Assessing the level and distribution of trace elements in individual cells using single cell ICP-MS analysis

Importance of the Topic

Understanding the distribution of trace elements at the level of individual cells is critical for insights into cellular heterogeneity, metabolic regulation, and the role of essential elements in health and disease. Traditional bulk measurements mask cell-to-cell variability, whereas single-cell ICP-MS enables direct quantification of element content in each cell, supporting research in toxicology, pharmacology, and biotechnology.

Objectives and Study Overview

This study demonstrates how a triple quadrupole ICP-MS system coupled with the scQuant plug-in for Qtegra™ ISDS software can quantify phosphorous and selenium in individual yeast cells. Hundreds of cells from a certified reference material were analyzed to determine the mass distribution of these elements across a cell population.

Methodology

Studied yeast cells (SELM-1 CRM) were reconstituted, washed, and counted by flow cytometry. Samples were diluted to ~50 000 cells/mL and introduced at 10 µL/min using a syringe pump. Transient signals for 31P16O+ and 80Se16O+ were generated in TQ-O2 mode to eliminate polyatomic interferences. The scQuant plug-in orchestrated sequential scanning of isotopes, captured millisecond-scale cell transients, and processed data automatically.

Instrumentation Used

• Thermo Scientific™ iCAP™ TQ ICP-MS in TQ-O2 mode
• MicroMist HE U-Series nebulizer and low-flow spray chamber (Glass Expansion)
• Chemyx syringe pump (10 µL/min sample delivery)
• Thermo Scientific™ Qtegra™ ISDS Software with scQuant plug-in

Main Results and Discussion

Signal intensities averaged ~165 000 cps for phosphorous and ~46 000 cps for selenium. Transport efficiency, assessed with 30 nm gold nanoparticles, was ~65%, yielding detection of ~68% of cells by phosphorous and ~58% by selenium. Selenium content per cell ranged from ~2.5 fg to ~72.5 fg, reflecting a broad distribution. Phosphorous measurements corresponded to mean values around 37 fg per cell (median ~31 fg, SD ~23 fg), consistent with DNA content. Histograms and box plots generated by scQuant illustrated element distribution and variability across the cohort.

Benefits and Practical Applications

• High-throughput single-cell quantification of multiple elements in one run
• Automated data processing with integrated visualization (histograms, box plots)
• Accurate assessment of transport efficiency and sensitivity in a single workflow
• Applicability to diverse fields: bioprocess monitoring, environmental toxicology, biomedical research

Future Trends and Potential Applications

Advances in scICP-MS are expected to increase throughput and multiplexing capabilities, enabling simultaneous analysis of additional elements and isotopes. Integration with microfluidic cell sorting and machine learning data analytics will further enhance resolution and interpretation of cellular element profiles. Applications may expand to clinical diagnostics, nanoparticle uptake studies, and real-time monitoring of bioprocesses.

Conclusion

This work validates the use of triple quadrupole ICP-MS with the scQuant plug-in for reliable single-cell measurement of trace elements. The approach provides quantitative mass distributions of phosphorous and selenium in yeast populations, offering a robust platform for investigating cellular heterogeneity and elemental homeostasis.

References

• Klein E.A. Selenium and vitamin E cancer prevention trial; Ann. N.Y. Acad. Sci. 2004, 1031, 234–241.
• Gilbert-López B. et al. Detection of over 100 selenium metabolites in selenized yeast by liquid chromatography electrospray time-of-flight mass spectrometry; J. Chromatogr. B 2017, 1060, 84–90.
• Álvarez-Fernández García R. et al. Addressing the presence of biologic selenium nanoparticles in yeast cells: analytical strategies based on ICP-TQ-MS; Analyst 2020, 145, 1457–1465.