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PicoShells: Hollow Hydrogel Microparticles for High-Throughput Screening of Clonal Libraries
Cayden Williamson1, Mark van Zee1, Dino Di Carlo2,3,4,5
1Department of Bioengineering, University of California, Los Angeles, CA, USA.
Methods in Molecular Biology (Clifton, N.J.)
|July 10, 2023
Summary
Microfluidic droplet technology creates PicoShells to encapsulate single cells for monoclonal colony growth. This method preserves cell viability and enables high-throughput phenotypic analysis and sorting for drug discovery.
Area of Science:
- Biotechnology
- Cell Biology
- Microfluidics
Background:
- Microfluidics facilitates the generation of uniform, micron-sized droplets for picolitre-volume reactions.
- These droplets can serve as micro-scale reaction chambers for chemical assays.
- Encapsulating single cells is crucial for various biological applications.
Purpose of the Study:
- To describe a novel method for encapsulating single cells within hydrogel microparticles called PicoShells.
- To demonstrate a cell-friendly fabrication process for PicoShells.
- To enable high-throughput phenotypic analysis and sorting of cells within PicoShells.
Main Methods:
- Utilized microfluidic droplet generation to encapsulate single cells.
- Employed a mild pH-based crosslinking method for hydrogel microparticle fabrication (PicoShells).
- Grew monoclonal cell colonies within PicoShells and analyzed/sorted them using fluorescence-activated cell sorting (FACS).
Main Results:
- Successfully fabricated hollow hydrogel microparticles (PicoShells) encapsulating single cells.
- The pH-based crosslinking method maintained high cell viability and avoided genomic modifications.
- Enabled phenotypic analysis and sorting of monoclonal colonies using FACS.
- Demonstrated the ability to release selected cells for downstream applications.
Conclusions:
- PicoShells provide a versatile platform for cell encapsulation, growth, and analysis.
- The fabrication method is compatible with scaled production and standard laboratory techniques.
- This technology is particularly useful for drug discovery, enabling the identification of protein expression in heterogeneous cells and directed cell evolution.
