Journal Article

A robotic platform for fluidically-linked human body-on-chips experimentation

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

2020

Overview

Here we describe of an ‘Interrogator’ instrument that uses liquid-handling robotics, a custom software package, and an integrated mobile microscope to enable automated culture, perfusion, medium addition, fluidic linking, sample collection, and in situ microscopic imaging of up to 10 Organ Chips inside a standard tissue culture incubator. The automated Interrogator platform maintained the viability and organ-specific functions of 8 different vascularized, 2-channel, Organ Chips (intestine, liver, kidney, heart, lung, skin, blood-brain barrier (BBB), and brain) for 3 weeks in culture when intermittently fluidically coupled through their medium reservoirs and endothelium-lined vascular channels using a common blood substitute medium. When an inulin tracer was perfused through the multi-organ Human Body-on-Chips (HuBoC) fluidic network, quantitative distributions of this tracer could be accurately predicted using a physiologically-based multi-compartmental reduced order (MCRO) in silico model of the experimental system derived from spatio-temporal transport equations and experimental data. This automated culture platform enables non-invasive imaging of cells within human Organ Chips and repeated sampling of both the vascular and interstitial compartments without compromising fluidic coupling, which should facilitate future HuBoc studies and pharmacokinetics (PK) analysis in vitro.