Sensing of Biomolecules - Bionanoelectronics: Bioinquiring and Bioinspired Devices - page 74

on the revealed information, the ultimate understanding of various diseases such
as cancer, the personalized treatment of various illnesses, and the early warning
detection of various diseases are expected. There are various techniques to detect
DNA and its associate sequence of bases, which are reviewed in ( Shendure and
Ji 2008 ). Sequencing techniques, such as the Sanger sequencing method, are utilized
for more than 30 years, but are very slow. In addition, it is very expensive: the price
for sequencing a microbial genome is 20,000-50,000 dollars, while a single human
genome costs 10-25 millions dollars. However, these methods attain an impressive
degree of accuracy, of 99.99% ( Xu et al. 2009 ), taking into account the complexity
of the problem, i.e., that a human genome contains three billion DNA base pairs.
So, a low-cost and rapid DNA sequencing technique is of high demand. Further,
we focus only on electronic detection of the DNA sequence which traverses a
nanopore. This is the most promising DNA sequencing method in terms of costs
and efficiency and, as will be seen, can be extended to protein detection or RNA
detection.
One of the most important properties used in DNA sequencing is that the DNA
backbone is negatively charged in solution, such that a single negative charge is
associated to each nucleotide, or two charges are associated to a pair of nucleotides
for dsDNA. The negative electrically charged DNA can be pull through a nanopore
with a diameter of 1-2 nm with the help of an electric field, and the bases are readout
with the help of two electrodes, followed by low-noise amplification and electronic
processing ( Zwolak and Di Ventra 2008 ). In general, electronic DNA sequencing
refers to ssDNA sequencing. This imposes a requirement on the nanopore diameter
to be no wider than 1-2 nm, which impedes the translocation of dsDNA, with a
diameter of 2 nm; the length of a nucleosite is 0.7 nm. These are amazingly low
dimensions, at the limit of common equipments in nanotechnology. However, as
we will see below, there are a large number of methods and materials to fabricate
nanosized nanopores. A nanopore device for DNA sequencing is displayed in
Fig. 2.19 . This figure shows that there are two main parts in the nanopore device
dedicated for DNA sequencing: a part consisting of two ionic chambers, with the
role of capturing and translocating the DNA sequence, and the part dedicated to
electronic detection.
The DNA capture and translocation occurs between the two ionic chambers
labeled with cis and trans . When a dc bias is applied across the membrane con-
taining the nanopore, the following effects occur: (1) an ionic current flows through
the pore, and (2) the negatively charged DNA is captured and dragged through
the nanopore. So, there are two related effects that take place in the nanopore
surroundings, i.e., capture of the DNA and its translocation through the nanopore.
DNA capture depends on the concentration of DNA in the solution and the strength
of the applied dc electric field, while the translocation is dependent of the applied
field (bias) and many other factors (viscosity, ionic concentrations, etc.), which
can be gathered together under the term DNA-pore interaction effects. During the
translocation, which occurs in a certain time duration t d , the DNA strand is blocking
the flow of ions located in the neighborhood of the pore. Since the DNA nucleotide
located in the pore has a much slower velocity than the ions, the presence of DNA