Advances in Nanopore Technology for Single-Nucleotide Polymorphism Detection: From Principles to Translational Precision Medicine

Abstract

Single-nucleotide polymorphisms (SNPs) are the most common type of variation in the human genome and crucial biomarkers for assessing susceptibility to disease, response to pharmacological intervention. Conventional methods of SNP detection, including Sanger sequencing, polymerase chain reaction (PCR), and microarray analysis, have been widely used; however, these are limited with regards to throughput, scalability, and point-of-care compatibility. Alternatively, nanopore-based sequencing technologies are new platforms, enabling real-time, label-free analysis at the single-molecule level. This review outlines the recent developments in the application of biological, solid-state, and hybrid nanopores as devices for SNP detection, focusing on their fundamental principles, highlights of notable platforms, and technological developments. Key milestones include advancements in sample preparation and translocation control, signal resolution optimization through geometric pore design and the use of ultrathin membranes, and the development of probe engineering strategies targeting allele-specific discrimination as well as minimizing background noise. These advances aim to improve the accuracy and clinical relevance of nanopore-mediated SNP detection, and the translational significance of precision medicine.