1536-1241 (c) 2016 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See http://www.ieee.org/publications_standards/publications/rights/index.html for more information. This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI 10.1109/TNB.2016.2596243, IEEE Transactions on NanoBioscience 1 Investigation into the Effects of Nucleotide Content on the Electrical Characteristics of DNA Plasmid Molecular Wires Noah Goshi + , Alaleh Narenji + , Chris Bui, John Mokili ++ , Sam Kassegne +,1 + MEMS Research Lab, Department of Mechanical Engineering, +++ Adjunct Assistant Research Professor, Department of Biology, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182, USA. Abstract: In this study, we investigate the effect of nucleotide content on the conductivity of plasmid length DNA molecular wires covalently bound to high aspect-ratio gold electrodes. The DNA wires were all between 2.20-2.35μm in length (>6000bp), and contained either 39%, 53%, or 64% GC base-pairs. We compared the current-voltage (I-V) and frequency-impedance characteristics of the DNA wires with varying GC content, and observed statistically significantly higher conductivity in DNA wires containing higher GC content in both AC and DC measurement methods. Additionally, we noted that the conductivity decreased as a function of time for all DNA wires, with the impedance at 100Hz nearly doubling over a period of seven days. All readings were taken in humidity and temperature controlled environments on DNA wires suspended above an insulative substrate, thus minimizing the effect of experimental and environmental factors as well as potential for nonlinear alternate DNA confirmations. While other groups have studied the effect of GC content on the conductivity of nano-scale DNA molecules (<50bp), we were able to demonstrate that nucleotide content can affect the conductivity of micron length DNA wires at scales that may be required during the fabrication of DNA-based electronics. Furthermore, our results provide further evidence that many of the charge transfer theories developed from experiments using nano-scale DNA molecules may still be applicable for DNA wires at the micro-scale. 1. Introduction Over the past several decades, research into DNA conductivity and charge transfer mechanism has attracted significant multidisciplinary interest due to potential applications in micro- and nano-scale electronic devices [1-3] and insights into oxidative damage and repair in DNA [4]. While a number of contradictory experimental results have been reported indicating conductive [5-6], semi-conductive [7-8], insulative [9-10], and super-conductive [11] behavior of DNA, as of late, there has been an increasing amount of evidence supporting a semi-conductive behavior [12-21]. Furthermore, while there is still debate over the exact mechanism of charge transport in DNA [22], two predominate charge transport (CT) theories have emerged, coherent tunneling (a single-step transfer between donor and acceptor [23,24]) and incoherent charge hopping (a series of hopping steps, in which the charge becomes localized between each step [3,24]). For longer DNA strands (greater than a few base-pairs), the charge hopping mechanism is expected to dominate over the coherent tunneling due to its weaker dependence on distance between donor and acceptor molecules [23]. In coherent tunneling mechanism, the charge (electron or hole) is transported across a bridge (DNA), in which all the highest-energy LUMOs (lowest unoccupied molecular orbits) are 1 Address correspondence to Sam Kassegne • Professor of Mechanical Engineering, MEMS Research Lab, Department of Mechanical Engineering, College of Engineering, San Diego State University, 5500 Campanile Drive, CA 92182-1323. E-mail: kassegne@mail.sdsu.edu • Tel: (619) 594-1815.