Robotic fluidic coupling and interrogation of multiple vascularized organ chips
Authors: Morgan Burt
Aaron Delahanty
Carlos F Ng
Stephanie Dauth
Sauveur S F Jeanty
Debarun Das
Rachelle Prantil-Baun
Henry Sanchez
Olivier Henry
Robert Mannix
Chris Hinojosa
Zachary Tranchemontagne
Tae-Eun Park
Norman Wen
Kyung-Jin Jang
Kevin K Parker
Youngjae Choe
Josue A Goss
Edward A FitzGerald
Alexander Cho
George J Touloumes
Mahadevabharath R Somayaji
Blakely O&#x27;Connor
David Benson Chou
Angeliki Chalkiadaki
Rachel Fleming
Jose Fernandez-Alcon
Anna Herland
Bret A Nestor
Oren Levy
John Ferrier
Tiama Hamkins-Indik
Michael Cronce
Susan Marquez
Lian Leng
Donald E Ingber
Alexandra Sontheimer-Phelps
Yuka Milton
Andrzej Przekwas
Moran Yadid
Guy Thompson 2nd
Janna Nawroth
Elizabeth Calamari
Geraldine A Hamilton
Ville Kujala
Sasan Jalili-Firoozinezhad
Thomas Grevesse
Thomas Ferrante
Toni Divic
Anthony Bahinski
Miles Ingram
Tessa Huffstater
Richard Novak
Daniel Levner
Ben Swenor
Ben M Maoz
Josiah Sliz
Journal: Nature Biomedical Engineering (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Organ chips; Pharmacokinetic; Pharmacodynamic; Multi-organ systems; Vascular perfusion
Affiliations: Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA., CFD Research Corporation, Huntsville, AL, USA., Division of Micro and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden., Disease Biophysics Group, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA., Department of Biomedical Engineering and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel., Emulate, Inc., Boston, MA, USA., Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal., Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA., Department of Biology, University of Freiburg, Freiburg, Germany., GlaxoSmithKline, Collegeville, PA, USA., Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. ., Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. ., Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. .

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. 

Retracted: No

PubPeer comments:
 Is the 100um scale bar in Figure 4 for the heart Parenchyma accurate, or is this an error? It seems that multiple scale bars within this figure are of unexpected sizes. ,