多孔材料毛细管采样及直接质谱分析方法研究

Development of simple, fast and highly sensitive analytical methods for biofluid is important for disease diagnosis and treatment. Biofluids such as blood and urine contain different kinds of drugs, metabolites, lipids, amino acids, peptides, and protein that are of significantly difference in chemical and biological properties. In order to realize fast and sensitive analysis of drugs and bioactive compounds, in this project, we propose to develop a novel thin layer porous material, that can be used to modify sampling capillary for direct mass spectrometry analysis of biofluids. A thin layer of porous material composed of metal organic frameworks and porous organic polymer will be coated onto the inner wall of a glass capillary. This thin layer serves as a selective carrier for drugs or other analyte molecules. Previously developed slug flow method will be further developed to facilitate a simple but effective means of enrichment using the capillary. The whole process of sample pretreatment and electrospray ionization are performed using a single sampling capillary, which could simplify the analysis process significantly. Finally, this proposed method will be applied for fast and sensitive analysis of anticancer drugs and lipids in small volumes of biofluid samples.

生物体液的简单、快速、高灵敏度分析对疾病诊疗具有重要意义。血液、尿液等生物体液中含有各种化学及生物物质，如药物、代谢物、脂类、氨基酸、多肽及蛋白质等，常被作为生物医学分析的标记物，其分子量、化学／生物性质及浓度相差迥异。为实现生物体液中药物及内源物质生物活性分析的有效质谱分析，在本课题中，我们提出发展薄层多孔材料，并用于修饰采样毛细管，进行快速直接质谱分析的新技术。将多孔材料（包括有机骨架材料、多孔有机聚合物）引入毛细管内作为体液样品中药物及具有生物活性物质的高选择性载体，结合前期建立的活塞流微萃取技术的快速物质交换能力，实现这些目标分子的快速、选择性富集。样品预处理过程与离子化均在毛细管内进行，可大大简化分析过程。在此基础上，发展基于薄层多孔材料修饰毛细管的快速富集的直接质谱分析新技术，应用于微量血液等生物体液中抗癌药物和脂类等的快速、高灵敏分析。

生物样品的简单、快速、高灵敏度分析对疾病诊疗具有重要意义。血液、尿液等样品中含有各种化学及生物物质，如药物、代谢物、脂类、氨基酸、多肽及蛋白质等，常被作为生物医学分析的标记物，其分子量、化学／生物性质及浓度相差迥异。为实现生物体液中药物及内源物质生物活性分析的有效质谱分析，在本课题中，我们发展了多孔功能材料修饰的采样探针，用于快速直接质谱分析。将多孔材料修饰于毛细管内或基板上作为生物样品中药物及脂质分子具有生物活性物质的高选择性载体，促进了这些目标分子的快速、选择性富集。发展了聚合物涂覆转移富集、活塞流微萃取、直接微采样等方法，大大简化了生物医学样品的前处理过程。在此基础上，发展了一系列直接质谱分析方法，应用于生物医学样品中药物和脂质等的快速、高灵敏分析。