20 min of deposition) potential to be used as Li+ conducting media for exhibited about 10 mAh/cm2 reversible capacity, 20 to 30 times that 3D-interlaced microbatteries. After optimization of a similar footprint, 2D cell. The key challenge in the improvement of etching process the conductivity, being a of 3DMBs performance is the development of new nanosize function of pore size and tortuosity, is expected electrode and electrolyte materials with highly percolating particle to approach that of commercial polymer distributions and short ion diffusion distances. These materials are membrane. The Li+ conduction mechanism is essential to provide four major characteristics required for powering under investigation. Electrochemical and structural study of electrodeposited thin-film nanoparticle copper

sulfide (Cu2S and CuS) cathodes for 3D-CMBs has been carried out. According to the SEM data, the deposition parameters, such as time of deposition, current density, temperature of the electrolytic bath, stirring rate and addition of PEGDME and PEI additives, affect the morphology of the copper sulfide films. Planar and 3DCMB cells with nanoparticle copper sulfide cathodes are under testing.

*A nano-battery technology developed at Tel Aviv University could pose the sought for solution for fast charge/discharge safer batteries that reduce the fire hazards recently reported in connection with Lithium based mobile batteries (NY Times August 15th, 2006). Fig.1: SEM images of nanoporous interlaced Si with incompletely etched partition between microcontainers

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Dr. Shachar Richter

he main research direction in this period focused on efficiency. On the last year we have focused several directions: some efforts on up-scaling of the active area of (i) development of novel molecular-based transistors, this Cell. This task is very challenging since the (ii) Demonstration of large-area bio-inspired solar cell nm-sized PSI layer could be easily damaged and (iii) development of new type of bio-compatible during the up-scaling process. Recently, we have materials. successfully fabricated a 0.01Cm2 solar cell with T several percents yield. The task was achieved Molecular-based Transistors. after a special type of conducting polymer was Recently, we have demonstrated a new type of molecular transistor. incorporated in the solar cell serving as a mediator This Central –Gate Molecular Vertical Transistor (C-Gate Molvet) between the sensitive bio-particles and the solid exhibits nm-scale channel length, ambipolar behavior and is extremely state template. sensitive to gate voltage. Using this device we have successfully demonstrates a molecular-quantum switch, protein-based transistor, Water soluble biomaterials2 and tunable-hysteresis devices. One of the great challenges in material science is to produce water soluble inorganic materials. Large-area bio-inspired solar cell1 These types of materials, usually hyrdophbic in Several years ago we have demonstrated the fabrication and operation nature, are required for various applications such as bio-inspired Solar-cell devices. This was done by introducing into bio-compatible materials and plastic electronics. microcavitiy arrays Photo-System I (PSI)-based nanoparticles. These Recently, M. Gozin (TAU), have shown that certain nanoparticles were found to convert photons to photovoltaic types of water soluble biological compound can energy with reasonable yield. A device made out of PSI-based SAM “swallow” hydrophobic compounds. We have used sandwiched between top transparent conducting electrode and this phenomenon to construct a water soluble bottom gold electrode yielded several percents energy conversion biocompatible glue (figure 3). This composite

Figure 1: Examples of Transfer characteristics of the C-Gate Molvet. Left. Protein- based C-Gate MolVet operated at low power and showing high gate sensitivity. Inset. Transfer properties in ambipolar mode. Right – Switching device. A Negative differential resistance peak can be created (left) or erased (right) by application of the appropriate gate voltage. Figure 2: Prototype of the 1. In collaboration with Prof. Chanoch Carmeli, Biochamistry, TAU 0.01Cm2 PSI-based solar cell 2. In collaboration with Dr. Michael Gozin, TAU showing ~2% yield.

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glue is composed of carbon nanotubes incorporated inside biological matrix. Our preliminary results indicate that this material is unique by its adhesion and mechanical properties.

Figure 3: Biocompatible water soluble glue. Left-Transmission Electron Microscopy (TEM) image of Nanotube network is incorporated in biological matrix. Right. High reolution image of the single wall nanotubes located inside the composite material.

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Prof. Judith Rishpon

Highly Sensitive NanoParticles Modified Electrodes for Fast medical and environmental Diagnostics

e further exploited nanoparticles modified 2. Electrodes modified with CNT and PNT were electrodes for increased sensitivity. We have used in a sensitive detection of pollutants. The utilized the unique electronic properties enzyme tyrosinase was immobilized on the of carbon nanotubes (CNT) and peptide electrode and used for the detection of phenolic nanotubes (PNT) in electrochemistry as compounds. The amplifying effect of the means of promoting the electron transfer nanoparticles is clearly envisaged below. andW as a substrate for binding and adsorption of reactive components. CNT and PNT were attached to carbon electrodes and employed as sensitive bioelectrochemical sensors. The electrode surface with and without CNT taken with is shown below:

3. The synergistic effect of combining both nanoparticles was also examined and the results are shown below: It is evident that electrodes modified with PNT and CNT produced the highest signal.

In particular we concentrated in:

1. Detection of heavy metals by differential pulse anodic stripping

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

4. CNT attached to electrodes were also exploited in highly sensitive electrochemical enzyme immuno-sensors for medical diagnostics. Hormones, viruses antibodies for viruses and disease markers were tested. For example an immunosensor for progesterone was developed and measured in milk. Also an immunosensor for C reactive protein (CRP) a protein that is a marker for heart failure and acute inflammation was developed and measured in human serum samples. The effect of the nanoparticles is evident, especially at low concentrations.

5. Screen print electrode modified with carbon nanotubes were used for the monitoring of 5. formaldehyde released from brain cancer cells in response to anti cancer pro-drug treatment.

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

Prof. Gil Rosenman

New Generation of Energy Storage Devices Based on Bio-Inspired Nanostructures Light Peptide Nanotubes Sources In cooperation with Prof. E. Gazit In cooperation with Prof. E. Gazit

Supercapacitors are promising energy storage devices due to their We discover pronounced quantum confinement unique combination of high power density and relatively large energy (QC) and photoluminescence (PL) phenomena density. We report on environmentally clean bio-supercapacitors in self-assembled peptide nanostructures based on peptide nanotubes (PNT)-modified electrodes. of different origin diphenylalanine (FF) Short aromatic dipeptides can self-assemble into ordered structures nanotubes deposited by a vapor deposition at the nano-scale. These assemblies include nanotubes, nanospheres, method, hydrogels self-assembly of short nano-plates and hydrogels with nano-scale order (Reches, Gazit, Fmoc (N-fluorenylmethoxycarbonyl)-based Science, 2003; Nature Nanotechology, 2006, 2007). Peptide molecules into fibrous formation, nanospheres nanotubes represent a novel class of nanotubes of biological origin as self-assembled from Fmoc-FF or Boc-(Di-tert- an appealing alternative to carbon nanotubes. It has been observed butyl dicarbonate)-FF monomers and natural that these biological nanostructures possess paramount properties self assembly of amyloidogenic proteins. Our of different origin allowing to find at the intersection Biology-Physics- observation of QC effects is a direct evidence Engineering new advanced nanotechnological applications using of highly ordered sub-nano-crystalline areas the PNT building blocks. embedded in the structures. The observed PL of The basis for the new nanotechnology presented in this report is the bio-nanotubes opens a new nanotechnology recently developed new biomolecules deposition method which field of bio-inspired materials for optical devices allows to drastically change the previous PNT deposition technology, such as biosensors, LED, biolasers and more. based on peptide evaporation from aqueous or organic solutions. The method may be applied to PNT coatings on unlimited area with high density and homogeneity, controllable thickness as well for fabricating patterned PNT structures. We found that vertically oriented peptide nanotubular bio-inspired structures demonstrate new surprising physical properties such as dielectric, electrochemical, and wettability which affords to develop environmentally clean nanodevices. A new PNT-based technology has been applied to development of “green” energy storage devices- Supercapacitors. Deposition of PNT arrays on carbon electrodes strongly increases efficiency of these electrochemical units due to high density PNT coating. In the developed electrostatic supercapacitors aromatic vertically oriented dipeptide nanotubes have been used for modification of carbon electrodes of supercapacitors. The 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 new methods for measuring the electronic properties of semiconductor materials and devices with nanometer spatial resolution. The various techniques are based on scanning probe microscopy in general Pand Kelvin probe microscopy (KPFM) in particular. Nano Research projects: • AFM tip– Semiconductor electrostatic interaction. • Nanoscale electrical characterization of operating semiconductor devices. • High Voltage AFM. • Direct Measurement of Density of States and other Transport Properties of Organic Materials and Devices. • UHV-KPFM of QDs and dopants in III-V semiconductors. • Organic self-assemebled monolayers on semiconductor. • Bio Field Effect Transistors.

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

Prof. Yosi Shacham-Diamand

Nano wires, interconnects and electrodes

esearch on the deposition of nano scale interconnects fro Ultra Large Scale integration (ULSI) and for nano electrodes. The research scope included basic research of nano scale metal alloys like CoWPB using a novel surface adsorption model that had been developed in TAU and the super filling of nano scale trenches by Cu. InR the nano electrode field we are active in the following projects: a. The ReNaChip Project - Brain –machine hybrid for the rehabilitation of a discrete motor learning function. Investigation in manufacturing of electro-analytical cell with sensing nano-electrodes. B. The SmartHand project – developing nano electrodes fro a new hand prosthesis, v. TOXICHIP – bioluminescent technology fro detecting toxicity in water and d. DipChip – electrochemical technology for detection o toxicity in water. Additionally we have a research project under the Magnet program for developing nano electrodes on plastic for MEMS applications.

Corporation with Industry and other universities in Nano issues 1. The SmartHand project: Tyndall Institute, Ireland, Aalborg University, Denmark, ARTS Lab and CRIM Lab, Scuola Superiore Sant’Anna, Pisa, University Hospital, Malmö, Sweden, Lund University, OSSUR inc ( Iceland) 2. The ReNaChip Project. UNEW (Newcastle University, UK), UPF (Spain), G.Tec (Austria), Lund University (Sweden), 3. dipChip: the University of Koblenz (Germany).

Corporation within TAU Corporation with: Prof. Matti Mintz (Applied Psyciology), Prof. H. Messer-Yaron (Eng.), Prof. J. Rishpon, Prof. A. Freeman and Prof. E. Gazit (Life Science), Prof. D. Benayahu (Medicine),

