Bio-detection using nanoscale electronic devices

1 nm 10 nm 100 nm 1  DNA Virus Bacteria Proteins 0.1 nm Nanotube Nanowire Next Generation CMOS Current CMOS Technology evolutionary technology revolutionary technology Nano-bio interface Nanofiber

Lieber, 2001 UCLA 2001 Attempts at real time electronic detection Dai 2000Dekker 2003 Detection in buffer environment Change of resistance

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 SEM Other proteins: Streptavidin biotin Avoiding nonspecific binding: PEG coating, carboxilation BBSA on MWNTs

Ploymer coated, biotin-immobilized device (approximately 50 streptavidins) Polymer coated device without biotin Ligand-receptor binding without false positives Response to biotinilated streptavidin Detection limit: 10 proteins

Electronic detection in Buffer Environment Working Pt electrode For Rg = 1 MOmh, V noise less than 0.1 mV. Vsd Isd Referenc e + _ Vg Ig = V / Rg V Rg

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 technologyunproven

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 30 pM Nanopore technologyunproven

1 nm 10 nm 100 nm 1  DNA Virus Bacteria Proteins 0.1 nm Nanotube Nanowire Next Generation CMOS Current CMOS Technology DNA detection - electronic Infineon HP Harvard UCLA Critical issues: sensitivity multiplexing

Protein Detection DNA Detection Lieber, C. M. et al. Science 2001, 293, Lieber, C. M. et al. Nano Lett. 2004, 4, Star, A. et al. Nano Lett. 2003, 41, Biosensing: NW vs NT ?

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

SD SiO 2 Si back gate V SD Single-strand DNA Complementary DNA Sequence Carbon Nanotube Transducer DNA Detection Using Carbon Nanotube Transistors DNA Duplex Formation Analytical Signal G VGVG DNA Immobilization Strategies 1) Metal Nanoparticles 2) Sticky Labels 3) Polymer Layer

Future directions: sensitivity enhancement, multiplexing Biotech applications: gene chips, protein chips, disease identification, bio-threat agent detection ….. Noise reductionUltradense arrays