posted on 2024-03-04, 17:24authored byArjav Shah, Shakul Pathak, Kun Li, Slaven Garaj, Martin Z. Bazant, Ankur Gupta, Patrick S. Doyle
Nanopore-based sensing platforms have transformed single-molecule
detection and analysis. The foundation of nanopore translocation experiments
lies in conductance measurements, yet existing models, which are largely
phenomenological, are inaccurate in critical experimental conditions
such as thin and tightly fitting pores. Of the two components of the
conductance blockade, channel and access resistance, the access resistance
is poorly modeled. We present a comprehensive investigation of the
access resistance and associated conductance blockade in thin nanopore
membranes. By combining a first-principles approach, multiscale modeling,
and experimental validation, we propose a unified theoretical modeling
framework. The analytical model derived as a result surpasses current
approaches across a broad parameter range. Beyond advancing our theoretical
understanding, our framework’s versatility enables analyte
size inference and predictive insights into conductance blockade behavior.
Our results will facilitate the design and optimization of nanopore
devices for diverse applications, including nanopore base calling
and data storage.