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Toxics 2016, 4(1), 5; doi:10.3390/toxics4010005

Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS): A New Tool for the Analysis of Toxicological Effects on Single Cell Level

Department of Chemicals and Product Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany
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Academic Editor: David Bellinger
Received: 22 December 2015 / Revised: 2 February 2016 / Accepted: 6 February 2016 / Published: 15 February 2016
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Abstract

Single cell imaging mass spectrometry opens up a complete new perspective for strategies in toxicological risk assessment and drug discovery. In particular, time-of-flight secondary ion mass spectrometry (ToF-SIMS) with its high spatial and depth resolution is becoming part of the imaging mass spectrometry toolbox used for single cell analysis. Recent instrumentation advancements in combination with newly developed cluster ion guns allow 3-dimensional reconstruction of single cells together with a spatially resolved compound location and quantification on nanoscale depth level. The exact location and quantification of a single compound or even of a set of compounds is no longer restricted to the two dimensional space within single cells, but is available for voxels, a cube-sized 3-dimensional space, rather than pixels. The information gathered from one voxel is further analysed using multivariate statistical methodology like maximum autocorrelation factors to co-locate the compounds of interest within intracellular organelles like nucleus, mitochondria or golgi apparatus. Furthermore, the cell membrane may be resolved, including adhering compounds and potential changes of the lipid patterns. The generated information can be used further for a first evaluation of intracellular target specifity of new drug candidates or for the toxicological risk assessment of environmental chemicals and their intracellular metabolites. Additionally, single cell lipidomics and metabolomics enable for the first time an in-depth understanding of the activation or inhibition of cellular biosynthesis and signalling pathways. View Full-Text
Keywords: ToF-SIMS; imaging mass spectrometry; MIMS; lipidomics; cryopreservation; single cell analysis ToF-SIMS; imaging mass spectrometry; MIMS; lipidomics; cryopreservation; single cell analysis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Jungnickel, H.; Laux, P.; Luch, A. Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS): A New Tool for the Analysis of Toxicological Effects on Single Cell Level. Toxics 2016, 4, 5.

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