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Bio-detection using nanoscale electronic devices H S NH H O O CH2OH N H O Nano-bio interface evolutionary technology Bacteria 1 Current CMOS Technology 100 nm Virus Next Generation CMOS Nanofiber Proteins 10 nm revolutionary technology Nanowire 1 nm DNA 0.1 nm Nanotube Attempts at real time electronic detection • Detection in buffer environment • Change of resistance Resistance v.s. Time 110000 Wet Film 100000 add protein 90000 Resistance (ohms) 80000 Dry 70000 60000 50000 Buffer 40000 Buffer + BSA 30000 20000 -1000 0 1000 2000 3000 4000 5000 Time (sec) Lieber, 2001 Dai 2000 Dekker 2003 UCLA 2001 6000 7000 8000 Charge states, electrostatic interactions in biology Electrostatic interactions DND histone complexation Protein folding, binding Polyelectrolites Electrophoresis Charge transfer, migration, transport Charge rearrangement through biology and electronics: the bio/electronics interface Nanotube-protein, nonspecific binding BBSA on MWNTs Other proteins: Streptavidin biotin Avoiding nonspecific binding: PEG coating, carboxilation SEM Ligand-receptor binding without false positives Response to biotinilated streptavidin streptavidin polymer biotin S D SiO2 Si back gate Vsd Ploymer coated, biotin-immobilized device (approximately 50 streptavidins) Vg Polymer coated device without biotin Detection limit: 10 proteins Electronic detection in Buffer Environment For Rg = 1 MOmh, V noise less than 0.1 mV. + _ Rg V Ig = V / Rg Working Pt electrode Vg Referenc e Vsd Isd Real time detection in a buffer environment A variety of detection schemes developed Polymer nanofibres for biosensing DNA detection approaches Nanowire based electronic sensing Lieber, Williams (HP) sensitivity Cantilever based detection Guntherodt, Basel, etc sensitivity Nanoparticle aggregation by DNA links Mirkin Nothwestern reliability DNA electrochemistry J. Barton Caltech mechanism ? Nanotube based sensing NASA Nanopore technology unproven DNA detection approaches DNA electrochemistry Agilent, Motorola, others in use, not sensitive enough Nanotube electrochemistry NASA Nanowire-based Lieber, Williams (HP) 25 pM Nanoparticle aggregation Mirkin Nothwestern 100 pM Cantilever based detection Guntherodt, Basel, etc Nanopore technology 30 pM unproven DNA detection - electronic Bacteria 1 100 nm Virus Proteins 10 nm Current CMOS Technology Infineon Next Generation CMOS HP Harvard Nanowire 1 nm DNA Nanotube UCLA Critical issues: 0.1 nm sensitivity multiplexing Biosensing: NW vs NT Protein Detection Lieber, C. M. et al. Science 2001, 293, 1289-1292 DNA Detection Star, A. et al. Nano Lett. 2003, 41, 2508-2512 ? Lieber, C. M. et al. Nano Lett. 2004, 4, 51-54 ssDNA immobilization approaches 1. Noncovalent anchoring Aromatic molecule binding, ssDNA thethering 2. Thiol attachment to gild nanoparticles Au nanoparticle deposition followed by thiol chemistry 3. Tethering to polymer coating PEI tethering, following our biotin immobilization approach 2 and 3 has been tried for proteins but not for DNA DNA Detection Using Carbon Nanotube Transistors DNA Immobilization Strategies Complementary DNA Sequence S O G Single-strand DNA VG S NH 1) Metal Nanoparticles O N D SiO2 Si back gate O DNA Duplex Formation VSD Carbon Nanotube Transducer S O 2) Sticky Labels N H NH H OH n O N x y Analytical Signal 3) Polymer Layer Future directions: sensitivity enhancement, multiplexing Noise reduction Ultradense arrays (a) 100 nm (b) 100 nm 1 m Biotech applications: gene chips, protein chips, disease identification, bio-threat agent detection …..
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