Nanopore-based sensing devices and applications to genome sequencing: a brief history and the missing pieces

A nanopore on an impermeable membrane, which separates two chambers containing electrolytic solution, can be used as a nanometre-sized Coulter counter for single-molecule biological sensing. With an applied potential, charged molecules are electrically dragged through the pore, and the analytical information is sequentially read out from the current blockades. Nucleic acid, which is an electrically charged polymer, is an ideal analyte for nanopore analysis and nanopore sequencing. With the advantages of high-speed, label-free and single-molecule resolution, a nanopore sequencer is considered to be the most promising candidate for the third-generation DNA sequencing. In this review, a brief history of nanopore sequencing to date is summarized and discussed along with future prospects. Although successfully demonstrated for known viral genome sequences, the nanopore sequencing technique still requires missing pieces like improved accuracy, automation and throughput for clinical diagnosis-level applications.