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Article ; Online: Imaging of Subcellular Distribution of Platinum in Single Cells Using Laser Ablation Inductively Coupled Plasma Mass Spectrometry.

Managh, Amy J / Greenhalgh, Calum J

Methods in molecular biology (Clifton, N.J.)

2024 Volume 2752, Page(s) 215–226

Abstract: Laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS) is a well-established and sensitive analytical technique, which provides high-resolution imaging of endogenous elements, element tagged-markers, metal-containing nanoparticles, and ... ...

Abstract	Laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS) is a well-established and sensitive analytical technique, which provides high-resolution imaging of endogenous elements, element tagged-markers, metal-containing nanoparticles, and metallodrugs within cells. Here we describe a protocol for imaging the subcellular distribution of platinum within A549 cells, following their incubation with the platinum-based anticancer agent, Oxaliplatin. We outline the essential steps in sample preparation and instrumental setup and discuss how the current generation of low-dispersion instruments facilitates new approaches to data acquisition and image processing. The protocol described herein can be easily adapted for other cell lines and metal-containing labeling agents.
MeSH term(s)	Diagnostic Imaging ; Spectrum Analysis ; Image Processing, Computer-Assisted ; Laser Therapy ; Platinum ; Mass Spectrometry
Chemical Substances	Platinum (49DFR088MY)
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3621-3_14
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Article ; Online: Laser ablation inductively coupled plasma mass spectrometry as a novel clinical imaging tool to detect asbestos fibres in malignant mesothelioma.

Voloaca, Oana M / Greenhalgh, Calum J / Cole, Laura M / Clench, Malcolm R / Managh, Amy J / Haywood-Small, Sarah L

Rapid communications in mass spectrometry : RCM

2020 Volume 34, Issue 21, Page(s) e8906

Abstract: Rationale: Malignant pleural mesothelioma is an extremely aggressive and incurable malignancy associated with prior exposure to asbestos fibres. Difficulties remain in relation to early diagnosis, notably due to impeded identification of asbestos in ... ...

Abstract	Rationale: Malignant pleural mesothelioma is an extremely aggressive and incurable malignancy associated with prior exposure to asbestos fibres. Difficulties remain in relation to early diagnosis, notably due to impeded identification of asbestos in lung tissue. This study describes a novel laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging approach to identify asbestos within mesothelioma models with clinical significance. Methods: Human mesothelioma cells were exposed to different types of asbestos fibres and prepared on plastic slides for LA-ICP-MS analysis. No further sample preparation was required prior to analysis, which was performed using an NWR Image 266 nm laser ablation system coupled to an Element XR sector-field ICP mass spectrometer, with a lateral resolution of 2 μm. Data was processed using LA-ICP-MS ImageTool v1.7 with the final graphic production made using DPlot software. Results: Four different mineral fibres were successfully identified within the mesothelioma samples based on some of the most abundant elements that make up these fibres (Si, Mg and Fe). Using LA-ICP-MS as an imaging tool provided information on the spatial distribution of the fibres at cellular level, which is essential in asbestos detection within tissue samples. Based on the metal counts generated by the different types of asbestos, different fibres can be identified based on shape, size, and elemental composition. Detection of Ca was attempted but requires further optimisation. Conclusions: Detection of asbestos fibres in lung tissues is very useful, if not necessary, to complete the pathological dt9iagnosis of asbestos-related malignancies in the medicolegal field. For the first time, this study demonstrates the successful application of LA-ICP-MS imaging to identify asbestos fibres and other mineral fibres within mesothelioma samples. Ultimately, high-resolution, fast-speed LA-ICP-MS analysis has the potential to be integrated into clinical workflow to aid earlier detection and stratification of mesothelioma patient samples.
MeSH term(s)	Asbestos/analysis ; Asbestos/chemistry ; Cell Line, Tumor ; Humans ; Lasers ; Lung Neoplasms/diagnostic imaging ; Lung Neoplasms/pathology ; Mass Spectrometry/methods ; Mesothelioma, Malignant/diagnostic imaging ; Mesothelioma, Malignant/pathology ; Microscopy/methods
Chemical Substances	Asbestos (1332-21-4)
Language	English
Publishing date	2020-07-23
Publishing country	England
Document type	Journal Article
ZDB-ID	58731-x
ISSN	1097-0231 ; 0951-4198
ISSN (online)	1097-0231
ISSN	0951-4198
DOI	10.1002/rcm.8906
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Article ; Online: Doubling Sensitivity in Multicollector ICPMS Using High-Efficiency, Rapid Response Laser Ablation Technology.

