Organ-on-a-chip meets high throughput screening: measuring transendothelial electrical resistance

We demonstrate a method to study low Trans Epithelial Electrical Resistance values in endothelial models. We exposed 36 HUVEC tubules to a varying concentration range of the toxicant staurosporine and acquired real-time data over 24 hours using OrganoTEER, showing a useful dynamic range down to 1 Ohm.cm2 and the capability of label-free real time barrier integrity measurements in a state of the art blood vessel on a chip model.


In vitro endothelial barrier models, such as the blood-brain barrier, are a crucial element of studying the safety and delivery mechanism of therapeutic drugs and toxicants. Endothelial models have much lower TEER values than their in vivo counterparts, which make them challenging to measure. In this study, we demonstrate the suitability of the OrganoTEER platform for TEER measurements on low TEER endothelial tubules grown in the OrganoPlate.

The developed system makes use of an electrode interface compatible with the OrganoPlate. TEER values can be determined for up to 80 perfused tubules in 40 independent chips within 60 seconds. The instrument can be placed within an incubator to enable automated long-term monitoring of TEER over the entire duration of an epithelial/endothelial study. Collagen I at 4mg/ml was deposited in the gel compartment using Phaseguide technology. HUVEC tubules were cultured against collagen I for 5 days and exposed to Staurosporine for 24 hours. Prior to toxicant addition, TEER values were recorded in the incubator to be used as t0 values. Medium containing a range of Staurosporine concentrations (0mM, 11 nM, 33 nM, 100 nM and 300 nM) was added to the perfusion and gel channels of the chips before starting a timelapse measurement.

We have shown the effect of staurosporine-induced toxicity for a wide range of concentrations. TEER values are being affected in both time and dose-dependent manners. Values were recorded down to 1 Ohm.cm2, showing a tenfold reduction from peak values. The sensitivity of this system is combined with the possibility to perform label-free measurement throughout incubation without interruption of the experiment.

We demonstrated the implementation of TEER measurements on an Organ-on-a-Chip platform in combination with a HUVEC based endothelial model, with TEER values reaching down to 1 Ohm.cm2. Based on these results, we propose this system for the study of healthy and damaged models of endothelial barrier tissues in a non-invasive way to provide a valuable tool for drug toxicity and transport studies in Organ-on-a-Chip models.