title: Single Molecule Bioelectronics and Their Application to Amplification-Free Measurement of DNA Lengths.
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 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.
authors.affiliation: Department of Physics and Astronomy, University of California at Irvine, Irvine, CA 92697, USA.|Department of Physics, Polatlı Faculty of Science and Arts, Gazi University, Polatlı 06900, Turkey.
authors.forename: O Tolga
authors.initials: OT
authors.lastname: Gül
authors.affiliation: Department of Chemistry, University of California at Irvine, Irvine, CA 92697, USA.
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Pugliese
authors.affiliation: Department of Physics and Astronomy, University of California at Irvine, Irvine, CA 92697, USA.|Department of Physics, North Dakota State University, Fargo, ND 58108, USA.
authors.forename: Yongki
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Physics and Astronomy, University of California at Irvine, Irvine, CA 92697, USA.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Sims
authors.affiliation: Department of Physics and Astronomy, University of California at Irvine, Irvine, CA 92697, USA.
authors.forename: Deng
authors.initials: D
authors.lastname: Pan
authors.affiliation: Department of Physics and Astronomy, University of California at Irvine, Irvine, CA 92697, USA.
authors.forename: Arith J
authors.initials: AJ
authors.lastname: Rajapakse
authors.affiliation: Department of Chemistry, University of California at Irvine, Irvine, CA 92697, USA. gweiss@uci.edu.|Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697, USA. gweiss@uci.edu.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Weiss
authors.affiliation: Department of Physics and Astronomy, University of California at Irvine, Irvine, CA 92697, USA. collinsp@uci.edu.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Collins
mesh_terms: D015374:Biosensing Techniques; D004247:DNA; D004259:DNA-Directed DNA Polymerase; D036103:Nanotechnology; D037742:Nanotubes, Carbon; D013698:Templates, Genetic; D014173:Transistors, Electronic
chemical_list: D037742:Nanotubes, Carbon; D004247:DNA; D004259:DNA-Directed DNA Polymerase
keywords: DNA polymerase; DNA sequencing; carbon nanotube sensors; single molecule enzymology