A plug-and-play transepithelial/transendothelial electric resistance (TEER)-upgraded organ-on-chip system to measure barrier dynamics in real-time

Abstract

The integration of transepithelial/transendothelial electrical resistance (TEER) measurement into organ-on-chip (OoC) platforms provides a unique opportunity to monitor the integrity of biological barriers in real-time. This is particularly important for detecting rapid changes in the temporal dynamics of intercellular junctional complexes in response to drug compounds, changes in host-microbiota interactions, and pathological disease states. Conventional TEER systems usually require special cell culture components or complex measurement technology that must be operated by experienced users. In this work, we present an innovative approach that represents an extension of the existing and well-established Dynamic42 chip platform by integrating semi-transparent TEER electrodes with fixed positions in combination with a measurement device. Remarkably, this system works in a plug-and-play manner and can continuously measure TEER inside the incubator without user intervention or invasive manipulation. Other important features of OoC, such as the microfluidic perfusion, multicellular cell colonization, and the possibility of microscopic examination, are not compromised by the integrated TEER electrodes. To demonstrate the performance of this new TEER system, we leveraged a 3D intestine-on-chip (IoC) model and investigated TEER during model assembly, barrier disruption, and recovery as a proof-of-concept. Moreover, we compared and discussed this with data from a conventional end-point fluorescence permeability assay to demonstrate the benefits of real-time measurements with higher sensitivity.