Introducing specificity and sensitivity in imaging mass spectrometry

成像质谱（IMS）提供关于样品中分子的定位的信息。它已成为一种强大的方式来描绘和表征的空间分布的生物分子通过直接分析薄组织切片。与组织结构直接相关的分子特异性图谱可以同时获得数百种不同的内源性化合物，包括蛋白质、肽、脂质和代谢物。* 在这项研究计划中，我们将利用我们在IMS方面的专业知识来解决生物成像领域尚未满足的重要需求。因此，本提案将侧重于开发分析方法，以提高IMS分析新型内源性分子（包括类固醇、胆固醇酯和神经酰胺）的特异性和灵敏度。必须开发富集方法，以促进识别可用于疾病诊断或预后或作为治疗反应指标的脂质靶点。将探讨两个主要研究方向 *。1)替代解吸/电离剂的开发。我们已经证明，在组织切片表面添加金属银可以特异性地成像胆固醇、脂肪酸以及其他烯烃。其他金属、金属氧化物和阳离子对各种类型的脂质和代谢物具有令人感兴趣的亲和力，可以有效地探索这些亲和力以实现对IMS的高度灵敏度和特异性。还将在对指纹进行法医分析的范围内对这些发展的结果进行研究，以确定区分性别的分子标记、滥用物质和爆炸物等非法化合物以及与指纹模式高度相关的放射性物质暴露后的分子标记：*2）开发化学定制的亲和表面，以从薄组织切片中特异性捕获靶向脂质和代谢物，同时保持其空间完整性。首先将组织切片放置在这些亲和表面上。分析物捕获后，将取出切片，并通过IMS分析保留的分子。* 通过他的研究计划，在IMS方法开发方面的持续努力将允许对生物样品中的脂质和代谢物进行更深入和独特的分析，以补充我实验室已经开发的那些。总的来说，这些新方法将有助于广泛的生物学应用，包括人类疾病和病症，以及了解细胞、器官和整个生物体的正常发育和功能。

Imaging Mass Spectrometry (IMS) provides information on the localization of molecules in a sample. It has become a powerful way to profile and characterize the spatial distribution of biomolecules through the direct analysis of thin tissue sections. Molecular-specific maps directly correlated with tissue architecture may be simultaneously obtained for several hundreds of different endogenous compounds including proteins, peptides, lipids and metabolites. ***In this research proposal, we will leverage our expertise in IMS to address important unmet needs in the field of biological imaging. Accordingly, this proposal will focus on the development of analytical methods to improve the specificity and sensitivity of IMS for the analysis of novel classes of endogenous molecules including steroids, cholesterol esters and ceramides. Enrichment methods must be developed to facilitate the identification of lipid targets that can be used in the diagnosis or prognosis of disease or as indicators of therapeutic response. Two main axis of research will be explored.***1) The development of alternative desorption/ionization agents. We already have demonstrated that the addition of metallic silver on the surface of tissue sections allows to specifically image cholesterol, fatty acids, as well as other olefins. Other metals, metal oxides and cations have interesting affinities for various classes of lipids and metabolites that can be usefully explored to implement high degrees of sensitivity and specificity to IMS. The sum of findings from these developments will also be investigated in the context of the forensic analysis of fingermarks to identify molecular markers which differentiate gender, illicit compounds such as substances of abuse and explosives and molecular markers after exposure to radioactive material with a high degree of correlation with fingerprint patterns:***2) The development of chemically tailored affinity surfaces to specifically capture targeted lipids and metabolites from thin tissue sections while maintaining their spatial integrity. Tissue sections will first be deposed on these affinity surfaces. After analyte capture, the sections will be removed and the retained molecules analyzed by IMS. ***Through his research program, continued efforts in IMS method development will allow a deeper and unique analysis of lipids and metabolites from biological samples complementary to those already developed in my laboratory. Overall, these new methods will be useful for a wide range of biological applications including human diseases and disorders as well as understanding normal development and functioning of cells, organs and whole organisms.