Robotic fluidic coupling and interrogation of multiple vascularized organ chips.

Journal: Nature biomedical engineering
Published Date: Jan 27, 2020

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.

Authors

  • Richard Novak
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Miles Ingram
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Susan Marquez
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Debarun Das
    CFD Research Corporation, Huntsville, AL, USA.
  • Aaron Delahanty
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Anna Herland
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Ben M Maoz
    Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
  • Sauveur S F Jeanty
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Mahadevabharath R Somayaji
    CFD Research Corporation, Huntsville, AL, USA.
  • Morgan Burt
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Elizabeth Calamari
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Angeliki Chalkiadaki
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Alexander Cho
    Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
  • Youngjae Choe
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • David Benson Chou
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Michael Cronce
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Stephanie Dauth
    Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
  • Toni Divic
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Jose Fernandez-Alcon
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Thomas Ferrante
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • John Ferrier
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Edward A FitzGerald
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Rachel Fleming
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Sasan Jalili-Firoozinezhad
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Thomas Grevesse
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Josue A Goss
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Tiama Hamkins-Indik
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Olivier Henry
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Chris Hinojosa
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Tessa Huffstater
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Kyung-Jin Jang
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Ville Kujala
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Lian Leng
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Robert Mannix
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Yuka Milton
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Janna Nawroth
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Bret A Nestor
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Carlos F Ng
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Blakely O'Connor
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Tae-Eun Park
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Henry Sanchez
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Josiah Sliz
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Alexandra Sontheimer-Phelps
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Ben Swenor
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Guy Thompson
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • George J Touloumes
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Zachary Tranchemontagne
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Norman Wen
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Moran Yadid
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Anthony Bahinski
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Geraldine A Hamilton
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Daniel Levner
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Oren Levy
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Andrzej Przekwas
    CFD Research Corporation, Huntsville, AL, USA.
  • Rachelle Prantil-Baun
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Kevin K Parker
    Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Donald E Ingber
    1 Wyss Institute for Biologically Inspired Engineering, Harvard University , Boston, Massachusetts.

Keywords

External Resources

Popular Topics
Recent Journals