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

Dr. Ronit Satchi-Fainaro

A novel combined targeted anticancer and anti- angiogenic polymer therapeutic for bone neoplasms

e developed a new therapeutic strategy for resistance. In the past few years, there is growing bone neoplasms using combined targeted evidence that taxanes and bisphosphonates have polymer-bound angiogenesis inhibitors. antiangiogenic properties. It has been found that We conjugated the aminobisphosphonate paclitaxel at ultra low dose is antiangiogenic. alendronate (ALN), and the potent anti- It is conceptually accepted that angiogenesis angiogenic agent TNP-470 with N-(2- inhibitors alone may not be sufficient to eradicate hydroxypropyl)W methacrylamide (HPMA) copolymer. Previous prostate cancer. Therefore, the generation of a work on caplostatin, an HPMA copolymer-TNP-470 conjugate, combination of drug delivery systems with bi- demonstrated that polymer conjugation of TNP-470 increases its specific antiangiogenic and antitumor properties half-life, water-solubility and tumor accumulation, while reducing is a novel approach. We developed a new its toxicity. Using reversible addition-fragmentation chain transfer strategy of targeted therapy for the treatment of (RAFT) polymerization, we synthesized a conjugate of HPMA prostate cancer bone metastases. Our strategy copolymer-ALN-TNP-470 bearing a cathepsin K-cleavable linker, rests upon the conjugation of a bone targeting a protease overexpressed in bone tissues. Free and conjugated moiety, the aminobisphosphonate alendronate, ALN-TNP-470 demonstrated their synergistic anti-angiogenic and the chemotherapeutic agent paclitaxel to and antitumor activity by inhibiting proliferation, migration and N-(2-hydroxypropyl) methacrylamide (HPMA) capillary-like tube formation of endothelial and osteosarcoma cells. copolymer. Water-soluble HPMA copolymers Our bi-specific conjugate reduced vascular hyperpermeability and accumulate in tumor tissues due to the enhanced remarkably inhibited human osteosarcoma growth in mice by 96%. permeability and retention effect. Taking HPMA copolymer-ALN-TNP-470 is the first narrowly dispersed anti- advantage of the multivalency of polymers, we angiogenic conjugate synthesized by RAFT polymerization that conjugated both drugs on the same polymeric targets both the tumor and endothelial compartments warranting backbone resulting with a nanoconjugate at a size its use on osteosarcomas and bone metastases. of ~100 nm. Paclitaxel was conjugated to HPMA copolymer through the dipeptide phenylalanine- Targeting bone metastases with a novel bi-specific lysine-p-aminobenzyl carbonate linker. This linker anticancer and anti-angiogenic polymer-alendronate- was cleaved by the lysosomal enzyme cathepsin B taxane conjugate overexpressed in tumor epithelial and endothelial Bone metastases are one of the main obstacles for the recuperation cells and free paclitaxel was released. HPMA of prostate cancer patients and in most, if not all, cases the reason copolymer-paclitaxel-dipeptide-alendronate why the disease becomes non-curable and devastating. At advanced nanoconjugate inhibited the proliferation of stages of bone metastases, the disease progresses to a phase when prostate carcinoma cells. Furthermore, our the standard systemic therapy progresses to a highly chemotherapy- conjugate demonstrated anti-angiogenic effect resistant state. Therefore, new strategies for the treatment of advanced on different steps of the angiogenic cascade such metastatic disease need to be rapidly developed. The taxane paclitaxel as proliferation, migration and tube-formation of and the bisphosphonate, alendronate are two drugs used as treatment endothelial cells. for bone metastatic prostate cancer. However these two drugs, Our goal with the new synthetic conjugate of when given at the standard doses cause side effects. Furthermore, HPMA copolymer-paclitaxel-dipeptide-alendronate patients treated with paclitaxel develop at a certain point drug will be “specificity with reduced toxicity”. It is

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

anticipated that specific targeted therapies will improve quality of 2. Sagi A, Segal E, Satchi-Fainaro R* and Shabat D*, life for patients and will provide an alternative to patient’s refractory Dramatic drug-release enhancement with an elimination-based AB self-immolative dendritic to taxane-based therapies, avoiding toxicities. 3 amplifier, Bioorganic and Medicinal Chemistry, 15, 3720–3727 (2007). * Corresponding authors. Targeting αvβ3 integrin on tumor vasculature using a 3. Chesler L, Goldenberg DD, Seales IT, Satchi-Fainaro novel polyglutamic acid-paclitaxel conjugate with the R, Grimmer M, Collins R, Struett C, Nguyen KN, Kim G, Tihan T, Bao Y, Brekken RA, Bergers G, Folkman divalent peptide E-[c(RGDfK)2] Angiogenesis, new capillary blood vessel growth from pre-existing J, Weiss WA, Malignant progression and blockade vasculature, is a critical factor in cancer progression. Therefore, anti- of angiogenesis in a murine transgenic model of neuroblastoma, Cancer Research, 67 (19), 9435- angiogenic therapy, alone or in combination with conventional 9442 (2007). cytotoxic therapy, may be a promising therapeutic approach. Paclitaxel 4. Ryppa C, Mann-Steinberg H, Fichtner I, Weber H, is a potent cytotoxic insoluble drug; however, it is hydrophobic and Satchi-Fainaro R, Biniossek M and Kratz F, In vitro causes side effects such as neutropenia, neuropathies, and when and in vivo evaluation of doxorubicin conjugates solubilized in Cremophor EL causes hypersensitivity reactions. with the bicyclic peptide E-[c(RGDfK)2] that target integrin α β , Bioconjugate Chemistry, 19(7), 1414- Polyglutamic acid (PGA)-paclitaxel is currently undergoing phase v 3 22. (2008). three clinical trials showing promising results. PGA is a water-soluble, 5. Segal E and Satchi-Fainaro R, Design and non-toxic and biodegradable polymer that accumulates in the tumor Development of polymer conjugates as bed by the enhanced permeability and retention (EPR) effect when antiangiogenic agents, Special Theme issue: it is used at a nano-scaled size of 10-100 nm. Here, we conjugated Polymer Therapeutics: Clinical Applications and PGA with paclitaxel and a targeting moiety, the cyclic RGD Challenges for Development, Advanced Drug peptidomimetic, E-[c(RGDfk) ], which actively targets the conjugate Delivery Reviews, in press (2008). 2 6. Satchi-Fainaro R*, Ferguson E* and Duncan to proliferating tumor endothelial cells overexpressing αvβ3 integrin. R, PELT: Polymer Enzyme Liposome Therapy. The resulting PGA-[c(RGDfk)2]-paclitaxel nanoconjugate measured at HPMA copolymer-phospholipase C and Dextrin- a diameter size of ~30 nm. The ester linker between the polymer and phospholipase A2 as model triggers, submitted the drug is hydrolytically labile and paclitaxel release occured under (2008). * Equal contribution. lysosomal acidic pH and the PGA itself was degradable by lysosomal 7. Ryppa C, Mann-Steinberg H, Biniossek M, Satchi- enzymes such as cysteine proteases, particularly cathepsin B. PGA-E- Fainaro R* and Kratz F*, In vitro evaluation of paclitaxel conjugates with the divalent [c(RGDfk)2]-paclitaxel inhibited the proliferation of endothelial cells, peptide E-[c(RGDfK)2] that target integrin αvβ3, their attachment to fibrinogen-coated wells, their migration towards International Journal of Pharmaceutics, in press vascular endothelial growth factor (VEGF) and their formation as (2008). *Corresponding authors. capillary-like tubes. These results warrant our conjugate as a novel targeted anti-angiogenic anticancer therapy. Book Chapters: 1. Satchi-Fainaro R and Mann-Steinberg H, TNP-470: The resurrection of the first synthetic angiogenesis References inhibitor, In: Angiogenesis: An integrative approach Papers from science to medicine. Editors: William Figg 1. Nahari D, Satchi-Fainaro R, Chen M, Task LB, Liu Z, Terada LS, Carroll and Judah Folkman, Springer-Verlag, Heidelberg, AB and Nwariaku F, Tumor Cytotoxicity and Endothelial Rac Inhibition Germany, Chapter 35, p. 387-406 (2008). Induced by TNP-470 in Anaplastic Thyroid Cancer, Molecular Cancer 2. Miller K and Satchi-Fainaro R, Polymer Therapeutics: Therapeutics, 6, 1329-1337 (2007). From novel concepts to clinical applications, In

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Wiley Encyclopedia of Chemical Biology, Ed. N. R. Civjan, John Wiley & Sons, Inc. In press (2008).

Patents: 1. Miller K and Satchi-Fainaro R, Antiangiogenic polymer therapeutics and use thereof, Provisional patent application 2008033-00-00 (2008). 2. Satchi-Fainaro R and Vicent Docón MJ, Novel polymers comprising an anti-angiogenesis agent and RGD or an analog thereof and uses thereof in the treatment of angiogenesis-related disease. Provisional patent application 20043912-00-00 (2008). 3. Satchi-Fainaro R, Segal E, Kopecek J, Kopeckova P, Pan H, A HPMA- alendronate-TNP-470 conjugate comprising a high load of alendronate and uses thereof in the treatment of bone related angiogenesis conditions. Provisional patent application 20043857-00-00 (2008). 4. Satchi-Fainaro R, Ofek P, Fisher W and Haag R, Compounds suited as nanocarriers for active agents and their use. EP08156816 (2008).

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

Dr. Yoram Selzer

n collaboration with the group of Prof. Ori Cheshnovsky References: we have developed a novel method to detect heating and 1. fabrication and charaterization of “on-edge” cooling processes in current carrying molecular junctions. junction for molecular electronics, Shamai T., Ophir A., Selzer Y., Appl. Phys. Lett. 2007, 91, 102108. The experimental approach is based on Raman scattering 2. detection of Heating in Current Carrying Molecular measurements of junctions under bias. The effective Junctions by Raman Scattering, Ioffe Z., Shamai T., temperature of the various modes are calculated from the Anti- Ophir A., Noy G., Yutsis I., Kfir K., Cheshnovsky O., IStokes/Stikes ratio signals for each mode1, 2. Selzer Y., Nature Nanotechnology 2008 doi 10.1038/ We have also developed a novel synthesis approach to metal nnano.2008.304 nanowires3. The resulting nanowires have an aspect ration of 3. Synthesis of very high aspect ratio metal nanowires by a self-propelling mechanism, Sharabani R., Saada 1:10,000. The nanowires are grown inside the pores of polycarbonate R., Noy G., Shapira E., Sadeh S., Selzer Y., Nano Lett. membranes. The novelty in the process is that the wires are grown in 2008, 8, 1169. a “meat grinder” fashion. Under certain conditions as the nanowires 4. Segmented nanowires as nano-scale grow they are also continuously pushed out of the membranes into thermocouples, Shapira E., Marchak D., Tsukerik A., the surrounding solution by means of a self-electrophoretic process. Selzer Y., Nanotechnology 2008, 19, 125501. The rate of the latter process is identical to the rate of elongation 5. fabrication of highly stable configurable metal quantum point contacts”, Itach N., Yutsis I., Selzer Y., and as a consequence, the reduction of ions takes place only within Nano Lett. 2008 ASAP. the pores, thus maintaining a uniform diameter. As a result, while the membranes are only 6μm long, the formed nanowires could be two orders of magnitude longer. This new synthetic approach is important first because it is intriguing in terms of the fundamental processes involved, and second because it opens new routes to fabricate one dimensional nano-scale materials with very high aspect ratios. We have demonstrated how segmented Au-Ni nanowires can be highly effective thermocouples with spatial resolution of few nanometers and temporal resolution in the microsecond range4. The performance of the devices is characterized by a self-heating procedure in which an ac heating current at ω frequency is applied on the wires while monitoring the resulting thermoelectric voltage

VTH at 2ω using a lock in technique. An analytical model has been developed that enables to determine the time response of the thermocouples from plots of VTH as a function of ω. We have also developed a new method to form Metal Quantum Point Contacts (MQPCs) with quantized conductance values in the range of 1-4G0. The contacts appear to be stable at room temperature for hours and can be deterministically switched between conductance values, or reform in case they break, using voltage pulses. The method enables to integrate MQPCs within nano-scale circuits to fully harness their unique advantages5.

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

Prof. Yoram Shapira

e have conducted a number of research separation at tetraphenyl-porphyrin/metal oxide programs that qualify as nano-science and interfaces”, J. Appl. Phys., 102, 53705, 2007. nano- technology related. 7. d. S. Warren, Yoram Shapira, H. Kisch, A. J. McQuillan, “Apparent semiconductor type reversal in anatase

TiO2 nanocrystalline films”, J. Phys. Chem. C, 111, 14286, 2007. 8. y. Zidon, Yoram Shapira, Th. Dittrich, “Interactions at tetraphenyl-porphyrin/InP interfaces observed W by surface photovoltage spectroscopy”, Appl. Surf. We have carried out Sci., 254, 3255, 2008. 9. M. Gurfinkel, H.D. Xiong, J. Suehle, J.B. Bernstein, • Experimental studies of nano-layers of organic molecules at Yoram Shapira, A.J. Lelis, D. Habersat, N. Goldsman, semiconductor surfaces. Some of the work has been done in “Characterization of transient gate oxide trapping collaboration with HMI, Berlin, Germany. in SiC MOSFETs using fast I-V techniques”, IEEE – • Theoretical work related to the studies mentioned above in Trans. Electron Devices, 55, 2004, 2008. collaboration with WIS. 10. E. Grünbaum, Z. Barkay, Yoram Shapira, K. Barnham, • Characterization project nano-layers of oxides and high-K gate D. B. Bushnell, M. Mazzer, P. Wilshaw, “Secondary Electron Emission Contrast of Quantum Wells in stacks on Si and SiC nano-scale devices and developed a physical GaAs p-i-n Junctions”, Microscopy and Microanalysis, model of these systems. in press, 2008. • Studies of photocatalysis on nano-crystalline layers of titanium dioxide. • Studies of nano-scale resolution imaging of the electronic structure at semiconductor surfaces by SEM.

