Rapid integration of screen-printed electrodes into thermoplastic organ-on-a-chip devices for real-time monitoring of trans-endothelial electrical resistance.

Abstract

Trans-endothelial electrical resistance (TEER) is one of the most widely used indicators to quantify thebarrier integrity of endothelial layers. Over the last decade, the integration of TEER sensors into organ-on-a-chip (OOC) platforms has gained increasing interest for its efficient and effective measurement of TEERin OOCs. To date, microfabricated electrodes or direct insertion of wires has been used to integrate TEERsensors into OOCs, with each method having advantages and disadvantages. In this study, we developed aTEER-SPE chip consisting of carbon-based screen-printed electrodes (SPEs) embedded in a poly(methylmethacrylate) (PMMA)-based multi-layered microfluidic device with a porous poly(ethylene terephthalate)membrane in-between. As proof of concept, we demonstrated the successful cultures of hCMEC/D3 cellsand the formation of confluent monolayers in the TEER-SPE chip and obtained TEER measurements for 4days. Additionally, the TEER-SPE chip could detect changes in the barrier integrity due to shear stress oran inflammatory cytokine (i.e., tumor necrosis factor-α). The novel approach enables a low-cost and facilefabrication of carbon-based SPEs on PMMA substrates and the subsequent assembly of PMMA layers forrapid prototyping. Being cost-effective and cleanroom-free, our method lowers the existing logistical andtechnical barriers presenting itself as another step forward to the broader adoption of OOCs with TEERmeasurement capability.