Effects of off-axis translocation through nanopores on the determination of shape and volume estimates for individual particles.

Resistive pulses generated by nanoparticles that translocate through a nanopore contain multi-parametric information about the physical properties of those particles. For example, non-spherical particles sample several different orientations during translocation, producing fluctuations in blockade current that relate to their shape. Due to the heterogenous distribution of electric field from the center to the wall of a nanopore while a particle travels through the pore, its radial position influences the blockade current, thereby affecting the quantification of parameters related to the particle's characteristics. Here, we investigate the influence of these off-axis effects on parameters estimated by performing finite element simulations of dielectric particles transiting a cylindrical nanopore. We varied the size, ellipsoidal shape, and radial position of individual particles, as well as the size of the nanopore. As expected, nanoparticles translocating near the nanopore wall produce increase current blockades, resulting in overestimates of particle volume. We demonstrated that off-axis effects also influence estimates of shape determined from resistive pulse analyses, sometimes producing a multiple-fold deviation in ellipsoidal length-to-diameter ratio between estimates and reference values. By using a nanopore with the minimum possible diameter that still allows the particle to rotate while translocating, off-axis effects on the determination of both volume and shape can be minimized. In addition, tethering the nanoparticles to a fluid coating on the nanopore wall makes it possible to determine an accurate particle shape with an overestimated volume. This work provides a framework to select optimal ratios of nanopore to nanoparticle size for experiments targeting free translocations.