Single cell ICP-MS analysis using the scQuant Plug-in

Significance of the topic

Trace elements play essential roles in cellular function, and subtle variations in metal content at the single cell level can reveal critical insights into metabolic pathways, drug uptake, and disease mechanisms. High-resolution analysis of individual cells addresses population heterogeneity and enables more precise biological interpretations.

Objectives and study overview

This technical note illustrates the implementation of the Thermo Scientific scQuant Plug-in within the Qtegra Intelligent Scientific Data Solution (ISDS) Software on a Thermo Scientific Q ICP-MS platform. The goal is to demonstrate a guided, high-throughput workflow for screening large numbers of individual cells (or nanoparticles) for trace metal composition and concentration.

Methodology

Single cells introduced into the ICP-MS plasma are fully atomized and ionized, generating discrete ion bursts (~0.5 ms) detected in time-resolved mode with dwell times below 10 ms. The scQuant Plug-in orchestrates sample delivery control, real-time signal discrimination via an nσ criterion to separate cell‐derived events from background, and automated integration of signal spikes to quantify mass per cell and count events per sample volume.

Used Instrumentation

• Thermo Scientific Qtegra ISDS Software with scQuant Plug-in
• Thermo Scientific iCAP TQ Series ICP-MS or equivalent quadrupole-based ICP-MS
• Chemyx syringe pump integrated via dedicated plug-in for low-flow sample introduction
• Dedicated single cell autosampler or digital I/O triggers for assay control

Main results and discussion

The scQuant Plug-in supports multi-element screening by sequentially measuring multiple isotopes within a single sample aspiration, eliminating the need to restart analyses. It independently calculates transport efficiencies by mass (to correct for spray chamber partitioning) and by counting (to account for physical losses and lysis). An iterative nσ algorithm accurately establishes background levels and quantifies cell events. Data visualization options include mass distribution histograms and box plots, alongside summary tables for each sample fraction.

Benefits and practical applications

• Automated, user-friendly workflow tailored to single cell and nanoparticle analysis
• Accurate quantification of analyte mass distribution and cell concentration
• Simultaneous multi-element analysis within a single run
• Enhanced traceability through syringe metadata integration
• Applications in metallomics, pharmacokinetics, environmental microplastic detection, and QA/QC in biopharma

Future trends and potential applications

Future developments may include integration of AI-driven data processing, microfluidic-based cell handling for higher throughput, expansion to diverse small entities (e.g., exosomes, viruses), and cloud-based reporting. Real-time adaptive acquisition strategies and enhanced automation will further broaden the technique’s impact.

Conclusion

The scQuant Plug-in enhances single cell ICP-MS by providing an integrated platform for automated event detection, accurate analyte quantification, and intuitive data visualization. Its multi-element capability and guided workflow make it a valuable tool for analytical chemistry laboratories investigating cellular and nanoparticle systems.

References

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