Bio detection using nanoscale electronic devices
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Bio-detection using nanoscale electronic devices. 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.

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Nano bio interface l.jpg
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


Slide3 l.jpg

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

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 l.jpg
Nanotube-protein, nonspecific binding

BBSA on MWNTs

SEM

Other proteins:

Streptavidin

biotin

Avoiding nonspecific binding:

PEG coating, carboxilation


Slide6 l.jpg

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


Electronic detection in buffer environment l.jpg

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


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Real time detection in a buffer environment

A variety of detection schemes developed



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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


Slide11 l.jpg

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 l.jpg
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


Slide13 l.jpg

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


Slide14 l.jpg

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


Slide15 l.jpg

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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