Solid-State Nanopore Sensors for Nucleic Acid Analysis - Nanopores: Sensing and Fundamental Biological Interactions - page 20

were bonded to the front side of the nanopore chip. These structures helped us
incrementally reduce device capacitance and thereby reduce dielectric noise.
Impedance spectra (magnitude and phase) were obtained for each architecture as
shown in Fig. 1.7d, e , and fitted to an equivalent RC circuit. A capacitance of 1 nF,
300 pF and 20 pF was extracted for architectures 1, 2 and 3 respectively,
corresponding to peak-to-peak noise values of approximately 1.2 nA, 400 pA and
200 pA at the 100 kHz bandwidth setting on the Axopatch 200B measurement
platform, as shown in Fig. 1.7f . Capacitance minimization has proven to be an
effective method in decreasing high frequency dielectric noise, improving signal-
to-noise ratio and enhancing the overall sensitivity of these nanopore sensors in
DNA translocation experiments.

1.3.6 DNA Translocation Through Solid-State Nanopores

The first demonstrations of DNA translocation through a solid-state nanopore were
shown by Li et al. [ 53 ]. Deep current blockades were observed as dsDNA was
electrophoretically driven through nanopores formed in thin Si 3 N 4 membranes
using the ion beam sculpting process described earlier. Further studies confirmed
the dependence of dsDNA transport kinetics on bias voltage, DNA length and DNA
conformation [ 52 ]. Li et al. further showed that by reducing the bias voltage by a
factor of two, the dwell time of the DNA molecule in the nanopore could be
approximately doubled [ 52 ]. Multiple configurations of the translocating molecule
in the nanopore were also observed in these experiments attributed to dsDNA
folding, a phenomenon observed primarily in large nanopores. Smaller ~3 nm
pores however, were shown to restrict the passage of folded molecules and pro-
moted only the linear passage of unfolded molecules. Heng et al. demonstrated that
by reducing nanopore diameter to below that of dsDNA, the electrophoretic sepa-
ration of ssDNA from dsDNA could be achieved using a solid-state nanopore [ 29 ].
Narrow ~2 nm pores were seen to block the passage of dsDNA and allowed the
passage of only ssDNA. Only by applying very high fields was dsDNA permeation
through these narrow pores indeed possible attributed to stretching transitions that
occur in dsDNA at forces exceeding 60 pN. Comer et al. further demonstrated that
very narrow 1.6 nm diameter synthetic nanopores could be effectively used to

unzip hairpin DNA [ 20 ]. Different modes of hairpin DNA transport were observed
in these experiments, the first mode referring to the unzipping of the double helix
structure to form ssDNA and the second mode referring to the stretching/distortion
of the double helix itself.
Chang et al. studied the effect of buffer concentration on DNA translocation
dynamics [ 11 ]. Current enhancements were observed in large SiO 2 nanopores at
low salt concentrations (100 mM KCl) as opposed to the typical blockades that
were observed at higher salt concentrations. A more rigorous study by Smeets et al.
and Chang et al. suggested that these current enhancements are due to counterion
condensation on the DNA backbone, thereby locally increasing the concentration of

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