Solid‐State Quad‐Nanopore Array for High‐Resolution Single‐Molecule Analysis and Discrimination

• Published in: Advanced materials (Weinheim) 2023-06, Vol.35 (24), p.e2211399-n/a
• Main Authors: Hu, Rui, Zhu, Rui, Wei, Guanghao, Wang, Zhan, Gu, Zhi‐Yuan, Wanunu, Meni, Zhao, Qing
• Format: Article
• Language: English
• Subjects: Analytical chemistry; Arrays; Biomolecules; biosensors; DNA - chemistry; Dwell time; Electric fields; finite‐element simulations; Materials science; Metals; Nanopores; Nanotechnology; Sensitivity enhancement; Serum albumin; Single Molecule Imaging - methods; single‐molecule detection; solid‐state nanopores; Temporal resolution
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202211399

The ability to detect and distinguish biomolecules at the single‐molecule level is at the forefront of today's biomedicine and analytical chemistry research. Increasing the dwell time of individual biomolecules in the sensing spot can greatly enhance the sensitivity of single‐molecule methods. This is particularly important in solid‐state nanopore sensing, where the detection of small molecules is often limited by the transit dwell time and insufficient temporal resolution. Here, a quad‐nanopore is introduced, a square array of four nanopores (with a space interval of 30–50 nm) to improve the detection sensitivity through electric field manipulation in the access region. It is shown that dwell times of short DNA strands (200 bp) are prolonged in quad‐nanopores as compared to single nanopores of the same diameter. The dependence of dwell times on the quad‐pore spacing is investigated and it is found that the “retarding effect” increases with decreasing space intervals. Furthermore, ultra‐short DNA (50 bp) detection is demonstrated using a 10 nm diameter quad‐nanopore array, which is hardly detected by a single nanopore. Finally, the general utility of quad‐nanopores has been verified by successful discrimination of two kinds of small molecules, metal‐organic cage and bovine serum albumin (BSA). Quad‐nanopore arrays are demonstrated to improve the sensitivity of solid‐state nanopore‐based sensing. The four closely arranged nanopores finely made by helium ion microscope alter the electric field distribution in the access region of the solid‐state nanopores, creating regions that have a “retarding effect” for a single charged molecule, as proved by experiments and simulations.