Solid-State Nanopore Sensors for Nucleic Acid Analysis - Nanopores: Sensing and Fundamental Biological Interactions - page 27

Perhaps the most striking example of nanopore functionalization impacting the
sensing capabilities of single nanopore channels involves the use of oxidized Si
nanopores functionalized with hairpin-loop, probe DNAs to selectively transport
short “target” (complementary) ssDNAs under an applied electrical field [ 36 ]. Iqbal
et al. functionalized SiO 2 nanopores with 20 base long hairpin-loop DNA probes
containing a 6 bp stem forming region. Mismatches were introduced in the target
ssDNA at points complementary to the stem forming region of the immobilized
probes. Higher flux and smaller translocation times were observed during the
passage of Perfectly Complementary (PC) DNA as opposed to single base mis-
match (1MM) DNA. This was attributed to an attractive potential between the
immobilized probe and the target PC-DNA resulting in hairpin unzipping and
facilitated transport of the PC sequence. In the case of 1MM however, a repulsive
potential was proposed between the target sequence and the probe resulting in
probe-target interaction without unzipping of the hairpin. Reduced biomolecule
flux and increased translocation times were also consistently observed in the cases
of two and three base mismatch DNAs (2MM and 3MM respectively) relative to
PC-DNA. These studies confirm that it is indeed possible to impart chemical
selectivity in single solid-state nanopores and this selectivity can be electrically
monitored through translocation signatures at the single-molecule level. Such
devices could help further unravel the physics of selective and facilitated transport
of biomolecules through nanoscale channels and could play an important role in
medical diagnostics.
1.4 Conclusions
Solid-state nanopore sensors are highly versatile platforms for the rapid, label-free
detection and analysis of single molecules, with potential application to next
generation DNA sequencing. The versatility of this technology allows for both
interfacing with biological systems at the nano-scale as well as large scale VLSI
integration promising reliable, affordable, mass producible biosensors with single
molecule sensing capabilities. This technology may also serve as a base to provide
further insight into the mechanisms driving biological processes, including cell
signaling and regulation through gated, selective ion channels, protein secretion
across cellular membranes and viral infection by phages. The applications for solid-
state nanopore technology are diverse. Point-of-care diagnostic devices employing
solid-state nanopores can be used to detect and monitor infectious diseases e.g.
influenza, an effective tool in public health strategies. In defense, solid-state
nanopores can be used for the rapid detection of high priority agents such as
Bacillus anthracis (anthrax) at very low concentrations. In drug screening and
medical applications, solid-state nanopores provide a means for label-free, real-
time kinetic analysis of biomolecular interactions at the single molecule level
including protein-protein, protein-DNA and receptor-ligand interactions. This tech-
nology finds broad application in bio-nanotechnology.