Geometric correction factor for transepithelial electrical resistance measurements in transwell and microfluidic cell cultures

Transepithelial electrical resistance (TEER) measurements are regularly used in in vitro models to quantitatively evaluate the cell barrier function. Although it would be expected that TEER values obtained with the same cell type and experimental setup were comparable, values reported in the literature show a large dispersion for unclear reasons. This work highlights a possible error in a widely used formula to calculate the TEER, in which it may be erroneously assumed that the entire cell culture area contributes equally to the measurement. In this study, we have numerically calculated this error in some cell cultures previously reported. In particular, we evidence that some TEER measurements resulted in errors when measuring low TEERs, especially when using Transwell inserts 12 mm in diameter or microfluidic systems that have small chamber heights. To correct this error, we propose the use of a geometric correction factor (GCF) for calculating the TEER. In addition, we describe a simple method to determine the GCF of a particular measurement system, so that it can be applied retrospectively. We have also experimentally validated an interdigitated electrodes (IDE) configuration where the entire cell culture area contributes equally to the measurement, and it also implements minimal electrode coverage so that the cells can be visualized alongside TEER analysis.
This work is part of the requirements to achieve the PhD degree in Electrical and Telecommunication Engineering at the Universitat Autònoma de Barcelona and it was supported by grants from CIBER-BBN, CSIC (PIE-201450E116) and Ministerio de Economía y Competitividad (SAF2014-62114-EXP and DPI2015-65401-C3-3-R). CIBER-BBN is funded by Instituto de Salud Carlos III. We are grateful to Drs. Pierre-Olivier Couraud (INSERM, France), Babette Weksler (Weill Cornell Medical College, New York, NY) and Ignacio Romero (Open University, Milton Keynes, UK) for kindly providing the hCMEC/D3 cell line. We would also acknowledge to Dr Mercedes Unzeta (Universitat Autònoma de Barcelona, Spain) for her advice and providing materials to perform the experiments with the cells.