Direction- and Salt-Dependent Ionic Current Signatures for DNA Sensing with Asymmetric Nanopores

Solid-state nanopores are promising tools for single-molecule detection of both DNA and proteins. In this study, we investigated the patterns of ionic current blockades as DNA translocates into or out of the geometric confinement of conically shaped pores across a wide range of salt conditions. We studied how the geometry of a nanopore affects the detected ionic current signal of a translocating DNA molecule over a wide range of salt concentration. The blockade level in the ionic current depends on the translocation direction at a high salt concentration, and at lower salt concentrations we find a nonintuitive ionic current decrease and increase within each single event for the DNA translocations exiting from confinement. We use a recently developed method for synthesizing DNA molecules with multiple position markers, which provides further experimental characterization by matching the position of the DNA in the pore with the observed ionic current signal. Finally, we employ finite element calculations to explain the shapes of the signals observed at all salt concentrations and show that the unexpected current decrease and increase are due to the competing effects of ion concentration polarization and geometric exclusion of ions. Our analysis shows that over a wide range of geometries, voltages, and salt concentrations, we are able to understand the ionic current signals of DNA in asymmetric nanopores, enabling signal optimization in molecular sensing applications.