References: 1. y. Zidon, Yoram Shapira, Th. Dittrich, “Modulated Charge Separation at Tetraphenyl-Porphyrin /Au Interfaces”, Appl. Phys. Letters, 90, 142103, 2007. 2. d. Deutsch, A. Natan, L. Kronik, Yoram Shapira, “Electrostatic properties of adsorbed polar molecules: Opposite behavior of a single molecule and a molecular monolayer”, J. Am. Chem. Soc., 129, 2989, 2007. 3. h. D. Xiong, D. Heh, M. Gurfinkel, Q. Li,Y . Shapira, C. Richter, G. Bersuker, R. Choi, J. S. Suehle, “Characterization of electrically active defects in high-k gate dielectrics by using low frequency noise and charge pumping measurements”, Microelectronic Engineering, 84, 2230, 2007. 4. y. Zidon, Yoram Shapira, Th. Dittrich, L. Otero, “Light induced charge

separation in thin H2TPP layers deposited on Au”, Phys. Rev. B, 75, 195327, 2007. 5. M. Gurfinkel, H.D. Xiong, J. Suehle, J.B. Bernstein, Yoram Shapira, A.J. Lelis, D. Habersat, N. Goldsman, “Characterization of transient gate oxide trapping in SiC MOSFETs”, IEEE – Trans. Devices and Materials Reliability, 84, 2230, 2007. 6. y. Zidon, Yoram Shapira, Th. Dittrich, “Illumination induced charge

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

Dr. Inna Slutsky

From nano-scale single synapse to information Endogenous amyloid-β proteins: processing in neural networks from single-protein interactions It is widely believed that memory is grounded in synaptic to physiological and pathological connections. However, the principles regulating encoding, storage functions and retrieval of information in synaptic networks remain elusive. Our It is generally agreed that accumulation of research is focused on the endogenous mechanisms controlling cerebral Aβ leads to synapse loss, the best memory capacity in adult brain. Our main target is to determine structural correlate of cognitive deficits in how the quality and quantity of ongoing neuronal activity affect Alzheimer’s disease (AD). However, physiological the properties of individual pre- and post-synaptic compartments, functions of endogenous Aβ peptides which neural connections (few synapses) and synaptic networks (thousands are secreted by neurons through life still need of synapses). To fulfill this goal, we are applying combination of to be identified. Furthermore, pathological electrophysiology, functional quantitative imaging, spectroscopy, processes leading to Aβ-mediated synaptic biochemistry, and molecular biology. Our recent results indicate that failure remain controversial. In this project we aim uncorrelated pattern of neuronal activity plays a key role in synaptic to determine the casual relationships between network organization and memory function. the pattern of neuronal activity, release of endogenous Aβ, and the number and plasticity of synapses in wild-type hippocampal neurons. This is achieved by using high-resolution optical imaging to detect vesicle release and plasticity at the level of individual presynaptic terminals, electrophysiology to monitor input-output relationships at the level of neuronal connections, FRET-based spectroscopy to estimate dynamics of protein-protein interactions, and biochemistry to measure APP-derived species in hippocampal culture. Our findings suggest that elevation in ongoing neuronal activity coupled to reduction in synapse capacity to transfer bursts might initiate compensatory synapse loss and subsequent memory decline in AD.

This project is supported by New Investigator Award Figure 1: Determining APP-Gαo interactions by FRET-based spectroscopy in presynaptic terminals of live hippocampal neurons. A, Low-magnification in Alzheimer’s Disease of American Federation confocal image of pyramidal neuron over-expressing APP-YFP and Gαo-CFP. for Ageing Research, Morasha-ISF program, and Image was taken using 510META LSM: detection of 520-550 nm emission with 405 National Institute for Psychobiology. nm excitation. B, High magnification confocal image of presynaptic terminals of the neuron depicted in A. C, A cartoon illustrating basic principles of the donor de- quenching technique as a tool for measuring FRET. D, A representative spectra of neuronal terminal expressing APP-YFP and Gαo-CFP, taken before (solid line) and after (dashed line) acceptor photo-destruction.

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Regulation of Hebbian plasticity by optimization of the

GABAB1a receptor activity A persistent challenge in unraveling mechanisms that regulate memory function is to bridge the gap between inter-molecular dynamics of single-proteins and behavior of single synapses in neuronal networks. In particular, the mechanisms linking dynamics of presynaptic G-protein-coupled receptors to plasticity of synaptic connections under physiological conditions are poorly understood. In this project we intend to determine relationships between the pattern of neuronal activity, inter-molecular interactions within the

GABABR signaling complex, and plasticity of presynaptic terminals in hippocampal pyramidal neurons. This is achieved by using real-time simultaneous measurements of molecular dynamics, transmitter release, and presynaptic plasticity at the level of individual presynaptic terminals. We examine possible interactions between presynaptic

GABABRs, G protein subunits, and CaV2 channels at resting state using fluorescence resonance energy transfer (FRET) methods. The degree of coupling between the proteins is tested as function of terminal location, transmitter release probability, and GABABR-mediated tonic inhibition using activity-dependent FM styryl dyes. The proposed research will elucidate basic principles underlying protein-protein interactions within the presynaptic GABABR signaling complex and their role in regulating presynaptic activity.

This project is supported by BSF and ISF programs.

References: 1. E. Abramov, I. Dolev, E. Ruff, and I. Slutsky. Endogenous amyloid-β regulates temporal code at single hippocampal synapses (submitted). 2. Slutsky, I., Abumaria, N., Wu, L.J., Huang, C. Li, B., Govindarajan, A., Zhao, M.G., Zhuo, M., Tonegawa, S., Liu, G. Magnesium Increases Synaptic Density and Plasticity and Enhances Memory (submitted).

3. I. Vertkin and I. Slutsky. Optimization of the GABAB1a receptor activity maintains Hebbian plasticity of presynaptic terminals (submitted).

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

Prof. Michael Urbakh

Dynamics in Small Confining Systems

Atomic scale friction on the transformation of internal vibrations of the We focus on a molecular level description of processes occurring moving object into directed motion, making use between and close to interacting surfaces which is needed to first of the nonlinear properties of friction. understand, and later manipulate friction. Methods for controlling friction using mechanical and chemical approaches are introduced. Electrochenically Variable Optics We have introduced novel electrowetting Single Molecular Force Spectroscopy systems containing an interface between two Dynamic force spectroscopy provides an ability to measure adhesive immiscible electrolytic solutions (ITIES) that can interactions at the single-molecule level with unprecedented change its shape under a small voltage variation, resolution, and to achieve deeper insight in the underlying which are two orders of magnitude lower than in mechanisms of molecular processes without the ‘‘scrambling’’ that conventional systems. Our research focuses on occurs due to ensemble averaging. To both explore the results of modeling ITIES-based electrically tunable optical force spectroscopy experiments and to reveal a molecular scale devices: (i) variable-focus lenses, (ii) variable energy landscapes, we establish relationships between equilibrium mirrors based on reversible adsorption of metal properties of the nanoscale systems and the characteristic features nanoparticles on droplets, and (iii) optical filters measured under non-equilibrium conditions. based on quantum dots localized at ITIES.

Molecular Scale Engines References: We have introduced a new approach to build microscopic engines 1. M.A. Lomholt, M. Urbakh, R. Metzler, and J. Klafter, on the microscopic and mesoscopic scales that move translationally Manipulating single enzymes by an external harmonic force, Phys. Rev. Lett., 98, Art. No. 168302 or rotationally and can perform useful functions such as pulling of a (2007). cargo. Characteristic of these engines is the possibility to determine 2. M. E. Flatte´, A. A. Kornyshev, and M. Urbakh, dynamically the directionality of the motion. The approach is based Giant Stark effect in quantum dots at liquid/liquid interfaces: A new option for tunable optical filters. PNAS, 105, 18212 (2008). 3. A. E. Filippov, M. Dienwiebel, J. W. M. Frenken, J. Klafter, and M. Urbakh, Torque and Twist against Superlubricity, Phys. Rev. Lett. 100, 046102 (2008).

Control of Friction by Shear Induced Phase Transitions in Mixed Lubricant Monolayers.

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Publications

4. Targeted drug-carrying 11. Ni–C powder synthesis by The following 41 researchers are currently bacteriophages as anti bacterial a submerged pulsed arc in involved in nano related research activity nanomedicines breakdown mode and use the facility and the support of the Yacoby I., Bar H. and Benhar I. (2007), N. Parkansky, G. Frenkel, B. Alterkop, nano center: Antimicrob Agents Chemother. 51 I. Beilis, R. L. Boxman, Z. Barkay, Yu. Noam Eliaz, Michael Gozin, Eshel Ben (6): 2156-63. Rosenberg, Journal of Alloys and Jacob, Touvia Miloh, Diana Golodnitsky, Compounds, 464 (2008) 483–487. Ori Cheshnovsky, Abraham Nitzan, 5. Targeted anti bacterial therapy Yoav Henis, Itai Benhar , Ehud Gazit, Yacoby, I. and Benhar I. (2007), Infect 12. Photosynthetic Reaction Center Gil Markovich, Haim Diamant, Ilan Disord Drug Targets. 7 (3): 221-9. Covalently Bound to Carbon Nanotubes Goldfarb, Judith Rishpon, Shachar 6. Targeted Bacteriophages as Itai Carmeli, Bernd Zebli, Ludmila Richter, Yael Hanein, Yossi Lereah, Gil Therapeutic Agents Frolov, Chanoch Carmeli, Shachar Rosenman, Alexander Palevski, Ron Yacoby, I. and Benhar I. (2008), Expert Richter and Alexander W. Holleitner. Lifshitz, Eran Rabani, Ronit Satchi- Opin Drug Targets. 5 (3): 321-329. Fainaro, Alexander Kotlyar, Rimona Adv. Mater. 2007, 19, 3901–3905. 7. Killing cancer cells by Margalit, Chanoch Carmeli, Guy 13. Photovoltaic activity of targeted drug-carrying phage Deutscher, Yossi Rosenwaks, Alexander photosystem I-based self- nanomedicines Gerber, Amihay Freeman, Reuven assembled monolayer Bar, H., Yacoby, I. and Benhar I. (2008) Boxman, Yoram Dagan, Yoram Selzer, Carmeli Itai, Frolov Ludmila, Carmeli BMC Biotech. 8: 37. Koby Scheuer, Emanuel Peled, Amir Chanoch, Richter Shachar, Journal Boag, Yosi Shacham-Diamand, Eran 8. Potential of Antibacterial of the American Chemical Society, v Rabani, Joseph Klafter, Michael Urbak, Nanomedicines 129 (41), pp 12352-12353, 2007. Yoram Shapira, Shlomo Ruschin, Dafna Yacoby, I. and Benhar I. (2008), 14. Fabrication of Serially Oriented Benayahu Nanomedicine, 3 (3): 329-41. The following list of publications includes Multilayers of Photosystem I much coauthoring of TAU researchers and 9. Solid lubricants on textured Proteins on Solid Surfaces by is presented as a single comprehensive surfaces obtained by pulsed air Auto-Metallization arc treatment Ludmila Frolov, Ofer Wilner, Chanoch list of 150 papers. A. Moshkovith, V. Perfiliev, D. Gindin, Carmeli and Itai Carmeli. Adv. Mater. N. Parkansky, R. Boxman, L. Rapoport, 2008, 20, 263–266. 1. Targeted filamentous Tribologia – Finish Journal of bacteriophages as therapeutic 15. Photoelectric Junctions Between Tribology 4, Vol. 26, pp. 15-20, 2007. agents GaAs and Photosynthetic Yacoby I, Benhar I. Expert Opin Drug 10. Magnetic properties of carbon Reaction Center Protein Deliv. 2008 Mar; 5 (3): 321-9. nano-particles produced by a Frolov, L.; Rosenwaks, Y.; Richter, S.; pulsed arc submerged in ethanol Carmeli, C.; Carmeli, I., J. Physical 2. Antibacterial nanomedicine N. Parkansky, B. Alterkop, R. L. Chemistry. C. 112 (35), pp 13426- Yacoby I, Benhar I. Nanomed. 2008 Boxman, G. Leitus, O. Berkh, Z. 13430. 2008. Jun; 3 (3): 329-41. Barkay, Yu. Rosenberg, N. Eliaz, 16. Dirty Superconductivity in 3. A Two-State Electronic Antigen Carbon, 46 (2008) 215–219. the Electron-doped cuprate and An Antibody Selected to Pr Ce CuO : Tunneling study Discriminate Between These 2-x x 4 States Y. Dagan, R. Beck and R. L. Greene, Artzy-Schnirman A, Brod E, Epel M, Phys. Rev. Lett., 99, 147004 (2007). Dines M, Hammer T, Benhar I, Reiter Y, Sivan U. Nano Lett. 2008 Sep 13.

