Brownian Motion Paving the Way for Molecular Translocation in Nanopores

Tracing fast nanopore‐translocating analytes requires a high‐frequency measurement system that warrants a temporal resolution better than 1 µs. This constraint may practically shift the challenge from increasing the sampling bandwidth to dealing with the rapidly growing noise with frequencies typically above 10 kHz, potentially making it still uncertain if all translocation events are unambiguously captured. Here, a numerical simulation model is presented as an alternative to discern translocation events with different experimental settings including pore dimension, bias voltage, the charge state of the analyte, salt concentration, and electrolyte viscosity. The model allows for simultaneous analysis of forces exerting on a large analyte cohort along their individual trajectories; these forces are responsible for the analyte movement leading eventually to the nanopore translocation. Through tracing the analyte trajectories, the Brownian force is found to dominate the analyte movement in electrolytes until the last moment at which the electroosmotic force determines the final translocation act. The mean dwell time of analytes mimicking streptavidin decreases from ≈6 to ≈1 µs with increasing the bias voltage from ±100 to ±500 mV. The simulated translocation events qualitatively agree with the experimental data with streptavidin. The simulation model is also helpful for the design of new solid‐state nanopore sensors. The study investigates the translocation dynamics based on COMSOL Multiphysics mimicking the actual experiment configurations. A key development of the model is the consideration of Brownian motion in addition to the already established electroosmotic and electrophoretic forces. The results are expected to be useful not only for the analysis of experimental results but also for the design of new solid‐state nanopore sensors.