Controlling the Conformation of Double-Stranded DNA during Translocation through a Glass Nanocapillary

Abstract

Nanopores have emerged as powerful single-molecule sensors, enabling the detection of analytes in a simple system purely based on the modulation of an ion current. Nanopore diameters of roughly 15 nanometres offer advantages in terms of fabrication, a higher frequency of translocation and reduced non-specific interaction with the pore wall. They also permit non-linear conformations of double-stranded DNA during translocation, such as a single fold which wraps a section of the strand back onto itself. We demonstrate that such folding can be controlled through the salt concentration of the measurement solution. The share of unfolded, linear translocations increases from below 50% to above 90% as the electrolyte concentration is reduced. Further measurements suggest this is due to electro-osmotic outflow from the pore set up by the charged nanochannel walls, which creates a barrier to entry for high-drag DNA conformations. The ability to control conformations is critical for sensing techniques which rely on unfolded, linear translocations to read information from the strand, such as DNA-carrier based protein sensing. In addition, the results show that nanofluidic flows through nanopores can be used to study polymer dynamics in fluid flow on the single-molecule level.