Perfused three-dimensional (3D) cultures enable long-term in situ growth and monitoring of 3D organoids making them well-suited for investigating organoid development, growth, and function. One of the limitations of this long-term on-chip perfused 3D culture is unintended and disruptive air bubbles. To overcome this obstacle, we invented an imaging platform that integrates an innovative microfluidic bubble pocket for long-term perfused 3D culture of gastrointestinal (GI) organoids. We successfully applied 3D printing technology to create polymer molds that cast polydimethylsiloxane (PDMS) culture chambers in addition to bubble pockets. Our developed platform traps unintended, or induced, air bubbles in an integrated PDMS pocket chamber, where the bubbles diffuse out across the gas permeable PDMS or an outlet tube. We demonstrated that our robust platform integrated with the novel bubble pocket effectively circumvents the development of bubbles into human and mouse GI organoid cultures during long-term perfused time-course imaging. Our platform with the innovative integrated bubble pocket is ideally suited for studies requiring long-term perfusion monitoring of organ growth and morphogenesis as well as function.
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January 2021
Research Article|
February 17 2021
An integrated microfluidic bubble pocket for long-term perfused three-dimensional intestine-on-a-chip model Available to Purchase
Kang Kug (Paul) Lee
;
Kang Kug (Paul) Lee
a)
1
Computational and Molecular Biology Laboratory, Department of Pharmacology and Systems Physiology, University of Cincinnati
, Cincinnati, Ohio 45267, USA
2
iNNO MeDevice, Inc.
, 7752 Montgomery Rd., Unit 25, Cincinnati, Ohio 45236, USA
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Toru Matsu-ura
;
Toru Matsu-ura
1
Computational and Molecular Biology Laboratory, Department of Pharmacology and Systems Physiology, University of Cincinnati
, Cincinnati, Ohio 45267, USA
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Andrew E. Rosselot;
Andrew E. Rosselot
1
Computational and Molecular Biology Laboratory, Department of Pharmacology and Systems Physiology, University of Cincinnati
, Cincinnati, Ohio 45267, USA
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Taylor R. Broda;
Taylor R. Broda
3
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center
, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
5
Center for Stem Cell and Organoid Medicine, Cincinnati Children's Hospital Medical Center
, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
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James M. Wells;
James M. Wells
3
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center
, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
4
Division of Endocrinology, Cincinnati Children's Hospital Medical Center
, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
5
Center for Stem Cell and Organoid Medicine, Cincinnati Children's Hospital Medical Center
, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
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Christian I. Hong
Christian I. Hong
a)
1
Computational and Molecular Biology Laboratory, Department of Pharmacology and Systems Physiology, University of Cincinnati
, Cincinnati, Ohio 45267, USA
3
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center
, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
5
Center for Stem Cell and Organoid Medicine, Cincinnati Children's Hospital Medical Center
, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
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Kang Kug (Paul) Lee
1,2,a)
Toru Matsu-ura
1
Andrew E. Rosselot
1
Taylor R. Broda
3,5
James M. Wells
3,4,5
Christian I. Hong
1,3,5,a)
1
Computational and Molecular Biology Laboratory, Department of Pharmacology and Systems Physiology, University of Cincinnati
, Cincinnati, Ohio 45267, USA
2
iNNO MeDevice, Inc.
, 7752 Montgomery Rd., Unit 25, Cincinnati, Ohio 45236, USA
3
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center
, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
5
Center for Stem Cell and Organoid Medicine, Cincinnati Children's Hospital Medical Center
, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
4
Division of Endocrinology, Cincinnati Children's Hospital Medical Center
, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
Biomicrofluidics 15, 014110 (2021)
Article history
Received:
November 06 2020
Accepted:
February 01 2021
Citation
Kang Kug (Paul) Lee, Toru Matsu-ura, Andrew E. Rosselot, Taylor R. Broda, James M. Wells, Christian I. Hong; An integrated microfluidic bubble pocket for long-term perfused three-dimensional intestine-on-a-chip model. Biomicrofluidics 1 January 2021; 15 (1): 014110. https://doi.org/10.1063/5.0036527
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