A modular microfluidic system based on a multilayered configuration to generate large-scale perfusable microvascular networks
Abstract The vascular network of the circulatory system plays a vital role in maintaining homeostasis in the human body. In this paper, a novel modular microfluidic system with a vertical two-layered configuration is developed to generate large-scale perfused microvascular networks in vitro. The two...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-01-01
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| Series: | Microsystems & Nanoengineering |
| Online Access: | https://doi.org/10.1038/s41378-020-00229-8 |
| _version_ | 1819330547464273920 |
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| author | Tao Yue Da Zhao Duc T. T. Phan Xiaolin Wang Joshua Jonghyun Park Zayn Biviji Christopher C. W. Hughes Abraham P. Lee |
| author_facet | Tao Yue Da Zhao Duc T. T. Phan Xiaolin Wang Joshua Jonghyun Park Zayn Biviji Christopher C. W. Hughes Abraham P. Lee |
| author_sort | Tao Yue |
| collection | DOAJ |
| description | Abstract The vascular network of the circulatory system plays a vital role in maintaining homeostasis in the human body. In this paper, a novel modular microfluidic system with a vertical two-layered configuration is developed to generate large-scale perfused microvascular networks in vitro. The two-layer polydimethylsiloxane (PDMS) configuration allows the tissue chambers and medium channels not only to be designed and fabricated independently but also to be aligned and bonded accordingly. This method can produce a modular microfluidic system that has high flexibility and scalability to design an integrated platform with multiple perfused vascularized tissues with high densities. The medium channel was designed with a rhombic shape and fabricated to be semiclosed to form a capillary burst valve in the vertical direction, serving as the interface between the medium channels and tissue chambers. Angiogenesis and anastomosis at the vertical interface were successfully achieved by using different combinations of tissue chambers and medium channels. Various large-scale microvascular networks were generated and quantified in terms of vessel length and density. Minimal leakage of the perfused 70-kDa FITC-dextran confirmed the lumenization of the microvascular networks and the formation of tight vertical interconnections between the microvascular networks and medium channels in different structural layers. This platform enables the culturing of interconnected, large-scale perfused vascularized tissue networks with high density and scalability for a wide range of multiorgan-on-a-chip applications, including basic biological studies and drug screening. |
| first_indexed | 2024-12-24T14:00:16Z |
| format | Article |
| id | doaj.art-7e67611ba7b84c1aa78556f97992189c |
| institution | Directory Open Access Journal |
| issn | 2055-7434 |
| language | English |
| last_indexed | 2024-12-24T14:00:16Z |
| publishDate | 2021-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Microsystems & Nanoengineering |
| spelling | doaj.art-7e67611ba7b84c1aa78556f97992189c2022-12-21T16:52:29ZengNature Publishing GroupMicrosystems & Nanoengineering2055-74342021-01-017111310.1038/s41378-020-00229-8A modular microfluidic system based on a multilayered configuration to generate large-scale perfusable microvascular networksTao Yue0Da Zhao1Duc T. T. Phan2Xiaolin Wang3Joshua Jonghyun Park4Zayn Biviji5Christopher C. W. Hughes6Abraham P. Lee7Department of Biomedical Engineering, University of CaliforniaDepartment of Biomedical Engineering, University of CaliforniaDepartment of Molecular Biology and Biochemistry, University of CaliforniaDepartment of Micro/Nano Electronics, Shanghai Jiao Tong UniversityDepartment of Electrical Engineering and Computer Science, University of CaliforniaDepartment of Applied Mathematics - Biology, Brown UniversityDepartment of Biomedical Engineering, University of CaliforniaDepartment of Biomedical Engineering, University of CaliforniaAbstract The vascular network of the circulatory system plays a vital role in maintaining homeostasis in the human body. In this paper, a novel modular microfluidic system with a vertical two-layered configuration is developed to generate large-scale perfused microvascular networks in vitro. The two-layer polydimethylsiloxane (PDMS) configuration allows the tissue chambers and medium channels not only to be designed and fabricated independently but also to be aligned and bonded accordingly. This method can produce a modular microfluidic system that has high flexibility and scalability to design an integrated platform with multiple perfused vascularized tissues with high densities. The medium channel was designed with a rhombic shape and fabricated to be semiclosed to form a capillary burst valve in the vertical direction, serving as the interface between the medium channels and tissue chambers. Angiogenesis and anastomosis at the vertical interface were successfully achieved by using different combinations of tissue chambers and medium channels. Various large-scale microvascular networks were generated and quantified in terms of vessel length and density. Minimal leakage of the perfused 70-kDa FITC-dextran confirmed the lumenization of the microvascular networks and the formation of tight vertical interconnections between the microvascular networks and medium channels in different structural layers. This platform enables the culturing of interconnected, large-scale perfused vascularized tissue networks with high density and scalability for a wide range of multiorgan-on-a-chip applications, including basic biological studies and drug screening.https://doi.org/10.1038/s41378-020-00229-8 |
| spellingShingle | Tao Yue Da Zhao Duc T. T. Phan Xiaolin Wang Joshua Jonghyun Park Zayn Biviji Christopher C. W. Hughes Abraham P. Lee A modular microfluidic system based on a multilayered configuration to generate large-scale perfusable microvascular networks Microsystems & Nanoengineering |
| title | A modular microfluidic system based on a multilayered configuration to generate large-scale perfusable microvascular networks |
| title_full | A modular microfluidic system based on a multilayered configuration to generate large-scale perfusable microvascular networks |
| title_fullStr | A modular microfluidic system based on a multilayered configuration to generate large-scale perfusable microvascular networks |
| title_full_unstemmed | A modular microfluidic system based on a multilayered configuration to generate large-scale perfusable microvascular networks |
| title_short | A modular microfluidic system based on a multilayered configuration to generate large-scale perfusable microvascular networks |
| title_sort | modular microfluidic system based on a multilayered configuration to generate large scale perfusable microvascular networks |
| url | https://doi.org/10.1038/s41378-020-00229-8 |
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