High-Resolution and Low-Noise Single-Molecule Sensing with Bio-Inspired Solid-State Nanopores

J Phys Chem Lett. 2024 May 23;15(20):5556-5563. doi: 10.1021/acs.jpclett.4c00615. Epub 2024 May 16.

Abstract

Solid-state nanopores have been extensively explored as single-molecule sensors, bearing the potential for the sequencing of DNA. Although they offer advantages in terms of high mechanical robustness, tunable geometry, and compatibility with existing semiconductor fabrication techniques in comparison with their biological counterparts, efforts to sequence DNA with these nanopores have been hampered by insufficient spatial resolution and high noise in the measured ionic current signal. Here we show that these limitations can be overcome by the use of solid-state nanopores featuring a thin, narrow constriction as the sensing region, inspired by biological protein nanopores that have achieved notable success in DNA sequencing. Our extensive molecular dynamics simulations show that these bio-inspired nanopores can provide high spatial resolution equivalent to 2D material nanopores and, meanwhile, significantly inhibit noise levels. A theoretical model is also provided to assess the performance of the bio-inspired nanopore, which could guide its design and optimization.

MeSH terms

  • DNA / chemistry
  • Molecular Dynamics Simulation*
  • Nanopores*
  • Sequence Analysis, DNA / methods

Substances

  • DNA