Angular-Inertia Regulated Stable and Nanoscale Sensing of Single Molecules Using Nanopore-In-A-Tube.

Nanopore is commonly used for high-resolution, label-free sensing, and analysis of single molecules. However, controlling the speed and trajectory of molecular translocation in nanopores remains challenging, hampering sensing accuracy. Here, the study proposes a nanopore-in-a-tube (NIAT) device that enables decoupling of the current signal detection from molecular translocation and provides precise angular inertia-kinetic translocation of single molecules through a nanopore, thus ensuring stable signal readout with high signal-to-noise ratio (SNR). Specifically, the funnel-shaped silicon nanopore, fabricated at a 10-nm resolution, is placed into a centrifugal tube. A light-induced photovoltaic effect is utilized to achieve a counter-balanced state of electrokinetic effects in the nanopore. By controlling the inertial angle and centrifugation speed, the angular inertial force is harnessed effectively for regulating the translocation process with high precision. Consequently, the speed and trajectory of the molecules are able to be adjusted in and around the nanopore, enabling controllable and high SNR current signals. Numerical simulation reveals the decisive role of inertial angle in achieving uniform translocation trajectories and enhancing analyte-nanopore interactions. The performance of the device is validated by discriminating rigid Au nanoparticles with a 1.6-nm size difference and differentiating a 1.3-nm size difference and subtle stiffness variations in flexible polyethylene glycol molecules.