基于MALDI-MS技术的新基质大黄酸在代谢组学研究中的应用

Rhein: a novel matrix for profiling and imaging of endogenous metabolites by matrix-assisted laser desorption/ionization-mass spectrometry

基质辅助激光解析电离质谱(MALDI-MS)是一项快速、高通量检测未知物质的新兴技术。然而,该技术对代谢物的检测分析往往被复杂的基质峰所干扰,限制了其在代谢组学领域的应用。研究发现,大黄酸能作为一种MALDI新基质用于阳离子模式下代谢物的检测。首先运用大黄酸分析了生理学浓度下多种强、弱碱性代谢物的标准品,结果表明与传统基质比较,大黄酸能获得基本无基质峰干扰的质谱图。进一步将大黄酸运用于生物样本的分析,选取小鼠内容物作为模型样本,显示该基质可用于复杂生物样本的代谢组分析。最后考察大黄酸的MALDI质谱成像能力,表明该基质可成功运用于小鼠肠段切片的代谢组原位成像。研究表明,大黄酸作为一种新型MALDI基质,能可靠、高效地完成基于MALDI-MS的代谢物检测及原位成像分析,对MALDI-MS技术广泛运用于代谢组学研究具有推动作用。

MALDI-MS is an emerging technique that enables rapid profiling of endogenous substances in a high throughput. Nevertheless, its application to metabolite analysis is often hindered by the presence of massive matrix background peaks using conventional matrices. Herein rhein was introduced as a novel matrix for MALDI-MS analysis of cation metabolites. Several strong and weak basic metabolites were measured using rhein. Compared to the previously reported ionless matrix NSA and conventional matrix CHCA, clean MALDI-MS spectra were obtained devoid of matrix signals. Subsequently, we applied this matrix to profile a biologically complex sample, mice intestinal contents. In addition, we have validated the applicability of rhein to MALDI-MS imaging, which allows for simultaneous mapping of hundreds of metabolites from single mouse ileum section. In summary, the discovery of rhein as a novel MALDI matrix enables efficient and reliable profiling and imaging of endogenous metabolites from biological samples with no matrix interferences, which will greatly promote the utility of MALDI- MS-based platform for metabolome studies.