Single-molecule surface enhanced Raman spectroscopy (SERS) is a sensitive technique for detecting low concentrations of adsorbed analytes on plasmonic nanosurfaces. Here, we observe that scavenging dissolved oxygen can further increase its sensitivity 10⁹–10¹⁰ times, enabling real single-molecule detection—in other words, detecting 1 molecule in 300–500 μL aqueous solution. Experimental evidence and computational modeling support propagation of the plasmonic field throughout the entire sample volume, which enables analyte detection outside the instrument field of view. The application of readily available and inexpensive oxygen scavengers enables ultra-high analytical sensitivity using affordable instrumentation, greatly facilitating single-molecule-level research in both well-equipped and resource-limited laboratories. Furthermore, the discovery may bring fresh insights into the fundamental understanding of SERS and plasmonic field transmission in aqueous solutions.

单分子表面增强拉曼光谱（SERS）是用于检测等离子体纳米表面上低浓度吸附分析物的灵敏技术。在这里，我们观察到清除溶解氧可以进一步提高其灵敏度10 ⁹ –10 ¹⁰可以进行真正的单分子检测，即检测300–500μL水溶液中的1个分子。实验证据和计算模型支持了等离子场在整个样品体积中的传播，这使得能够在仪器视野之外检测分析物。易于使用且价格便宜的除氧剂的应用使用负担得起的仪器实现了超高的分析灵敏度，极大地促进了装备精良和资源有限的实验室中单分子水平的研究。此外，该发现可能为水溶液中SERS和等离子场传输的基本理解带来新的见解。