近日，上海交通大学生物医学工程学院的叶坚及其研究团队取得一项新进展。经过不懈努力，他们对通过单分子计数的数字胶体增强拉曼光谱进行研究。相关研究成果已于2024年4月17日在国际权威学术期刊《自然》上发表。

作为概念验证，该研究团队表明，通过运用数字（纳米）胶体增强拉曼光谱技术，能够在极低浓度下实现广泛目标分子的可重复量化，这主要依赖于单分子计数，且其精度仅受限于测量过程中的泊松噪声。由于金属胶体纳米粒子，如羟胺还原银胶体，能有效增强这些振动特征，且这些纳米粒子可在常规条件下大规模制造，研究人员预计数字（纳米）胶体增强拉曼光谱将成为一种可靠且超灵敏的检测技术，尤其适用于各种分析物的检测，包括对人类健康至关重要的分析物。

据悉，众多科学和工程领域长期致力于实现一个主要目标：在复杂混合物中以极低浓度对各种分子进行定量检测，从致癌诱变剂和早期疾病标志物，到环境污染物和生物恐怖剂。其中，无需借助外部标签或修饰即可实现分析物检测的技术尤为宝贵，通常也是首选。在这方面，表面增强拉曼光谱因其能够依据分子固有的独特振动特征，有效检测复杂混合物中的分子种类而备受关注。然而，由于低分析物浓度下信号异质性的不可控以及再现性的不足，表面增强拉曼光谱的进一步发展一直充满挑战。

附：英文原文

Title: Digital colloid-enhanced Raman spectroscopy by single-molecule counting

Author: Bi, Xinyuan, Czajkowsky, Daniel M., Shao, Zhifeng, Ye, Jian

Issue&Volume: 2024-04-17

Abstract: 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. Moreover, technologies that can detect these analytes without external labels or modifications are extremely valuable and often preferred. In this regard, surface-enhanced Raman spectroscopy can detect molecular species in complex mixtures on the basis only of their intrinsic and unique vibrational signatures. 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 concentrations. 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.

DOI: 10.1038/s41586-024-07218-1

Source: https://www.nature.com/articles/s41586-024-07218-1