<i>Colloquium</i>: Physical approaches to DNA sequencing and detection

TLDR

Genome‑based medicine now relies on rapid, cost‑effective sequencing, and physical approaches using nanochannels or nanopores offer a promising alternative to conventional chemical and optical methods for single‑nucleotide interrogation. The study aims to develop a revolutionary sequencing method that enables cost‑effective, rapid interrogation of individual genomes. This colloquium reviews the physics underlying nanochannel and nanopore DNA detection, evaluates their advantages and drawbacks, and outlines future research directions.

Abstract

With the continued improvement of sequencing technologies, the prospect of genome-based medicine is now at the forefront of scientific research. To realize this potential, however, a revolutionary sequencing method is needed for the cost-effective and rapid interrogation of individual genomes. This capability is likely to be provided by a physical approach to probing DNA at the single-nucleotide level. This is in sharp contrast to current techniques and instruments that probe (through chemical elongation, electrophoresis, and optical detection) length differences and terminating bases of strands of DNA. Several physical approaches to DNA detection have the potential to deliver fast and low-cost sequencing. Central to these approaches is the concept of nanochannels or nanopores, which allow for the spatial confinement of DNA molecules. In addition to their possible impact in medicine and biology, the methods offer ideal test beds to study open scientific issues and challenges in the relatively unexplored area at the interface between solids, liquids, and biomolecules at the nanometer length scale. This Colloquium emphasizes the physics behind these methods and ideas, critically describes their advantages and drawbacks, and discusses future research opportunities in the field.