基质辅助激光解析离子化质谱（MALDI-MS）由于低样品消耗、高效的分析能力，在生物分子检测中具有不可取代的地位。然而，实际样品中带负电荷、高极性化合物（寡糖、磷酸化肽和核酸分子等）由于缺少质子化位点难以被离子化；在复杂体系中易于被离子化能力强的分子抑制，小分子化合物易被大量使用的基质分子干扰而难以检测。在这项研究中，我们拟开展反应性基质研究，针对含有巯基、寡糖和炔基修饰的核酸分子的检测，在含有基质功能的共轭分子中引入羰基、胺基和叠氮等反应基团，利用羰基-巯基，羰基-胺基和炔-叠氮等基团间选择性反应和形成产物分子高效离子化特点，高灵敏和选择性检测实际样品中目标生物分子。通过系统研究生物样品体系中选择性反应条件和影响因素，及MALDI-MS基质化合物的性质，发展一系列反应性基质，建立基于反应性基质分析生物分子的MALDI-MS检测平台。

Matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) is an indispensable tool for accurate detections of biomolecules due to its advantages of low sample consumption and high measurement efficiency. However, challenges remain for using MALDI-MS to detect the molecules presented in biological samples with much polarity and more negative charges, such as oligosaccharides, phosphopeptides and oligonucleotides etc. Because such molecules are not easily ionized for the absence of protonated sits, and are often suppressed by the molecules that ease to ionization; small molecules are also disturbed by the use of large amount of matrix compounds since their ions appear in close m/z region. To facilitate selective detections of target biomolecules, in this project we will focus on development of reactive matrixes, that is, the designed matrix compounds contain of a reactive functional group (carbonyl, azide); the functional group will react with target molecule based on the reactions of thiol-ene, or alkyne–azide, forming highly ionized complexes for detection. During this study, a series of reactive matrixes will be designed and evaluated, and a MALDI-MS platform that uses reactive matrixes to detect biomolecules will be built, meanwhile, theoretical basis and mechanical respects behind the development of reactive matrixes will be explored. We believe that this study will promote our understanding of reactions and matrixes and uses of MALDI-MS for detection of biomolecules in complex mixtures.