Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies
Microphysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including 3D matrices and microperfusion. Here, we report an approach to co-culture multiple different MPSs linked together physiologically on re-...
| Κύριοι συγγραφείς: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Άλλοι συγγραφείς: | |
| Μορφή: | Άρθρο |
| Έκδοση: |
Nature Publishing Group
2018
|
| Διαθέσιμο Online: | http://hdl.handle.net/1721.1/115178 https://orcid.org/0000-0002-5248-871X https://orcid.org/0000-0003-1137-0413 https://orcid.org/0000-0001-8851-1224 https://orcid.org/0000-0001-7890-7209 https://orcid.org/0000-0003-3227-4631 https://orcid.org/0000-0002-6673-087X https://orcid.org/0000-0001-8272-6419 https://orcid.org/0000-0001-6975-5047 https://orcid.org/0000-0003-3491-4962 https://orcid.org/0000-0002-0050-989X https://orcid.org/0000-0001-5358-5450 https://orcid.org/0000-0002-1801-5548 |
| _version_ | 1826192431631040512 |
|---|---|
| author | Edington, Collin D Chen, Wen Li Geishecker, Emily R Kassis, Timothy Soenksen Martinez, Luis Ruben Bhushan, Brij M Maass, Christian Alexander Tsamandouras, Nikolaos Valdez Macias, Jorge Luis Cook, Christi Dionne Yu, Jiajie Suter, Emily C Shockley, Michael J Velazquez, Jason G Velazquez, Jeremy J. Stockdale, Linda Papps, Julia P Lee, Iris Vann, Nicholas W. Contreras Gamboa, Mario e LaBarge, Matthew E Zhong, Zhe Wang, Xin Boyer, Laurie Ann Lauffenburger, Douglas A Carrier, Rebecca Communal, Catherine Tannenbaum, Steven R Trumper, David L Cirit, Murat Griffith, Linda G |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Edington, Collin D Chen, Wen Li Geishecker, Emily R Kassis, Timothy Soenksen Martinez, Luis Ruben Bhushan, Brij M Maass, Christian Alexander Tsamandouras, Nikolaos Valdez Macias, Jorge Luis Cook, Christi Dionne Yu, Jiajie Suter, Emily C Shockley, Michael J Velazquez, Jason G Velazquez, Jeremy J. Stockdale, Linda Papps, Julia P Lee, Iris Vann, Nicholas W. Contreras Gamboa, Mario e LaBarge, Matthew E Zhong, Zhe Wang, Xin Boyer, Laurie Ann Lauffenburger, Douglas A Carrier, Rebecca Communal, Catherine Tannenbaum, Steven R Trumper, David L Cirit, Murat Griffith, Linda G |
| author_sort | Edington, Collin D |
| collection | MIT |
| description | Microphysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including 3D matrices and microperfusion. Here, we report an approach to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms that are compatible with the quantitative study of a range of compounds, including lipophilic drugs. We describe three different platform designs - "4-way", "7-way", and "10-way" - each accommodating a mixing chamber and up to 4, 7, or 10 MPSs. Platforms accommodate multiple different MPS flow configurations, each with internal re-circulation to enhance molecular exchange, and feature on-board pneumatically-driven pumps with independently programmable flow rates to provide precise control over both intra- and inter-MPS flow partitioning and drug distribution. We first developed a 4-MPS system, showing accurate prediction of secreted liver protein distribution and 2-week maintenance of phenotypic markers. We then developed 7-MPS and 10-MPS platforms, demonstrating reliable, robust operation and maintenance of MPS phenotypic function for 3 weeks (7-way) and 4 weeks (10-way) of continuous interaction, as well as PK analysis of diclofenac metabolism. This study illustrates several generalizable design and operational principles for implementing multi-MPS "physiome-on-a-chip" approaches in drug discovery. |
| first_indexed | 2024-09-23T09:12:38Z |
| format | Article |
| id | mit-1721.1/115178 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T09:12:38Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1151782022-09-30T14:03:59Z Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies Edington, Collin D Chen, Wen Li Geishecker, Emily R Kassis, Timothy Soenksen Martinez, Luis Ruben Bhushan, Brij M Maass, Christian Alexander Tsamandouras, Nikolaos Valdez Macias, Jorge Luis Cook, Christi Dionne Yu, Jiajie Suter, Emily C Shockley, Michael J Velazquez, Jason G Velazquez, Jeremy J. Stockdale, Linda Papps, Julia P Lee, Iris Vann, Nicholas W. Contreras Gamboa, Mario e LaBarge, Matthew E Zhong, Zhe Wang, Xin Boyer, Laurie Ann Lauffenburger, Douglas A Carrier, Rebecca Communal, Catherine Tannenbaum, Steven R Trumper, David L Cirit, Murat Griffith, Linda G Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. Research Laboratory of Electronics Edington, Collin D Chen, Wen Li Geishecker, Emily R Kassis, Timothy Soenksen Martinez, Luis Ruben Bhushan, Brij M Maass, Christian Alexander Tsamandouras, Nikolaos Valdez Macias, Jorge Luis Cook, Christi Dionne Yu, Jiajie Suter, Emily C Shockley, Michael J Velazquez, Jason G Velazquez, Jeremy J. Stockdale, Linda Papps, Julia P Lee, Iris Vann, Nicholas W. Contreras Gamboa, Mario e LaBarge, Matthew E Zhong, Zhe Wang, Xin Boyer, Laurie Ann Lauffenburger, Douglas A Carrier, Rebecca Communal, Catherine Tannenbaum, Steven R Trumper, David L Cirit, Murat Griffith, Linda G Microphysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including 3D matrices and microperfusion. Here, we report an approach to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms that are compatible with the quantitative study of a range of compounds, including lipophilic drugs. We describe three different platform designs - "4-way", "7-way", and "10-way" - each accommodating a mixing chamber and up to 4, 7, or 10 MPSs. Platforms accommodate multiple different MPS flow configurations, each with internal re-circulation to enhance molecular exchange, and feature on-board pneumatically-driven