Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension
Cells in a tumor microenvironment are exposed to spatial and temporal variations in oxygen tension due to hyperproliferation and immature vascularization. Such spatiotemporal oxygen heterogeneity affects the behavior of cancer cells, leading to cancer growth and metastasis, and thus, it is essential...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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AIP Publishing
2020
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| Online Access: | https://hdl.handle.net/1721.1/128366 |
| _version_ | 1811088277504000000 |
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| author | Koens, Rei Tabata, Yugo Serrano, Jean Carlos Aratake, Satoshi Yoshino, Daisuke Kamm, Roger Dale Funamoto, Kenichi |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Koens, Rei Tabata, Yugo Serrano, Jean Carlos Aratake, Satoshi Yoshino, Daisuke Kamm, Roger Dale Funamoto, Kenichi |
| author_sort | Koens, Rei |
| collection | MIT |
| description | Cells in a tumor microenvironment are exposed to spatial and temporal variations in oxygen tension due to hyperproliferation and immature vascularization. Such spatiotemporal oxygen heterogeneity affects the behavior of cancer cells, leading to cancer growth and metastasis, and thus, it is essential to clarify the cellular responses of cancer cells to oxygen tension. Herein, we describe a new double-layer microfluidic device allowing the control of oxygen tension and the behavior of cancer cells under spatiotemporal oxygen heterogeneity. Two parallel gas channels were located above the media and gel channels to enhance gas exchange, and a gas-impermeable polycarbonate film was embedded in the device to prevent the diffusion of atmospheric oxygen. Variations in oxygen tension in the device with the experimental parameters and design variables were investigated computationally and validated by using oxygen-sensitive nanoparticles. The present device can generate a uniform hypoxic condition at oxygen levels down to 0.3% O2, as well as a linear oxygen gradient from 3% O2 to 17% O2 across the gel channel within 15 min. Moreover, human breast cancer cells suspended in type I collagen gel were introduced in the gel channel to observe their response under controlled oxygen tension. Hypoxic exposure activated the proliferation and motility of the cells, which showed a local maximum increase at 5% O2. Under the oxygen gradient condition, the increase in the cell number was relatively high in the central mild hypoxia region. These findings demonstrate the utility of the present device to study cellular responses in an oxygen-controlled microenvironment. |
| first_indexed | 2024-09-23T13:59:40Z |
| format | Article |
| id | mit-1721.1/128366 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:59:40Z |
| publishDate | 2020 |
| publisher | AIP Publishing |
| record_format | dspace |
| spelling | mit-1721.1/1283662022-09-28T17:34:36Z Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension Koens, Rei Tabata, Yugo Serrano, Jean Carlos Aratake, Satoshi Yoshino, Daisuke Kamm, Roger Dale Funamoto, Kenichi Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. Department of Biological Engineering Cells in a tumor microenvironment are exposed to spatial and temporal variations in oxygen tension due to hyperproliferation and immature vascularization. Such spatiotemporal oxygen heterogeneity affects the behavior of cancer cells, leading to cancer growth and metastasis, and thus, it is essential to clarify the cellular responses of cancer cells to oxygen tension. Herein, we describe a new double-layer microfluidic device allowing the control of oxygen tension and the behavior of cancer cells under spatiotemporal oxygen heterogeneity. Two parallel gas channels were located above the media and gel channels to enhance gas exchange, and a gas-impermeable polycarbonate film was embedded in the device to prevent the diffusion of atmospheric oxygen. Variations in oxygen tension in the device with the experimental parameters and design variables were investigated computationally and validated by using oxygen-sensitive nanoparticles. The present device can generate a uniform hypoxic condition at oxygen levels down to 0.3% O2, as well as a linear oxygen gradient from 3% O2 to 17% O2 across the gel channel within 15 min. Moreover, human breast cancer cells suspended in type I collagen gel were introduced in the gel channel to observe their response under controlled oxygen tension. Hypoxic exposure activated the proliferation and motility of the cells, which showed a local maximum increase at 5% O2. Under the oxygen gradient condition, the increase in the cell number was relatively high in the central mild hypoxia region. These findings demonstrate the utility of the present device to study cellular responses in an oxygen-controlled microenvironment. 2020-11-05T20:02:03Z 2020-11-05T20:02:03Z 2020-03 2019-09 2020-08-17T16:50:30Z Article http://purl.org/eprint/type/JournalArticle 2473-2877 https://hdl.handle.net/1721.1/128366 Koens, Rei et al. "Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension." APL Bioengineering 4, 1 (March 2020): 016106. © 2020 Author(s) en http://dx.doi.org/10.1063/1.5127069 APL Bioengineering Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf AIP Publishing American Institute of Physics (AIP) |
| spellingShingle | Koens, Rei Tabata, Yugo Serrano, Jean Carlos Aratake, Satoshi Yoshino, Daisuke Kamm, Roger Dale Funamoto, Kenichi Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension |
| title | Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension |
| title_full | Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension |
| title_fullStr | Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension |
| title_full_unstemmed | Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension |
| title_short | Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension |
| title_sort | microfluidic platform for three dimensional cell culture under spatiotemporal heterogeneity of oxygen tension |
| url | https://hdl.handle.net/1721.1/128366 |
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