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Robotic fluidic coupling and interrogation of multiple vascularized organ chips.


ABSTRACT: Organ chips can recapitulate organ-level (patho)physiology, yet pharmacokinetic and pharmacodynamic analyses require multi-organ systems linked by vascular perfusion. Here, we describe an 'interrogator' that employs liquid-handling robotics, custom software and an integrated mobile microscope for the automated culture, perfusion, medium addition, fluidic linking, sample collection and in situ microscopy imaging of up to ten organ chips inside a standard tissue-culture incubator. The robotic interrogator maintained the viability and organ-specific functions of eight vascularized, two-channel organ chips (intestine, liver, kidney, heart, lung, skin, blood-brain barrier and brain) for 3 weeks in culture when intermittently fluidically coupled via a common blood substitute through their reservoirs of medium and endothelium-lined vascular channels. We used the robotic interrogator and a physiological multicompartmental reduced-order model of the experimental system to quantitatively predict the distribution of an inulin tracer perfused through the multi-organ human-body-on-chips. The automated culture system enables the imaging of cells in the organ chips and the repeated sampling of both the vascular and interstitial compartments without compromising fluidic coupling.

SUBMITTER: Novak R 

PROVIDER: S-EPMC8057865 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Robotic fluidic coupling and interrogation of multiple vascularized organ chips.

Novak Richard R   Ingram Miles M   Marquez Susan S   Das Debarun D   Delahanty Aaron A   Herland Anna A   Maoz Ben M BM   Jeanty Sauveur S F SSF   Somayaji Mahadevabharath R MR   Burt Morgan M   Calamari Elizabeth E   Chalkiadaki Angeliki A   Cho Alexander A   Choe Youngjae Y   Chou David Benson DB   Cronce Michael M   Dauth Stephanie S   Divic Toni T   Fernandez-Alcon Jose J   Ferrante Thomas T   Ferrier John J   FitzGerald Edward A EA   Fleming Rachel R   Jalili-Firoozinezhad Sasan S   Grevesse Thomas T   Goss Josue A JA   Hamkins-Indik Tiama T   Henry Olivier O   Hinojosa Chris C   Huffstater Tessa T   Jang Kyung-Jin KJ   Kujala Ville V   Leng Lian L   Mannix Robert R   Milton Yuka Y   Nawroth Janna J   Nestor Bret A BA   Ng Carlos F CF   O'Connor Blakely B   Park Tae-Eun TE   Sanchez Henry H   Sliz Josiah J   Sontheimer-Phelps Alexandra A   Swenor Ben B   Thompson Guy G   Touloumes George J GJ   Tranchemontagne Zachary Z   Wen Norman N   Yadid Moran M   Bahinski Anthony A   Hamilton Geraldine A GA   Levner Daniel D   Levy Oren O   Przekwas Andrzej A   Prantil-Baun Rachelle R   Parker Kevin K KK   Ingber Donald E DE  

Nature biomedical engineering 20200127 4


Organ chips can recapitulate organ-level (patho)physiology, yet pharmacokinetic and pharmacodynamic analyses require multi-organ systems linked by vascular perfusion. Here, we describe an 'interrogator' that employs liquid-handling robotics, custom software and an integrated mobile microscope for the automated culture, perfusion, medium addition, fluidic linking, sample collection and in situ microscopy imaging of up to ten organ chips inside a standard tissue-culture incubator. The robotic inte  ...[more]

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