Tip-Enhanced Raman Imaging of Single-Stranded DNA with Single Base Resolution

Zhe He, Zehua Han, Megan Kizer, Robert J. Linhardt, Xing Wang, Alexander M. Sinyukov, Jizhou Wang, Volker Deckert, Alexei V. Sokolov, Jonathan Hu, Marlan O. Scully

Research output: Contribution to journalArticlepeer-review


Tip-enhanced Raman scattering (TERS) is a promising optical and analytical technique for chemical imaging and sensing at single molecule resolution. In particular, TERS signals generated by a gap-mode configuration where a silver tip is coupled with a gold substrate can resolve a single-stranded DNA (ssDNA) molecule with a spatial resolution below 1 nm. To demonstrate the proof of subnanometer resolution, we show direct nucleic acid sequencing using TERS of a phage ssDNA (M13mp18). M13mp18 provides a known sequence and, through our deposition strategy, can be stretched (uncoiled) and attached to the substrate by its phosphate groups, while exposing its nucleobases to the tip. After deposition, we scan the silver tip along the ssDNA and collect TERS signals with a step of 0.5 nm, comparable to the bond length between two adjacent DNA bases. By demonstrating the real-time profiling of a ssDNA configuration and furthermore, with unique TERS signals of monomeric units of other biopolymers, we anticipate that this technique can be extended to the high-resolution imaging of various nanostructures as well as the direct sequencing of other important biopolymers including RNA, polysaccharides, and polypeptides.

Original languageEnglish (US)
Pages (from-to)753-757
Number of pages5
JournalJournal of the American Chemical Society
Issue number2
StatePublished - Jan 16 2019
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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