Innovative electrode and chip designs for transendothelial electrical resistance measurements in organs-on-chips

Many different epithelial and endothelial barriers in the human body ensure the proper functioning of our organs by controlling which substances can pass from one side to another. In recent years, organs-on-chips (OoC) have become a popular tool to study such barriers in vitro. To assess the proper functioning of these barriers, we can measure the transendothelial electrical resistance (TEER) which indicates how easily ions can cross the cell layer when a current is applied between electrodes on either side. TEER measurements are a convenient method to quantify the barrier properties since it is a non-invasive and label-free technique. Direct integration of electrodes for TEER measurements into OoC allows for continuous monitoring of the barrier, and fixed integration of the electrodes improves the reproducibility of the measurements. In this review, we will give an overview of different electrode and channel designs that have been used to measure the TEER in OoC. After giving some insight into why biological barriers are an important field of study, we will explain the theory and practice behind measuring the TEER in in vitro systems. Next, this review gives an overview of the state of the art in the field of integrated electrodes for TEER measurements in OoC, with a special focus on alternative chip and electrode designs. Finally, we outline some of the remaining challenges and provide some suggestions on how to overcome these challenges.