Super‐Resolution Detection of DNA Nanostructures Using a Nanopore

Abstract 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.