Craig, Grant / Managh, Amy J / Stremtan, Ciprian / Lloyd, Nicholas S / Horstwood, Matthew S A

Analytical chemistry

2018 Volume 90, Issue 19, Page(s) 11564–11571

Abstract: The introduction of rapid response laser ablation cells and sample transport technologies to laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) has enabled signal pulse durations for a single laser ablation shot of less than 10 ms. ... ...

Abstract	The introduction of rapid response laser ablation cells and sample transport technologies to laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) has enabled signal pulse durations for a single laser ablation shot of less than 10 ms. These developments have resulted in marked improvements in analytical throughput, resolution, and sensitivity vital for the generation of large, highly spatially resolved elemental maps. The focus on mapping, particularly bioimaging, has obscured the possibility of applying the sensitivity advantage of rapid response technologies to other LA-ICPMS applications, such as high-precision isotope ratio analysis on multicollector (MC) ICPMS. In this work a commercially available rapid response sample transport system and a conventional configuration were compared for LA-MC-ICPMS analysis. Ablation of known reference materials demonstrated "sensitivity" or sample ion yield of 7-9% using the rapid response sample transport system, more than double that for the conventional setup. This increase in efficiency was demonstrated to improve precision for the Pb isotope ratio analysis of the MPI-DING reference glasses and improve the spatial resolution of Hf isotope ratio analysis of reference zircons.
Language	English
Publishing date	2018-09-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.8b02896
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Article ; Online: High-Speed, Integrated Ablation Cell and Dual Concentric Injector Plasma Torch for Laser Ablation-Inductively Coupled Plasma Mass Spectrometry.

Douglas, David N / Managh, Amy J / Reid, Helen J / Sharp, Barry L

Analytical chemistry

2015 Volume 87, Issue 22, Page(s) 11285–11294

Abstract: In recent years, laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) has gained increasing importance for biological analysis, where ultratrace imaging at micrometer resolution is required. However, while undoubtedly a valuable ... ...

Abstract	In recent years, laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) has gained increasing importance for biological analysis, where ultratrace imaging at micrometer resolution is required. However, while undoubtedly a valuable research tool, the washout times and sensitivity of current technology have restricted its routine and clinical application. Long periods between sampling points are required to maintain adequate spatial resolution. Additionally, temporal signal dispersion reduces the signal-to-noise ratio, which is a particular concern when analyzing discrete samples, such as individual particles or cells. This paper describes a novel, two-volume laser ablation cell and integrated ICP torch designed to minimize aerosol dispersion for fast, efficient sample transport. The holistic design utilizes a short, continuous diameter fused silica conduit, which extends from the point of ablation, through the ICP torch, and into the base of the plasma. This arrangement removes the requirement for a dispersive component for argon addition, and helps to keep the sample on axis with the ICP cone orifice. Hence, deposition of sample on the cones is theoretically reduced with a resulting improvement in the absolute sensitivity (counts per unit mole). The system described here achieved washouts of 1.5, 3.2, and 4.9 ms for NIST 612 glass, at full width half, 10%, and 1% maximum, respectively, with an 8-14-fold improvement in absolute sensitivity, compared to a single volume ablation cell. To illustrate the benefits of this performance, the system was applied to a contemporary bioanalytical challenge, specifically the analysis of individual biological cells, demonstrating similar improvements in performance.
MeSH term(s)	Gadolinium/chemistry ; Humans ; Lasers ; Mass Spectrometry/instrumentation ; Mass Spectrometry/methods ; T-Lymphocytes, Regulatory/cytology
Chemical Substances	Gadolinium (AU0V1LM3JT)
Language	English
Publishing date	2015-11-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.5b02466
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Article: High-Speed, Integrated Ablation Cell and Dual Concentric Injector Plasma Torch for Laser Ablation-Inductively Coupled Plasma Mass Spectrometry

