Capture and Translocation of Nucleic Acids into Sub-5 nm Solid-State Nanopores - Nanopores: Sensing and Fundamental Biological Interactions - page 251

to those in free electrophoresis, with both folded and unfolded configurations, but in
sub-5 nm pores translocation proceeds only in an unfolded manner, where the net
electrophoretic force on the DNA is greatly reduced by hydrodynamic interactions
and friction with the nanopore surface. The distribution of dwell-times ( t D ) in small
pores was both analytically and numerically predicted to resemble a Poissonian
distribution, due to these interactions of the DNA with the wall of the nanopore.
Similar results are obtained from experimental data, and the characteristic
timescales related to collisions and translocations may be extracted using exponen-
tial fits to the distribution tails. Small nanopores produce translocations that have a
mean dwell time t D that is orders of magnitude longer than that for larger pores,
which is advantageous for many practical applications. The dwell time is reduced
by a combination of factors: friction with the membrane, net electrophoretic force,
and the electroosmotic drag of condensed counterions on the DNA.
We find that the application of salt gradients across the pore permits manipula-
tion of the electric field profile in and around the pore. This implies that (1) The
capture rate can be increased by altering the critical radius for biased diffusion and
increasing the local potential near the pore that governs the threading efficiency. (2)
The translocation time can be extended, presumably due to the increased EOF of
cations acting to slow down the velocity of the negatively charged DNA during its
translocation process.
Yet there are many aspects of translocation dynamics that remain unexplored.
One particularly important question is that of a biopolymer's velocity profile as
it passes through the pore. For many applications, it would be advantageous if
the translocating biopolymer maintained a constant velocity throughout, since
this would simplify the signal interpretation. Even given a non-uniform velocity
profile, understanding the interactions and dynamics responsible would enable
adjustment of materials and fabrication to exert some measure of control over
this parameter. The question of velocity is very closely linked to the ultimate
resolution of a nanopore. At present, solid-state nanopores are tens of nanometers
thick, limiting the ultimate sensing resolution to a minimum of ~30 bases. This
restricts the resolution of some practical applications, such as DNA sequencing.
In order to improve the nanopore resolution, advances in materials fabrication are
required in order to provide stable, geometrically well-defined nanopores that may
ultimately enable differentiation of single base-pairs (~0.5 nm), or even of short
sequences. Finally, control over the selectivity of nanopores and dynamics of
biopolymer transport may be achieved by chemically modifying the internal
and external surfaces of nanopores [ 19 , 47 ]. Progress in material design, fabrica-
tion, and sub-nanometer pore control, coupled with a better understanding of the
physical parameters that govern voltage-induced biomolecular motion through
small pores, will be essential for opening new horizons in single biomolecule
sensing.
Acknowledgements We acknowledge stimulating discussions contributing to this chapter with
B. McNally, A. Singer, Y. Rabin, A. Grosberg, D. Nelson, A. Kolomeisky and W. Morrison. A.M.
acknowledges support from NIH award HG-004128, and NSF award PHY-0646637.