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17. Hole superconductivity in the 24. Critical swelling of particle- 31. Extraordinary Hall effect in Co-Pd electron-doped superconductor encapsulating vesicles bilayers

Pr2xCexCuO4 E. Haleva and H. Diamant, Phys. Rev. O. Shaya, M. Karpovski and A. Gerber, Y. Dagan and R. L. Greene, Phys. Rev. Lett., Vol. 101, 078104, 2008. Jour. Appl. Phys, 102, 043910 (2007). B 76, 024506 (2007). 25. Swelling of particle-encapsulating 32. Perspective of spintronics 18. Field-induced nodal order random manifolds applications based on the parameter in the tunneling E. Haleva and H. Diamant, Phys. Rev. Extraordinary Hall Effect (Invited

spectrum of YBa2Cu3O7−x E, Vol. 75, 021132, 2008. review) superconductor A. Gerber and O. Riss, 26. POSS-Polyimide Nanocomposite G. Leibovitch, R. Beck, Y. Dagan, S. Jour. Nanoelectronics and Films: Simulated Hypervelocity Hacohen and G. Deutscher, Phys. Optoelectronics, 3, 35 (2008). Space Debris and Atomic Oxygen Rev. B 77, 094522 (2008). Effects 33. Offset reduction in Hall Effect 19. A spatial interpretation of R. Verker, E. Grossman, I. Gouzman measurements using a non- emerging superconductivity in and N. Eliaz, High Performance switching Van der Pauw lightly doped cuprates Polymers, 20 (4/5) (2008), 475-491. technique Guy Deutscher and P. G. de Gennes, O. Riss, E. Shaked, M. Karpovsky and 27. The Use of SIMS in Quality C.R. Physique. 2007; 8: 937. A. Gerber, Rev. Scientific Instruments, Control and Failure Analysis of 79, 073901 (2008). 20. Polar Kerr Effect Measurements Electrodeposited Items Inspected of YBaCuO: Evidence for Broken for Hydrogen Effects 34. In-plane and out-of-plane shape Symmetry Near the Pseudogap E. Kossoy, Y. Khoptiar, C. Cytermann, transitions of heteroepitaxially temperature G. Shemesh, H. Katz, H. Sheinkopf, self-assembled nanostructures Jin Xia, E. Schemm, G. Deutscher et I. Cohen and N. Eliaz, Corrosion I. Goldfarb, Surf. Sci., 601, 2756, 2007. al., Phys. Rev. Lett. 2008; 100: 127002. Science, 50 (2008), 1481-1491. 35. Step-mediated size-selection 21. Observation of Andreev – Saint- 28. Enzymatically attenuated in situ and ordering of heteroepitaxial james reflections in nano-scale release of silver ions to combat nanocrystals planar superconductor to bacterial biofilms: a feasibility I. Goldfarb, Nanotechnology, 18, ferromagnet contacts study 335304, 2007. S. Hacohen-Gourgy, B. Almog and H. Ben-Yoav, A. Freeman, J. Drug Del. 36. Mechanical tuning of two- G. Deutscher, Appl. Phys. Lett. 92, Sci. Tech., 18 (1) 25-29, 2008 dimensional photonic crystal 152502 (2008). 29. Towards Hall Effect Spintronics cavity by micro electro 22. Field-induced nodal order A. Gerber, Jour. Magn. Matt. 310, mechanical flexures parameter in the tunneling 2749 (2007). O. Levy, B. Z. Steinberg, A. Boag, spectrum of YBaCuO S. Krylov, I. Goldfarb, Sensors & 30. Linear positive superconductor Actuators A: Phys. 139, 47, 2007. magnetoresistance and quantum G. Leibovitch, R. Beck, Y. Dagan, S. interference in ferromagnetic 37. CoWBP capping barrier layer for Hacohen and G. Deutscher, Phys. metals sub 90 nm Cu interconnects Rev. B 77, 094522 (2008) A. Gerber, I. Kishon, I.Ya. Korenblit, R. Ofek Almog, Y. Sverdlov, I. 23. Long-range hydrodynamic O. Riss, A. Segal, M. Karpovski and B. Goldfarb, Y. Shacham-Diamand, response of particulate liquids Raquet, Phys. Rev. Lett. 99, 027201 Microelectron. Eng., 84, 2450, 2007. and liquid-laden solids (2007). H. Diamant, Isr. J. Chem., Vol. 47, pp. 225-231, 2007.

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38. Real space identification of 44. A Complete Scheme for Creating 51. Efficient procedure of preparation the CZT(110) surface atomic Predefined Networks of Individual and properties of long uniform structure by scanning tunneling Carbon Nanotubes G4-DNA nanowires microscopy Ze’ev R. Abrams, Zvi Ioffe, Alexander Borovok N, Molotsky T, Ghabboun G. Cohen-Taguri, M. Levinshtein, A. Tsukernik, Ori Cheshnovsky and J, Porath D, Kotlyar A. 2008 Anal Ruzin and I. Goldfarb, Surf. Sci., 602, Yael Hanein, Nano Letters, Vol. 7, pp. Biochem., 374, 71-78. 712, 2008. 2666-2671, 2007. 52. Formation of polyaniline layer 39. Self-organization of cobalt- 45. Integrating peptide nanotubes in on DNA by electrochemical silicide nanoislands on stepped micro-fabrication processes polymerization Si(111) N. B. Sopher, Z. R. Abrams, M. Reches, Bardavid Y., Ghabboun J., Porath I. Goldfarb and M. Levinshtein, J. E. Gazit and Y. Hanein, J. Micromech. D., Kotlyar A. B., Yitzchaik S. 2008 Nanosci. Nanotechnol., 8, 801, 2008. Microeng. Vol. 17, pp. 2360-2365, Polymer, 49, 2217–2222 2007. 40. A Novel Fullerene-NMDA- 53. High-resolution STM imaging of Receptor Antagonist Compound 46. Iron assisted growth of copper- novel single G4 DNA molecules Reduces Axonal Loss and tipped multi-walled carbon Shapir E, Sagiv L, Borovok N., Neurological Disability a Model of nanotubes Molotski T., Kotlyar A. B., Porath D. Progressive Multiple Sclerosis Z. R. Abrams, D. Szwarcman, Y. 2008 J. Phys. Chem., 112, 9267-9269. Basso, A.S.; Frenkel, D.; Quintana, F.J.; Lereah, G. Markovich and Y. Hanein, 54. Assembling of G-strands into Costa-Pinto, F.A.; Farez, M.; Petrovic- Nanotechnology, Vol. 18, pp. novel tetra-molecular parallel G4- Stojkovic, S.; Puckett, L.; Monsonego, 495602, 2007. DNA nanostructures using avidin- A.; Engel, Y.; Bar-Shir, A.; Gozin, M.; 47. Electro-chemical and biological biotin recognition Weiner, H. L., J. Clin. Inv. 2008, 118 (4), properties of carbon nanotube Borovok N,. Irm N, Zikich D., 1532-1543. based multi-electrode arrays Ghabboun J., Livshits G. Porath D., 41. Multipeak negative-differential- Kotlyar A, 2008 Nucl. Acid Res., 36: 48. Tamir Gabay, Moti Ben-David, Itshak resistance molecular device 5050-5060. Kalifa, Raya Sorkin, Ze’ev R. Abrams1, Mentovich, E. D.; Chalifa, I.; Caster, A.; Eshel Ben-Jacob and Yael Hanein, 55. Radiationless Transitions of G4 Holtzman, A.; Rosenberg, N.; Marom, Nanotechnology, Vol. 18, pp. 035201, Wires and dGMP H.; Gozin, M.; Richter S., Small 2008, 4 2007. Gepshtein R. Huppert D., Lubitz I., (1), 55-58. Amdursky N., Kotlyar A. B., 2008, J. 49. Specific and efficient adsorption 42. Bio-delivery of Fullerene Phys. Chem., 112, 12249-12258. of phosphorothioated DNA on Derivative Au-based surfaces and electrodes 56. Versatile Binding Sites of Belgorodsky, B.; Fadeev, L.; Kolsenik J.; Ghabboun J, Sowwan M, Cohen β-Lactoglobulin Gozin, M., Bioconjugate Chem. 2007, H., Molotsky T., Borovok N., Dwir B., Belgorodsky, B.; Fadeev, L.; Gozin, M., 18 (4), 1095-1100. Kapon E., Kotlyar A., Porath D. 2007 Biochim. Biophys. Acta, Proteins and 43. Can Apomyoglobin Form a Appl. Phys. Lett., 91, 173101. Proteomics 2008, accepted. Complex with a Spherical Ligand? 50. Electronic structure of single DNA 57. Phage therapy as a solution for Interactions between Apo- molecules resolved by transverse antibiotic resistance of bacteria myoglobin and [C ]fullerene 60 scanning tunneling spectroscopy Yacoby, I., Vaks, L. and Benhar, I. Afr. J. derivative Shapir E, Cohen H, Calzolari A, Biotech. In Press Kolsenik, J.; Belgorodsky, B.; Fadeev, Cavazzoni C, Ryndyk D. A, Cuniberti L.; Gozin, M., J. Nanosci. Nanotech. G, Kotlyar A, Di Felice R, Porath D. 2007, 7, 1389-1394. 2008 Nature Mat., 7, 68-74.

