In 1997, Kneipp et al. and Nie and Emory independently reported the first examples of single-molecule detection using surface-enhanced Raman scattering (SERS). These seminal works sparked a surge of interest in SERS, while introducing a new question: how can it be conclusively proven that just one molecule is being probed?
This is a preview of subscription content, access via your institution
Subscribe to Nature+
Get immediate online access to Nature and 55 other Nature journal
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Kneipp, K. et al. Single molecule detection using surface-enhanced Raman scattering (SERS). Phys. Rev. Lett. 78, 1667–1670 (1997).
Nie, S. & Emory, S. R. Probing single molecules and single nanoparticles by surface-enhanced Raman scattering. Science 275, 1102–1106 (1997).
Etchegoin, P. G., Meyer, M. & Le Ru, E. C. Statistics of single molecule SERS signals: is there a Poisson distribution of intensities? Phys. Chem. Chem. Phys. 9, 3006–3010 (2007).
Kudelski, A. & Pettinger, B. SERS on carbon chain segments: monitoring locally surface chemistry. Chem. Phys. Lett. 321, 356–362 (2000).
Le Ru, E. C., Meyer, M. & Etchegoin, P. G. Proof of single-molecule sensitivity in surface enhanced Raman scattering (SERS) by means of a two-analyte technique. J. Phys. Chem. B 110, 1944–1948 (2006).
Dieringer, J. A., Lettan, R. B., Scheidt, K. A. & Van Duyne, R. P. A frequency domain existence proof of single-molecule surface-enhanced Raman spectroscopy. J. Am. Chem. Soc. 129, 16249–16256 (2007).
de Albuquerque, C. D. L., Sobral-Filho, R. G., Poppi, R. J. & Brolo, A. G. Digital protocol for chemical analysis at ultralow concentrations by surface-enhanced Raman scattering. Anal. Chem. 90, 1248–1254 (2018).
Tapio, K. et al. A versatile DNA origami-based plasmonic nanoantenna for label-free single-molecule surface-enhanced Raman spectroscopy. ACS Nano 15, 7065–7077 (2021).
Taylor, R. W. et al. Watching individual molecules flex within lipid membranes using SERS. Sci. Rep. 4, 5940 (2014).
Huang, J.-A. et al. SERS discrimination of single DNA bases in single oligonucleotides by electro-plasmonic trapping. Nat. Commun. 10, 5321 (2019).
G.Q.W. acknowledges support from the Leverhulme Trust, RPG-2020-400.
The authors declare no competing interests.
About this article
Cite this article
Wallace, G.Q., Graham, D. Pushing the limits. Nat Rev Chem 6, 842–843 (2022). https://doi.org/10.1038/s41570-022-00444-z