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Bio-detection using nanoscale electronic devices
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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
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Attempts at real time electronic detection
Detection in buffer environment Change of resistance Lieber, 2001 Dai 2000 Dekker 2003 UCLA 2001
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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
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Nanotube-protein, nonspecific binding
BBSA on MWNTs SEM Other proteins: Streptavidin biotin Avoiding nonspecific binding: PEG coating, carboxilation
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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
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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
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Real time detection in a buffer environment
A variety of detection schemes developed
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Polymer nanofibres for biosensing
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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
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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 pM Cantilever based detection Guntherodt, Basel, etc 30 pM Nanopore technology unproven
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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
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? Biosensing: NW vs NT Protein Detection DNA Detection
Lieber, C. M. et al. Science 2001, 293, DNA Detection Star, A. et al. Nano Lett , 41, ? Lieber, C. M. et al. Nano Lett. 2004, 4, 51-54
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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
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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
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Future directions: sensitivity enhancement, multiplexing
Noise reduction Ultradense arrays Biotech applications: gene chips, protein chips, disease identification, bio-threat agent detection …..
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