  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 into the access resistance
and associated conductance blockade in thin nanopore membranes. By combining a
first-principles approach, multi-scale 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 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.
