__NOTOC__ A nanopore is a small hole in an electrically insulating membrane, that can be used as a single-molecule detector. It may be considered a Coulter counter for much smaller particles. It can be a biological protein channel in a high electrical resistance lipid bilayer or a pore in a solid-state membrane. The detection principle is based on monitoring the ionic current of an electrolyte solution passing through the nanopore as a voltage is applied across the membrane. When the nanopore is of molecular dimensions, passage of molecules (e.g., DNA) cause interruptions of the "open" current level, leading to a "translocation event" signal. The passage of RNA or single-stranded DNA molecules through the membrane-embedded alpha-hemolysin channel (1.5 nm diameter), for example, causes a ~90% blockage of the current (measured at 1 M KCl solution) . The observation that a passing strand of RNA containing different bases results in different blocking levels has led to the nanopore sequencing hypothesis. Such sequencing, if successful, could revolutionize the field of genomics, as sequencing would be simplified and have the potential for dramatic improvements in power and cost over current versions that use fluorescence/luminescence and optical instrumentation to detect this photon signal. Apart from rapid DNA sequencing, other applications include separation of single stranded and double stranded DNA in solution, and the determination of length of polymers. At this stage, nanopores are making contributions to the understanding of polymer biophysics, as well as to single-molecule analysis of DNA-protein interactions.
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