Introducing specificity and sensitivity in imaging mass spectrometry

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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.