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58. Directed Metallization of Single 64. Preparation and analysis of a two 70. Insights into modeling Enzyme Molecules with Preserved componemnts breath figure at Streptozotocin-induced diabetes Enzymatic Activity the nano scale in ICR mice Sefi Vernick, Hila Moscovich-Dagan, Richard Kofman, Marco Allione, Yaron Dekel, Yifat Glucksam, Inbar Carmit Porat-Ophir, Judith Rishpon, Franck Celestini, Zahava Barky and Elron-Gross and Rimona Margalit Amihay Freeman and Yosi Shacham- Yossi Lereah. Euro. Phys. J. D, in press. (2008) Lab Animal, in press. Diamand, IEEE Transactions on 65. Size effects on Melting and 71. Control and prevention of Nanotechnology, In Press. Wetting in the Ga-Pb Nano-Alloys bacterial infections in burns by 59. Protein Crystal-Mediated Marco Allione, Richard Kofman, new formulations based on drug/ Biotemplating Franck Celestini and Yossi Lereah, carrier systems Noa Cohen-Hadar, YarivWine, Shira Presented in XIV Int Symp. on Small Yifat Glucksam, Inbar Gross-Elron, Lagziel-Simis, Hila Moscovich-Dagan, Particles and Inorganic Clusters Arthur Raskin, Pavel Gornbein, Yael Dror, Felix Frolow and Amihay (Isspic 14), will be published in the Nathan Keller, Rimona Margalit and Freeman, Journal of Porous Media , relevant book/journal. Ilana Schumacher (2008). Military In Press. Medicine, in press. 66. Phason dynamics in nonlinear 60. Carbon nanotube micro- photonic quasicrystals 72. Treatment of resistant human electrodes for neuronal Barak Freedman, Ron Lifshitz, Jason colon cancer xenografts by interfacing W. Fleischer and Mordechai Segev, a fluoxetine-doxorubicin E. Ben-Jacob and Y. Hanein, Journal Nature Materials, 6 (2007) 776-781. combination enhances of Materials Chemistry, In press 2008 therapeutic responses 67. Nonlinear dynamics of comparable to an aggressive 61. A Dissipative Particle Dynamics nanomechanical and bevacizumab regimen Model of Carbon Nanotubes micromechanical resonators Mirit Argov, Rina Kashi, Dan Peer and Orly Liba, David Kauzlari´c, Ze´ev Ron Lifshitz and M.C. Cross, Review Rimona Margalit (2008) Cancer Lett., R. Abrams, Yael Hanein, Andreas of Nonlinear Dynamics and in press. Greiner and Jan G. Korvink, Complexity, 1 (2008) 1-52. Molecular Simulation, In press 2008. 73. Tuning Colloidal Syntheses to 68. Nonlinear photonic quasicrystals Control Co2+ Insertion in Ferrite 62. Differential interference of for novel optical devices Nanocrystals chlorpromazine with the Alon Bahabad, Ron Lifshitz, Noa G. Shemer, E. Tirosh, T. Livneh and G. membrane interactions of Voloch and Ady Arie, Phil. Mag., 88, Markovich, J. Phys. Chem. C, Vol. 111, oncogenic K-Ras and its effects on (2008) 2285-2293. p. 14334-14338, 2007. cell growth 69. Classical to quantum S. Eisenberg, K. Giehl, Y. I. Henis and 74. Plasmon Resonance Enhanced transition of a driven nonlinear M. Ehrlich 2008 J. Biol. Chem., in Absorption and Circular nanomechanical resonator press. Dichroism Itamar Katz, Ron Lifshitz, Alex Retzker I. Lieberman, G. Shemer, T. Fried, E. 63. Molecular analysis of and Raphael Straub, New J. Phys. M. Kosower, G. Markovich, Angew. recombinase-mediated cassette (2008) in press. Preprint (arXiv: Chem. Int. Ed., Vol. 47, p. 4855-4857, exchange reactions catalyzed by 0807.3164). 2008 integrase of coliphage HK022 Malchin N., Molotsky T., Yagil E., Kotlyar A., Kolot M., 2008, Res Microbiol. (In press)

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75. Scanning Tunneling Spectroscopy 83. Inelastic effects in molecular 90. Resonant Tunneling of Electrons study of Temperature junction transport: Scattering and in Quantum Wires (Review) Dependent Magnetization self-consistent calculations for V. Krive , A. Palevski, R. I. Shekhter Switching Dynamics in Magnetic the Seebeck coefficient and M. Jonson, to be published in Nanoparticle Arrays M. Galperin, M.A. Ratner and A. December 2008 in Journal of Low E. Tirosh, N. Taub, S. A. Majetich, G. Nitzan, Molecular Physics, 106, 397- Temperature Physics. Markovich, Isr. J. Chem., in press 404 (2008). 91. Inverse proximity effect in 76. Dipolophoresis of nanoparticles 84. Molecules take the heat superconductor-ferromagnet Miloh T., Physics of Fluids, Vol. 20 (Perspective) bilayer structures (2008), 063303. A. Nitzan, Science, 317, 759 (2007). Jing Xia, V. Shelukhin, M. Karpovski, A. Kapitulnik and A. Palevski, 77. A unified theory of dipolophoresis 85. Cooperative effects in molecular Submitted to Physical Review Letters for nanoparticles conduction (2008). Miloh T., Physics of Fluids, Vol. 20, A. Landau, L. Kronik and A. Nitzan, J. 107105 (2008). Comp. Theor. Nanoscience, 5, 535- 92. Electroless plating of silicon 544 (2008). nitride using (3-aminopropyl) 78. Electro convection about triethoxysilane conducting particles 86. Inelastic effects in molecular Holtzman, A. Richter, S., Journal of Yariv. E., Miloh T.. J. Fluid Mechanics. junctions in the Coulomb and the Electrochemical Society, v 155, Vol. 595, 163-172 (2008). Kondo regimes: Nonequilibrium D196-D202, 2008, equation-of-motion approach 79. Boundary effect in electro- M. Galperin, M. A. Ratner and A. 93. Electrochemical lab on a chip magnetic-phoresis Nitzan, Phys. Rev. B 76, 035301 for high-throughput analysis of Yariv E., Miloh T., J. Fluid Mechanics (2007). anticancer drugs efficiency (in press) (2008). R. Popovtzer; T. Neufeld, A. 87. Molecular Transport Junctions: 80. Macro-scale description of Popovtzer; I. Rivkin, R. Margalit, D. Vibrational Effects transient electro-kinetic Engel, A. Nudelman, A. Rephaeli, J. M. Galperin, M.A. Ratner and A. phenomena over polarizable Rishpon and Y. Shacham-Diamand, Nitzan, J. Phys.: Condens. Matter, 19, dielectric solids Nanomedicine, Vol 4 (2), pp 121-6, 103201 (2007). Yossifon G, Frankel I. and Miloh T.. J. 2008. Fluid Mechanics (in press) (2008). 88. Heat conduction in molecular 94. Electrochemical Biosensors for junctions 81. Nuclear Coupling and Polarization pollutants in the environment M. Galperin, M. A. Ratner and A. in Molecular Transport Junctions: M. Badihi-Mossberg and V. Buchner, Nitzan, Phys. Rev. B 75, 155312 Beyond Tunneling to Function J. Rishpon, Electroanalysis, Vol. 19, (2007). M. Galperin, M.A. Ratner, A. Nitzan pp 2015-2028, 2007 and A. Troisi, Science, 319, 1056 89. Quantum phase transition in 95. An Electrochemical (2008). ultra small doubly connected Immunosensor for C-Reactive superconducting cylinders 82. Theory of light-induced current Protein based on Multi-walled Sternfeld, R. Koret, H. Shtrikman, in molecular-tunneling junctions Carbon Nanotube-Modified A. Tsukernik, M. Karpovski and excited with intense shaped Electrodes A. Palevski, Physica C: Super pulses M. Buch and J Rishpon, conductivity, Volume 468, Issue 4, 15 B. Fainberg, M. Jouravlev and A. Electroanalysis , in Press, 2008. February 2008, Pages 337-340 Nitzan, Phys. Rev. B 76, 245329 (2007).

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96. Interface modification and 103. Electrostatics Properties of 110. Fabrication and charaterization bonding of lithium tantalate Molecular Gated BioFETS of “on-edge” junction for crystals M.Shaked, O.Shaya, A. Doron, A. molecular electronics Torchinsky and G. Rosenman, Appl. Cohen, I. Levy and Y. Rosenwaks, Shamai T., Ophir A., Selzer Y, Appl. Phys. Letts, 92, 052903 (2008). Proc. of 2008 International Symp. on Phys. Lett. 2007, 91, 102108. Industrial Electronics, Cambridge. 97. Interface engineering and direct 111. Synthesis of very high aspect bonding of Lithium tantalate 104. Distinguishing between dipoles ratio metal nanowires by a self- crystals and field effects in molecular propelling mechanism Torchinsky, G. Rosenman, J. gated transistors Sharabani R., Saada R., Noy G., Electronic Materials, DOI: 10.1007/ O.Shaya, M.Shaked, A. Doron, A. Shapira E., Sadeh S., Selzer Y. Nano s11664-008-0508-2 (2008). Cohen, I. Levy and Y. Rosenwaks, Lett., 2008, 8, 1169. Appl. Phys. Lett.. 93, 043509-11, 98. Patterned arrays of ordered 112. Segmented nanowires as nano- (2008) peptide nanostructures scale thermocouples Aronov D, Adler-Abramovich L, 105. Y. Shacham-Diamand , JSSE, Vol. Shapira E., Marchak D., Tsukerik A., Gazit E, Rosenman G., J. Nanosci. 11, 2007, p 929-938. Selzer Y., Nanotechnology 2008, 19, Nanotech., 8: 1-8 (2008). 125501. 106. Coupled Lasers Rotation Sensor 99. Electron-induced surface (CLARS) 113. Fabrication of highly stable reactivity modification in Zinc J. Scheuer, B. Z. Steinberg, to be configurable metal quantum oxide-based thin films published in J. Lightwave Technol. point contacts V. Sabayev, D. Aronov, L. Oster, G. Itach N., Yutsis I., Selzer Y., Nano Lett., 107. Direct rotation-induced intensity Rosenman, Appl. Phys Letts, 93, 2008 ASAP. modulation in circular Bragg 144104 (2008). micro-lasers 114. Controlled patterning of peptide 100. Electronic Characterization of J. Scheuer, Opt. Express, 15, 15053 nanotubes and nanospheres Si(100)-Bound Alkyl Monolayers (2007). using inkjet printing technology Using Kelvin Probe Force Adler-Abramovich L, Gazit E., J Pept 108. Secure key generation using an Microscopy Sci. 2008 Feb; 14 (2): 217-23. ultra-long fiber laser: transient Magid, L. Burstein, O. Seitz, L. Segev, analysis and experiment 115. Bioactive nanostructures branch L. Kronik and Y. Rosenwaks, J. Phys. Zadok, J. Scheuer, J. Sendowski out Chem. C. 112, 7145-7150, (2008) and A. Yariv, Opt. Express, 16, 16680 Gazit, E, Nature Nanotechnology, 3, 101. Measurements of the Einstein (2008) 8-9 (2008). relation in doped and undoped 109. Detection of Heating in Current 116. Patterned Arrays of Ordered molecular thin films Carrying Molecular Junctions by Peptide O. Tal, I. Epstein, O. Baboor, C. K. Raman Scattering Adler-Abramovich, L., Aronov, Chan, A. Kahn, Y. Ganot, N. Tessler Ioffe Z. Shamai T., Ophir A., Noy G., D., Gazit, E. and Rosenman , and Y. Rosenwaks, Phys. Rev. B, , Yutsis I., Kfir K., Cheshnovsky O., G., Nanostructures. J. Nanosci. Rapid Comm., 77, 201201-4, (2008). Selzer Y., Nature Nanotechnology Nanotech. (in press) (2008). 102. Charging of thin dielectric Films 2008 doi 10.1038/nnano.2008.304. 117. The role of the 14-20 domain of Following Focused Ion Beam the islet amyloid polypeptide in Irradiation amyloid formation S. Yogev, Y. Levine, M. Molotskii and Gilead, S. and Gazit, E., Exp. Diabet. Y. Rosenwaks, J. Appl. Phys. 103, Res. 2008: 256954. 64107-64112 (2008).

