Novel Approaches in Low‐Cost, High‐Throughput Gene Sequencing

Abstract

Whole‐genome DNA sequencing is evolving from a costly collective effort, requiring the work of several laboratories in parallel, to a single‐user, single‐device laboratory tool. This technological revolution will open the realm of personal medicine where treatment of diseases are adjusted to suit the genetic background of an individual. Such a breakthrough in genetics can only be achieved through the advent of high‐throughput and affordable sequencing methods — some of which are detailed in this article. Several particularly novel DNA sequencing concepts have been proposed to reach the $1000‐per‐genome goal. Cost reduction is envisioned by the use of massively parallel processes, where sequence information is obtained by detecting single DNA molecules or colonies of DNA strands amplified from single molecules. Other methods are based on the direct sequential readout of the genetic code on a single DNA strand, but the detection schemes currently lack the required single‐nucleotide resolution. The article concludes by describing a nanotechnology‐based method for DNA sequencing at high throughput that couples a novel scheme for electrophoresis together with near‐field optical detection of separated bands at a sensitivity level down to a few molecules. With further development, the technology can evolve into a low‐cost sequencing scheme similar to the reliable and accurate four‐color DNA Sanger sequencing method.