Improved Conductance Blockage Modeling of Cylindrical Nanopores, from 2D to Thick Membranes

The ionic current blockage from a nanopore sensor is a fundamental metric for characterizing its dimensions and identifying molecules translocating through it. Yet, most analytical models predicting the conductance of a nanopore in both open and obstructed states remain inaccurate. Here, using an oblate spheroidal coordinate framework to study the electrical response of nanopore access regions, we reveal that the widely used model from Kowalczyk et al. significantly overestimates access region contributions when blocked by a cylindrical object, like DNA. To address this, we present an improved analytical model for the obstructed access resistance, which we establish as highly accurate through finite-element simulations, especially for ultrathin membranes and long narrow channels. Equipped with an improved nanopore conductance model, this work provides tools for more accurate calculation of the pore size and for the expected blockade from DNA, of high practical value for many biosensing applications.