Douglas, David N / Managh Amy J / Reid Helen J / Sharp Barry L

Analytical chemistry. 2015 Nov. 17, v. 87, no. 22

2015

Abstract	In recent years, laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) has gained increasing importance for biological analysis, where ultratrace imaging at micrometer resolution is required. However, while undoubtedly a valuable research tool, the washout times and sensitivity of current technology have restricted its routine and clinical application. Long periods between sampling points are required to maintain adequate spatial resolution. Additionally, temporal signal dispersion reduces the signal-to-noise ratio, which is a particular concern when analyzing discrete samples, such as individual particles or cells. This paper describes a novel, two-volume laser ablation cell and integrated ICP torch designed to minimize aerosol dispersion for fast, efficient sample transport. The holistic design utilizes a short, continuous diameter fused silica conduit, which extends from the point of ablation, through the ICP torch, and into the base of the plasma. This arrangement removes the requirement for a dispersive component for argon addition, and helps to keep the sample on axis with the ICP cone orifice. Hence, deposition of sample on the cones is theoretically reduced with a resulting improvement in the absolute sensitivity (counts per unit mole). The system described here achieved washouts of 1.5, 3.2, and 4.9 ms for NIST 612 glass, at full width half, 10%, and 1% maximum, respectively, with an 8â14-fold improvement in absolute sensitivity, compared to a single volume ablation cell. To illustrate the benefits of this performance, the system was applied to a contemporary bioanalytical challenge, specifically the analysis of individual biological cells, demonstrating similar improvements in performance.
Keywords	aerosols ; argon (noble gases) ; glass ; image analysis ; mass spectrometry ; silica
Language	English
Dates of publication	2015-1117
Size	p. 11285-11294.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021%2Facs.analchem.5b02466
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Article ; Online: Exploration of Matrix Effects in Laser Ablation Inductively Coupled Plasma Mass Spectrometry Imaging of Cisplatin-Treated Tumors.

Greenhalgh, Calum J / Karekla, Ellie / Miles, Gareth J / Powley, Ian R / Costa, Catia / de Jesus, Janella / Bailey, Melanie J / Pritchard, Catrin / MacFarlane, Marion / Pringle, J Howard / Managh, Amy J

Analytical chemistry

2020 Volume 92, Issue 14, Page(s) 9847–9855

Abstract: The use of a low aerosol dispersion ablation chamber within a laser ablation inductively coupled plasma mass spectrometer (LA-ICP-MS) setup allows for high-resolution, high-speed imaging of the distribution of elements within a sample. Here we show how ... ...

Abstract	The use of a low aerosol dispersion ablation chamber within a laser ablation inductively coupled plasma mass spectrometer (LA-ICP-MS) setup allows for high-resolution, high-speed imaging of the distribution of elements within a sample. Here we show how this enhanced capability creates new analytical problems and solutions. We report the distribution of platinum at the cellular level in non-small cell lung cancer (NSCLC) explant models after treatment with clinically relevant doses of cisplatin. This revealed for the first time a correlation between the platinum signal and the presence of carbon deposits within lung tissue. We show how complementary ion beam analysis techniques, particle-induced X-ray emission (PIXE) and elastic backscattering spectrometry (EBS), can be used to explore potential matrix effects in LA-ICP-MS data. For these samples, it was confirmed that the enhancement was unlikely to have resulted from a matrix effect alone. Thus, the presence of carbon deposits within tissue has potential implications for the effective distribution of the cisplatin drug.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Carbon/chemistry ; Carcinoma, Non-Small-Cell Lung ; Cisplatin/therapeutic use ; Humans ; Laser Therapy ; Lung Neoplasms/chemistry ; Lung Neoplasms/drug therapy ; Mass Spectrometry/methods ; Spheroids, Cellular ; Tissue Culture Techniques
Chemical Substances	Antineoplastic Agents ; Carbon (7440-44-0) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2020-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.0c01347
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Article: Exploration of Matrix Effects in Laser Ablation Inductively Coupled Plasma Mass Spectrometry Imaging of Cisplatin-Treated Tumors

Greenhalgh, Calum J / Karekla, Ellie / Miles, Gareth J / Powley, Ian R / Costa, Catia / de Jesus, Janella / Bailey, Melanie J / Pritchard, Catrin / MacFarlane, Marion / Pringle, J. Howard / Managh, Amy J

Analytical chemistry. 2020 June 17, v. 92, no. 14

2020

Abstract: The use of a low aerosol dispersion ablation chamber within a laser ablation inductively coupled plasma mass spectrometer (LA-ICP–MS) setup allows for high-resolution, high-speed imaging of the distribution of elements within a sample. Here we show how ... ...

