上海交通大学肖泽宇等研究人员合作发现，自堆叠小分子可用于超灵敏的无底物拉曼成像。该研究于2024年8月21日在线发表于国际一流学术期刊《自然—生物技术》。

研究人员报告了一组具有bis-thienyl-substituted benzobisthiadiazole结构的小分子，这些小分子通过自堆叠而非外部基材来增强拉曼信号。在该方法中，称为堆叠诱导电荷转移增强拉曼散射（SICTERS），自堆叠的小分子形成了有序的空间排列，使相邻分子之间能够进行三维电荷转移。

SICTERS纳米探针的拉曼散射截面比具有相似粒径的传统SERS金纳米探针高1350倍。SICTERS在体内成像灵敏度、分辨率和深度方面优于表面增强拉曼散射（SERS）。SICTERS能够进行非侵入性血液和淋巴管的拉曼成像，这是SERS尚未实现的。SICTERS代表了一种增强拉曼散射的替代技术，为设计超灵敏的无基质拉曼成像探针提供了指导。

据介绍，拉曼光谱学使用SERS纳米探针是一种超灵敏且高精度的体内成像技术。然而，由于用于增强拉曼信号的金属基材存在生物安全性问题，SERS纳米探针的临床转化受到了阻碍。

附：英文原文

Title: Self-stacked small molecules for ultrasensitive, substrate-free Raman imaging in vivo

Author: Gao, Shuai, Zhang, Yongming, Cui, Kai, Zhang, Sihang, Qiu, Yuanyuan, Liao, Yunhui, Wang, Haoze, Yu, Sheng, Ma, Liyang, Chen, Hongzhuan, Ji, Minbiao, Fang, Xiaohong, Lu, Wei, Xiao, Zeyu

Issue&Volume: 2024-08-21

Abstract: Raman spectroscopy using surface-enhanced Raman scattering (SERS) nanoprobes represents an ultrasensitive and high-precision technique for in vivo imaging. Clinical translation of SERS nanoprobes has been hampered by biosafety concerns about the metal substrates used to enhance Raman signals. We report a set of small molecules with bis-thienyl-substituted benzobisthiadiazole structures that enhance Raman signal through self-stacking rather than external substrates. In our technique, called stacking-induced charge transfer-enhanced Raman scattering (SICTERS), the self-stacked small molecules form an ordered spatial arrangement that enables three-dimensional charge transfer between neighboring molecules. The Raman scattering cross-section of SICTERS nanoprobes is 1350 times higher than that of conventional SERS gold nanoprobes of similar particle size. SICTERS outperforms SERS in terms of in vivo imaging sensitivity, resolution and depth. SICTERS is capable of noninvasive Raman imaging of blood and lymphatic vasculatures, which has not been achieved by SERS. SICTERS represents an alternative technique to enhance Raman scattering for guiding the design of ultrasensitive substrate-free Raman imaging probes.

DOI: 10.1038/s41587-024-02342-9

Source: https://www.nature.com/articles/s41587-024-02342-9