Sub‐10 nm Silicon‐Based Pyramidal Nanopore Enabling High Performance Single Protein Molecule Detection

ABSTRACT Solid‐state nanopores are pivotal for next‐generation single‐protein detection, yet reconciling high fabrication efficiency, precision, and signal quality remains challenging. In this study, we integrate pyramidal silicon nanopores—valued for electric field focusing and high capture efficiency—with a silicon dioxide (SiO 2 ) layer designed to minimize nonspecific protein adsorption. This strategy aims to balance rapid translocation rates with clear blockade signals. Furthermore, we have developed a large‐scale fabrication method capable of producing uniformly arranged silicon‐based pyramidal nanopores with diameters below 10 nm. This technique combines wet etching, real‐time ionic current monitoring, and thermal oxidation, enabling precise size control down to 7 nm. We evaluated 7 nm, 12 nm, and 14 nm nanopores for detecting α‐synuclein (α‐syn), immunoglobulin G (IgG), and ferritin (FTN), respectively. All nanopore sizes achieved efficient target detection, yielding resolvable blockade signals alongside high capture rates and fast translocation speeds. Notably, α‐syn detection demonstrated improved overall performance in terms of event rate, signal quality, and blockade signal resolution, with similarly effective results observed for IgG and FTN. These results demonstrate the strong potential of this nanopore platform for protein detection.