Slowing Down DNA Translocation and Neutral Single Molecules Detection through Solid-State Nanopores by Pressure

Abstract

Charged single molecules of DNA can be detected and characterized with a voltage-biased solid-state nanopore immersed in an electrolyte solution. This has stimulated intense research towards understanding and utilizing this nano-sensor device for the analysis of a wide variety of charged polymer molecules, and for the ultimate goal: DNA sequencing. As one of its fundamental challenges, DNA translocation speed through solid-state nanopores (∼30 base/us) is too fast for instruments to “read” each base signal compared to their protein counterparts.By taking advantage of the ability of solid-state membranes to sustain large pressure drops without breaking, we show here that a pressure-induced fluid flow, in and near the nanopore, provides an additional force to control the motion of the molecule through the pore. This pressure-derived force, combined with the voltage bias, enables solid-state nanopores to detect and characterize very short molecules, and near-neutral molecules. For uniformly charged polymers like DNA, the pressure-derived force can be countered by the voltage-derived force to slow the molecule motion without reducing the ionic current signal. Modest pressures applied to a voltage-biased nanopore greatly extend their utility as single molecule detectors by enabling neutral molecule capture and detection, as well as control of molecule translocation speeds through the pore. We demonstrate nearly an order-of-magnitude improvement in length discrimination. This broader range of detectable molecule sizes, charge states, and spatial conformations considerably expands the applicability of nanopore detection technologies.