Micro-droplet-based calibration for quantitative elemental bioimaging by LA-ICPMS

In this work, a novel standardization strategy for quantitative elemental bioimaging is evaluated. More specifically, multi-element quantification by laser ablation-inductively coupled plasma-time-of-flight mass spectrometry (LA-ICP-TOFMS) is performed by multi-point calibration using gelatin-based...

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Bibliographic Details
Published in:	Analytical and bioanalytical chemistry 2022-01, Vol.414 (1), p.485-495
Main Authors:	Schweikert, Andreas, Theiner, Sarah, Wernitznig, Debora, Schoeberl, Anna, Schaier, Martin, Neumayer, Sophie, Keppler, Bernhard K., Koellensperger, Gunda
Format:	Article
Language:	eng
Subjects:	ABCs 20th Anniversary Ablation Analysis Analytical Chemistry Antitumor agents Biochemistry Calibration Characterization and Evaluation of Materials Chemistry Chemistry and Materials Science Diameters Droplets Food Science Gelatin Inductively coupled plasma Inductively coupled plasma mass spectrometry Laboratory Medicine Laser ablation Laser Therapy - methods Mass spectrometry Mass Spectrometry - methods Mass spectroscopy Medical imaging Methods Monitoring/Environmental Analysis Phosphorus Platinum Quality control Reference materials Research Paper Spectrum Analysis Standardization Tumors
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Summary:	In this work, a novel standardization strategy for quantitative elemental bioimaging is evaluated. More specifically, multi-element quantification by laser ablation-inductively coupled plasma-time-of-flight mass spectrometry (LA-ICP-TOFMS) is performed by multi-point calibration using gelatin-based micro-droplet standards and validated using in-house produced reference materials. Fully automated deposition of micro-droplets by micro-spotting ensured precise standard volumes of 400 ± 5 pL resulting in droplet sizes of around 200 μm in diameter. The small dimensions of the micro-droplet standards and the use of a low-dispersion laser ablation setup reduced the analysis time required for calibration by LA-ICPMS significantly. Therefore, as a key advance, high-throughput analysis (pixel acquisition rates of more than 200 Hz) enabled to establish imaging measurement sequences with quality control- and standardization samples comparable to solution-based quantification exercises by ICP-MS. Analytical figures of merit such as limit of detection, precision, and accuracy of the calibration approach were assessed for platinum and for elements with biological key functions from the lower mass range (phosphorus, copper, and zinc). As a proof-of-concept application, the tool-set was employed to investigate the accumulation of metal-based anticancer drugs in multicellular tumor spheroid models at clinically relevant concentrations. Graphical abstract
ISSN:	1618-2642 1618-2650