Super‐Resolution Detection of DNA Nanostructures Using a Nanopore

High‐resolution analysis of biomolecules has brought unprecedented insights into fundamental biological processes and dramatically advanced biosensing. Notwithstanding the ongoing resolution revolution in electron microscopy and optical imaging, only a few methods are presently available for high‐resolution analysis of unlabeled single molecules in their native states. Here, label‐free electrical sensing of structured single molecules with a spatial resolution down to single‐digit nanometers is demonstrated. Using a narrow solid‐state nanopore, the passage of a series of nanostructures attached to a freely translocating DNA molecule is detected, resolving individual nanostructures placed as close as 6 nm apart and with a surface‐to‐surface gap distance of only 2 nm. Such super‐resolution ability is attributed to the nanostructure‐induced enhancement of the electric field at the tip of the nanopore. This work demonstrates a general approach to improving the resolution of single‐molecule nanopore sensing and presents a critical advance towards label‐free, high‐resolution DNA sequence mapping, and digital information storage independent of molecular motors. Glass nanopores with 3–4 nm diameters demonstrate super‐resolution single‐molecule sensing capability, which can be used to detect DNA nanostructures separated only by 18 bp (≈6 nm). The super‐resolution is attributed to the electric field enhancement at the nanopore tip and the slowdown of the DNA, with great potential for label‐free, high‐resolution DNA sequence mapping and digital information storage.