Promoting single-file DNA translocations through nanopores using electro-osmotic flow.

Double-stranded DNA translocates through sufficiently large nanopores either in a linear single-file fashion or in a folded hairpin conformation when captured somewhere along its length. We show that the folding state of DNA can be controlled by changing the electrolyte concentration, pH, and polyethylene glycol content of the measurement buffer. At pH 8 in 1M LiCl or 0.35M KCl, single-file translocations make up more than 90% of the total. We attribute the effect to the onset of electro-osmotic flow from the pore at low ionic strength. Our hypothesis on the critical role of flows is supported by the preferred orientation of entry of a strand that has been folded into a multi-helix structure at one end. Control over DNA folding is critical for nanopore sensing approaches that use modifications along a DNA strand and the associated secondary current drops to encode information.