ABSTRACT

The research on nanopores, especially on solid-state nanopores, emerged and was promoted by the upsurge of genetic analysis around the world. Since the chain-termination method proposed by Sanger et al. in 1977 [1] first provided a feasible way to detect nucleic acid sequences, the DNA sequencing technologies have followed suit, and the development rate has equaled and now even outpaces Moore’s law [2]. These DNA sequencing technologies provided an opportunity for finding genomic information to prevent, diagnose, and cure human diseases, and it led medical research and medical care to a new era. However, the sequencing cost was huge (~$10 million) by traditional Sanger sequencing technology due to the enormous amount (~3 billion base pairs) of DNA found in human genomes, which made it made it unfeasible for DNA sequencing to be a part of routine medical practice. In 2008, the cyclic-array sequencing technology (including wash-and-scan, PCR, and termination processes) took the first leap in the DNA sequencing field. The second-generation DNA sequencers (e.g., 454 Genome Sequencers, Illumina, HelioScope, and SOLiD) have gradually replaced the first-generation ones and reduced more than three-fold the cost in sequencing 1 megabase. More details about the second-generation sequencing technologies can be found in previous reviews.