Parallelizable Microfluidic Platform to Model and Assess In Vitro Cellular Barriers: Technology and Application to Study the Interaction of 3D Tumor Spheroids with Cellular Barriers

Biosensors, vol. 11, pp. 314

Abstract

Endothelial and epithelial cellular barriers play a vital role in the selective transport of solutes and other molecules. The properties and function of these barriers are often affected in case of inflammation and disease. Modelling cellular barriers in vitro can greatly facilitate studies of inflammation, disease mechanisms and progression, and in addition, can be exploited for drug screening and discovery. Here, we report on a parallelizable microfluidic platform in a multiwell plate format with ten independent cell culture chambers to support the modelling of cellular barriers co-cultured with 3D tumor spheroids. The microfluidic platform was fabricated by microinjection molding. Electrodes integrated into the chip in combination with a FT-impedance measurement system enabled transepithelial/transendothelial electrical resistance (TEER) measurements to rapidly assess real-time barrier tightness. The fluidic layout supports the tubeless and parallelized operation of up to ten distinct cultures under continuous unidirectional flow/perfusion. The capabilities of the system were demonstrated with a co-culture of 3D tumor spheroids and cellular barriers showing the growth and interaction of HT29 spheroids with a cellular barrier of MDCK cells.

Authors 12

1. Arya Lekshmi Nair Aachen Currently with Mimetas

   Mimetas (Netherlands) · Natural and Medical Sciences Institute · University of Tübingen

   Affiliation as printed

   Currently with Mimetas, De Limes 7, 2342 DH Oegstgeest, The Netherlands

   NMI Natural and Medical Sciences Institute, University of Tübingen, Markwiesenstraße 55, 72770 Reutlingen, Germany

2. Lena Mesch

   University of Tübingen

   Affiliation as printed

   Institut für Neuroanatomie und Entwicklungsbiologie, University of Tübingen, Österbergstraße 3, 72074 Tübingen, Germany

3. Ingo Schulz

   Microfluidic ChipShop (Germany)

   Affiliation as printed

   Microfluidic ChipShop GmbH, Stockholmer Str. 20, D-07747 Jena, Germany

4. Holger Becker

   Microfluidic ChipShop (Germany)

   Affiliation as printed

   Microfluidic ChipShop GmbH, Stockholmer Str. 20, D-07747 Jena, Germany

5. Julia Raible

   Natural and Medical Sciences Institute · University of Tübingen

   Affiliation as printed

   NMI Natural and Medical Sciences Institute, University of Tübingen, Markwiesenstraße 55, 72770 Reutlingen, Germany

6. Heiko Kiessling

   Natural and Medical Sciences Institute · University of Tübingen

   Affiliation as printed

   NMI Natural and Medical Sciences Institute, University of Tübingen, Markwiesenstraße 55, 72770 Reutlingen, Germany

7. Ulrich Rothbauer

   Heidelberg University · Natural and Medical Sciences Institute · University of Tübingen

   Affiliation as printed

   Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany

   NMI Natural and Medical Sciences Institute, University of Tübingen, Markwiesenstraße 55, 72770 Reutlingen, Germany

8. Christian Schmees

   Natural and Medical Sciences Institute · University of Tübingen

   Affiliation as printed

   NMI Natural and Medical Sciences Institute, University of Tübingen, Markwiesenstraße 55, 72770 Reutlingen, Germany

9. Marius Busche

   Natural and Medical Sciences Institute · University of Tübingen

   Affiliation as printed

   NMI Natural and Medical Sciences Institute, University of Tübingen, Markwiesenstraße 55, 72770 Reutlingen, Germany

10. Sebastian Trennheuser

    University of Tübingen

    Affiliation as printed

    Institute of Pharmacy, Pharmaceutical Biotechnology, Auf der Morgenstelle 8, D-72076 Tübingen, Germany

11. Gert Fricker

    University of Tübingen

    Affiliation as printed

    Institute of Pharmacy, Pharmaceutical Biotechnology, Auf der Morgenstelle 8, D-72076 Tübingen, Germany

12. Martin Stelzle corresponding

    Natural and Medical Sciences Institute · University of Tübingen

    Affiliation as printed

    NMI Natural and Medical Sciences Institute, University of Tübingen, Markwiesenstraße 55, 72770 Reutlingen, Germany