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118. Cognitive Performance Recovery 123. In vitro and in vivo evaluation of 127. Polymer Therapeutics: From of Alzheimer’s Disease Model doxorubicin conjugates with the novel concepts to clinical

Mice by Modulating Early divalent peptide E-[c(RGDfK)2] applications, In Wiley

Soluble Amyloidal Assemblies that target integrin αvβ3 Encyclopedia of Chemical Frydman-Marom, A. Rechter, M. Ryppa C, Mann-Steinberg H, Biology Shefler, I., Bram, Y., Shalev , D. E. and Fichtner I, Weber H, Satchi- Miller K and Satchi-Fainaro R, Ed. N. Gazit, E., Angew. Chem. Int. Ed. Engl. Fainaro R, Biniossek M and Kratz R. Civjan, John Wiley & Sons, Inc. In (accepted) (2008). F, Bioconjugate Chemistry, 19 (7), press (2008). 1414-22. (2008). 119. The Effect of rf-Irradiation on 128. Polymer Enzyme Liposome Electrochemical Deposition and 124. Design and Development Therapy. HPMA copolymer- its Stabilization by Nanoparticle of polymer conjugates as phospholipase C and Doping antiangiogenic agents, Dextrin-phospholipase A2 Yael Katsir, Lior Miller, Yakir Aharonov Special Theme issue: Polymer as model triggers, European and Eshel Ben Jacob, Journal of Therapeutics: Clinical Journal of Pharmaceutics and the Electrochemical Society, 154, 4, Applications and Challenges for Biopharmaceutics D249-D259 (2007). Development Satchi-Fainaro R, Ferguson E and Segal E and Satchi-Fainaro R, Duncan R, PELT: in press (2008). 120. Tumor Cytotoxicity and Advanced Drug Delivery Reviews, in Endothelial Rac Inhibition 129. In vitro evaluation of paclitaxel press (2008). Induced by TNP-470 in Anaplastic conjugates with the divalent

Thyroid Cancer 125. In vitro evaluation of paclitaxel peptide c(RGDfK)2 that target

Nahari D, Satchi-Fainaro R, Chen M, conjugates with the divalent integrin αvβ3, International

Task LB, Liu Z, Terada L. S, Carroll AB peptide E-[c(RGDfK)2] that target Journal of Pharmaceutics

and Nwariaku F, Molecular Cancer integrin αvβ3 Ryppa C, Mann-Steinberg H, Therapeutics, 6, 1329-1337 (2007). Ryppa C, Mann-Steinberg H, Biniossek M, Satchi-Fainaro R and Biniossek M, Satchi-Fainaro R and Kratz F, in press (2008). 121. Dramatic drug-release Kratz F, International Journal of enhancement with an 130. XPS and TOFSIMS study of Pharmaceutics, in press (2008). elimination-based AB3 self- electrodeposited molybdenum immolative dendritic amplifier 126. The resurrection of the first oxysulfide cathodes for lithium Sagi A, Segal E, Satchi-Fainaro R and synthetic angiogenesis inhibitor and lithium-ion microbatteries Shabat D, Bioorganic and Medicinal Satchi-Fainaro R and Mann-Steinberg V. Yufit, D. Golodnitsky, L. Burstein, Chemistry, 15, 3720–3727 (2007). H, TNP-470, In: Angiogenesis: An M. Nathan, E. Peled., J Solid State integrative approach from science Electrochem (2008) 12, 273–285. 122. Malignant progression and to medicine. Editors: William Figg blockade of angiogenesis in 131. A novel Proton-Exchange and Judah Folkman, Springer-Verlag, a murine transgenic model of Membrane based on single-step Heidelberg, Germany, Chapter 35, p. neuroblastoma preparation of functionalized 387-406 (2008). Chesler L, Goldenberg DD, Seales IT, ceramic powder containing Satchi-Fainaro R, Grimmer M, Collins surface-anchored sulfonic acid R, Struett C, Nguyen KN, Kim G, Saul Reichman, Larisa Burstein, Tihan T, Bao Y, Brekken RA, Bergers Emanuel Peled, JPS, 2008. G, Folkman J, Weiss WA, Cancer Research, 67 (19), 9435-9442 (2007).

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132. Drying-Mediated Hierarchical 139. Distribution of carrier 146. Comparative study of human Self-Assembly of Nanoparticles: multiplication rates in CdSe and erythrocytes by digital A Dynamical Coarse-Grained InAs nanocrystals holographic microscopy, Approach Eran Rabani and Roi Baer, Nano. confocal microscopy, and Orly Kletenik-Edelman, Elina Lett., in press (2008). impedance volume analyzer Ploshnik, Asaf Salant, Roy Shenhar, Rappaz, Benjamin, Barbul, 140. Probing microscopic origins of Uri Banin and Eran Rabani, J. Phys. Alexander, Emery Yves, Korenstein, confined subdiffusion by first- Chem. C 112, 4498-4506. (2008). Rafi, Magistretti, Pierre J., Marquet, passage observables Pierre, Cytometry part A Volume: 133. Real-time path integral approach S. Condamin, V. Tejedor, R. Voituriez 73A Issue: 10 Pages: 895-903 to nonequilibrium many-body and J. Klafter, PNAS, 105, No. 15, Published: OCT 2008 quantum systems, Lothar 5675-5680 (2008) Mühlbacher and Eran Rabani, Phys. 147. Giant Stark effect in quantum 141. Analyzing friction forces with the Rev. Lett. 100, 176403 (2008). dots at liquid/liquid interfaces: Jarzynski equality A new option for tunable optical 134. Constructing Spin Interference R. Berkovich, J. Klafter and M. filters Devices from Nanometric Rings Urbakh, J. of Phys. Condensed M. E. Flatte, A. A. Kornyshev and M. Guy Cohen, Oded Hod and Eran Matter, 20, 354008 (2008) Urbakh, PNAS, 105, 18212, 2008 Rabani, Phys. Rev. B 76, 235120 142. Fluorescence recovery after (2007). 148. Torque and Twist against photobleaching: The case of Superlubricity 135. Long-Range Electronic to anomalous diffusion Alexander E. Filippov, Martin Vibrational Energy Transfer in A. Lubelski and J. Klafter, Biophys. Dienwiebel, Joost W. M. Frenken, Nanocrystals Journal, 94, 4646-4653 (2008) ,Joseph Klafter and Michael Assaf Aharoni, Dan Oron, Uri Banin, 143. Temporal correlation functions Urbakh,Phys. Rev. Lett. 100, 046102 Eran Rabani and Joshua Jortner, of concentration fluctuations: An (2008) Phys. Rev. Lett. 100 057404 (2008). anomalous case 149. Understanding voltage-induced 136. Negative Differential Spin A. Lubelski and J. Klafter, J. Phys. localization of nanoparticles at a Conductance by Population Chem. B 112, 12740-12747 (2008) liquid–liquid interface M. E. Flatte, Switching 144. Fluorescence correlation A. A. Kornyshev and M. Urbakh, J. Guy Cohen and Eran Rabani, Mol. spectroscopy (FCS): The case of Phys.: Condens. Matter 20 (2008) Phys. 106, 341-347 (2008). anomalous diffusion 073102 137. Theory of Resonance Energy A. Lubelski and J. Klafter, Biophys. 150. Controlling microscopic friction Transfer Involving Nanocrystals: Journal (in press 2008) through mechanical oscillations The Role of High Multipoles 145. Fractal probability laws, R. Guerra, A. Vanossi and M. Urbakh, Roi Baer and Eran Rabani, J. Chem. I. Eliazar and J. Klafter, Phys. Rev. E77, Physical review E 78, 036110 (2008) Phys. 128, 184710 (2008) no. 061125 (2008) 151. Critical size for intracluster 138. Magneto-Resistance of proton transfer from water to an Nanoscale Molecular Devices anion Based on Aharonov-Bohm Wolf I, Shapira A, Giniger R, Miller Y, Interferometry Gerber R. B, Cheshnovsky, Angew. Oded Hod, Roi Baer and Eran Chem. Int. Ed. 47 (2008) (pp: 6272- Rabani , J. Phys.: Cond. Mat. 20, 6274 ) 383201 (2008).

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152. Interactions at tetraphenyl- 155. Surface plasmon interferometer 158. Cell-based screening for porphyrin/InP interfaces in silicon-on-insulator: novel membranal and cytoplasmatic observed by surface concept for an integrated markers using dielectric photovoltage spectroscopy biosensor: comment spectroscopy Y. Zidon, Yoram Shapira, Th. Dittrich, R, Ruschin S., Optics Express 15, 21 Ron A, Singh RR, Fishelson N, Shur Appl. Surf. Sci., 254, 3255, 2008 Pages: 13649-13650 (2007) I, Socher R, Benayahu D, Shacham- Diamand Y. Biophys Chem. 2008 153. Monolithic rare-earth doped sol- 156. Application of the laser capture Jun; 135 (1-3): 59-68. Epub 2008 gel tapered rib waveguide laser microdissection technique for Mar 29. Peled A, Chiasera A, Nathan M, molecular definition of skeletal Ferrari M, Ruschin S., Apllied Physics cell differentiation in vivo. 159. Site localization of membrane- Letters 92 Issue: 22 (2008) Benayahu D, Socher R, Shur I., bound proteins on whole Methods Mol Biol. 2008; 455: 191- cell level using atomic force 154. SPR waveguide sensor based 201. microscopy on combined sensing of phase Ron A, Singh RR, Fishelson N, Socher and amplitude changes - art. no. 157. Comparative study using R, Benayahu D, Shacham-Diamand 64750R scanning electron techniques for Y., Biophys Chem. 2008 Feb; 132 (2- Levy R, Ruschin S.: Integrated imaging of micro-architecture 3): 127-38. Epub 2007 Nov 12 . Optics: Devices, Materials and and antigen appearance. Technologies XI Book Series: Socher R, Benayahu D., J Microsc. Proceedings of the Society of 2008 May;230 (Pt 2):233-9. Photo-optical Instrumentation Engineers (SPIE) Volume: 6475 Pages: R4750-R4750, Published: 2007

121 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY Patents

Accepted Submitted 9. Optoelectronic Device and Method of Manufacturing Same 1. Nanotube Network and Method Chanoch Carmeli, Itai Carmeli, 1. Light Guide Rotation Rate of Fabricating the Same Ludmila Frolov-Life Sciences; Detector with Coupled Optical Yael Hanein, Ze’ev Abrams- Shachar Richter-Exact Sciences; Yossi Resonators, 7385177 Engineering, Miron Hazani-Life Rosenwaks-Engineering; Alexander Ben Zion Steinberg - Engineering, Sciences, Ori Cheshnovsky, Zvi Ioffe- Govorov Amir Boag - Engineering Exact Sciences 10. Optoelectronic Device and 2. System for Determining 2. Metal Nanowire Thin-Films Method of Fabricating The Same Endothelial Dependent Gil Markovich, Daniel Azulai, Olga Chanoch Carmeli, Itai Carmeli, Vasoactivity, 7374541 Krichevski-Exact Sciences Ludmila Frolov-Life Sciences; Giora Amitzur, Eli Zimerman - 3. Novel Nanostructures and Shachar Richter-Exact Sciences; Yossi Medicine; Shmuel Einav, Eran Peleg- Method of Preparation Rosenwaks-Engineering Engineering Fernando Patolsky, Roey Elnathan, 11. Molecular Optoelectronic Device 3. Controlled Enzymatic Removal Raisa Kantaev-Exact Sciences and Method of Fabricating The and Retrieval of Cells, 7364565 4. Antiproliferative Compounds , Same Amihay Freeman-Life Sciences Compositions and Methods of Chanoch Carmeli, Itai Carmeli, 4. Fuel Cell with Proton Conducting Use Ludmila Frolov-Life Sciences; Yossi Membrane, 7413824, 169049 Irit Gil-Ad-Medicine, Moshe Portnoy- Rosenwaks-Engineering Emanuel Peled, Tair Duvdevani, Avi Exact Sciences, Avraham Weizman- 12. Electrowetting Devices Melman, Adi Aharon-Exact Sciences Medicine, Liat Lomnitski Michael Urbakh-Exact Sciences, 5. Fuel Cell with Proton Conductive 5. Novel Psychotropic Agents Charles Monroe, Alexei A. Kornyshev, Membrane and with Improved Having Glutamate NMDA Activity Anthony R. John, Alice E. Sylvia Water and Fuel Management, Irit Gil-Ad-Medicine, Moshe Portnoy- 13. Photonic Crystal Resonator, A 1410453 Exact Sciences, Avraham Weizman- Coupled Cavity Waveguide, and A Emanuel Peled, Tair Duvdevani, Medicine Gyroscope Arnon Blum, Vladimir Livshits, Adi 6. Psychtropic Compounds, Ben Zion Steinberg, Amir Boag, Aharon-Exact Sciences Compositions and Methods of Jacob Scheuer-Engineering 6. Method and Apparatus for Use 14. Rectifying Antenna Device Treating Tumors Using Low Irit Gil-Ad-Medicine, Moshe Portnoy- Yael Hanein-Engineering, Amir Strength Electric Field, 7395112 Exact Sciences, Avraham Weizman- Boag-Engineering, Jacob Scheuer- Yona Keisar, Rafi Korenstein, Igor Medicine, Liat Lomnitski Engineering Entin-Medicine; Yosef Rosemberg 7. Molecular Electronic Devices and 15. Electro-Optical Modulator and Methods of Fabricating Same Method of Fabricating The Same Shachar Richter, Ariel Caster, Elad David Mendlovic, Damian Goldring- Mentovich-Exact Sciences Engineering 8. Vertical Transistors 16. Modified Optical Resonator Shachar Richter, Elad Mentovich- Structure Exact Sciences, Itshak Kalifa David Mendlovic, Damian Goldring- Engineering

