Trends in single-cell analysis by use of ICP-MS

Mueller, Larissa; Traub, Heike; Jakubowski, Norbert; Drescher, Daniela; Baranov, Vladimir; Kneipp, Janina

doi:10.1007/s00216-014-8143-7

Cited by 124 publications

(104 citation statements)

References 78 publications

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“…Depending on the instrumentation, LA-ICP-MS allows resolutions up to about 1 m. 15 resolution are shown in Figure 5, which still demonstrates highly distinct Eu-VSOP accumulation patterns predominantly near the vessel lumen, consistent with the results of TEM. 11 Some vesicle-like accumulations deeper in the plaque area are visible as well and might represent accumulations at microvesicles.…”

Section: Discussionsupporting

confidence: 78%

“…Therefore the concept of element microscopy was suggested recently. 15 Various applications of this technique in bioanalytical and biomedical research have been reported in the literature, for instance, the analysis of brain tissue in studies of neurodegenerative diseases or tumor growth. 16 17 When used for quantification, LA-ICP-MS requires adequate calibration standards.…”

mentioning

confidence: 99%

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LA-ICP-MS Allows Quantitative Microscopy of Europium-Doped Iron Oxide Nanoparticles and is a Possible Alternative to Ambiguous Prussian Blue Iron Staining

Scharlach¹,

Müller²,

Wagner³

et al. 2016

j biomed nanotechnol

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The development of iron oxide nanoparticles for biomedical applications requires accurate histological evaluation. Prussian blue iron staining is widely used but may be unspecific when tissues contain substantial endogenous iron. Here we tested whether microscopy by laser ablation coupled to inductively coupled plasma mass spectrometry (LA-ICP-MS) is sensitive enough to analyze accumulation of very small iron oxide particles (VSOP) doped with europium in tissue sections. For synthesis of VSOP, a fraction of Fe3+ (5 wt%) was replaced by Eu3+, resulting in particles with 0.66 mol% europium relative to iron (Eu-VSOP) but with otherwise similar properties as VSOP. Eu-VSOP or VSOP was intravenously injected into ApoE-/- mice on Western cholesterol diet and accumulated in atherosclerotic plaques of these animals. Prussian blue staining was positive for ApoE-/- mice with particle injection but also for controls. LA-ICP-MS microscopy resulted in sensitive and specific detection of the europium of Eu-VSOP in liver and atherosclerotic plaques. Furthermore, calibration with Eu-VSOP allowed calculation of iron and particle concentrations in tissue sections. The combination of europium-doped iron oxide particles and LA-ICP-MS microscopy provides a new tool for specific and quantitative analysis of particle distribution at the tissue level and allows correlation with other elements such as endogenous iron.

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Section: Discussionsupporting

confidence: 78%

mentioning

confidence: 99%

LA-ICP-MS Allows Quantitative Microscopy of Europium-Doped Iron Oxide Nanoparticles and is a Possible Alternative to Ambiguous Prussian Blue Iron Staining

Scharlach¹,

Müller²,

Wagner³

et al. 2016

j biomed nanotechnol

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“…Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) enables quantitation of metal contents at the single-cell level with additional insights on sub-cellular localization of NPs, however this image-based method also suffers from low throughput (tens to hundreds of cells typically analysed) and relatively low sensitivity (requiring millions of atoms per cell)151617. Single particle ICP-MS (SP-ICP-MS) is another ICP-based method that utilizes time-resolved mode to enable direct quantification of the number concentration, size distribution of NPs, and their state of agglomeration1819.…”

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confidence: 99%

High-throughput quantitation of inorganic nanoparticle biodistribution at the single-cell level using mass cytometry

et al. 2017

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Inorganic nanoparticles (NPs) are studied as drug carriers, radiosensitizers and imaging agents, and characterizing nanoparticle biodistribution is essential for evaluating their efficacy and safety. Tracking NPs at the single-cell level with current technologies is complicated by the lack of reliable methods to stably label particles over extended durations in vivo. Here we demonstrate that mass cytometry by time-of-flight provides a label-free approach for inorganic nanoparticle quantitation in cells. Furthermore, mass cytometry can enumerate AuNPs with a lower detection limit of ∼10 AuNPs (3 nm core size) in a single cell with tandem multiparameter cellular phenotyping. Using the cellular distribution insights, we selected an amphiphilic surface ligand-coated AuNP that targeted myeloid dendritic cells in lymph nodes as a peptide antigen carrier, substantially increasing the efficacy of a model vaccine in a B16-OVA melanoma mouse model. This technology provides a powerful new level of insight into nanoparticle fate in vivo.

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“…Various techniques for quantitative molecular analysis of cells do exist (e.g. mass spectrometry [1], polymerase chain reaction (PCR) [2]), yet they require destructive procedures and usually apply to whole cell populations instead of single cells. Therefore, these techniques provide only single time-points and cannot provide insight into discrete and dynamic molecular events in living cells.…”

Section: Introductionmentioning

confidence: 99%

Towards quantitative molecular mapping of cells by Raman microscopy: using AFM for decoupling molecular concentration and cell topography

et al. 2016

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Raman micro-spectroscopy (RMS) is a non-invasive technique for imaging live cells in-vitro. However, obtaining quantitative molecular information from the Raman spectra is difficult because the intensity of a Raman band is proportional to the number of molecules in the sampled volume, which depends on the local molecular concentration and the thickness of the cell. In order to understand these effects, we combined RMS with atomic force microscopy (AFM), a technique that can measure accurately the thickness profile of the cells. Solution-based calibration models for RNA and albumin were developed to create quantitative maps of RNA and proteins in individual fixed cells. The maps were built by applying the solution-based calibration models, based on partial least square fitting (PLS), on raster-scan Raman maps, after accounting for the local cell height obtained from the AFM. We found that concentrations of RNA in the cytoplasm of mouse neuroprogenitor stem cells (NSCs) were as high as 25±6 mg/m, while proteins were distributed more uniformly and reaching concentrations as high as ~50±12 mg/ml. The combined AFM-Raman datasets from fixed cells were also used to investigate potential improvements for normalization of Raman spectral maps. For all Raman map of fixed cells (n=10), we found a linear relationship between the scores corresponding to the first component (PC1) and cell height profile obtained by AFM. We used PC1 scores to reconstruct the relative height profiles of independent cells (n=10), and obtained correlation coefficients with AFM maps higher than 0.99. Using this normalization method, qualitative maps of RNA and protein were obtained concentrations for live NSCs. While this study demonstrates the potential of using AFM and RMS for measuring concentration maps for individual NSCs in-vitro, further studies are required to establish the robustness of the normalization method based on principal component analysis when comparing Raman spectra of cells with large morphological differences.

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Trends in single-cell analysis by use of ICP-MS

Cited by 124 publications

References 78 publications

LA-ICP-MS Allows Quantitative Microscopy of Europium-Doped Iron Oxide Nanoparticles and is a Possible Alternative to Ambiguous Prussian Blue Iron Staining

LA-ICP-MS Allows Quantitative Microscopy of Europium-Doped Iron Oxide Nanoparticles and is a Possible Alternative to Ambiguous Prussian Blue Iron Staining

High-throughput quantitation of inorganic nanoparticle biodistribution at the single-cell level using mass cytometry

Towards quantitative molecular mapping of cells by Raman microscopy: using AFM for decoupling molecular concentration and cell topography

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