Super-Resolution Detection of DNA Nanostructures Using a Nanopore

Kaikai Chen, Adnan Choudhary, Sarah E. Sandler, Christopher Maffeo, Caterina Ducati, Aleksei Aksimentiev, and Ulrich F. Keyser
Advanced Materials 2207434 (2023)
DOI:  BibTex

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 unlabelled single molecules in their native states. Here, we demonstrate label-free electrical sensing of structured single molecules with a spatial resolution down to single-digit nanometres. Using a narrow solid-state nanopore, we detect the passage of a series of nanostructures attached to a freely translocating DNA molecule, resolving individual nanostructures placed as close as 6 nm apart and with a surface-to-surface gap distance of only 2 nm. We attribute such super-resolution ability to the nanostructure-induced enhancement of the electric field at the tip of the nanopore. Our 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.