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Open AccessArticle

Single Molecule Bioelectronics and Their Application to Amplification-Free Measurement of DNA Lengths

1
Department of Physics and Astronomy, University of California at Irvine, Irvine, CA 92697, USA
2
Department of Physics, Polatlı Faculty of Science and Arts, Gazi University, Polatlı 06900, Turkey
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Department of Chemistry, University of California at Irvine, Irvine, CA 92697, USA
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Department of Physics, North Dakota State University, Fargo, ND 58108, USA
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Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Prabir Patra
Biosensors 2016, 6(3), 29; https://doi.org/10.3390/bios6030029
Received: 3 May 2016 / Revised: 8 June 2016 / Accepted: 15 June 2016 / Published: 24 June 2016
(This article belongs to the Special Issue Graphene and Carbon Nanotube Based Biosensors)
As biosensing devices shrink smaller and smaller, they approach a scale in which single molecule electronic sensing becomes possible. Here, we review the operation of single-enzyme transistors made using single-walled carbon nanotubes. These novel hybrid devices transduce the motions and catalytic activity of a single protein into an electronic signal for real-time monitoring of the protein’s activity. Analysis of these electronic signals reveals new insights into enzyme function and proves the electronic technique to be complementary to other single-molecule methods based on fluorescence. As one example of the nanocircuit technique, we have studied the Klenow Fragment (KF) of DNA polymerase I as it catalytically processes single-stranded DNA templates. The fidelity of DNA polymerases makes them a key component in many DNA sequencing techniques, and here we demonstrate that KF nanocircuits readily resolve DNA polymerization with single-base sensitivity. Consequently, template lengths can be directly counted from electronic recordings of KF’s base-by-base activity. After measuring as few as 20 copies, the template length can be determined with <1 base pair resolution, and different template lengths can be identified and enumerated in solutions containing template mixtures. View Full-Text
Keywords: DNA polymerase; carbon nanotube sensors; single molecule enzymology; DNA sequencing DNA polymerase; carbon nanotube sensors; single molecule enzymology; DNA sequencing
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MDPI and ACS Style

Gül, O.T.; Pugliese, K.M.; Choi, Y.; Sims, P.C.; Pan, D.; Rajapakse, A.J.; Weiss, G.A.; Collins, P.G. Single Molecule Bioelectronics and Their Application to Amplification-Free Measurement of DNA Lengths. Biosensors 2016, 6, 29.

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