Bio-detection using nanoscale electronic devices

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

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

Charge states, electrostatic interactions in biology 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 SEM Other proteins: Streptavidin biotin Avoiding nonspecific binding: PEG coating, carboxilation

Ligand-receptor binding without false positives SiO2 Si back gate polymer Vg Vsd biotin streptavidin Response to biotinilated streptavidin Polymer coated device without biotin Ploymer coated, biotin-immobilized device (approximately 50 streptavidins) 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 Reference + _ 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 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 30 pM Nanopore technology unproven

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

? Biosensing: NW vs NT Protein Detection DNA 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 G Single-strand DNA 1) Metal Nanoparticles VG S D SiO2 DNA Duplex Formation Si back gate 2) Sticky Labels VSD Analytical Signal Carbon Nanotube Transducer 3) Polymer Layer

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