Seeing, Counting, Identifying, and Distinguishing Single Molecules from Their Mixtures via Raman Spectroscopy.

Hong, Li Hong; Zhang, Jian Zhi; Gao, Zi Han; Yang, Jie; Yang, Hai Yao; Liu, Jun Ming; Li, Zhi-Yuan · Nano Lett · 2025

basic_science · Level V

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Abstract

Seeing, counting, identifying, and distinguishing molecules one by one in their mixture phases is recognized as a big challenge in molecular science. Here we employ this using a single-molecule surface-enhanced Raman spectroscopy (SM-SERS) strategy combining giant electromagnetic enhancement (EME) from plasmonic nanogaps and giant chemical enhancement (CME) from monolayer WS<sub>2</sub>. For a dilute mixture of rhodamine B (RhB), rhodamine 6G (R6G), and crystal violet (CV) at concentrations of as low as 10<sup>-16</sup> M, this SM-SERS substrate enables the sighting, counting, identification, and distinction of individual molecules. High-credibility results are achieved rapidly (50 ms acquisition) using 785 nm near-infrared laser excitation to record and analyze distinct Raman spectra. This EME-CME synergy SM-SERS strategy offers a powerful capability of optically probing and monitoring the spatial-temporal evolution of the physical, chemical, and biological properties of molecules, which would open up a new frontier of molecular science.