Abstract

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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