Mass spectrometry has evolved into an indispensable tool in the (bio)chemical sciences. However, analyses are typically performed on extracted molecules from homogenised samples meaning the spatial context in which molecules are present is sacrificed. Understanding not only what molecules are present, but where there are located within a tissue or a cell and how they are altered during the progression of disease is of utmost importance for understanding complex biochemical processes occurring in spatially heterogeneous tissues. In this presentation, I will demonstrate how recent advances in mass spectrometry imaging (MSI) now provide a suite of potent approaches to study chemical diversity direct from complex surfaces like biological tissues. Unlike other imaging approaches, MSI allows the parallel imaging of thousands of molecules without the need for labels and with cellular-level resolution.
I will give an introduction to matrix-assisted laser desorption/ionisation-MSI (MALDI-MSI) and its applications for visualising biochemical processes within tissues. Particular emphasis will be placed on innovative technology developments made by my group that enable enhanced chemical resolution and detection of previously undetectable molecular classes. These include the development of MALDI-MSI ion sources for Orbitrap mass spectrometers, highly parallelised MS/MS imaging acquisitions sequences, laser-induced post-ionisation (MALDI-2) methods and the imaging of isomeric lipids using selective gas-phase ion/molecule reactions. Also, I will highlight several applications of these technologies for studying localised biochemical alterations in tissues.