Laboratory of Integrated Biomedical Micro/ and Applications (LIBNA) Rashid Bashir Micro and Nanotechnology Laboratory (MNTL), Electrical and , Bioengineering, University of Illinois at Urbana-Champaign BioMEMS and Bionanotechnology Grand Challenges & ‘Opportunities’ ! Research Team: Prof. Rashid Bashir ([email protected]) Apply micro/nano-technology to develop novel devices and • POC sensors for food, water, clinical Dr. D. Akin, Dr. J. Moon, P. Bajaj, V. Chan, O. Elibol, Y. Liu, K. Park, J. Reddy, systems that have a biomedical impact or are bio-inspired diagnostics, etc. B. M. Venkatesan, N. Watkins, Z. Ahsan. S. Salamt Collaborators: • Personalized disease management and point Diagnostics Bio-inspired Biochip Cartridge Prof. D. Bergstrom (MCMP, Purdue), Prof. Arun Bhunia (FS, Purdue), Prof. M of care sensors Ladisch (ABE, Purdue), Prof. A. Alam (ECE, Purdue) Fabrication • Personalized DNA sequencer Prof. M. Toner (Harvard), Prof. W. Rodriguez (Harvard), Prof. S. Clare (IUSOM) Micro & Current Funding Agencies: Nanotechnology • Integrated implantable intelligent diagnostics and therapeutics

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hν http://libna.micro.uiuc.edu/ Tissue Micro-devices for Bio-inspired 3 Engineering Cell Biology Materials Integrated Chips for Study of Micro-fluidic Devices as ‘Petri-dish on a Chip’ Microorganisms and Cells Nanomechanical Sensors for Viral Detection Integrated Devices for Electrical MEMS On-chip Ab- Micro-scale Nano Cantilevers, Detection of CD4+ Cells from Blood • Micro-fluidic Bacterial culture on a silicon chip Fluidic Filters Dielectro - based Impedance -probe NanoFETs , Nanopore Sensors Lab-on-a-chip for for DNA Detection phoresis Capture Spectroscopy Array Nano-pores People With HIV/AIDS Detection of Live Bacteria Ports Mehmet Toner, William Rodriguez (Harvard/MGH) 4545 • Applications in food, pharmaceuticals, health, Chang, Andreadakis, Objectives: Cumulative Total (Millions) Liu, Park, Li, Huang, Geng, Kosari, Vasmatzis, 4040 Bhunia, Ladisch, Bashir Bashir Rashid Bashir and diagnostics markets!! To develop technology for the rapid detection 3535 ν 3030 h • Urgent need for rapid, cheap, easy to use 2525 700µ Glass cover of virus particles in fluid and air using m Pin sensors for blood analysis for global health 2020 Overall Approach 15 Nanomechanical Cantilever Sensors applications 15 10 Cavities/ In/Out ports 10 Wells Sample Prep Detection/ Data Analysis/ • Detection of CD4+ cells (T -lymphocytes) from 5 5 Concentration ID Results Epoxy adhesive whole blood for detection of HIV 0 0 Starting 19861988 1988 1990 1992 1992 1996 1994 1995 200 1998 0 2000 2004 2002 2004 Sample Filters Conc. Selective Viability Cell Mech/Elect./ • Normal patient has ~ 600cells – 1500cells/ul Sub-Saharan Africa Asia Latin America 2.3x105 cfu/ml + DEP 8.7x104 cfu/ml + DEP Silicon Nanowires and Frequency Shift, ?f = 60 kHz Europe & N. America* Eastern Europe & CentralNorth Asia Africa & Middle East Dielectrophoresis Sorting Capture Detection Lysing Optical Nanoplates for DNA and • When count < 200cells/ul, therapy is initiated Caribbean 2.3x105 cfu/ml + no DEP Sterile HLB Filters an Traps for Detection Protein Detection ⇒ Mass change, ?m = 9 fg 170% 111% Biological Entities DNA, protein Elibol, Reddy, Nair, 1.00E+07 160% 110% Li, Akin, Bhunia, Bashir Bergstrom, Alam, Bsahir ⇒ This corresponds 1 vaccinia virus. DI-water Bashir, Bhunia, Ladisch 109% 10 cells/ µL 150% 1.00E+06 No fluid 50 cells/ µL 108% 200 cells/ µL 140% 330 cells/ µL 107% 1000 cells/ µL ~1 hr 1.00E+05 Oxygen 130% µ f1 = 1.21 ?f=60kHz 2500 cells/ L Sugars 106% Trapping/Lysing of Nano-Mechanical Micro-Mechanical MHz f = 1.27 5000cells/ µL 120% Bacteria/Viruses In 0 105% Cantilever Sensors for Cantilevers for Detection MHz 1.00E+04

