Investigations in MALDI-MSI using a high repetition rate laser

Project completed 2013.

Professor Mike Hannon, School of Chemistry
Dr Josephine Bunch, School of Chemistry
Professor Ed Rainger, Institute of Cardivascular Sciences
Professor Peter Tino, School of Computer Science

This project seeks to address a number of current limitations in Matrix Assisted Laser Desorption Ionisation Mass Spectrometry imaging (MALDI-MSI) and to develop highly sensitive, high resolution, high throughput MALDI methods for improved imaging of small molecules in thin sections of tissue. These techniques will be applied to models of atherosclerosis to indicate how alterations in the lipid environment of sample tissue may contribute to the establishment and maintenance of chronic inflammation, since this aspect of the disease process is important but currently little understood.

Mass spectrometry imaging is a powerful approach for analysing the spatial distribution of inorganic and organic species in thin tissue sections. Imaging via MALDI has been successfully applied to the imaging of drugs, metabolites, lipids, peptides and proteins in a diverse range of soft tissues. Current limitations of the technique include relatively poor spatial resolution (typically 50-150 um), lengthy analysis times (typically between 3 and 12 hours per tissue section) and low sensitivity for some analytes.

In this project a combination of novel and optimised mass spectrometry imaging techniques will be used to investigate ApoE deficient tissue sections. Powerful data analysis techniques will enable highly spatially resolved images of unlabelled lipids in tissue to be processed in large volumes. This methodology will enable obscure patterns and low-level differences between data sets to be determined with an efficacy and efficiency not possible otherwise, leading to an improved understanding of the development of atherosclerosis within the lipid environment.

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