Next-Generation Nanopore Sensors for Enhanced Detection of Nanoparticles

ABSTRACT Nanopore sensing is a technique based on the Coulter principle to analyze and characterize nanoscale materials with single entity resolution. 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 heterogenous 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, we report the development of nanopore sensors enhanced by a polymer electrolyte system, enabling the analysis of heterogenous nanoparticle mixtures at low ionic strength. We present a finite element model to explain the anomalous conductive/resistive pulse signals observed and compare these results with experiments. Furthermore, we demonstrate the wide applicability of the method by characterizing metallic nanospheres of varied sizes, plasmonic nanostars with various degrees of branching, and protein-based spherical nucleic acids with different oligonucleotide loadings. Our system will complement the toolbox of nanomaterials characterization techniques and will enable real-time optimization workflow for engineering a wide range of nanomaterials.