122 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY PATENTS

17. Nonlinear-Optics Metamaterial 24. Micro-Scale Mechanical Rate 33. Production of Heteromeric Device Fof Terahertz Radiation Sensors Proteins in Bacteria Menachem Nathan, Avraham Gover, Viacheslav Krylov-Engineering, Itai Benhar, Rahel Hakim-Life Yotam Schatzberg-Engineering David Schreiber-Engineering, Yosi Sciences Shacham-Diamand-Engineering 18. Method and Device for 34. Stable Enzymatic Preparations Wettability Modification of 25. Chemical Properties Monitoring; and Methods of Use Thereof Materials Devices and Systems Amihay Freeman, Noa Hadar-Life Gil Rosenman, Daniel Aronov- Yosi Shacham-Diamand- Sciences Engineering, Jurijs Dehtjars Engineering, Eli Lusky-Engineering 35. Self-Assembled FMOC-FF 19. Method of Vapor Deposition of 26. Nano Imprinting Lithography Hydrogels Biomolecules and Self-Assembled Tagging for Security and Ehud Gazit, Assaf Mahler, Meital Bionanostructures and Patterning Authentication Applications Reches-Life Sciences of The Same Jacob Scheuer-Engineering 36. Formation of Organic Ehud Gazit, Lihi Adler-Abramovich- 27. Linearized Optical Digital-To- Nanostructure Array Life Sciences, Daniel Aronov, Gil Analog Modulator Ehud Gazit, Meital Reches-Life Rosenman-Engineering Ofer Amrani, Shlomo Ruschin, Yossef Sciences 20. Printing Method and Apparatus Ehrlichman-Engineering 37. Naphthoquinone Derivatives Gil Rosenman, Daniel Aronov- 28. Method for Enhancing Useful For Prevention of Amyloid Engineering The Sensitivity of Optical Deposits and Treatment of 21. Biologically Active Metal-Coated Interferometric Sensors Alzheimer’s Disease Proteins Shlomo Ruschin, Ronen Levy- Ehud Gazit, Roni Scherzer, Daniel Yosi Shacham-Diamand- Engineering Segal-Life Sciences Engineering, Amihay Freeman-Life 29. Treating Weakened Vessel Wall 38. System for Dellivery of Protein in Sciences, Sefi Vernick-Engineering, Such as Vulnerable Plaque or Insoluble Fibrillar or Aggregate Hila Moscovich-Dagan-Engineering Aneurysms Form 22. Method for Electrochemical Shmuel Einav, Ariel Sverdlik, Zeev Rimona Margalit, Yaron Dekel-Life Deposition of Monolayers on Aronis-Engineering, Ran Kornowski- Sciences Metallic Surfaces and Objects Medicine, Ifat Levi-Engineering 39. Coral-Derived Collagen and Coated with an Organic 30. Intervascular Probe Methods of Farming Same Monolayer Shmuel Einav-Engineering, Ran Yehuda Benayahu (Hudi-non Nathan Croitoru, Nikolay Fishelson, Kornowski-Medicine, Benny Pesach formal)-Life Sciences, Dafna Alexandra Inberg, Yosi Shacham- Benayahu-Medicine, Yoel Kashman- Diamand-Engineering 31. Recombinant Fusion Protein and Exact Sciences, Amira Rudi-Exact Polynucleotide Construct for 23. Methods of Detecting Cancer Sciences, Yoram Lanir, Ido Sella-Life Immunotoxin Production Cells and Use of Same for Sciences, Einat Raz Itai Benhar, Yariv Mazor-Life Sciences Diagnosing and Monitoring Treatment of The Disease 32. Photocatalytic Hydrogen Judith Rishpon-Life Sciences, Production and Polypeptides Yosi Shacham-Diamand, Rachela Capable of Same Popovtzer-Engineering, Tova Iftach Yacoby, Ehud Gazit, Nathan Neufeld-Life Sciences Nelson, Itai Benhar-Life Sciences

123 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY PATENTS

40. A HPMA-Alendronate-TNP-470 42. Novel Polymers Comprising An 46. Enhancement of Light Energy Conjugate Comprising A High Anti-Angiogenesis Agent and Conversion Efficiency by Load of Alendronate and Uses RGD or An Analog Thereof and YBRID Nanoparticles Oriented Thereof in The Treatment of Bone Uses Thereof in The Treatment of Photosystem I Mono and Related Angiogenesis Conditions Angiogenesis Related Diseases Multilayer Based Optoelectronic Ronit Satchi-Fainaro, Ehud Segal- Ronit Satchi-Fainaro-Medicine, Maria Devices Medicine, Jindrich Kopecek, Pavla Jesus Vicent Docon Yossi. Rosenwaks , H. Carmeli, L. Kopeckova, Pan Huaizhong Frolov, S. Richter, I. Carmeli 43. Compounds Suited as 41. Conjugates of A Polymer, A Nanocarriers for Active Agents 47. Optical Detection of Crystalline Bisphosphonate and An Anti- and Their Use Regions in Self Assembled Angiogenesis Agent and Their Ronit Satchi-Fainaro-Medicine- Organic Biomolecules Use in The Treatment and Sackler Faculty, Paula Ofek-Life N. Amdursky, E. Gazit, G. Rosenman Monitoring of Bone Related Sciences, Rainer Haag 48. Method of Growth of Diseases 44. Antiangiogenic Polymer Homogeneous Crack-Free YBCO Ronit Satchi-Fainaro, Keren Miller- Therapeutics and Use Thereof Layers Medicine, Doron Shabat-Exact Ronit Satchi-Fainaro R, K. Miller Guy Deutscher, Mishael Azoulay and Sciences, Rotem Erez-Exact Sciences Boaz Almog. 45. Method and Device for Detecting Weak Optical Signals Yosi Shacham-Diamand

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

Chanoch Carmeli and Shachar Ilan Goldfarb Yossi Rosenwaks Richter 1. With US Air Force: Self-Organization 1. Intel Research, Israel - Organic self-

1. Photosystem I based nano bio of CoSi2 Nanostructures into Two- assemebled monolayers for bioFET photovoltaic cell. Clal Biotechnology. Dimensional Patterns. Supported devices by the US Air Force (Grant No# FA8655-07-1-3016 from the Ehud Gazit European Offices of the US Air Dr. Yoram Dagan: 1. Cancer diagnostics, by Force Research and Development 1. The provskite based superconductor nanotechnology based biosensor (EOARD)). frromagnet transistor, Israel Science that profiles tissues acoustically. 2. With “SemiConductor Devices”: Foundation Bikura program, Amendis LTD. Cross-Sectional Scanning Tunneling 2008-2011, 599,100 NIS (My part) Microscopy of Superlattices. Supported by SemiConductor Yael Hanein Devices (SCD). Judit Rishpon 1. Carbon nanotube based devices, 1. A generic platform for milk sensors. with El-Mul technologies. Rimona Margalit Supported by the Nofar program 2. Carbon nanotubes and MEMS, with (Ministry of Industry, Trade and RAFAEL 1. In vitro studies on cancer cell lines, Labor) in collaboration with S.A.E. with Zetiq Technologies LTD. Afikim and the Hebrew University Jerusalem. 2. Electrochemical immunosensor. supported by Quest International Miami USA

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

Reuven Boxman Self-Organized Growth of Silicide 3. Dr. M. Pawlyta, from Poland (for 2 nanostructures on Si Surfaces. months) 1. The lab participated in the EU Supported by the Israel Science coordination action DESHNAF – Foundation (ISF) Grant No. 410/08 Super Hard Nano-composite Films - in collaboration with W.D. Kaplan Ron Lifshitz by Plasma Processing. (Technion) and E. Rabani (TAU). 1. Lab of Mordechai Segev, Physics, 2. With E.Rabani: Pushing the Limits Technion. Haim Diamant of the “Bottom-Up” Approach: 2. Lab of Michael Roukes, Physics, Self-Organized Growth of Silicide Caltech. 1. Microrheology and instability of nanostructures on Si Surfaces. 3. Group of Michael C. Cross, Physics, compressed surfactant monolayers. Supported by the Israel Science Caltech. Collaboration with T. A. Witten and Foundation (ISF) Grant No. 410/08 K. Y. C. Lee, James Franck Institute, - in collaboration with W.D. Kaplan University of Chicago. Supported (Technion) and E. Rabani (TAU). Shachar Richter by the US–Israel Binational Science Foundation. 1. Electrical properties of DNA- 2. Instability of deposited liquid strips. Guy Deutscher Block Copolymer Nanoparticles. Collaboration with O. Agam, Racah Mukhles Sowwa (El-Kuts University, 1. With P.G. de Gennes and with the Institute of Physics, The Hebrew Palestinian Authority, Andreas group of Prof. Kapitulnik at Stanford. University. Herrmenn, Groningen University, Nrtherlands) 2. Molecular Capacitance, Hagai Abraham Nitzan Alexander Kotlyar Cohen, Weizmann Institute of 1. Prof. Mark Ratner, Dept. of Chemistry, 1. Prof. Dmitry Klinov,. Shemyakin- Science, Israel Northwestern University, Evanston, IL Ovchinnikov Institute of Bioorganic 3. Optoelectronic properties of 2. Prof. Leeor Kronik, Dept. of Materials Chemistry, Russian Academy of Optoelectronic Properties of Hybrids and Interfaces, Weizmann Institute. Sciences, Moscow, Russia. made out of Carbon Nanotubes 2. Prof. Julio Gómez Herrero, Dept. of and the Photosystem I (Alexander Condensed Matter, Free University W. Holleitner, Technische Universität Ehud Gazit of Madrid, Madrid Spain München, Germany) 3. Prof. Leonid Gurevich Aalborg 4. Dr. Mukhles Sowwan, Material 1. Integration of peptide University Institute of Physics Science Engineering Department, nanostructures in Alginate systems. and Nanotechnology Section for Al-Quds University, Abu dis. Prof. Smadar Cohen Faculty of Biotechnology, Aalborg, Denmark. Health Sciences - Ben Gurion 4. Dr. Danny Porath, Dept. of Chemical University of the Negev. Physics, The Hebrew University of Michael Gozin 2. Bio-physical characterization of Jerusalem, Jerusalem, Israel. peptide-based hydrogels. Dr. Dror 1. Prof. Howard Weiner, Center for Seliktar BioMedical Engineering, Neurlogic Diseases, Harvard Medical Technion. School, Boston, MA. Yossi Lereah 2. Dr. Eyal Mishani, Hebrew university, 1. Group of Prof. Richard Kofman, Nice Jerusalem, Hadassah hospital, Dept. Ilan Goldfarb University (France) of Medical Biophysics & Nuclear 1. With the Technion: Pushing the 2. Group of Prof. Hannes Lichte, Medicine Limits of the “Bottom-Up” Approach: Dresden University (Germany)