Impedence (ohm) 110% Microfluidic Devices Detection of Viruses of Spores Q ~ 5 ~7.5 hrs 104% Other Park, Akin, Bashir 100% Gupta, Akin, Broyles, Davila, Walter, Aronson, k = 0.006 1.00E+03 Processes Energy 103% Bashir Micro-fluidicFilteration , 90% Ladisch, Bashir N/m Lysing Biochips Metabolism channels Cell 102% 1.00E+02 Na+ 80% 1.00E+02 1.00E+03 1.00E+04 1.00E+05 1.00E+06 ATP 101% Frequency (Hz) + 70% K H2O 100% CO2 60% Na+ Z Relative at Admittance 100Hz 99% Disposable cartridge for CD4+ cell capture and electrical detection of cell count Ion Lactic Acid Relative Admittance at 935.76Hz Functionalized • Owicki et al., Biosens. 50% 98% Nanosensor Array Channels Acetic Acid • Biochips functionalized with antibodies for cell capture Carbonic Acid Bioelectron. (1992) 40% 97% • Electrical analysis of cellular ions 30% 96% • Measurement technique meets the target specification 0 2 4 6 8 10 12 “Lab on a Chip” with microfluidics and micro/nanosensors Courtesy of • Further measurements theAIDs patient sample R, Gomez, et al, IEEE/ASME JMEMS, Vol. 14, No. 4, 829-838, Aug 2005. Time [hours] Seyet, LLC • Prototype development– (licensed to private company)

A. Gupta, et al. Proc. Nat. Acad. Sci. 2006 Cheng, Liu, Irimia, Dimirci, Zamir, Rodriguez, Toner, Bashir, Lab Chip, 2007 Solid State Nanopore Channels with DNA Selectivity Bacterial Mediated Nano-therapeutics

Confocal Images of Intracellularly Delivered Nanobots • Frontiers in biology Æ Single Molecule D. Akin, J.P. Robinson, A. Bhunia, R. Bashir Sequencing using Top-Down Silicon Field Effect Sensor Array of NIH Nanomedicine Development Center: • Biological pores and channels can perform Phi29 Packaging Nanomotor for Nanomedicine Objective: sensing for genomics, proteomics, and Systems- DNA and Proteins To develop biologically-inspired intelligent devices Biology research R. Bashir, ECE, BME for intracellular monitoring and therapeutic 40 nm • Nanotechnology-based (top-down/bottoms up) D. Bergstrom, MCMP intervention of signal transduction networks are needed for making these approaches usable, M. A. Alam, ECE Procapsid and robust and form arrays of addressable pores. S. Clare, IUSOM (gp8) 50 nm • Point of Care Sensors for Detection Connector of Disease Markers from Body fluids (gp10) pRNA-enzyme • Label Free Electrical Detection of Complex (gp16) Procapsid: an elongated prohead that serves as Protein and DNA binding using Top- the virus shell Connector: positioned at the entrance to the virus shell and feeds DNA into the shell Down Silicon Nanosensors RNA-enzyme complex: converts chemical energy to mechanical energy needed for packing • Interdisciplinary team: , Microfluidics, Receptors, Functionalization Approaches, http://www.vet.purdue.edu/PeixuanGuo/NDC/ A side view with red DNA being moved. Medicine Thrust 3: Development of active nanomotor Thrust 1: Re-Engineering the Phi29 Motor for Thrust 2: Mechanistic Studies of the Re- arrays that enable drug delivery and Incorporation into Lipid Bilayers Engineered Membrane Adapted Motor diagnostics D Functionalized ra in Nanosensor Array

S o ur ce Akin, Sturgis, Regheb, Sherman, Burkholder, S. Iqbal, D. Akin, R. Bashir, Nature Robinson, Bhunia, Bashir, Nanotechnology, April, 2007 Nature Nanotechnology, 2007

O. Elibol, et al. Applied Physics Letters, 2003 O. Elibol, et al. Submitted