A Solid-state Sub-nm Pore for Single-mer Resolution Sequencing

TL;DR

This paper presents a novel solid-state nanopore with sub-nanometer resolution capable of directly sequencing individual DNA bases and amino acids with high accuracy, stability, and reusability.

Contribution

Introduction of an oxidized pyramidal sub-nm pore (OPSP) that enables direct, high-accuracy single-mer sequencing without computational correction.

Findings

Achieves sub-1-nm spatial resolution and SNR up to 15.

Raw read accuracies exceed 98.5% for DNA and 95.5% for peptides.

Demonstrates durability and stability over six months.

Abstract

Nanopore sequencing accuracy is inherently limited by the quality of data from individual molecular translocation events, requiring advances beyond traditional sequencing-by-synthesis methods. We introduce an oxidized pyramidal sub-nm pore (OPSP) integrated in a threeterminal sensing platform, where the sub-nm silicon pore functions as an electrode for detecting displacement currents across an oxide barrier, induced by counter-ion migration within the electric double layer. This platform achieves sub-1-nm-scale spatial resolution and a signal-tonoise ratio (SNR) up to 15 for biopolymer sequencing, enabling direct identification of individual bases in single-stranded DNA and single amino acids in peptides, with raw-read accuracies exceeding 98.5% and 95.5%, respectively, without consensus-based computational correction. The OPSP demonstrates high acid tolerance, reusability in varied chemical environments, and operational stability for over six months. This work establishes OPSP as a durable, high-accuracy platform for single-mer resolution sequencing, defining a reliable and robust paradigm for next-generation sequencing technologies.