Slowing and controlling the translocation of DNA in a solid-state nanopore

Abstract

DNA sequencing methods based on nanopores could potentially represent a low-cost and high-throughput pathway to practical genomics, by replacing current sequencing methods based on synthesis that are limited in speed and cost. The success of nanopore sequencing techniques requires the solution to two fundamental problems: (1) sensing each nucleotide of a DNA strand, in sequence, as it passes through a nanopore; (2) delivering each nucleotide in a DNA strand, in turn, to a sensing site within the nanopore in a controlled manner. It has been demonstrated that a DNA nucleotide can be sensed using electric signals, such as ionic current changes caused by nucleotide blockage at a constriction region in a protein pore or a tunneling current through the nucleotide-bridged gap of two nanoelectrodes built near a solid-state nanopore. However, it is not yet clear how each nucleotide in a DNA strand can be delivered in turn to a sensing site and held there for a sufficient time to ensure high fidelity sensing. This latter problem has been addressed by modifying macroscopic properties, such as a solvent viscosity, ion concentration or temperature. Also, the DNA transistor, a solid state nanopore dressed with a series of metal–dielectric layers has been proposed as a solution. Molecular dynamics simulations provide the means to study and to understand DNA transport in nanopores microscopically. In this article, we review computational studies on how to slow down and control the DNA translocation through a solid-state nanopore