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

Yossi Rosenwaks Yosi Shacham-Diamand Gil Markovich 1. H. Haick, Technion – Self-assembled 1. The SmartHand project: Tyndall 2. Prof. Sara Majetich, Carnegie-Mellon monolayers on Si. Institute, Ireland, Aalborg University, University, Pittsburgh, PA 2. North Western University, USA-Si Denmark, ARTS Lab and CRIM Lab, 3. Prof. Hennes Lichte, Dresden Nanowires Scuola Superiore Sant’Anna, Pisa, Technical University, Dresden, 3. Julich, Germany - UHV-KPFM of University Hospital, Malmö, Sweden, Germany dopants in III-V semiconductors. Lund University, OSSUR inc ( Iceland) 4. Dr. Tsachi Livneh, Nuclear Research 4. Soreq research center - UHV-KPFM 2. The ReNaChip Project. UNEW Center, Beer-Sheva of Quantum dots (Newcastle University, UK), UPF 5. Prof. Oded Shoseyov, Dr. Danny (Spain), G.Tec (Austria), Lund Porath, Hebrew University University (Sweden). Ronit Satchi-Fainaro 3. DipChip: the University of Koblenz 1. Jindřich Kopeček, Department of (Germany) Alexander Palevski Pharmaceutics and Pharmaceutical 1. Quantum wires and dots (Ministry Chemistry, Center for Controlled of Science, Ukraine-Israel) Chemical Delivery, University of Itai Benhar collaboration with Prof. I. V. Krive Utah, 20 S. 2030 E. Rm. 205B, Salt 1. Antibody-based electronic switches. (Kharkov University). Lake City, Utah 84112-9452, USA. Collaboration with Uri Sivan and 2. Proximity effect in S/F systems (US- 2. Taturo Udagawa, Vascular Biology Yoram Reiter of the Technion Israel BSF) with Prof. A. Kapitulnik, Program and Department of Stanford University. Surgery, Karp Family Research Laboratories, Children’s Hospital Dr. Yoram Dagan Boston and Harvard Medical School, 1. Ultrafast optical spectroscopy of Inna Slutsky 1 Blackfan Circle, Boston, MA 02115, electron-doped cuprates, with Jure 1. Paul Slesinger, Salk Institute, San U.S.A. Demsar, Konstanz University. Diego 3. María Jesús Vicent, Centro de 2. Probing Local and Macroscopic 2. Bernhard Bettler, Basel University, Investigación Príncipe Felipe, orders in cuprates: with Richard L. Switzerland Medicinal Chemistry Unit, Polymer Greene, University of Maryland. 3. Gerd Multhaup, Free University, Therapeutics Laboratory, Av. Berlin Autopista del Saler 16, E-46012 4. Baruch Minke, Hebrew University Valencia, Spain. Guy Deutscher 1. Rainer Haag, Organic and Macromolecular Chemistry, 1. A spatial interpretation… with P.G. Eran Rabani Department of Chemistry and de Gennes, Institut Pierre et Marie Biochemistry, Freie University , Curie, Paris. 1. Prof. Davud Reichman. Columbia, NY Berlin, Germany 2. Polar Kerr effect…with the group 2. Prof. Andrew Millis, Columbia, NY 2. Felix Kratz, Tumor Biology Center, of Aharon Kapitulnik, Stanford 3. Dr. Irene Burghadt, Ecole Normal Breisacher Straße 117, 79106 University. Superior, Paris Freiburg, Germany 4. Prof. Rossky, University of Texas, Ausin 5. Prof. Uri Banin, Hebrew University Alexander Gerber 6. Prof. Roi Baer, Hebrew University 1. Magnetic semiconductors, with 7. Prof. Itamar Wilner, Hebrew University of L’Aquilla, Italy University

127 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY TAU Nano Related Faculty Scientific Groups

Physics Chemistry optic and electro-magneto-optical devices and their applications in biology, Prof. David Andelman Prof. Ori Cheshnovsky chemistry and technology Polymeric nano-templates and nano- Nanoscale optics in STM junctions, [email protected] structures (theory) Electronic properties of clusters [email protected] [email protected] Prof. Emanuel Peled and Prof. Diana Goldnitsky Prof. Eshel Ben-Jacob Prof. Haim Diamant Nano materials and thin films for Nano Bio Electronics Theory of Complex Fluids electrochemical energy storage and [email protected] [email protected] conversion [email protected] Dr. Yoram Dagan Dr. Michael Gozin Superconductivity and ferro-magnetism Preparation, characterization and Dr. Moshe Portnoy in the nanoscale biomedical applications of fullerene/ Nanoscale composite materials for [email protected] nanotube protein complexes; novel catalysis and biomedicine fullerene-derived amino acids and [email protected] Prof. Guy Deutscher peptides (with Prof. A. Kotlyar) Melting of nano-grains, [email protected] Prof. Eran Rabani superconductivity in nano-grain Theory of nano-materials (theory) composites Dr. Oded Hod [email protected] [email protected] Computational Nano-Materials Science: towards electronic, spintronic, and Dr. Shachar Richter Prof. Alexander Gerber electro-mechanical devices at the Molecular electronics of self assembly Giant magneto-resistance in nano- nanoscale layers composites [email protected] [email protected] [email protected] Prof. Joseph Klafter Dr. Yael Roichman Prof. Ron Lifshitz Single molecule dynamics, nanomotors Optical assembly of new materials and Electro-mechanical properties of and nanofriction (theory) devices nanostructures (theory) [email protected] [email protected] [email protected] Prof. Gil Markovich Dr. Yoram Selzer Prof. Alexander Palevski Synthesis and physical studies of colloidal The physics and chemistry of singles E-transport in low-dimensional nanoparticles and their assemblies molecule junctions semiconductor nanostructures [email protected] [email protected] [email protected] Prof. Abraham Nitzan Prof. Michael Urbakh Electronic processes at molecular Theoretical studies and modeling in interfaces (theory) fields of nanomechanics’ frictions at the [email protected] nanoscale, single molecular spectroscopy and molecular motors • Prof. Fernando Patolsky [email protected] The synthesis and characterization of new nanoscale materials for the development of nanoelectronic, electro-

128 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY TAU Nano Related Faculty Scientific Groups

Engineering Prof. Gil Rosenman Life Sciences Ferroelectric nanodomain polarization Prof. A. Boag and B. Steinberg reversal and development of a new Prof. Ari Barzilai Photonic crystals generation of nonlinear photonic devices The molecular mechanism of optic nerve [email protected] [email protected] degeneration and regeneration [email protected] Prof. Reuven Boxman, Prof. Prof. Yossi Rosenwaks S.Goldsmith, Dr. Nahum Parkansky Nano-probing, scanning probe Prof. Itai Benhar and Dr. Vladimir Zhitomirsky microscopy Targeted drug-carrying phage Electrical discharge and plasma lab [email protected] nanoparticles [email protected] [email protected] Prof. Yosi Shacham- Diamand Dr. Noam Eliaz Nano-chemical processes for Prof. Chanoch Carmeli Design, synthesis and characterization microelectronics and integration of Application of the photosynthetic of new osteoconductive functionally biological material on chip for acute reaction center proteins, PS I in the graded hydroxyapatite coatings; toxicity detection fabrication of novel nanobio-photovoltaic biomaterials, electrochemistry, SPM [email protected] devices [email protected] [email protected] Prof. Shlomo Ruschin Prof. Eliezer Kit and Yoram Shapira Micro-electrooptics Prof. Amihay Freeman Interface between bio-molecules and [email protected] Biotemplating of stabilized protein nano-electronic structures and devices crystals; directed metallization of [email protected] Prof. Arie Ruzin biologically active proteins and cells Solid state detectors and devices [email protected] Prof. Ilan Goldfarb laboratory Growth of epitaxial nanostructures, STM [email protected] Prof. Ehud Gazit [email protected] Self-assembly of short aromatic peptides: Prof. Yoram Shapira from amyloid disease to nanotechnology Dr. Yael Hanein Tailoring of silicon surfaces by [email protected] Microfluidics for self-assembly, electrochemical grafting and deposition nanotubes-neurons interfaces of biomolecules Prof. Yoav Henis [email protected] [email protected] Nano-scale lipid domains and their role in Ras signaling Prof. David Mendlovic Dr. Jacob Scheuer [email protected] Silicon nano-photonic dynamic devices Integrated nano-photonics, slow light [email protected] and polymer optics Prof. Alexander Kotlyar [email protected] DNA-based organic nano wires Prof. Touvia Miloh [email protected] Nano-mechanics, fluid dynamics in nano- channels; elastic nano-fibers (theory) Prof. Rimona Margalit [email protected] Drug delivery by nano-particles based on biomaterials: biophysical properties, Prof. Menachem Nathan cell-particle interactions and therapeutic Micro-batteries, Optical biosensors responses [email protected] [email protected]

129 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY TAU Nano Related Faculty Scientific Groups

Dr. Dan Peer Mathematics Medicine Selective targeting and reprogramming of leukocytes using fully degradable Prof. Zeev Schuss Prof. Dafna Benayahu nanomedicines • Ionic permeation in protein channels of Nano manipulation of stem cells [email protected] biological membranes and applications differentiation to become biomedical to models of neurons and cardiac devices Prof. Judith Rishpon myocytes [email protected] Application of nano technologies in [email protected] electrochemical biosensors • Prof. Rafi Korenstein [email protected] Electrical enhancement of drug nano- carrier, nanoscale cell membrane dynamics [email protected]

Dr. Ronit Satchi-Fainaro Targeting tumor vasculature with polymer conjugates of angiogenesis inhibitors [email protected]

Dr. Ella Sklan Interactions of positive strand RNA viruses with the host cell [email protected]

Dr. Inna Slutsky Information processing: From nano-scale single synapse to memory function [email protected]

Dr. Ilan Tsarfaty Nanoparticles based Met-HGF/SF molecular imaging [email protected]

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

Prof. Ori Cheshnovsky

The scientific committee of the Center for Nanoscience and Nanotechnology

Prof. Guy Deutscher, Chairman of the scientific and managing committee

Prof. Ori Cheshnovsky, Head of the Center for Nanoscience and Nanotechnology

Prof. Ilan Goldfarb, Faculty of Engineering

Dr. Yael Hanein, Faculty of Engineering, representative – core researchers

Prof. Rimona Margalit, Faculty of Life Sciences

Prof. Gil Markovich, School of Chemistry and Astronomy

Prof. Alexander Palevski, School of Physics

Dr. Dan Peer, Faculty of Life Sciences

Prof. Yossi Rosenwaks, Faculty of Engineering

Dr. Inna Slutsky , Faculty of Medicine

Dr. Moshe Evenor, Managing Director

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

Administrative and Technical staff

Name Function Dr. Moshe Evenor Administrative manager Lauren Itzhak Secretary Dr. Zahava Barkay ESEM lab director Dr. Yossi Lereah HRTEM researcher and lab director Dr. Alexander Tsukernik Electronic microscope and E-Beam lithography lab manager Gregory Avrushchenko Nano Center Site Engineer Moshe Eliyahu AFM Laboratory Assaf Hazzan Clean Rooms Engineer (Nano center)

TAU micro and nano central characterization & fabrication facility - personnel

Name Position Directors Prof. Ori Cheshnovsky Academic co-director Dr. Yael Hanein Academic co-director Administration Inna Veksler Processing Mark Oksman Chief Engineer Maurice Saidian Equipment Engineer Assaf Hazzan Equipment Engineer Alexander Gurevitch Process Engineer David Shreiber Training (student) Elad Koren Bonder (Student) AFMs Noam Sidelman-Mor Atomic force microscopy SEMs Dr. Alexander Tsukernik e-beam microscopy and lithography Denis Glozman, Netta Hendler Training (Students) ESEM Dr. Zahava Barkay ESEM Glove boxes Gregory Avrushchenko Lab Engineer

132 The Center for Nanoscience and Nanotechnology AT TEL AVIV UNIVERSITY