High throughput transepithelial electrical resistance (TEER) measurements on perfused membrane-free epithelia

Lab on a Chip, vol. 21, pp. 1676–1685

Abstract

Assessment of epithelial barrier function is critically important for studying healthy and diseased biological models. Here we introduce an instrument that measures transepithelial electrical resistance (TEER) of perfused epithelial tubes in the microfluidic OrganoPlate platform. The tubules are grown in microfluidic channels directly against an extracellular matrix, obviating the need for artificial filter membranes. We present TEER measurements on Caco-2 intestinal and renal proximal tubule epithelium. Forty tubules on one single plate were interrogated in less than a minute. We show that TEER measurement is significantly more sensitive than a fluorescent reporter leakage assay in response to staurosporine. We demonstrate a 40-channel time-lapse data acquisition over a 25 hour time period under flow conditions. We furthermore observed a 50% reduction in Caco-2 TEER values following exposure to a cocktail of inflammatory cytokines. To our best knowledge, this is the first instrument of its kind that allows routine TEER studies in perfused organ-on-a-chip systems without interference by artificial filter membranes. We believe the apparatus will contribute to accelerating routine adoption of perfused organ-on-a-chip systems in academic research and in industrial drug development.

Authors 14

1. Arnaud Nicolas Aachen Division of Analytical Biosciences Mimetas B. V

   Leiden University · Mimetas (Netherlands)

   Affiliation as printed

   Division of Analytical Biosciences

   LACDR

   Leiden

   Mimetas B. V

   The Netherlands

   Division of Analytical Biosciences, LACDR, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

   Mimetas B. V., J.H. Oortweg 19, Leiden, The Netherlands

2. Frederik Schavemaker Aachen Mimetas B. V

   Mimetas (Netherlands)

   Affiliation as printed

   Leiden

   Mimetas B. V

   The Netherlands

   Mimetas B. V., J.H. Oortweg 19, Leiden, The Netherlands

3. Kinga Kosim Aachen Mimetas B. V

   Mimetas (Netherlands)

   Affiliation as printed

   Leiden

   Mimetas B. V

   The Netherlands

   Mimetas B. V., J.H. Oortweg 19, Leiden, The Netherlands

4. Dorota Kurek Aachen Mimetas B. V

   Mimetas (Netherlands)

   Affiliation as printed

   Leiden

   Mimetas B. V

   The Netherlands

   Mimetas B. V., J.H. Oortweg 19, Leiden, The Netherlands

5. M. Haarmans Aachen Mimetas B. V

   Mimetas (Netherlands)

   Affiliation as printed

   Leiden

   Mimetas B. V

   The Netherlands

   Mimetas B. V., J.H. Oortweg 19, Leiden, The Netherlands

6. Martin Bulst
   Affiliation as printed

   04828 Bennewitz

   Germany

   Sciospec GmbH

   Sciospec GmbH, Leipziger Str. 43b, 04828 Bennewitz, Germany

7. Kyounghun Lee
   Affiliation as printed

   04828 Bennewitz

   Germany

   Sciospec GmbH

   Sciospec GmbH, Leipziger Str. 43b, 04828 Bennewitz, Germany

8. Seraphine Valeska Wegner
   Affiliation as printed

   04828 Bennewitz

   Germany

   Sciospec GmbH

   Sciospec GmbH, Leipziger Str. 43b, 04828 Bennewitz, Germany

9. Thomas Hankemeier Aachen Division of Analytical Biosciences

   Leiden University

   Affiliation as printed

   2333 CC Leiden

   Division of Analytical Biosciences

   LACDR

   Leiden University

   The Netherlands

   Division of Analytical Biosciences, LACDR, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

10. Jos Joore Aachen Mimetas B. V

    Mimetas (Netherlands)

    Affiliation as printed

    Leiden

    Mimetas B. V

    The Netherlands

    Mimetas B. V., J.H. Oortweg 19, Leiden, The Netherlands

11. Karel Domanský Aachen Mimetas B. V

    Mimetas (Netherlands)

    Affiliation as printed

    Leiden

    Mimetas B. V

    The Netherlands

    Mimetas B. V., J.H. Oortweg 19, Leiden, The Netherlands

12. Henriëtte L. Lanz Aachen Mimetas B. V

    Mimetas (Netherlands)

    Affiliation as printed

    Leiden

    Mimetas B. V

    The Netherlands

    Mimetas B. V., J.H. Oortweg 19, Leiden, The Netherlands

13. Paul Vulto Aachen Mimetas B. V

    Mimetas (Netherlands)

    Affiliation as printed

    Leiden

    Mimetas B. V

    The Netherlands

    Mimetas B. V., J.H. Oortweg 19, Leiden, The Netherlands

14. Sebastiaan J. Trietsch corresponding Aachen Mimetas B. V

    Mimetas (Netherlands)

    Affiliation as printed

    Leiden

    Mimetas B. V

    The Netherlands

    Mimetas B. V., J.H. Oortweg 19, Leiden, The Netherlands