Pressure-driven perfusion system to control, multiplex and recirculate cell culture medium for Organs-on-Chips

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Organ-on-Chip (OoC) devices are increasingly used to mimic the tissue microenvironment of cells in intact organs. This includes microchannels to mimic, for example, fluidic flow through vessels. Present methods for controlling microfluidic flow in these systems rely on gravity, rocker systems or external pressure pumps. For many purposes, pressure pumps give the most consistent flow profiles but they are not well-suited for high throughput as might be required for testing drug responses. Here, we describe a method which allows multiplexing of microfluidic channels in OoC devices plus the accompanying custom software necessary to run the system. Moreover, we show the approach is also suited to for recirculation of culture medium, an essential cost consideration when expensive culture reagents are used that are not “spent” through uptake by the cells during transient unidirectional flow.

Authors 5

1. Mees N. S. de Graaf Aachen Department of Anatomy and Embryology

   Leiden University Medical Center

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333ZC Leiden, the Netherlands

2. Aisen Vivas

   Max Planck University of Twente Center for Complex Fluid Dynamics · University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, 7500AE Enschede, University of Twente, The Netherlands

   BIOS Lab on a Chip Group, MESA+ Institute for Nanotechnology, Technical Medical Centre, Max Planck Institute for Complex Fluid Dynamics, University of Twente, 7500AE Enschede, The Netherlands

3. Andries D. van der Meer

   University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, 7500AE Enschede, University of Twente, The Netherlands

4. Christine L. Mummery Aachen Department of Anatomy and Embryology

   Leiden University Medical Center · University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, 7500AE Enschede, University of Twente, The Netherlands

   Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333ZC Leiden, the Netherlands

5. Valeria V. Orlova corresponding Aachen Department of Anatomy and Embryology

   Leiden University Medical Center

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333ZC Leiden, the Netherlands