Biomedical Engineering Reference
In-Depth Information
is given by Zwolak and Di Ventra ( 2008 )
I Š 2 e 2
h
L .E F / R .E F /
.E F E N / 2 V;
(2.35)
where L and R are coupling coefficients, which have very different values for
each base, due to their different extensions and corresponding wavefunctions. On
the contrary, the energy levels of different bases have almost the same distance to
the Fermi energy E F .
An important condition for DNA sequencing is that DNA must have a slow
translocation velocity, necessary for nucleotide orientation by the transverse field
in hundreds of ps when the nucleotide reaches the electrodes. This is expressed as
E jj E ? :
(2.36)
Using the above method, it is estimated that the three billion bases of a human
ssDNA can be sequenced in approximately 7 h ( Zwolak and Di Ventra 2008 ). Again,
the main disadvantage of the transverse current sequence technique is the noise,
especially the ionic noise, caused by ionic fluctuations.
There are methods dedicated to sequencing DNA based on similar principles.
For instance, the method based on the capacitance change of a MOS capacitor
with an integrated nanopore [see ( Zwolak and Di Ventra 2008 ) and the references
therein]. In this case, voltage fluctuations are monitored instead of currents, as in
the examples above. The sensitivity required from this method is high, since DNA
sequencing means in this situation the detection of differences between the dipole
moments of different bases, which could be retrieved from voltage oscillations
at translocation through the nanopore ( Gracheva et al. 2006 ). The molecular
capacitances of nucleotides are displayed in Table 2.2 ( Lu and Zhang 2008 ).
Tab le 2.2 suggests that the DNA bases A and G have a distinct capacitance
signature compared to C and T. If we compare the above capacitances with that of a
plate capacitor with an area of 0:1 nm 2 and a distance between plates of 1.5 nm, the
difference in the base capacitances could be equivalent with a difference in effective
permittivity between 2 and 5.
There are also various optical methods based on nanopores, but the label-free
character of these methods is partially lost due to the use of DNA magnification
sequence and florescent tagged ssDNA.
There
are
two
types
of
nanopores
used
for
DNA
sequencing:
biologi-
cal
nanopores
and
solid-state
nanopores,
more
exactly
dielectric
nanopores
Tabl e 2. 2
Base capacitances
Base Molecular capacitance (aF )
A0.29
G0.22
C
0.94
T
0.94
 
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