The continued discovery of new RNA modalities (non-coding, micro, enhancer,..) has resulted in an increased desire for detecting, sequencing, and identifying RNA segments for a variety of applications in food safety, water, and environmental protection, plant and animal pathology, clinical diagnosis and research, and bio-security. We have recently demonstrated that molecular conformation profoundly influences the conductance of nucleic acids and that RNA can support long-range charge transport in specific sequences.<br/><br/>In this work, we measure RNA:DNA hybrids from a pathogenic strain from E.Coli. We show that single-molecule conductance techniques can be used to extract biologically relevant information from short RNA oligonucleotides and that these measurements are sensitive to aM target concentrations, are capable of being multiplexed, and can detect targets of interest in the presence of other, possibly interfering RNA sequences. We also demonstrate that the charge transport properties of RNA:DNA hybrids are sensitive to single-nucleotide polymorphisms, thus enabling differentiation between specific serotypes of Escherichia coli. Using a combination of spectroscopic and computational approaches, we determine that the conductance sensitivity primarily arises from changes the mutations have on the conformational structure of the molecules, rather than the direct chemical substitutions (Figure 1). This work is the first molecular conductance study of a biologically relevant sequence and opens new possibilities for developing electrically-based sensor and diagnostic platforms.

Using single-molecule RNA: DNA electrical conductance measurements for ultra-sensitive pathogen detection

2019 Fall National Meeting

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