Sample preparation methodologies for MALDI-MS imaging and related topics.

The diverse applications of MALDI MSI are explored in this thesis with an emphasis on the sample preparation procedure and method development for small molecule analysis for a range of samples. The two main themes that have been focussed on are the pharmaceutical and metabolomic applications of this state of the art technique.MALDI MSI has been evaluated as a technique for the detection and imaging of antiasthmatic compounds in lung tissue. Four compounds were assessed initially with conventional MALDI MS experiments, followed by both direct and indirect tissue imaging experiments. Pharmaceutical tablet formulations have also been assessed using MALDI MSI to map the active component throughout the excipients contained within the tablet providing information that is critical to the manufacturing process such as the homogeneity of the active pharmaceutical ingredient (API) throughout the tablet.MALDI MSI has been applied to the relatively new addition to the 'omics sciences, metabolomics. A non-targeted metabolomics approach has been used to study both plant and animal tissue in an attempt to gain a greater understanding of the complex biological processes that occur within both types of tissue. Wheat grain was used as the model system to conduct the experiments and evaluate the application of both UV MALDI MS and IR LDI MS for plant metabolomics. These techniques provided complementary information to published literature, however the novel aspect of this study was the incorporation of imaging experiments for UV MALDI MS; this allowed the metabolites to be visualised in the wheat grain section. MALDI MSI was also used to explore the differences between mice with chronic relapsing experimental autoimmune encephalomyelitis; the animal model of multiple sclerosis alongside healthy controls. Spinal cord samples were analysed and the main difference was tentatively attributed to choline levels.