Autonomous molecular sensing with a chemically stateful solid-state nanopore: Toward next-generation single-molecule sensors capable of distinguishing between DNA bases and amino acids

2026/07/31

An international collaborative research team led by Associate Professor Makusu Tsutsui and Professor Tomoji Kawai of the Institute of Scientific and Industrial Research at the University of Osaka; Dr. Ryuichiro Abe, Specially Appointed Associate Professor (Full-time) at Research Institute for Microbial Diseases at the University of Osaka; Professor Hirofumi Daiguji of the Graduate School of Engineering at the University of Tokyo and Associate Professor Wei-Lun Hsu (at the time of the study) of the Graduate School of Engineering at the University of Tokyo; Dr. Kazumichi Yokota, Principal Researcher of the National Institute of Advanced Industrial Science and Technology (AIST); and Dr. Denis Garoli of the Italian Institute of Technology (IIT), has developed a new single-molecule sensor technology that uses solid nanopores—which change their state through chemical reactions—to identify DNA base molecules and amino acids one by one (Figure 1).

 

A nanopore is a tiny hole on the nanometer scale (1 nanometer is one-billionth of a meter). By passing molecules through this hole, the type and properties of the molecules can be determined from changes in ionic current. Since there is no need to label molecules with reagents and they can be observed directly in real time, applications in DNA analysis, protein analysis, and medical diagnostics are advancing.
In this study, the researchers utilized the mechanism by which solid nanopores repeatedly undergo precipitation and dissolution. The pores do not remain fully open; instead, they briefly form a small passageway from a closed state and then close again immediately. When a molecule passes through during this brief opening, the amplitude, width, and interval of the current signal vary slightly for each molecule. The research team used machine learning to analyze these current waveforms and successfully identified four types of DNA base molecules and seven types of amino acids.
These research findings were published online in the journal ACS Nano, published by the American Chemical Society, on Thursday, July 30, 2026, at 11:00 PM (Japan Standard Time).

 

fig1 Figure 1. Conceptual diagram of a solid-state nanopore sensor that opens and closes automatically

 

 

Papers

Journal: ACS Nano
Title: Autonomous molecular sensing with a chemically stateful solid-state nanopore
Authors: Makusu Tsutsui, Yuki Komoto, Kazumichi Yokota, Wei-Lun Hsu, Denis Garoli, Ali Douaki, Germán Lanzavecchia, Ryuichiro Abe, Hirofumi Daiguji, Tomoji Kawai

DOI: 10.1021/acsnano.6c08258