Advances and Challenges in Solid-State Nanopores for DNA Sequencing.

Abstract

Solid-state nanopore sensing, a state-of-the-art technology for single-molecule detection, has rapidly advanced in recent years and demonstrates significant potential in DNA sequencing. This technology determines the nucleotide sequences by analyzing the electrical or optical signal variations that occur when DNA molecules pass through the nanopore. It offers notable advantages, including high-throughput, single-molecule detection, real-time monitoring, and the elimination of the need for polymerase chain reaction (PCR) amplification, thereby presenting broad application prospects in areas such as the diagnosis and treatment of genetic diseases. This paper reviews the solid-state nanopore DNA sequencing technology by discussing advancements in nanopore types, preparation techniques, and sequencing detection methods. It examines various nanopore materials, including silicon-based materials and two-dimensional (2D) materials, as well as preparation techniques such as transmission electron microscopy (TEM), focused ion beam (FIB) etching, and controlled breakdown (CBD). Additionally, it elucidates sequencing detection mechanisms, including ion-current blockade, transverse-current detection, and optical detection. However, this technology faces numerous challenges in its implementation and future commercialization. For instance, limited spatial resolution hampers single-base identification; the rapid translocation speed of DNA impacts time resolution; and various types of noise significantly disrupt detection signals. In response, researchers have proposed several solutions, including local thinning of the film, adjustment of surface charges, and optimization of detection materials and structures. With interdisciplinary integration and technological innovation, solid-state nanopore DNA sequencing technology is expected to make breakthroughs, bringing transformations to life sciences research and medical diagnosis.