Bio-detection using nanoscale electronic devices

CH2OHNHNHSOHHOO

1 nm

10 nm

100 nm

1

DNA

Virus

Bacteria

Proteins

0.1 nm

Nanotube

Nanowire

Next Generation CMOS

Current CMOS Technology

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rev

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Nano-bio interface

Nanofiber

-1000 0 1000 2000 3000 4000 5000 6000 7000 800020000

30000

40000

50000

60000

70000

80000

90000

100000

110000

add protein

Resistance v.s. Time

Wet Film

Buffer + BSA

Buffer

Dry

Resistance(ohms)

Time(sec)

Lieber, 2001 UCLA 2001

Attempts at real time electronic detection

 

Dai 2000 Dekker 2003

• Detection in buffer environment

• Change of resistance

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

SEM

Other proteins:Streptavidinbiotin

Avoiding nonspecific binding:

PEG coating, carboxilation

BBSA on MWNTs

S DSiO2

Si back gate

polymer

VgVsd

biotin

streptavidin

Ploymer coated, biotin-immobilized device (approximately 50 streptavidins)

Polymer coated device without biotin

Ligand-receptor binding without false positives

Response to biotinilated streptavidin

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

VRg

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

1 nm

10 nm

100 nm

1

DNA

Virus

Bacteria

Proteins

0.1 nm

Nanotube

Nanowire

Next Generation CMOS

Current CMOS Technology

DNA detection - electronic

Infineon

HP

Harvard

UCLA

Critical issues:

sensitivity

multiplexing

Protein Detection

DNA Detection

Lieber, C. M. et al. Science 2001, 293, 1289-1292

Lieber, C. M. et al. Nano Lett. 2004, 4, 51-54

Star, A. et al. Nano Lett. 2003, 41, 2508-2512

Biosensing: NW vs NT

?

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 coatingPEI tethering, following our biotin immobilization

approach

2 and 3 has been tried for proteins but not for DNA

S D

SiO2

Si back gate

VSD

Single-strandDNA

ComplementaryDNA

Sequence

Carbon Nanotube Transducer

DNA Detection Using Carbon Nanotube Transistors

DNADuplex

Formation

AnalyticalSignal

G

VG

DNA Immobilization Strategies

SNOONHONNHxyOOHHn

S

1) Metal Nanoparticles

2) Sticky Labels

3) Polymer Layer

Future directions: sensitivity enhancement, multiplexing

Biotech applications: gene chips, protein chips, disease identification, bio-threat agent detection …..

Noise reduction

(a) (b)100 nm

100 nm

1 m

Ultradense arrays