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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.

Authors

Melissa K. Passarelli

Alexander Pirkl

Rudolf Moellers

Dmitry Grinfeld

Felix Kollmer

Rasmus Havelund

Carla F. Newman

Peter S. Marshall

Henrik Arlinghaus

Andy West

Stevan Horning

Ewald Niehuis

Alexander Makarov

Colin T. Dollery

Ian S. Gilmore



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 http://eprints.nottingham.ac.uk/id/eprint/48339
Publisher URL https://www.nature.com/articles/nmeth.4504
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf
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.

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The 3D OrbiSIMS.pdf (303 Kb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf


Passarelli et al Nature Methods 2017_SI Supp figs.pdf (3.5 Mb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf


Passarelli et al Nature Methods 2017_SI_brain sectoin protocol.pdf (690 Kb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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