基于逆向空间偏移拉曼光谱分析技术的无损药物检测方法研究

发展新型药物检测技术不仅能够杜绝假药对健康和生命的危害，更可以避免假药对社会道德和商业风气等产生不良影响。该研究工作，通过建立逆向空间偏移拉曼光谱（SORS）实验装置，克服了传统拉曼探测深度有限（约几百微米）的应用瓶颈，以无损、非接触的方式，克服不/半透明容器光学背景对光谱测量结果产生的影响，实现多种空间偏移量（Δs）条件下，样品特征光谱信息检测与分析，为开发基于逆向SORS技术的新型药物检测方法奠定实验基础。实验装置搭建过程中，采用785 nm半导体激光器与WITec UHTS300型拉曼光谱仪构建逆向SORS光谱分析装置。通过使用准直光束照射锥透镜形成环形激发光斑，并控制锥透镜与样品之间的距离，实现Δs连续可控变化。利用所搭建的光谱检测装置，分别测量聚乙烯方瓶（厚度为1.5 mm）和聚四氟乙烯离心管（厚度为4 mm）内对乙酰氨基酚和甲硝唑的拉曼特征光谱。利用环形光束照射会抑制容器峰强度这一特点，选取容器拉曼特征峰作为标准峰，分别对点光斑（Spot）和环形（Ring）光斑测量结果进行归一化处理，并将其强度相减（Ring-Spot），得到逆向SORS光谱测量结果。实验结果表明，逆向SORS光谱检测方法能够克服表层容器光学背景对测量结果产生的干扰性因素，真实反映不/半透明容器内样品的分子指纹光谱信息。在实验测量范围内，当环形光束半径增大1倍时，聚乙烯方瓶内对乙酰氨基酚拉曼特征峰强度增大6倍，而聚四氟乙烯离心管内的甲硝唑各特征峰强度增强1倍。以上实验结果表明，逆向SORS技术能够准确检测不/半透明容器内，或有漫散射介质覆盖的样品深层化学成分的指纹光谱。通过提高系统信噪比并优化系统结构与功能，在建立小型化、集成化检测系统的条件下，逆向SORS技术可与现有的多种药物检测技术相互补充，发展成一种快捷、准确、操作简便的新型药物检测手段。

Study on a Non-Destructive Drug Testing Method Based on Spatially Offset Raman Spectroscopy

The identification of counterfeit medicines has been a serious problem confronted by the contemporary world, particularly for the developing countries. Thus, anti-counterfeit innovations can help find solutions on avoiding the hazards to health and lives, as well as for the harmful effects on social morality and commercial culture. In this work, a modular Inverse Spatially Offset Raman Spectroscopy (Inverse SORS) system was built for overcoming the limitations of traditional Raman spectroscopy whose detection depth is confined to a few hundred micrometers. Besides, it can also effectively avoid the background of the container for realizing the detection and analysis of deep chemical components in a non-destructive and non-intrusive way by using different spatially offset values (Δs), which will lay the foundation for a simple and efficient method for direct detection of drugs. A 785 nm diode laser and WITec UHTS300 Raman spectrometer were employed to construct Inverse SORS system. During the experiments, a collimated beam passed through an axicon lens to form a ring beam, and its radius was adjusted by controlling the distance between the cone lens and sample. The Raman spectra of paracetamol and metronidazole in polyethylene（PE）bottles (with a 1.5 mm thickness) and polytetrafluoroelene （PTFE） centrifuge tubes (with a 4 mm thickness) were respectively measured by using a built-in spectral detection device. One of the container’s Raman peaks was selected as the reference peak for normalizing and processing acquired results. The featured Raman spectra of drugs were obtained by a scaled subtraction of the two spectra (Ring-Spot). The experimental results showed that the Inverse SORS not only avoided the optical background from the opaque container, but also truly presented the molecular fingerprint information of the sample inside. When the radius of the ring beam doubled its size, the intensity of acquired paracetamol spectra increased by six times, whereas the characteristics of Raman peaks of metronidazole in the PTFE tube increased by 100%. The above results showed that the inverse SORS can accurately detect the fingerprint spectrum of the chemical components inside the opaque/translucent container. Moreover, by optimizing system performance and adopting a variety of data processing methods, inverse SORS technology, which is expected to be a fast, accurate and convenient detection method, will be an indispensable complement to the existing pharmaceutical analysis technologies.