A Quantitative Framework for Asymmetric Nanoparticle Translocation Through Conical Nanopores

ABSTRACT Although confined transport plays a pivotal role in high‐resolution sensing, the physical origin of direction‐dependent translocation through asymmetric nanopores remains poorly quantified. Here, we demonstrate that asymmetric free‐energy barriers and electro‐osmotic flow (EOF) distributions at two entrances of a conical nanopore fundamentally govern nanoparticle translocation dynamics. Precisely engineered conical nanopores with asymmetric three‐dimensional geometries are fabricated by focused ion beam with single‐nanometer precision and space‐programmable ion dose. We demonstrate that such structural asymmetry induces pronounced dependence in nanoparticle translocation. Specifically, negatively charged nanoparticles translocating from the base (large‐size entrance) to the tip (small‐size entrance) exhibit substantially higher translocation flux and velocity than those moving in the reverse direction. These asymmetric transport behaviors originate from the synergistic effects of unequal energy barriers and heterogeneous EOF distributions. Combining experiments, simulations, and theoretical analysis, we quantitatively resolve the directional differences in energy barriers and EOF at both nanopore entrances. These findings establish a quantitative framework for understanding asymmetric confined translocation and provide guiding principles for rational design in nanofluidic systems for high‐resolution sensing, molecular analysis, and nanofluidic manipulation.