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Tip-enhanced Raman scattering (TERS) is a promising optical and analytical technique. TERS signals generated by a gap-mode configuration where a tip is coupled with a gold substrate can resolve DNA and RNA molecules at a single-molecule resolution. Through our deposition procedure, the molecules can be stretched, uncoiled, and attached to the substrate by its phosphate groups while exposing its nucleobases to the tip. The proof-of-principle RNA sequencing approach significantly advances a direct RNA sequencing technique without RNA labeling or amplification via reverse transcriptase RT-PCR. The demonstrated technique holds promise for next-generation DNA and RNA sequencing.
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Jonathan Hu, Zhe He, Alexei Sokolov, Xing Wang, Marlan Scully, "Resolving the sequence of DNA and RNA strands by tip-enhanced Raman spectroscopy," Proc. SPIE PC12005, Smart Photonic and Optoelectronic Integrated Circuits 2022, PC1200503 (5 March 2022); https://doi.org/10.1117/12.2610375