High-throughput generation of microfluidic-templating microgels for large-scale single-cell encapsulation

Microfluidics-based fabrication of cell-laden microgels has shown great potential for applications in cell therapy and tissue engineering, however, the difficulty in chip operation and compromised cell viability due to cell sedimentation and channel blockage remain a major challenge for functional c...

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Main Authors: Haoyue Zhang, Chengze Li, Yujie Zhang, Chuanfeng An, Hanting Li, Jiahui Yu, Yonghao Zhang, Wei He, Huanan Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Sensors
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fsens.2022.1037723/full
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author Haoyue Zhang
Chengze Li
Yujie Zhang
Chuanfeng An
Chuanfeng An
Chuanfeng An
Hanting Li
Jiahui Yu
Yonghao Zhang
Wei He
Huanan Wang
author_facet Haoyue Zhang
Chengze Li
Yujie Zhang
Chuanfeng An
Chuanfeng An
Chuanfeng An
Hanting Li
Jiahui Yu
Yonghao Zhang
Wei He
Huanan Wang
author_sort Haoyue Zhang
collection DOAJ
description Microfluidics-based fabrication of cell-laden microgels has shown great potential for applications in cell therapy and tissue engineering, however, the difficulty in chip operation and compromised cell viability due to cell sedimentation and channel blockage remain a major challenge for functional cell-laden microgels preparation. Herein, we presented the design and optimization of integrated microfluidic chip for large-scale preparation of cell-laden microgels with controllable size and complex microstructure. Specifically, to avoid severe cell sedimentation and uneven distribution in the parallelized microchannel, we simulated cell movement state using computational fluid dynamics simulation. It was found that higher laminar flow velocity gradient and higher precursor viscosity can significantly improve the uniform cell distribution in parallelized channels and reduce the product difference between channels. Moreover, we designed multiple-layered microfluidic chips allowing multiple inputting liquids for the fabrication of microgels with complex structures. This integrated chip facilitated cell encapsulation at a maximum production rate of 240 ml/h of cell suspension with retained cell viability and functionality. Therefore, our study provided a biocompatible and high-throughput strategy for large-scale preparation of cell-laden microgels, which can enable significant advances for clinical-relevant applications of cell-laden microgels, including cell therapy, tissue regeneration and 3D bioprinting.
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spelling doaj.art-f18c846a43fb454989cf7f2e08262c2c2022-12-22T02:32:51ZengFrontiers Media S.A.Frontiers in Sensors2673-50672022-10-01310.3389/fsens.2022.10377231037723High-throughput generation of microfluidic-templating microgels for large-scale single-cell encapsulationHaoyue Zhang0Chengze Li1Yujie Zhang2Chuanfeng An3Chuanfeng An4Chuanfeng An5Hanting Li6Jiahui Yu7Yonghao Zhang8Wei He9Huanan Wang10Key State Laboratory of Fine Chemicals, School of Bioengineering, Dalian University of Technology, Dalian, ChinaKey State Laboratory of Fine Chemicals, School of Bioengineering, Dalian University of Technology, Dalian, ChinaKey State Laboratory of Fine Chemicals, School of Bioengineering, Dalian University of Technology, Dalian, ChinaKey State Laboratory of Fine Chemicals, School of Bioengineering, Dalian University of Technology, Dalian, ChinaGuangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, ChinaCentral Laboratory, Longgang District People’s Hospital of Shenzhen and The Second Affiliated Hospital of The Chinese University of Hong Kong, Shenzhen, ChinaKey State Laboratory of Fine Chemicals, School of Bioengineering, Dalian University of Technology, Dalian, ChinaKey State Laboratory of Fine Chemicals, School of Bioengineering, Dalian University of Technology, Dalian, ChinaKey State Laboratory of Fine Chemicals, School of Bioengineering, Dalian University of Technology, Dalian, ChinaKey State Laboratory of Fine Chemicals, School of Bioengineering, Dalian University of Technology, Dalian, ChinaKey State Laboratory of Fine Chemicals, School of Bioengineering, Dalian University of Technology, Dalian, ChinaMicrofluidics-based fabrication of cell-laden microgels has shown great potential for applications in cell therapy and tissue engineering, however, the difficulty in chip operation and compromised cell viability due to cell sedimentation and channel blockage remain a major challenge for functional cell-laden microgels preparation. Herein, we presented the design and optimization of integrated microfluidic chip for large-scale preparation of cell-laden microgels with controllable size and complex microstructure. Specifically, to avoid severe cell sedimentation and uneven distribution in the parallelized microchannel, we simulated cell movement state using computational fluid dynamics simulation. It was found that higher laminar flow velocity gradient and higher precursor viscosity can significantly improve the uniform cell distribution in parallelized channels and reduce the product difference between channels. Moreover, we designed multiple-layered microfluidic chips allowing multiple inputting liquids for the fabrication of microgels with complex structures. This integrated chip facilitated cell encapsulation at a maximum production rate of 240 ml/h of cell suspension with retained cell viability and functionality. Therefore, our study provided a biocompatible and high-throughput strategy for large-scale preparation of cell-laden microgels, which can enable significant advances for clinical-relevant applications of cell-laden microgels, including cell therapy, tissue regeneration and 3D bioprinting.https://www.frontiersin.org/articles/10.3389/fsens.2022.1037723/fullcomputational fluid dynamics simulationmicrofluidic dropletsintegrated microfluidic chipalginatecell-laden microgel
spellingShingle Haoyue Zhang
Chengze Li
Yujie Zhang
Chuanfeng An
Chuanfeng An
Chuanfeng An
Hanting Li
Jiahui Yu
Yonghao Zhang
Wei He
Huanan Wang
High-throughput generation of microfluidic-templating microgels for large-scale single-cell encapsulation
Frontiers in Sensors
computational fluid dynamics simulation
microfluidic droplets
integrated microfluidic chip
alginate
cell-laden microgel
title High-throughput generation of microfluidic-templating microgels for large-scale single-cell encapsulation
title_full High-throughput generation of microfluidic-templating microgels for large-scale single-cell encapsulation
title_fullStr High-throughput generation of microfluidic-templating microgels for large-scale single-cell encapsulation
title_full_unstemmed High-throughput generation of microfluidic-templating microgels for large-scale single-cell encapsulation
title_short High-throughput generation of microfluidic-templating microgels for large-scale single-cell encapsulation
title_sort high throughput generation of microfluidic templating microgels for large scale single cell encapsulation
topic computational fluid dynamics simulation
microfluidic droplets
integrated microfluidic chip
alginate
cell-laden microgel
url https://www.frontiersin.org/articles/10.3389/fsens.2022.1037723/full
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