Rapid nanopore discrimination between single polynucleotide molecules

We extend these observations and provide evidence that each of several different DNA polymers can be identified by a unique pattern in ‘‘event diagrams,’’ which are plots of translocation duration vs. blockade current for an ensemble of events

A. Meller; L. Nivon; E. Brandin; J. Golovchenko; D. Branton

2002

Scholarcy highlights

  • Departments of *Molecular and Cellular Biology and §Physics, Division of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; †Center for Advanced Biotechnology, Biomedical Engineering, Boston University, Boston, MA 02215; and ‡The Rowland Institute for Science, Cambridge, Contributed by Daniel Branton, November 24, 1999
  • Single-channel recording of the translocation duration and current flow during traversal of individual polynucleotides yielded a unique pattern of events for each of the several polymers tested
  • Statistical data derived from this pattern of events demonstrate that in several cases a nanopore can distinguish between polynucleotides of similar length and composition that differ only in sequence
  • Because an extended molecule of DNA or RNA can occupy, and block, much of an otherwise open aqueous channel, the passage of a single polynucleotide can be monitored by recording the translocation duration and blockade current
  • Studies with RNAs of differing base composition have begun to suggest how nanopores could be used to discriminate between different nucleic acid polymers. We extend these observations and provide evidence that each of several different DNA polymers can be identified by a unique pattern in ‘‘event diagrams,’’ which are plots of translocation duration vs. blockade current for an ensemble of events
  • Each DNA molecule was characterized by the duration of the blockade it produced, tD, and the average blockade current, IB
  • Because the ability to discriminate and characterize unlabeled DNA molecules is a central requirement for high-throughput DNA analysis, it will be important to extend our experimental approach and apply our understanding of translocation through nanopores to the analysis of a broader range of molecules than is examined here

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