Yuanhui Li1 Juan Artes1 Josh Hihath1

1, University of California, Davis, Davis, California, United States

Oligonucleotides have emerged as extremely important molecules in nanoscience. With their unparalleled programming and self-assembly characteristics, these materials have allowed the development of many precision nanoscale systems. However, the primary importance of these molecules has remained in their biological function. In particular, RNA has recently attracted significant interest for a variety of applications: the sequences found in vivo provide direct information about gene expression, its role in cell regulation has become evident, and the fact that it is naturally amplified inside the cell makes it an ideal target for sensor applications. For all of these reasons it is important to understand the electronic properties of both DNA and RNA duplexes. While the electronic properties of DNA have been the subject of intense research over the last several decades, and incredible progress has been made using photochemical and electrochemical measurements to understand DNA’s charge transfer characteristics, studies into the charge transport properties of RNA have been more limited. Here we report on single-molecule conductance measurements performed on DNA duplexes and RNA:DNA hybrids using the Single-Molecule Break Junction (SMBJ) approach with the goal of creating a measurement platform capable of identifying specific pathogenic serotypes from an electrical conductance measurement of microbial RNA. In moving toward this goal, we will discuss the necessity of controlling the local environment of DNA and RNA in order to obtain reproducible conductance values and understand the inherent charge transport properties. We will explore the role of secondary structure on the charge transport characteristics by controlling this environment, and compare the results with alternative duplexes such as RNA:DNA hybrids. We will also discuss the effects of sequence changes and the roles of A:T, A:U, and G:C base pairs within the stack on the transport characteristics. Finally, we will discuss how understanding charge transport in these systems can be leveraged to develop functional sensor technologies, and demonstrate that single-molecule conductance measurements can be used to identify biologically relevant sequences for specific serotypes of pathogenic species such as E. coli. This work opens new possibilities for electrically-based sensor and diagnostic platforms for food safety, water and environmental protection, plant and animal pathology, clinical diagnosis and research, and bio-security.