基于擦拭型SERS纸芯片的中药材染色快速检测体系构建

In recent years, Chinese Herbal Medicine (CHM) is always illegally adulterated with dyes, which seriously endangered the medication safety and affected the CHM industry as well. After comprehensively analyzing the advantages and disadvantages of existing detection techniques such as microfluidic paper-based analytical devices (μPADs) and surface enhanced Raman spectroscopy (SERS), based on our fundamental and preliminary research, we propose a new type of wiping-paper SERS chip in conjunction with chemometrics methods to establish a rapid detection system for dyed CHM. Wiper sampling can simplify the cumbersome and time-consuming preparation and purification of medicinal materials. The chip prefabricated with directional separation and concentration channel can further decrease the complexity of the dyes mixture and soluble CHM matrix free of driving force, whilst the Au@SiO2 nanoparticle preprocess can present the paper-based chip with sensitivity and specificity of SERS detection. After sampling of dye-adulterated CHM with the μPADs, the in situ SERS spectra can be directly collected on the chip, or if necessary, point-by-point SERS spectra can be recorded along the channel of the chip after directional separation and concentration. The SERS spectra obtained by the two modes can then be investigated with several chemometrics algorithms including model-free analysis, independent component analysis, 2 dimensional correlation analysis and consensus strategy, etc., whose results will support each other and further improve the discrimination accuracy. After newly developing a SERS spectral library of more than 40 common dyes on the μPADs, multiple dyes’ detection based on only one SERS spectrum can be realized without accompanying references in the application, resulting in ease of practical operation and high efficiency of determination. We hope to build a Sensitive, Specific, Steady and Speedy (4S) detection system for dyed CHM, aiming to provide a promising technical support to curb the alarming phenomenon.

近年来中药材染色掺假事件时有发生，严重危害用药安全，影响中药产业的健康发展。本课题在分析现有纸芯片、表面增强拉曼光谱（SERS）等检测技术及课题组前期研究基础上，创新设计研究通道型SERS纸芯片与化学计量学方法相结合的中药材染色快速检测体系：其中纸芯片擦拭采样简化了染色药材制样-采样过程，芯片通道可实现混合染料与药材溶出基质的定向分离-富集，Au@SiO2等纳米颗粒预胶化可以提高纸芯片上检测的灵敏度和特异性。染色药材经擦拭后可直接采集原位SERS与分离-富集后的逐点SERS，两种方式获得的光谱分别开展无模型、独立组分、二维相关分析等算法和共识策略研究，软件计算结果相互印证，可进一步提高检测准确度。新建40余种常见染料纸芯片上SERS光谱库，实际应用中无需随行对照，即可实现简便、高效的检测。本课题拟构建的中药材染色快速检测体系灵敏、专属、稳健、快捷，有望为遏制此类现象提供一种新的支撑技术。

项目主要开展了纸芯片SERS的设计制备及表征、染色中药材原位擦拭-SERS检测方法、常见40种染料SERS光谱建库、基于功能化纸芯片的定向分离-逐点SERS检测、二维相关等多种化学计量学算法等研究，检测方法网络化实现并试运行。项目组发表了8篇SCI论文（其中6篇为第一标注、2篇为第二标注）、申请了5项专利（其中4项已授权、1项在实质审查）。本项目的成果集结后，形成“我国药品拉曼光谱新型快检体系构建与推广”，申报了2018年中国药学会科学技术奖并获得三等奖。本项目建立起来的中药材染色快速检测体系，实际应用中无需随行对照，即可实现简便、高效的检测，有望为遏制中药材染色掺假现象提供一种新的灵敏、专属、稳健、快捷的支撑技术。