Slowing single-stranded DNA translocation through a solid-state nanopore by decreasing the nanopore diameter

Abstract

To slow the translocation of single-stranded DNA (ssDNA) through a solid-state nanopore, a nanopore was narrowed, and the effect of the narrowing on the DNA translocation speed was investigated. In order to accurately measure the speed, long (5.3 kb) ssDNA (namely, ss-poly(dA)) with uniform length (±0.4 kb) was synthesized. The diameters of nanopores fabricated by a transmission electron microscope were controlled by atomic-layer deposition. Reducing the nanopore diameter from 4.5 to 2.3 nm slowed down the translocation of ssDNA by more than 16 times (to 0.18 μs base(-1)) when 300 mV was applied across the nanopore. It is speculated that the interaction between the nanopore and the ssDNA dominates the translocation speed. Unexpectedly, the translocation speed of ssDNA through the 4.5 nm nanopore is more than two orders of magnitude higher than that of double-stranded DNA (dsDNA) through a nanopore of almost the same size. The cause of such a faster translocation of ssDNA can be explained by the weaker drag force inside the nanopore. Moreover, the measured translocation speeds of ssDNA and dsDNA agree well with those calculated by molecular-dynamics (MD) simulation. The MD simulation predicted that reducing the nanopore diameter to almost the same as that of ssDNA (i.e. 1.4 nm) decreases the translocation speed (to 1.4 μs base(-1)). Narrowing the nanopore is thus an effective approach for accomplishing nanopore DNA sequencing.

Discrimination of three types of homopolymers in single-stranded DNA with solid-state nanopores through external control of the DNA motion

“…Details of the preparation process used for the 5.3-kb ss-poly(dA) are described in ref. 24 , which reported that the variation in the length of ss-poly(dA) was approximately 5.3-kb ± 0.4-kb. In this paper, we hereafter refer to 5.3-kb ± 0.4-kb ss-poly(dA) as poly(dA) 5.3k .…”

The promises and challenges of solid-state sequencing

“…In order to pass single-stranded DNA, the diameter of the pore must be at least 1.4 nm (ref. 7 ), so even pores in atomically-thin membranes (such as those made of graphene, which are discussed in the Review by Stephanie Heerema and Cees Dekker 4 ) will be sensitive to the DNA bases that lie outside the pore on each side (Fig. 1a).…”

Fabrication of solid‐state nanopores and its perspectives

“…It was shown that repetitive deposition cycles of ALD can be used to fabricate ultra‐thin solid membranes appropriate for low aspect ratio nanopores fabrication . ALD was also suggested to be able to coat all exposed surfaces including inside of the nanopore and thus effectively decrease nanopore diameter . Lee et al.…”