Direct quantification of transendothelial electrical resistance in organs-on-chips

Marieke Willemijn van der Helm, Mathieu Odijk, Jean-Philippe Frimat, Andries Dirk van der Meer, Jan C.T. Eijkel, Albert van den Berg, Loes Irene Segerink

Research output: Contribution to journalArticleAcademicpeer-review

41 Citations (Scopus)
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Abstract

Measuring transendothelial or transepithelial electrical resistance (TEER) is a widely used method to monitor cellular barrier tightness in organs-on-chips. Unfortunately, integrated electrodes close to the cellular barrier hamper visual inspection of the cells or require specialized cleanroom processes to fabricate see-through electrodes. Out-of-view electrodes inserted into the chip's outlets are influenced by the fluid-filled microchannels with relatively high resistance. In this case, small changes in temperature or medium composition strongly affect the apparent TEER. To solve this, we propose a simple and universally applicable method to directly determine the TEER in microfluidic organs-on-chips without the need for integrated electrodes close to the cellular barrier. Using four electrodes inserted into two channels – two on each side of the porous membrane – and six different measurement configurations we can directly derive the isolated TEER independent of channel properties. We show that this method removes large variation of non-biological origin in chips filled with culture medium. Furthermore, we demonstrate the use of our method by quantifying the TEER of a monolayer of human hCMEC/D3 cerebral endothelial cells, mimicking the blood-brain barrier inside our microfluidic organ-on-chip device. We found stable TEER values of 22 Ω cm2±1.3 Ω cm2 (average ± standard error of the mean of 4 chips), comparable to other TEER values reported for hCMEC/D3 cells in well-established Transwell systems. In conclusion, we demonstrate a simple and robust way to directly determine TEER that is applicable to any organ-on-chip device with two channels separated by a membrane. This enables stable and easily applicable TEER measurements without the need for specialized cleanroom processes and with visibility on the measured cell layer
Original languageEnglish
Pages (from-to)924-929
Number of pages6
JournalBiosensors and bioelectronics
Volume85
DOIs
Publication statusPublished - 2016

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