新型杂化贵金属代谢质谱芯片材料研制及体外诊断应用

具有杂化缝隙结构和表面化学的质谱芯片材料能够根据缝隙与小分子代谢物尺寸匹配效应，结合表面化学识别作用，选择富集检测临床样本中的小分子代谢组及代谢标志物。现有杂化贵金属代谢质谱芯片的种类较少，研究往往使用具有特定单一组分缝隙结构贵金属材料进行质谱分析，在临床体外诊断应用中极为受限。本项目面向小分子代谢组学与体外诊断，研制杂化贵金属代谢质谱芯片，即由多种贵金属材料复合、具有功能化表面的芯片材料耦合激光解吸电离飞行时间质谱分析，具有广阔的科学意义与应用前景，主要包含以下三方面内容：一）制备一系列具有新型杂化组分、结构形貌的芯片材料，考察尺寸匹配效应和等离激元效应，研究其作为质谱芯片的性能；二）实现质谱芯片材料表面功能化与优化，研究功能化质谱芯片材料在特定小分子代谢物低浓度定量检测中的应用；三）应用质谱芯片方法鉴定临床样本体系（干血片、尿液等）的小分子代谢组，筛查分析新的疾病代谢标志物及组合。

Metabolomic mass spectrometry chip materials enjoy hybrid crevice structures and surface chemistry, which may selectively enrich and detect small metabolites from clinical specimens. Notably, there are only limited hybrid noble metal chip materials and most of current research relies on single noble metal material for in vitro diagnostics (IVD). In this project, we propose to construct efficient hybrid noble metal chip materials with new alloy structures and surface aptamer probes for applications in metabolomics and IVD. The project contains three major aspects including: (I) preparation of a series of novel chip materials with multiple compositions, structures, and morphologies for designed size-exclusive and plasmonic effects in mass spectrometry analysis; (II) functionalization and optimization of chip surface for low-concentrated small metabolites in quantification experiments; (III) application in clinical specimens such as dried blood spot and urine samples for identification of metabolomic biomarker panels and diagnosis of metabolic diseases.