pumps with independently programmable flow rates to provide precise control over both intra- and inter-MPS flow partitioning and drug distribution. We first developed a 4-MPS system, showing accurate prediction of secreted liver protein distribution and 2-week maintenance of phenotypic markers. We then developed 7-MPS and 10-MPS platforms, demonstrating reliable, robust operation and maintenance of MPS phenotypic function for 3 weeks (7-way) and 4 weeks (10-way) of continuous interaction, as well as PK analysis of diclofenac metabolism. This study illustrates several generalizable design and operational principles for implementing multi-MPS "physiome-on-a-chip" approaches in drug discovery. United States. Army Research Office (Grant W911NF-12-2-0039) 2018-05-02T17:51:41Z 2018-05-02T17:51:41Z 2018-03 2017-11 2018-04-27T17:16:22Z Article http://purl.org/eprint/type/JournalArticle 2045-2322 http://hdl.handle.net/1721.1/115178 Edington, Collin D. et al. “Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies.” Scientific Reports 8, 1 (March 2018) © 2018 The Author(s) https://orcid.org/0000-0002-5248-871X https://orcid.org/0000-0003-1137-0413 https://orcid.org/0000-0001-8851-1224 https://orcid.org/0000-0001-7890-7209 https://orcid.org/0000-0003-3227-4631 https://orcid.org/0000-0002-6673-087X https://orcid.org/0000-0001-8272-6419 https://orcid.org/0000-0001-6975-5047 https://orcid.org/0000-0003-3491-4962 https://orcid.org/0000-0002-0050-989X https://orcid.org/0000-0001-5358-5450 https://orcid.org/0000-0002-1801-5548 http://dx.doi.org/10.1038/s41598-018-22749-0 Scientific Reports Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Scientific Reports |
| spellingShingle | Edington, Collin D Chen, Wen Li Geishecker, Emily R Kassis, Timothy Soenksen Martinez, Luis Ruben Bhushan, Brij M Maass, Christian Alexander Tsamandouras, Nikolaos Valdez Macias, Jorge Luis Cook, Christi Dionne Yu, Jiajie Suter, Emily C Shockley, Michael J Velazquez, Jason G Velazquez, Jeremy J. Stockdale, Linda Papps, Julia P Lee, Iris Vann, Nicholas W. Contreras Gamboa, Mario e LaBarge, Matthew E Zhong, Zhe Wang, Xin Boyer, Laurie Ann Lauffenburger, Douglas A Carrier, Rebecca Communal, Catherine Tannenbaum, Steven R Trumper, David L Cirit, Murat Griffith, Linda G Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies |
| title | Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies |
| title_full | Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies |
| title_fullStr | Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies |
| title_full_unstemmed | Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies |
| title_short | Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies |
| title_sort | interconnected microphysiological systems for quantitative biology and pharmacology studies |
| url | http://hdl.handle.net/1721.1/115178 https://orcid.org/0000-0002-5248-871X https://orcid.org/0000-0003-1137-0413 https://orcid.org/0000-0001-8851-1224 https://orcid.org/0000-0001-7890-7209 https://orcid.org/0000-0003-3227-4631 https://orcid.org/0000-0002-6673-087X https://orcid.org/0000-0001-8272-6419 https://orcid.org/0000-0001-6975-5047 https://orcid.org/0000-0003-3491-4962 https://orcid.org/0000-0002-0050-989X https://orcid.org/0000-0001-5358-5450 https://orcid.org/0000-0002-1801-5548 |
| work_keys_str_mv | AT edingtoncollind interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT chenwenli interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT geisheckeremilyr interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT kassistimothy interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT soenksenmartinezluisruben interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT bhushanbrijm interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT maasschristianalexander interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT tsamandourasnikolaos interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT valdezmaciasjorgeluis interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT cookchristidionne interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT yujiajie interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT suteremilyc interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT shockleymichaelj interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT velazquezjasong interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT velazquezjeremyj interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT stockdalelinda interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT pappsjuliap interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT leeiris interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT vannnicholasw interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT contrerasgamboamarioe interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT labargematthewe interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT zhongzhe interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT wangxin interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT boyerlaurieann interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT lauffenburgerdouglasa interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT carrierrebecca interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT communalcatherine interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT tannenbaumstevenr interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT trumperdavidl interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT ciritmurat interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies AT griffithlindag interconnectedmicrophysiologicalsystemsforquantitativebiologyandpharmacologystudies |