Open AccessArticle
Single Molecule Bioelectronics and Their Application to Amplification-Free Measurement of DNA Lengths
by
O. Tolga Gül 1,2,†, Kaitlin M. Pugliese 3,†, Yongki Choi 1,4,†, Patrick C. Sims 1, Deng Pan 1, Arith J. Rajapakse 1, Gregory A. Weiss 3,5,* and Philip G. Collins 1,*
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
3
Department of Chemistry, University of California at Irvine, Irvine, CA 92697, USA
4
Department of Physics, North Dakota State University, Fargo, ND 58108, USA
5
Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697, USA
†
These authors contributed equally to this work.
Cited by 14 | Viewed by 7956
Abstract
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
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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.
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