Study of Localization of Endogenous Metals on Thin Tissue Sections by LA-ICP-MS

Significance of the topic

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) bioimaging enables spatially resolved multi-element analysis of thin biological tissue sections, bridging metallomics and histology. This approach provides critical insights into metal distribution related to disease progression, cellular viability, and cofactor localization, supporting advances in clinical diagnostics, pathology research, and pharmaceutical development.

Objectives and study overview

The study aimed to demonstrate the performance of fully integrated LA-ICP-MS systems (Agilent 8900 ICP-QQQ and 7900 ICP-MS coupled with ESL213 laser ablation) for mapping endogenous metals in heart and liver tissues. Key goals included correlating metal localization with histological features and evaluating analytical reproducibility and sensitivity.

Methodology and instrumentation

Instrumentation

• Agilent 8900 ICP-QQQ and 7900 ICP-MS platforms
• ESL213 laser ablation system controlled via MassHunter software with ActiveView2 plug-in

Sample preparation

• 10 µm tissue sections from human myocardial infarction and C57BL/6 mouse liver
• Azan staining to visualize fibrotic regions in heart samples

Analytical procedure

• LA-ICP-MS in O₂ mass-shift mode (8900) and H₂/He modes (7900)
• Acquisition of spatially resolved signals for 31P, 44Ca, 56Fe, 95Mo, and 98Mo
• Image reconstruction using iolite 4 software

Main results and discussion

Myocardial infarction

• Azan staining revealed fibrotic regions in chronic MI tissue
• LA-ICP-MS showed decreased 31P, 44Ca, and 56Fe in infarcted areas, indicating reduced cell viability

Mouse liver imaging

• Consistent distributions of 95Mo and 98Mo confirm reliable molybdenum detection
• 56Fe localized around blood vessels, correlating with heme-bound iron in red blood cells
• Overlay images demonstrated distinct localization of Mo cofactors and Fe proteins

The findings validate LA-ICP-MS’s capability for high-resolution elemental mapping in biological tissues.

Benefits and practical applications

LA-ICP-MS bioimaging offers

• Non-destructive multiplex elemental mapping
• Correlative analysis with histology for biomarker identification
• Quantitative assessment of metal cofactors in metabolic and pathological studies
• Enhanced QA/QC workflows in clinical and pharmaceutical laboratories

Future trends and potential applications

Emerging developments

• Integration with single-cell analysis for subcellular metallomics
• Advanced mass spectrometry modes for improved sensitivity and isotopic resolution
• Automated image-analysis pipelines powered by machine learning
• 3D bioimaging via depth profiling and tomography

Conclusion

The integrated Agilent ICP-QQQ/ICP-MS and ESL laser ablation platform delivers robust, high-resolution elemental bioimaging. This methodology enhances understanding of metal homeostasis in health and disease, offering versatile tools for clinical research and translational applications.

References

1. Jiménez Nosti A. et al. Direct and Traceable Mass Purity Certification of Protein Standards using LC-ICP-MS/MS. Agilent publication, 2022, 5994-5073EN.
2. Tanaka Y. et al. Evaluation of the Elemental Content of a Single Cell using Fast Time Resolved Analysis (TRA)-ICP-MS. Agilent publication, 2022, 5994-4460EN.