Abstract	The use of a low aerosol dispersion ablation chamber within a laser ablation inductively coupled plasma mass spectrometer (LA-ICP–MS) setup allows for high-resolution, high-speed imaging of the distribution of elements within a sample. Here we show how this enhanced capability creates new analytical problems and solutions. We report the distribution of platinum at the cellular level in non-small cell lung cancer (NSCLC) explant models after treatment with clinically relevant doses of cisplatin. This revealed for the first time a correlation between the platinum signal and the presence of carbon deposits within lung tissue. We show how complementary ion beam analysis techniques, particle-induced X-ray emission (PIXE) and elastic backscattering spectrometry (EBS), can be used to explore potential matrix effects in LA-ICP–MS data. For these samples, it was confirmed that the enhancement was unlikely to have resulted from a matrix effect alone. Thus, the presence of carbon deposits within tissue has potential implications for the effective distribution of the cisplatin drug.
Keywords	X-radiation ; aerosols ; analytical chemistry ; atomic absorption spectrometry ; carbon ; cisplatin ; lung neoplasms ; lungs ; platinum ; spectrometers
Language	English
Dates of publication	2020-0617
Size	p. 9847-9855.
Publishing place	American Chemical Society
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.0c01347
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Article ; Online: Human Tolerogenic Dendritic Cells Regulate Immune Responses through Lactate Synthesis.

Marin, Eros / Bouchet-Delbos, Laurence / Renoult, Ophélie / Louvet, Cédric / Nerriere-Daguin, Véronique / Managh, Amy J / Even, Amandine / Giraud, Matthieu / Vu Manh, Thien Phong / Aguesse, Audrey / Bériou, Gaelle / Chiffoleau, Elise / Alliot-Licht, Brigitte / Prieur, Xavier / Croyal, Mikael / Hutchinson, James A / Obermajer, Natasa / Geissler, Edward K / Vanhove, Bernard /

Blancho, Gilles / Dalod, Marc / Josien, Régis / Pecqueur, Claire / Cuturi, Maria-Cristina / Moreau, Aurélie

Cell metabolism

2019 Volume 30, Issue 6, Page(s) 1075–1090.e8

Abstract: Cell therapy is a promising strategy for treating patients suffering from autoimmune or inflammatory diseases or receiving a transplant. Based on our preclinical studies, we have generated human autologous tolerogenic dendritic cells (ATDCs), which are ... ...

Abstract	Cell therapy is a promising strategy for treating patients suffering from autoimmune or inflammatory diseases or receiving a transplant. Based on our preclinical studies, we have generated human autologous tolerogenic dendritic cells (ATDCs), which are being tested in a first-in-man clinical trial in kidney transplant recipients. Here, we report that ATDCs represent a unique subset of monocyte-derived cells based on phenotypic, transcriptomic, and metabolic analyses. ATDCs are characterized by their suppression of T cell proliferation and their expansion of Tregs through secreted factors. ATDCs produce high levels of lactate that shape T cell responses toward tolerance. Indeed, T cells take up ATDC-secreted lactate, leading to a decrease of their glycolysis. In vivo, ATDCs promote elevated levels of circulating lactate and delay graft-versus-host disease by reducing T cell proliferative capacity. The suppression of T cell immunity through lactate production by ATDCs is a novel mechanism that distinguishes ATDCs from other cell-based immunotherapies.
MeSH term(s)	Animals ; Autoimmune Diseases/therapy ; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Female ; Humans ; Immune Tolerance ; Immunosuppression ; Lactic Acid/biosynthesis ; Lymphocyte Activation ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Monocytes/immunology
Chemical Substances	Lactic Acid (33X04XA5AT)
Language	English
Publishing date	2019-12-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2176834-1
ISSN	1932-7420 ; 1550-4131
ISSN (online)	1932-7420
ISSN	1550-4131
DOI	10.1016/j.cmet.2019.11.011
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Article: Single Cell Tracking of Gadolinium Labeled CD4+ T Cells by Laser Ablation Inductively Coupled Plasma Mass Spectrometry

