We present an extracellular matrix (ECM)-based gradient generator that provides a culture surface with continuous chemical concentration gradients created by interstitial flow. The gelatin-based microchannels harboring gradient generators and in-channel micromixers were rapidly fabricated by sacrificial molding of a 3D-printed water-soluble sacrificial mold. When fluorescent dye solutions were introduced into the channel, the micromixers enhanced mixing of two solutions joined at the junction. Moreover, the concentration gradients generated in the channel diffused to the culture surface of the device through the interstitial space facilitated by the porous nature of the ECM. To check the functionality of the gradient generator for investigating cellular responses to chemical factors, we demonstrated that human umbilical vein endothelial cells cultured on the surface shrunk in response to the concentration gradient of histamine generated by interstitial flow from the microchannel. We believe that our device could be useful for the basic biological study of the cellular response to chemical stimuli and for the in vitro platform in drug testing.
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July 2020
Research Article|
July 16 2020
ECM-based microfluidic gradient generator for tunable surface environment by interstitial flow
Azusa Shimizu;
Azusa Shimizu
1
School of Integrated Design Engineering, Graduate School of Science and Technology, Keio University
, 3-14-1 Hiyoshi, Kohoku-Ku, Yokohama, Japan
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Wei Huang Goh
;
Wei Huang Goh
2
Engineering Product Development, Singapore University of Technology and Design
, Singapore
487372
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Shun Itai;
Shun Itai
1
School of Integrated Design Engineering, Graduate School of Science and Technology, Keio University
, 3-14-1 Hiyoshi, Kohoku-Ku, Yokohama, Japan
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Rahul Karyappa;
Rahul Karyappa
2
Engineering Product Development, Singapore University of Technology and Design
, Singapore
487372
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Michinao Hashimoto
;
Michinao Hashimoto
a)
2
Engineering Product Development, Singapore University of Technology and Design
, Singapore
4873723
Digital Manufacturing and Design (DManD) Centre, Singapore University of Technology and Design
, Singapore
487372
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Hiroaki Onoe
Hiroaki Onoe
a)
1
School of Integrated Design Engineering, Graduate School of Science and Technology, Keio University
, 3-14-1 Hiyoshi, Kohoku-Ku, Yokohama, Japan
4
Department of Mechanical Engineering, Faculty of Science and Technology, Keio University
, 3-14-1 Hiyoshi, Kohoku-Ku, Yokohama, Japan
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Biomicrofluidics 14, 044106 (2020)
Article history
Received:
April 16 2020
Accepted:
July 08 2020
Citation
Azusa Shimizu, Wei Huang Goh, Shun Itai, Rahul Karyappa, Michinao Hashimoto, Hiroaki Onoe; ECM-based microfluidic gradient generator for tunable surface environment by interstitial flow. Biomicrofluidics 1 July 2020; 14 (4): 044106. https://doi.org/10.1063/5.0010941
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