4.5 Article

Sizing DNA using a nanometer-diameter pore

Journal

BIOPHYSICAL JOURNAL
Volume 87, Issue 4, Pages 2905-2911

Publisher

CELL PRESS
DOI: 10.1529/biophysj.104.041814

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Funding

  1. NCRR NIH HHS [2 P41 RR05969, P41 RR005969] Funding Source: Medline
  2. NIA NIH HHS [K02 AG021626] Funding Source: Medline

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Each species from bacteria to human has a distinct genetic fingerprint. Therefore, a mechanism that detects a single molecule of DNA represents the ultimate analytical tool. As a first step in the development of such a tool, we have explored using a nanometer-diameter pore, sputtered in a nanometer-thick inorganic membrane with a tightly focused electron beam, as a transducer that detects single molecules of DNA and produces an electrical signature of the structure. When an electric field is applied across the membrane, a DNA molecule immersed in electrolyte is attracted to the pore, blocks the current through it, and eventually translocates across the membrane as verified unequivocally by gel electrophoresis. The relationship between DNA translocation and blocking current has been established through molecular dynamics simulations. By measuring the duration and magnitude of the blocking current transient, we can discriminate single-stranded from double-stranded DNA and resolve the length of the polymer.

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