Improving the Conductance Blockage Model 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 for sizing and identifying molecules translocating through. Yet, models for precisely predicting the conductance of a nanopore in both an open and a blocked state are lacking, which leads to significant errors in the determination of the expected blockage depth from a given translocating molecule and of the pore diameter and length. Here, using oblate spheroidal coordinates as a framework to study the conductance of a nanopore, we demonstrate that the widely used Kowalczyk et al. model significantly overestimates the contribution from the access region in the presence of a cylindrical obstruction. We present a highly precise analytical model for the blocked conductance of 2D nanopores and extend it to cylindrical pores of varying membrane thicknesses. Using finite element simulations, our results show that errors in the calculation of the conductance blockage are maximal for pores with aspect ratios of d/L≈5, but are minimal for both d/L≫1 and d/L≪1. The model presented is especially precise for ultra-thin membranes, with prediction errors below 3% for all pore sizes tested with a membrane thickness of 0.3 nm. By improving on the conductance model of the nanopore system, more accurate estimates of the expected blockage depth from a translocating molecule and of pore dimensions can be obtained, with great practical value for many biosensing applications.