Oral Presentation 26th Annual Lorne Proteomics Symposium 2021

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 [1], highly parallelised MS/MS imaging acquisitions sequences [2], laser-induced post-ionisation methods [3-4] and the imaging of isomeric lipids using selective gas-phase ion/molecule reactions [5]. The coupling of MSI with high resolving power analysers also enables localised molecular dynamics to be visualised in tissues, and we have applied this in mouse models of respiratory disease. These advances pave the way of dynamic MSI where lipid turnover rates are provided concurrently with imaging data, thus providing a new window into tissue heterogeneity.

References

(1)        Belov, M. E., Ellis, S. R., Dilillo, M., Paine, M. R. L., Danielson, W. F., Anderson, G. A., de Graaf, E. L., Eijkel, G. B., Heeren, R. M. A., McDonnell, L. A., Design and Performance of a Novel Interface for Combined Matrix-Assisted Laser Desorption Ionization at Elevated Pressure and Electrospray Ionization with Orbitrap Mass Spectrometry. Anal. Chem. 2017, 89, 7493-7501.

(2)        Ellis, S. R., Paine, M. R. L., Eijkel, G. B., Pauling, J. K., Husen, P., Jervelund, M. W., Hermansson, M., Ejsing, C. S., Heeren, R. M. A., Automated, Parallel Mass Spectrometry Imaging and Structural Identification of Lipids. Nat. Methods 2018, 15, 515-518.

(3)        Ellis, S., Soltwisch, J., Paine, M. R. L., Dreisewerd, K., Heeren, R., Laser Post-Ionisation Combined with a High Resolving Orbitrap Mass Spectrometer for Enhanced MALDI-MS Imaging of Lipids. Chem. Commun. 2017, 53, 7246-7249

(4)        Bowman, A. P., Bogie, J. F. J., Hendriks, J. J. A., Haidar, M., Belov, M., Heeren, R. M. A., Ellis, S. R., Evaluation of Lipid Coverage and High Spatial Resolution MALDI-Imaging Capabilities of Oversampling Combined with Laser Post-Ionisation. Anal. Bioanal. Chem. 2020, 412, 2277-2289.

(5)        Paine, M. R. L., Poad, B. L. J., Eijkel, G. B., Marshall, D. L., Blanksby, S. J., Heeren, R. M. A., Ellis, S. R., Mass Spectrometry Imaging with Isomeric Resolution Enabled by Ozone‐Induced Dissociation. Angew. Chem. Int. Ed. 2018, 57, 10530-10534.

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