Multi-element determination in populations of single cells by quadrupole ICP-MS

Importance of the Topic

The ability to profile elemental composition at the single cell level overcomes limitations of bulk analysis by revealing heterogeneity within cell populations. This is critical in life sciences, clinical diagnostics, environmental monitoring, and studies of rare cell subpopulations.

Objectives and Study Overview

This work aimed to design and implement new hardware and software for quadrupole ICP-MS to perform multi-element quantification in individual yeast cells. The study compares single cell measurements against conventional digested cell bulk analysis.

Methodology and Instrumentation

Sample Preparation:

• Dried yeast (Saccharomyces cerevisiae) suspended in Milli-Q water and allowed to settle, extracting upper supernatant.
• Parallel bulk digestion of yeast using microwave-assisted acid digestion for method validation.

ICP-MS Analysis:

• Agilent 7800/7900 single quadrupole ICP-MS with MassHunter 4.4 and Fast TRA screening mode.
• 1.0 mm quartz torch, total consumption nebulizer, single pass spray chamber for CAP LC.
• Gas modes: no gas for Au, Mg, P, Mn, Co, Cu; He for K; H2 for Ca, Fe.
• Operating parameters: RF power 1600 W, sample depth 7.0 mm, nebulizer gas 0.77 L/min, dilution gas 0.10 L/min, dwell time 0.1 ms, acquisition time 20 s.

Main Results and Discussion

Time-resolved data showed approximately 500 discrete pulse signals per 20 s with 0.4 ms width, corresponding to ionized single cell events. Signal distributions for 16 elements including Au, Mg, P, K, Mn, Fe, Co, Cu, and Zn were clearly distinguishable from background noise. Cell counts remained consistent across elements, indicating stable sample density. Cross validation with digested samples revealed that single cell measurements yielded about half the element mass compared to bulk analysis, highlighting the need to refine threshold settings and counting stability.

Benefits and Practical Applications

Single cell ICP-MS allows automated, multi-element quantification in individual cells, enabling high-throughput phenotyping of cellular heterogeneity. Applications include antibody-based metal-tag detection, QA/QC in biomanufacturing, environmental toxicology, and biomedical research.

Future Trends and Potential Applications

Advancements may include development of certified single cell reference materials, automated threshold optimization, integration with imaging techniques, and coupling with multi-omics platforms. Emerging uses span clinical diagnostics, targeted drug screening, environmental pathogen monitoring, and single cell microbiology.

Conclusion

The newly developed quadrupole ICP-MS hardware and software successfully performed multi-element analysis of single yeast cells, yielding results comparable in magnitude to conventional bulk digestion. This approach paves the way for detailed elemental profiling of individual cells.

References

• C. Giesen, H. A. O. Wang, D. Schapiro et al., Nature Methods 11, 417-422 (2014)
• A. S. Groombridge, S. Miyashita, S. Fujii et al., Analytical Sciences 29(6):597-603 (2013)