Single molecule conductance of DNA bases and sequencing
by
y tunneling
g
Stuart Lindsay
[email protected]
u .L n
y@ u. u
Colin Nuckolls, Hiatao Liu, Jinyao Tang (Columbia)
Peiming
Zh
Zhang
Jin He
Otto
Sankey
Ashley Kibel
Di Cao
Shuai Chang
Pei Peng
Shou Huang
Hao Liu
Lisha Lin Feng
Liang
Myeong
Lee
P
Peter
Pelletier,
P ll
Michael
h l Young, Allison
ll
Davies
Pavel Jelenik, Predrag Krstic (ONRL)
1
Our Proposal forSequencing by Recognition
(A readout for nanopores)
Combines
• Chemical Recognition.
• “Binary” go/no-go readout – no
spectroscopy required
• “Tunable” – e.g., distinguish methylated C
• No labels/target modification required
• Tunnel current readout.
• Fast
• Direct
Dir ct electronic
l ctr nic int
interface
rf c
• Single-base resolution
• Nanopores
• Single molecule, precessive reads
• Genomic-length reads?
2
Sequencing
q
g by
y Recognition
g
V1.0
(Nature Biotechnology 26 1146 2008)
• Self-assembled tunnel junction – Watson-Crick on one
p
p
on the other.
side,, Guanidinium-phosphate
• As shown, only one base per reader – assembly required.
3
An STM
STM-based
based model
4
STM model: move the reader to
simulate DNA movement
Au(111)
V
i
Reads Oligomer base composition
(Nanotechnology 20
075102 2009)
But onlyy at a
resolution of ca. 10
bases!
6
What’ss happening in these junctions?
What
Tunneling path is just too long – multiple
contacts/large area junction required.
Are single molecule reads even possible?
7
• Form monolayer of nucleoside on Au electrode
• Put DNA base on Probe
• Bring probe to surface,
surface allow tunnel current to stabilize
stabilize, turn
off servo and record I(t)
• Requires sub Angstrom stability for many seconds
Typical
Telegraph
elegraph
Noise Data
Measured Conductances depend on
Gap
I vs V for “Plateau”
Plateau Data
Bond Lifetimes
2AA th idi
2AA-thymidine
A
A-Thymidine
Th idi
All 45 ms
G-Cytidine
Changes with # H-bonds
1,8 Octane dithiol
Measured and Calculated
C d t
Conductances
Base-nucleoside Gmeas. (nS) Gpred.
pair
(nS)
A-deoxythymidine 0.76±0.01 1.62
2AAdeoxythymidine
G-deoxycytidine
0.80±0.03
1.43
0.66±0.007 0.96
13
Tunneling for DNA reads
• DFT seems to work within a factor of
two or so – validates a proposed new
tunneling scheme (“Trans
( Trans base
base-pair
pair
tunneling”) to read DNA
• Gold-gold+thiol
Gold gold+thiol bonds break nearly as
rapidly as h-bond clusters! Cannot use
gold electrodes.
electrodes