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The study of cell-cell interaction in high-throughput is critically important in many biological systems, including oncology, immunology, and tissue engineering. However, the passive co-encapsulation of one type A cell and one type B cell per single droplet, termed 1-1-1 encapsulation, has been dictated by double Poisson distribution, which yields only ~5% efficiency with common cell loading density. Such low efficiency makes it impractical for biological analyses at scale. Here, we demonstrate a passive 1-1-1 co-encapsulation microfluidic device that leverages close packing of cells with hydrodynamic sheath flow to achieve over two-fold improvement compared to the double Poisson model.
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Conformal single cell hydrogel coating with electrically induced tip streaming of an AC cone
Encapsulation of single cells in a thin hydrogel provides a more precise control of stem cell niches and better molecular transport. Despite the recent advances in microfluidic technologies to allow encapsulation of single cells, existing methods rely on special crosslinking agents that are pre-coated on the cell surface and subject to the variation of the cell membrane, which limits their widespread adoption. This work reports a high-throughput single-cell encapsulation method based on the “tip streaming” mode of alternating current (AC) electrospray, with encapsulation efficiencies over 80% after tuned centrifugation. Dripping with multiple cells is curtailed due to gating by the sharp conic meniscus of the tip streaming mode that only allows one cell to be ejected at a time. Moreover, the method can be universally applied to both natural and synthetic hydrogels, as well as various cell types, including human multipotent mesenchymal stromal cells (hMSCs). Encapsulated hMSCs maintain good cell viability over an extended culture period and exhibit robust differentiation potential into osteoblasts and adipocytes. Collectively, electrically induced tip streaming enables high-throughput encapsulation of single cells with high efficiency and universality, which is applicable for various applications in cell therapy, pharmacokinetic studies, and regenerative medicine.
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- Award ID(s):
- 2047903
- PAR ID:
- 10333262
- Date Published:
- Journal Name:
- Biomaterials Science
- Volume:
- 9
- Issue:
- 9
- ISSN:
- 2047-4830
- Page Range / eLocation ID:
- 3284 to 3292
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D0BM02100H
