Simulation of Electronic Sensing of Biomolecules in Translocation Through a Nanopore in a Semiconductor Membrane - Nanopores: Sensing and Fundamental Biological Interactions - page 152

7.1 Introduction

In the middle of the 1990s, single molecule translocation through a proteinaceous
nanopore was proposed as a new tool for DNA characterization [ 1 ]. Single stranded
DNA molecules have a diameter of 1-2 nm [ 2 ] which is comparable to the pore
size of biological ion channels [ 3 ]. It was suggested that by utilizing the natural
nano-scale features of a proteinaceous pore, one can obtain direct information on
the DNA molecular structure. Indeed, when an electric field drives a DNA molecule
through the proteinaceous nanopore in a lipid bilayer placed in an electrolyte
solution, the DNA molecule partially or totally blocks the pore reducing the ionic
current through it. Hence, the passage of each DNA molecule can be detected as a
transient decrease of ionic current whose duration is proportional to the DNA
length. Many experiments have been done in this context [ 1 , 4 - 10 ] demonstrating
the correlation between the length of the DNA chain and the duration of the ionic
current blockade. Later works revealed additional factors such as temperature [ 5 ],
driving voltage (applied electric field) [ 9 ], and DNA pairing [ 4 , 6 , 7 , 10 ] affecting
the DNA translocation rate. Moreover, in the case of mono-nucleotide chains, this
technique has been able to discriminate between polymers of different molecular
compositions [ 4 , 6 , 10 ].
Although proteinaceous nanopores are convenient DNA characterization tools,
they have shortcomings as the pore is of a fixed size, and its stability and low noise
characteristics are restricted to well defined chemical, mechanical, electrical
and thermal conditions [ 11 ]. In recent years, artificial solid-state nanopores made
of silicon and silicon compounds began to replace the original bio-nanopores,
and promise to overcome limitations of the latter [ 11 - 16 ]. As with proteinaceous
nanopores, the correlation between DNA translocation and ionic current bloc-
kage has been established by both simulations and experiments [ 13 , 17 , 18 ]. By
measuring the duration and magnitude of the blocking current transient, the polymer
length of single-stranded DNA can be determined [ 13 ]. However, for both bio-
nanopore and solid-state nanopore systems, complete characterization of DNA
molecules is still at its early stage. Nevertheless, quoting our colleagues: “with
further improvements, the method could in principle provide direct, high-speed
detection of the sequence of bases in single molecules of DNA or RNA” [ 1 ].
In addition to ionic current blockage, translocation of DNA molecules through
nanopores in Semiconductor-Oxide-Semiconductor (SOS) membrane induces a
change of the electrostatic potential on the semiconductor layers of the membrane.
Hence, as DNA permeates the pore, its electronic signature can be recorded in the
form of a voltage trace.
Sequencing DNA strands with a nanopore device has not been achieved yet.
Although it has been demonstrated that voltage signals resulting from DNA trans-
location through a capacitor membrane can be recorded [ 18 , 19 ], the temporal
resolution of such measurements precludes from recording signals that could be
associated with translocation of individual nucleotides. While new experimental