Capture and Translocation of Nucleic Acids into Sub-5 nm Solid-State Nanopores - Nanopores: Sensing and Fundamental Biological Interactions - page 250

the actual ratio of speeds between 400 and 2,000 bp should be (2,000/400) 1.4 9.5.

This value is similar to our experimental result, which shows a slope ratio of ~7 for
these two DNA samples (see line). These results are also consistent with the
simulations performed by Luan and Aksimentiev, in which electroosmotic drag
functions as an additional stalling force on the DNA [ 28 ]. However, it is not clear
what the quantitative effect of a salt gradient on transport speed should be, primar-
ily because the actual salt gradient profile inside the nanopore is complex and, to
date, experimentally unquantified.
While the dynamic profile of DNA translocating through a nanopore is a subject
of great importance for nanopore applications, a comprehensive model that
accounts for biopolymer interactions with the membrane and pore walls, electro-
phoretic effects, and biopolymer hydrodynamics, has yet to be developed. Empiri-
cally, we know that the electric field in a nanopore exerts forces of tens of pN on the
dsDNA, sufficient to overcome the entropic free-energy barrier associated with
linearizing the biopolymer, as well as interactions with surfaces and any EOF which
acts to slow the translocation process. A quantitative prediction of the actual
instantaneous velocity or dwell time distributions will require a more sophisticated
understanding of the complex salt gradient profile within the pore.

¼

10.4 Conclusion

The studies reviewed here assess current progress toward understanding the dynamics
of biopolymer capture and translocation through small solid-state nanopores, as
illustrated by the case of double-stranded DNA. A theoretical model for DNA
capture has been outlined, composed of two distinct steps: diffusion to the vicinity
of the pore, and threading of one end into the pore. DNA coils diffusing randomly
throughout the cis chamber are electrically focused towards the pore when they enter
a hemisphere of influence described by the critical radius r *. Once a coil reaches the
pore mouth, the threading process is governed by an energy barrier that is highly
biased by the local electrical potential near the pore. Investigation of DNA length
dependence on the capture rate revealed that for shorter DNA, threading is the rate-
limiting step, in which regime capture rate varies exponentially with square root of
DNA length. For long DNA, diffusion to the pore is the rate-limiting step, and thus
the overall capture rate is insensitive to DNA length. These two features are
extremely useful, as they imply that small nanopores are capable of capturing
even long biopolymers with the same efficiency as shorter biopolymers, despite
the fact that longer molecules naturally diffuse slower. Observations of capture rate
for a single DNA length as a function of voltage further confirmed theoretical
predictions for these two dynamical regimes.
The dynamics of translocation are currently accessible primarily by examining
the distribution of dwell times, t D , of molecules in the nanopore under different
conditions. The size of the nanopore is a particularly critical parameter; in large
pores DNA molecules are driven through the pore with forces that are comparable