Bio-detection using nanoscale electronic devices

1. Bio-detection using nanoscale electronic devices

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

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

4. 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

5. Nanotube-protein, nonspecific binding BBSA on MWNTs SEM Other proteins: Streptavidin biotin Avoiding nonspecific binding: PEG coating, carboxilation

6. streptavidin polymer biotin S D SiO2 Si back gate Vsd Vg Ligand-receptor binding without false positives Response to biotinilated streptavidin Polymer coated device without biotin Ploymer coated, biotin-immobilized device (approximately 50 streptavidins) Detection limit: 10 proteins

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

8. Real time detection in a buffer environment A variety of detection schemes developed

9. Polymer nanofibres for biosensing

10. 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

11. 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

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

13. Biosensing: NW vs NT Protein Detection Lieber, C. M. et al.Science2001, 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

14. 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

15. 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

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