(222b) Tunneling Spectroscopy for Sequence and Structural Label Determination in Single DNA and RNA Molecules
- Conference: AIChE Annual Meeting
- Year: 2019
- Proceeding: 2019 AIChE Annual Meeting
- Group: Topical Conference: Chemical Engineers in Medicine
- Time: Monday, November 11, 2019 - 3:51pm-4:12pm
Using tunneling spectroscopy measurements, we probed the molecular orbitals of chemically distinct nucleobases within DNA and RNA macromolecules immobilized with restricted conformational freedom on a chemically-modified surface. From these measurements, theoretical models for quantum tunneling were combined with transition voltage spectroscopy to obtain twelve biophysical parameters unique to the nucleotides within the electronic tunneling junction. The twelve parameters serve as a comprehensive molecular fingerprint for the nucleotides, facilitating their discrimination and identification of structure-dependent chemical labels through machine learning. We show a high accuracy for both nucleotide discrimination (>99.8%) and chemical label identification (>98%) with a relatively modest molecular coverage (35 repeat measurements).
These results have significant implications for the development of robust and accurate high-throughput nanoelectronic DNA and RNA sequencing techniques. Additionally for RNA, we have shown the potential for simultaneous sequencing and structural mapping of single unknown RNA molecules, paving the way for probing the sequence-structure-function relationship within the transcriptome at an unprecedented level of detail.
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