Robotic fluidic coupling and interrogation of multiple vascularized organ chips

Richard Novak, Miles Ingram, Susan Marquez, Debarun Das, Aaron Delahanty, Anna Herland, Ben M. Maoz, Sauveur S.F. Jeanty, Mahadevabharath R. Somayaji, Morgan Burt, Elizabeth Calamari, Angeliki Chalkiadaki, Alexander Cho, Youngjae Choe, David Benson Chou, Michael Cronce, Stephanie Dauth, Toni Divic, Jose Fernandez-Alcon, Thomas FerranteJohn Ferrier, Edward A. FitzGerald, Rachel Fleming, Sasan Jalili-Firoozinezhad, Thomas Grevesse, Josue A. Goss, Tiama Hamkins-Indik, Olivier Henry, Chris Hinojosa, Tessa Huffstater, Kyung Jin Jang, Ville Kujala, Lian Leng, Robert Mannix, Yuka Milton, Janna Nawroth, Bret A. Nestor, Carlos F. Ng, Blakely O’Connor, Tae Eun Park, Henry Sanchez, Josiah Sliz, Alexandra Sontheimer-Phelps, Ben Swenor, Guy Thompson, George J. Touloumes, Zachary Tranchemontagne, Norman Wen, Moran Yadid, Anthony Bahinski, Geraldine A. Hamilton, Daniel Levner, Oren Levy, Andrzej Przekwas, Rachelle Prantil-Baun, Kevin K. Parker, Donald E. Ingber*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)407-420
Number of pages14
JournalNature Biomedical Engineering
Volume4
Issue number4
DOIs
StatePublished - 1 Apr 2020

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