Nanopore sensing and beyond: Electrochemical systems for optically-coupled single-entity studies, stimulus-responsive gating applications, and point-of-care sensors

Nanopores play essential roles in biological processes, such as ion channels and pumps in cellular membranes, and in technological applications such as DNA sequencing. Advancements in nanofabrication techniques have enabled the routine integration of nanopores into solid-state devices, resulting in a plethora of analytical applications. This review explores recent developments in nanopore-enabled electrochemical systems, which have transcended traditional resistive pulse sensing to offer novel capabilities in single-entity studies, stimulus-responsive gating, and point-of-care diagnostics. We highlight recent studies on the design and utility of nanopore electrode arrays, which serve as nanocontainers capable of isolating and analyzing single entities, and extend the discussion to hierarchically organized, stimulus-responsive systems that regulate species transport across nanopores, enriching analytes for ultrasensitive detection. In addition, we review the utilization of probe-assisted nanopore sensing, demonstrating its efficacy in selectively binding and detecting target molecules and ions. Finally, we outline future directions for nanopore-based systems to enhance robustness, achieve high-throughput analysis, and incorporate artificial intelligence for materials design and data analysis, promising transformative impacts on diagnostics and biological research.