Quantitative detection of various molecules at very low concentrations in complex mixtures has been the main objective in many fields of science and engineering, from the detection of cancer-causing mutagens and early disease markers to environmental pollutants and bioterror agents^1,2,3,4,5. Moreover, technologies that can detect these analytes without external labels or modifications are extremely valuable and often preferred⁶. In this regard, surface-enhanced Raman spectroscopy can detect molecular species in complex mixtures on the basis only of their intrinsic and unique vibrational signatures⁷. However, the development of surface-enhanced Raman spectroscopy for this purpose has been challenging so far because of uncontrollable signal heterogeneity and poor reproducibility at low analyte concentrations⁸. Here, as a proof of concept, we show that, using digital (nano)colloid-enhanced Raman spectroscopy, reproducible quantification of a broad range of target molecules at very low concentrations can be routinely achieved with single-molecule counting, limited only by the Poisson noise of the measurement process. As metallic colloidal nanoparticles that enhance these vibrational signatures, including hydroxylamine–reduced-silver colloids, can be fabricated at large scale under routine conditions, we anticipate that digital (nano)colloid-enhanced Raman spectroscopy will become the technology of choice for the reliable and ultrasensitive detection of various analytes, including those of great importance for human health.

对复杂混合物中极低浓度的各种分子进行定量检测一直是许多科学和工程领域的主要目标，从检测致癌诱变剂和早期疾病标记物到环境污染物和生物恐怖剂^{1,2,3,4 ,5} .此外，无需外部标记或修改即可检测这些分析物的技术非常有价值，并且通常是首选⁶。在这方面，表面增强拉曼光谱可以仅根据其固有且独特的振动特征来检测复杂混合物中的分子种类⁷。然而，迄今为止，由于信号异质性不可控以及低分析物浓度下的重现性差，为此目的开发表面增强拉曼光谱一直具有挑战性⁸。在这里，作为概念证明，我们表明，使用数字（纳米）胶体增强拉曼光谱，可以通过单分子计数常规地实现对极低浓度的各种目标分子的可重复定量，仅受测量过程的泊松噪声。由于增强这些振动特征的金属胶体纳米颗粒（包括羟胺还原银胶体）可以在常规条件下大规模制造，我们预计数字（纳米）胶体增强拉曼光谱将成为可靠和可靠的技术的首选技术。对各种分析物进行超灵敏检测，包括对人类健康非常重要的分析物。