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Updated: Jul 18, 2026

Single-cell Analysis of Immunophenotype and Cytokine Production in Peripheral Whole Blood via Mass Cytometry
Published on: June 26, 2018
Single-cell deep phenotyping of cytokine release unmasks stimulation-specific biological signatures and distinct
Kevin Portmann1, Aline Linder1, Nicole Oelgarth1
1Laboratory for Functional Immune Repertoire Analysis, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland.
Insights
This study introduces a novel microfluidic platform for dynamic, single-cell cytokine secretion analysis. The advanced assay reveals distinct immune cell subpopulations and secretion dynamics, improving risk assessment for immunotherapies.
Area of Science:
- Immunology
- Biotechnology
- Cell Biology
Background:
- Cytokines are crucial immune mediators, but their dysregulated secretion can cause adverse effects like cytokine release syndromes.
- Immunotherapies can induce cytokine dysregulation, necessitating robust risk assessment during drug development.
- Traditional cytokine release assays (CRAs) lack insight into heterogeneous cellular dynamics.
Purpose of the Study:
- To develop an advanced single-cell microfluidic platform for dynamic quantification of cytokine secretion.
- To overcome the limitations of current CRAs in assessing cellular heterogeneity.
- To gain deeper insights into immune cell secretion behavior and stimulation pathways.
Main Methods:
- Development of a single-cell microfluidic-based platform for cytokine secretion analysis.
- Dynamic quantification of cytokine secretion at the single-cell level.
- Analysis of distinct immune cell subpopulations and their secretion profiles.
Main Results:
- The platform identified diverse secretion dynamics, quantities, and phenotypically distinct subpopulations for various cytokines.
- Early measurements (1 hour) revealed distinct stimulation-dependent secretion dynamics and cytokine signatures.
- The approach provided high sensitivity and dynamic resolution, offering insights into individual immune cell secretion.
Conclusions:
- The developed microfluidic platform enables dynamic, single-cell analysis of cytokine secretion.
- This technology enhances understanding of immune cell behavior and cytokine release pathways.
- The platform offers crucial information for improved risk assessment in drug development and immunotherapy.
Abstract:
Cytokines are important mediators of the immune system, and their secretion level needs to be carefully regulated, as an unbalanced activity may lead to cytokine release syndromes. Dysregulation can be induced by various factors, including immunotherapies. Therefore, the need for risk assessment during drug development has led to the introduction of cytokine release assays (CRAs). However, the current CRAs offer little insight into the heterogeneous cellular dynamics. To overcome this limitation, we developed an advanced single-cell microfluidic-based cytokine secretion platform to quantify cytokine secretion on the single-cell level dynamically. Our approach identified different dynamics, quantities, and phenotypically distinct subpopulations for each measured cytokine upon stimulation. Most interestingly, early measurements after only 1 h of stimulation revealed distinct stimulation-dependent secretion dynamics and cytokine signatures. With increased sensitivity and dynamic resolution, our platform provided insights into the secretion behavior of individual immune cells, adding crucial additional information about biological stimulation pathways to traditional CRAs.
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