Next‐Generation Nanopore Sensors Based on Conductive Pulse Sensing for Enhanced Detection of Nanoparticles

Abstract Nanopore sensing has been successfully used to characterize biological molecules with single‐molecule resolution based on the resistive pulse sensing approach. However, its use in nanoparticle characterization has been constrained by the need to tailor the nanopore aperture size to the size of the analyte, precluding the analysis of heterogeneous samples. Additionally, nanopore sensors often require the use of high salt concentrations to improve the signal‐to‐noise ratio, which further limits their ability to study a wide range of nanoparticles that are unstable at high ionic strength. Here, a new paradigm in nanopore research that takes advantage of a polymer electrolyte system to comprise a conductive pulse sensing approach is presented. A finite element model is developed to explain the conductive pulse signals observed and compare these results with experiments. This system enables the analytical characterization of heterogeneous nanoparticle mixtures at low ionic strength . Furthermore, the wide applicability of the method is demonstrated by characterizing metallic nanospheres of varied sizes, plasmonic nanostars with various degrees of branching, and protein‐based spherical nucleic acids with different oligonucleotide loadings. This system will complement the toolbox of nanomaterials characterization techniques to enable real‐time optimization workflow for engineering a wide range of nanomaterials.