Quantitative Analysis of Factors Affecting the Event Rate in Glass Nanopore Sensors

While the solid-state nanopore sensors have shown exceptional promise with their single-molecule sensitivity and label-free operations, one of the most significant challenges in the nanopore sensor is the limited analyte translocation event rate that leads to prolonged sensor response time. This issue is more pronounced when the analyte concentration is below the nanomolar (nM) range, owing to the diffusion-limited mass transport. In this work, we systematically studied the experimental factors beyond the intrinsic analyte concentration and electrophoretic mobility that affect the event rate in glass nanopore sensors. We developed a quantitative model to capture the impact of nanopore surface charge density, ionic strength, nanopore geometry, and translocation direction on the event rate. The synergistic effects of these factors on the event rates were investigated with the aim to find the optimized experimental conditions for operating the glass nanopore sensor from the response time standpoint. The findings in the study would provide useful and practical insight to enhance the device response time and achieve a lower detection limit for various glass nanopore-sensing experiments.