Bio-detection using nanoscale electronic devices

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Bio-detection using nanoscale electronic devices
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Nano-bio interface
Bacteria
1 ?
Current CMOS Technology
100 nm
evolutionary technology
Next Generation CMOS
Virus
Nanofiber
Proteins
10 nm
Nanowire
1 nm
revolutionary technology
Nanotube
DNA
0.1 nm
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Attempts at real time electronic detection

• Detection in buffer environment
• Change of resistance

 
Lieber, 2001
UCLA 2001
Dai 2000
Dekker 2003
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Charge states, electrostatic interactions in
biology
Electrostatic interactions DND histone
complexation Protein folding, binding Polyelectr
olites 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
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
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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 100
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
Harvard
Proteins
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
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
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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 ..