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通过减小纳米孔直径来减缓单链 DNA 通过固态纳米孔的迁移。

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

机构信息

Central Research Laboratory, Hitachi, Ltd., 1-280 Higashi-koigakubo, Kokubunji, Tokyo 185-8601, Japan.

出版信息

Nanotechnology. 2014 Jul 11;25(27):275501. doi: 10.1088/0957-4484/25/27/275501. Epub 2014 Jun 24.

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.

摘要

为了减缓单链 DNA(ssDNA)通过固态纳米孔的迁移速度,我们对纳米孔进行了缩窄,并研究了缩窄对 DNA 迁移速度的影响。为了准确测量速度,我们合成了具有均匀长度(±0.4 kb)的长(5.3 kb)ssDNA(即 ss-poly(dA))。通过透射电子显微镜制造的纳米孔的直径通过原子层沉积进行控制。当在纳米孔两端施加 300 mV 的电压时,将纳米孔直径从 4.5nm 减小到 2.3nm,可使 ssDNA 的迁移速度降低 16 倍以上(至 0.18 μs 碱基(-1))。据推测,纳米孔与 ssDNA 之间的相互作用主导了迁移速度。出乎意料的是,ssDNA 通过 4.5nm 纳米孔的迁移速度比几乎相同尺寸的纳米孔中双链 DNA(dsDNA)的迁移速度高两个数量级以上。这种更快的 ssDNA 迁移速度可以通过纳米孔内较弱的拖曳力来解释。此外,ssDNA 和 dsDNA 的测量迁移速度与分子动力学(MD)模拟计算的结果吻合较好。MD 模拟预测,将纳米孔直径减小到几乎与 ssDNA 相同(即 1.4nm),会降低迁移速度(至 1.4 μs 碱基(-1))。因此,缩窄纳米孔是实现纳米孔 DNA 测序的有效方法。

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