The 3D OrbiSIMS—label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power

Passarelli, Melissa K.; Pirkl, Alexander; Moellers, Rudolf; Grinfeld, Dmitry; Kollmer, Felix; Havelund, Rasmus; Newman, Carla F.; Marshall, Peter S.; Arlinghaus, Henrik; Alexander, Morgan R.; West, Andy; Horning, Stevan; Niehuis, Ewald; Makarov, Alexander; Dollery, Colin T.; Gilmore, Ian S.

Abstract

© 2017 Nature America, Inc., part of Springer Nature. All rights reserved. We report the development of a 3D OrbiSIMS instrument for label-free biomedical imaging. It combines the high spatial resolution of secondary ion mass spectrometry (SIMS; under 200 nm for inorganic species and under 2 μm for biomolecules) with the high mass-resolving power of an Orbitrap (>240,000 at m/z 200). This allows exogenous and endogenous metabolites to be visualized in 3D with subcellular resolution. We imaged the distribution of neurotransmitters - gamma-aminobutyric acid, dopamine and serotonin - with high spectroscopic confidence in the mouse hippocampus. We also putatively annotated and mapped the subcellular localization of 29 sulfoglycosphingolipids and 45 glycerophospholipids, and we confirmed lipid identities with tandem mass spectrometry. We demonstrated single-cell metabolomic profiling using rat alveolar macrophage cells incubated with different concentrations of the drug amiodarone, and we observed that the upregulation of phospholipid species and cholesterol is correlated with the accumulation of amiodarone.

Citation

Passarelli, M. K., Pirkl, A., Moellers, R., Grinfeld, D., Kollmer, F., Havelund, R., …Gilmore, I. S. (2017). The 3D OrbiSIMS—label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power. Nature Methods, 14(12), 1175-1183. https://doi.org/10.1038/nmeth.4504

• Journal Article Type: Article
• Acceptance Date: Oct 10, 2017
• Online Publication Date: Nov 13, 2017
• Publication Date: Nov 13, 2017
• Deposit Date: Nov 23, 2017
• Publicly Available Date: Nov 23, 2017
• Journal: Nature Methods
• Print ISSN: 1548-7091
• Electronic ISSN: 1548-7105
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 12
• Pages: 1175-1183
• DOI: https://doi.org/10.1038/nmeth.4504
• Keywords: Drug discovery, Imaging, Mass spectrometry, Metabolomics
• Public URL: https://nottingham-repository.worktribe.com/output/894962
• Publisher URL: https://www.nature.com/articles/nmeth.4504
• Additional Information: Received: 24 April 2017; Accepted: 10 October 2017; First Online: 13 November 2017; : EN is a director and shareholder of ION-TOF GmbH Muenster, Germany. AP, RM, FK, and HA are employees of ION-TOF GmbH. DG, SH and AM are employees of Thermo Fisher Scientific, the corporation that produces Orbitrap mass spectrometers. CN, PM, AW and CD (at the time of this study) are employees of GlaxoSmithKline.