基于微液流表面采样与组织印记技术的空间分辨前处理平台及其代谢组质谱成像应用研究

项目针对目前质谱成像技术灵敏度低、基质效应高以及定量能力差的问题，将组织印记萃取(Tissue Imprinting)技术与连续液流微液接点(Continuous-Flow Liquid Micro-junction, 简称微液流)表面采样技术联用实现具有空间分辨率的代谢物纯化、富集以及高效解析的前处理平台，再将平台在线联用液相色谱质谱分析实现高灵敏度和定量能力的质谱成像。项目将着重于创新开发组织印记萃取涂层，包括针对低响应低丰度的代谢物的选择性印记涂层，以及具有高萃取容量和代谢物覆盖范围的杂化材料涂层。同时，结合固相萃取领域的定量校正理论实现组织中内源性代谢物的绝对定量。最后，开发的平台将应用于脑组织成像中，更准确的探索更多脑部疾病以及药物治疗研究中的生物标志物。新技术有望使质谱成像技术成为生物研究/医学诊断上更可靠的分析依据。

To solve the current problems of mass spectrometry imaging including low sensitivity, high matrix effect and low quantitation capability, tissue imprinting and continuous-flow liquid micro-junction surface sampling techniques will be combined to realize spatially resolved sample preparation platform for purification, enrichment and desorption of endogenous metabolites in tissue, and then the platform will be coupled with liquid chromatography-mass spectrometry system to realize quantitative mass spectrometry imaging with high sensitivity. Project will be focused on development of novel tissue imprinting coatings, including selective coatings for metabolites with low response and low abundance, and hybrid nanomaterials coating with high extraction capacity and metabolites coverage. Moreover, calibration methods previously proposed for quantitation in solid phase micro-extraction will be used to develop absolute quantitation methods of endogenous metabolites in tissue here. Finally, this method will be applied to metabolomic mass spectrometry imaging of brain tissue, and finding of more biomarkers for pathology and drug therapy of brain diseases. It is expected that the new technique can move mass spectrometry imaging technique forward on the road to be more reliable analytical basis of biological researches or medical diagnosis in the future.