Tip-enhanced Raman imaging of single-stranded DNA with single base resolution

He, Zhe
Han, Zehua
Kizer, Megan
Linhardt, Robert J.
Wang, Xing
Sinyukov, Alexander M.
Wang, Jizhou
Deckert, Volker
Sokolov, Alexei V.
Hu, Jonathan
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Full Citation
Tip-enhanced Raman imaging of single-stranded DNA with single base resolution, Z. He, Z. Han, M. Kizer, R. Linhardt, X. Wang, A. Sinyukov, J. Wang, V. Deckert, A. Sokolov, J. Hu, M. Scully, Journal of the American Chemical Society, 141, 753−757, 2019.
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.
Journal of the American Chemical Society, 141, 753−757
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Journal of the American Chemical Society