Sensing of Biomolecules - Bionanoelectronics: Bioinquiring and Bioinspired Devices - page 76

where is a coefficient determined by the contact surface area of the DNA and
the pore surface, and v is the DNA velocity. If we assume that the DNA velocity is
constant, we get

F drag D F driving : (2.30)

The above equality assures us that the DNA velocity is the same irrespective of the
folded or unfolded DNA conformation. Some other important effects related to the
blocking current are summarized below ( Zwolak and Di Ventra 2008 ).
Denoting by I 0 the open pore current and by I b

the blocking current for an N

folded DNA, we have

.I 0 I b /t d D const: (2.31)

which implies that the charge is conserved at translocation of the folded DNA, which
has an equivalent linear region of length NL N ,whereL N is the length of the folded
DNA sequence. The open pore current is given by

I 0 D e nE z ; (2.32)

where n is the charge carrier density, is the ion mobility, and E z Š V=L p , with
V the voltage drop on the nanopore and L p the nanopore length. Considering the
volume exclusion as the unique cause of the blocking current, the carrier density
during the blockade event is

n b D Fn; (2.33)

where F D 1 V n =V p with V n .V p / the volume of a nucleotide (pore volume for
one repeat unit of the polynucleotide) or

.I 0 I b /=I 0 D 1 F:

(2.34)

The generic nanopore for DNA sequencing based on blockade ionic current is
'-hemolysin, which has a diameter of 1.4 nm. Various experiments have demon-
strated that the ionic blockade current is able to provide information about base
signatures and other characteristics of DNA, RNA, etc. For example, in experi-
ments with RNA formed from poly(A), poly(U), and poly(C) sequences ( Akeson
et al. 1999 ), it was found that the translocation time of poly(U) is 1:4s=nucleotide
(nt), while the translocation time for poly(A) is 22s=nt, for a pore bias of 0.12 V. In
turn, poly(C) gives 95% blockade of ionic current and translocates in about 5s=nt,
while poly(U) and poly(A) give 85% blockade of ionic current. Poly(A) contains a
secondary helical structure, so its translocation time is larger than that of poly(U),
where such a secondary structure is absent.
The problem with the DNA sequence technique based on blockade ionic currents
is that, when a resolution of a single base is required, the ionic blockade current
varies with only few percents, considering that the change in blockade ionic
current is due only to the excluded volume. However, the noise of the ionic current,
composed of intrinsic noise of the ionic carriers and that produced by the structural
fluctuations of the nucleotides, exceeds by far the few percent value, being around