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Modular Droplet-Based Microfluidic Platform for Functional Phenotypic Screening of Natural Killer Cells
Florian Aubermann1,2,3, Senne Seneca1,2, Tomáš Hofman4
1Department of Cellular Biophysics, Max Planck Institute for Medical Research, 69120, Heidelberg, Germany.
Small Methods
|April 21, 2025
Summary
This study introduces a microfluidic platform to analyze Natural Killer (NK) cell serial killing ability. The technology enables the selection of NK cells based on their functional killing phenotypes, advancing innate immunity research.
Area of Science:
- Immunology
- Microfluidics
- Cell Biology
Background:
- Natural Killer (NK) cells are crucial for innate immunity but show variable target cell killing abilities.
- The mechanisms driving NK cell functional heterogeneity are not well understood.
Purpose of the Study:
- To develop a droplet-based microfluidic platform for identifying and selecting NK cells with serial killing capacity.
- To enable the study of complex functional phenotypes in NK cells.
Main Methods:
- Encapsulation of primary human NK cells with target cells in droplets using a microfluidic device.
- Development of a convolutional neural network (CNN) pipeline for quantifying cytotoxicity and serial killing events.
- Implementation of MultiCell-Sort, a real-time image-based droplet sorter, for functional cell selection.
Main Results:
- The platform accurately quantifies NK cell cytotoxicity and serial killing events.
- MultiCell-Sort successfully selects live NK cells based on functional phenotypes derived from cell-cell interactions.
- Demonstration of a novel microfluidic approach for phenotyping heterogeneous NK cell populations.
Conclusions:
- The presented microfluidic platform offers a novel method for analyzing and sorting NK cells based on their functional killing capabilities.
- This technology can facilitate the discovery of regulators and markers associated with NK cell heterogeneity.
- Advances understanding of innate immune effector cell function and selection.
