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Characterization of individual polynucleotide molecules using a membrane channel

John J. KasianowiczBiotechnology Division, National Institute of Science and Technology, 222/A353, Gaithersburg, MD 20899; Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138; and Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064Eric BrandinBiotechnology Division, National Institute of Science and Technology, 222/A353, Gaithersburg, MD 20899; Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138; and Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064Daniel BrantonBiotechnology Division, National Institute of Science and Technology, 222/A353, Gaithersburg, MD 20899; Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138; and Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064David W. DeamerBiotechnology Division, National Institute of Science and Technology, 222/A353, Gaithersburg, MD 20899; Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138; and Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064
1996en
ABI

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We show that an electric field can drive single-stranded RNA and DNA molecules through a 2.6-nm diameter ion channel in a lipid bilayer membrane. Because the channel diameter can accommodate only a single strand of RNA or DNA, each polymer traverses the membrane as an extended chain that partially blocks the channel. The passage of each molecule is detected as a transient decrease of ionic current whose duration is proportional to polymer length. Channel blockades can therefore be used to measure polynucleotide length. With further improvements, the method could in principle provide direct, high-speed detection of the sequence of bases in single molecules of DNA or RNA.

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