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

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 (>240,00...

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Main Authors: 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.
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Published: Nature Publishing Group 2017
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Online Access:https://eprints.nottingham.ac.uk/48339/
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author 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.
author_facet 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.
author_sort Passarelli, Melissa K.
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-483392020-05-04T19:17:36Z https://eprints.nottingham.ac.uk/48339/ 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. 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. Nature Publishing Group 2017-11-13 Article PeerReviewed 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. and Gilmore, Ian S. (2017) The 3D OrbiSIMS—label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power. Nature Methods . ISSN 1548-7091 Drug discovery Imaging Mass spectrometry Metabolomics https://www.nature.com/articles/nmeth.4504 doi:10.1038/NMETH.4504 doi:10.1038/NMETH.4504
spellingShingle Drug discovery
Imaging
Mass spectrometry
Metabolomics
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.
The 3D OrbiSIMS—label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power
title The 3D OrbiSIMS—label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power
title_full The 3D OrbiSIMS—label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power
title_fullStr The 3D OrbiSIMS—label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power
title_full_unstemmed The 3D OrbiSIMS—label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power
title_short The 3D OrbiSIMS—label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power
title_sort 3d orbisims—label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power
topic Drug discovery
Imaging
Mass spectrometry
Metabolomics
url https://eprints.nottingham.ac.uk/48339/
https://eprints.nottingham.ac.uk/48339/
https://eprints.nottingham.ac.uk/48339/