Post on 21-Dec-2015
1 nm
10 nm
100 nm
1
DNA
Virus
Bacteria
Proteins
0.1 nm
Nanotube
Nanowire
Next Generation CMOS
Current CMOS Technology
evo
luti
on
ary
te
chn
olo
gy
rev
olu
tio
na
ry t
ech
no
log
y
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
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