Managh, Amy J / Bushell Andrew / Edwards Sheldon L / Geissler Edward K / Hutchinson James A / Hutchinson Robert W / Reid Helen J / Sharp Barry L / Wood Kathryn J

Analytical chemistry. 2013 Nov. 19, v. 85, no. 22

2013

Abstract: Cellular therapy is emerging as a promising alternative to conventional immunosuppression in the fields of hematopoietic stem cell (HSC) transplantation, autoimmune disease, and solid organ transplantation. Determining the persistence of cell-based ... ...

Abstract	Cellular therapy is emerging as a promising alternative to conventional immunosuppression in the fields of hematopoietic stem cell (HSC) transplantation, autoimmune disease, and solid organ transplantation. Determining the persistence of cell-based therapies in vivo is crucial to understanding their regulatory function and requires the combination of an extremely sensitive detection technique and a stable, long-lifetime cell labeling agent. This paper reports the first application of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to perform single cell detection of T cell populations relevant to cellular immunotherapy. Purified human CD4âº T cells were labeled with commercially available Gd-based magnetic resonance imaging (MRI) contrast agents, Omniscan and Dotarem, which enabled passive loading of up to 10â¸ Gd atoms per cell. In mixed preparations of labeled and unlabeled cells, LA-ICP-MS was capable of enumerating labeled cells at close to the predicted ratio. More importantly, LA-ICP-MS single cell analysis demonstrated that the cells retained a sufficient label to remain detectable for up to 10 days post-labeling both in vitro and in vivo in an immunodeficient mouse model.
Keywords	animal models ; atomic absorption spectrometry ; autoimmune diseases ; CD4-positive T-lymphocytes ; gadolinium ; hematopoietic stem cells ; humans ; immunosuppression ; immunotherapy ; magnetic resonance imaging ; organ transplantation
Language	English
Dates of publication	2013-1119
Size	p. 10627-10634.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021%2Fac4022715
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Article ; Online: Single cell tracking of gadolinium labeled CD4+ T cells by laser ablation inductively coupled plasma mass spectrometry.

Managh, Amy J / Edwards, Sheldon L / Bushell, Andrew / Wood, Kathryn J / Geissler, Edward K / Hutchinson, James A / Hutchinson, Robert W / Reid, Helen J / Sharp, Barry L

Analytical chemistry

2013 Volume 85, Issue 22, Page(s) 10627–10634

Abstract	Cellular therapy is emerging as a promising alternative to conventional immunosuppression in the fields of hematopoietic stem cell (HSC) transplantation, autoimmune disease, and solid organ transplantation. Determining the persistence of cell-based therapies in vivo is crucial to understanding their regulatory function and requires the combination of an extremely sensitive detection technique and a stable, long-lifetime cell labeling agent. This paper reports the first application of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to perform single cell detection of T cell populations relevant to cellular immunotherapy. Purified human CD4(+) T cells were labeled with commercially available Gd-based magnetic resonance imaging (MRI) contrast agents, Omniscan and Dotarem, which enabled passive loading of up to 10(8) Gd atoms per cell. In mixed preparations of labeled and unlabeled cells, LA-ICP-MS was capable of enumerating labeled cells at close to the predicted ratio. More importantly, LA-ICP-MS single cell analysis demonstrated that the cells retained a sufficient label to remain detectable for up to 10 days post-labeling both in vitro and in vivo in an immunodeficient mouse model.
MeSH term(s)	Animals ; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/physiology ; Cell Tracking/methods ; Contrast Media ; Gadolinium/pharmacokinetics ; Humans ; Laser Therapy/methods ; Magnetic Resonance Imaging ; Mass Spectrometry/methods ; Mice ; Mice, Inbred BALB C ; Tissue Distribution
Chemical Substances	Contrast Media ; Gadolinium (AU0V1LM3JT)
Language	English
Publishing date	2013-10-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/ac4022715
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