The ongoing discoveries of RNA modalities (for example, non-coding, micro and enhancer) have resulted in an increased desire for detecting, sequencing and identifying RNA segments for applications in food safety, water and environmental protection, plant and animal pathology, clinical diagnosis and research, and bio-security. Here, we demonstrate that single-molecule conductance techniques can be used to extract biologically relevant information from short RNA oligonucleotides, that these measurements are sensitive to attomolar target concentrations, that they are capable of being multiplexed, and that they 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 the effects that the mutations have on the conformational structure of the molecules, rather than from the direct chemical substitutions. We believe that this approach can be further developed to make an electrically based sensor for diagnostic purposes.

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The authors thank M. Marco, W. Ju and D. Heeney for assistance with the BLASTn databases. This work is supported by the University of California, the Davis RISE program, the National Science Foundation (NSF, CBET-1605338) and the ONR (N00014-16-1-2658). M.P.A. acknowledges support from the NSF under grant nos. 102781 (CHE) and 1231927 (ECCS). E.E.O. acknowledges support from the Turkish Academy of Sciences under TUBA GEBIP grant.

Author information

Author notes

    • Juan M. Artés

    Present address: Chemistry Department, University of Massachusetts Lowell, Lowell, MA, USA


  1. Electrical and Computer Engineering Department, University of California Davis, Davis, CA, USA

    • Yuanhui Li
    • , Juan M. Artés
    • , Mashari Alangari
    •  & Joshua Hihath
  2. Biophysics and Photosynthesis, Vrije Universiteit Amsterdam, Amsterdam, Netherlands

    • Juan M. Artés
  3. Bionanodesign Laboratory, Department of Biomedical Engineering, TOBB University of Economics and Technology, Ankara, Turkey

    • Busra Demir
    • , Sumeyye Gokce
    •  & Ersin Emre Oren
  4. Department of Materials Science & Nanotechnology Engineering, TOBB University of Economics and Technology, Ankara, Turkey

    • Busra Demir
    • , Sumeyye Gokce
    •  & Ersin Emre Oren
  5. Department of Electrical Engineering, University of Washington, Seattle, WA, USA

    • Hashem M. Mohammad
    •  & M. P. Anantram


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J.H., Y.L., E.E.O. and M.P.A. designed the research. Y.L., J.M.A., M.A. and J.H. performed and analysed CD and SMBJ experiments. B.D., S.G. and E.E.O. performed and analysed molecular dynamics simulations and provided a structural interpretation of the experimental data. B.D., E.E.O., H.M.M. and M.P.A. performed and analysed the DFT and transport calculations. Y.L. and J.H. wrote the paper with input from all authors. All authors contributed to revising the manuscript and agreed on its final content.

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The authors declare no competing interests.

Corresponding authors

Correspondence to M. P. Anantram or Ersin Emre Oren or Joshua Hihath.

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