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Molecules 2016, 21(3), 346; doi:10.3390/molecules21030346

Nanopore Event-Transduction Signal Stabilization for Wide pH Range under Extreme Chaotrope Conditions

1
Department of Biology, Connecticut College, Box #5564, 270 Mohegan Ave., New London, CT 06320, USA
2
Department of Computer Science, Connecticut College, Box #5564, 270 Mohegan Ave., New London, CT 06320, USA
3
Meta Logos Inc., 124 White Birch Dr., Guilford, CT 06437, USA
4
Department of Pathology and Anatomical Sciences, College of Medicine, University of Missouri, 1 Hospital Dr., Columbia, MO 65202, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Peter Willett
Received: 10 February 2016 / Revised: 2 March 2016 / Accepted: 2 March 2016 / Published: 14 March 2016
(This article belongs to the Special Issue Chemoinformatics)
View Full-Text   |   Download PDF [3290 KB, uploaded 17 March 2016]   |  

Abstract

Operation of an α-hemolysin nanopore transduction detector is found to be surprisingly robust over a critical range of pH (6–9), including physiological pH = 7.4 and polymerase chain reaction (PCR) pH = 8.4, and extreme chaotrope concentration, including 5 M urea. The engineered transducer molecule that is captured in the standard α-hemolysin nanopore detector, to transform it into a transduction detector, appears to play a central role in this stabilization process by stabilizing the channel against gating during its capture. This enables the nanopore transduction detector to operate as a single molecule “nanoscope” in a wide range of conditions, where tracking on molecular state is possible in a variety of different environmental conditions. In the case of streptavidin biosensing, results are shown for detector operation when in the presence of extreme (5 M) urea concentration. Complications involving degenerate states are encountered at higher chaotrope concentrations, but since the degeneracy is only of order two, this is easily absorbed into the classification task as in prior work. This allows useful detector operation over a wide range of conditions relevant to biochemistry, biomedical engineering, and biotechnology. View Full-Text
Keywords: channel current cheminformatics; nanopore detector; single-molecule biophysics; stationary signal analysis; biosensor channel current cheminformatics; nanopore detector; single-molecule biophysics; stationary signal analysis; biosensor
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Winters-Hilt, S.; Stoyanov, A. Nanopore Event-Transduction Signal Stabilization for Wide pH Range under Extreme Chaotrope Conditions. Molecules 2016, 21, 346.

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