| AVS 65th International Symposium & Exhibition | |
| Applied Surface Science Division | Tuesday Sessions |
| Session AS+BI-TuM |
| Session: | Applied Surface Science: From Electrochemistry to Cell Imaging, a Celebration of the Career of Nicholas Winograd |
| Presenter: | Ian S. Gilmore, National Physical Laboratory, UK |
| Authors: | C. Newell, Francis Crick Institute, UK Y. Panina, Francis Crick Institute, UK L. Matjacic, National Physical Laboratory, UK V. Cristaudo, National Physical Laboratory, UK A.P. Bailey, Francis Crick Institute, UK R. Havelund, National Physical Laboratory, UK M. Yuneva, Francis Crick Institute, UK A.P. Gould, Francis Crick Institute, UK I.S. Gilmore, National Physical Laboratory, UK |
| Correspondent: | Click to Email |
Ground-breaking advances in single-cell genomics and transcriptomics are revealing the heterogeneity of cells in tissue and are transforming biological understanding. There is a great need for metabolomics with single-cell resolution. Recent advances in both SIMS and MALDI imaging have pushed the spatial resolution boundary to a few micrometres [1-3].
Here, we report on the 3D OrbiSIMS [1] which combines a gas cluster ion beam (GCIB) that is able to simultaneously achieve a spatial resolution of < 2 μm with high mass resolving power (>240 k) and mass accuracies of ~1 ppm. The GCIB significantly reduces fragmentation of metabolites compared with small cluster ion beams and we provide fragmentation data for a variety of metabolites for different energy per atom conditions.
We demonstrate the OrbiSIMS capability with two biological examples. Firstly, a study of the cuticular lipid composition and distribution of drosophila and how these change with various environmental and genetic manipulations. Drosophila secrete many different classes of lipids to form a protective surface barrier against environmental challenges and hydrocarbons which play a separate role as pheromones that influence sexual behaviour. Secondly, to identify metabolic heterogeneity in mammary gland tumours. One of the hallmarks of cancer is deregulated metabolism, often characterised by increased glucose and glutamine uptake for energetic and anabolic purposes. Metabolic changes contribute to well-established tumour heterogeneity, which is a major challenge for anti-cancer therapeutics. We demonstrate a protocol to co-register high-resolution OrbiSIMS metabolite images with immunohistochemistry microscopy images of the same sample.
References
1 Passarelli, M. K. et al. The 3D OrbiSIMS-label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power. Nature Methods14, 1175, doi:10.1038/nmeth.4504 (2017).
2 Kompauer, M., Heiles, S. & Spengler, B. Autofocusing MALDI mass spectrometry imaging of tissue sections and 3D chemical topography of nonflat surfaces. Nature Methods14, 1156, doi:10.1038/nmeth.4433 (2017).
3 Dreisewerd, K. & Yew, J. Y. Mass spectrometry imaging goes three dimensional. Nature Methods14, 1139, doi:10.1038/nmeth.4513 (2017).