Organ-on-a-Chip Platform with an Integrated Screen-Printed Electrode Array for Real-Time Monitoring Trans-Epithelial Barrier and Bubble Formation.

Abstract

Cellular tight junctions play a key role in establishing a barrier between different compartments of the body by regulating the selective passage of different solutes across epithelial and endothelial tissues. Over the past decade, significant efforts have been conducted to develop more clinically relevant "organ-on-a-chip" models with integrated trans-epithelial electrical resistance (TEER) monitoring systems to help better understand the fundamental underpinnings of epithelial tissue physiology upon exposure to different substances. However, most of these platforms require the use of high-cost and time-consuming photolithography processes, which limits their scalability and practical implementation in clinical research. To address this need, we have developed a low-cost microfluidic platform with an integrated electrode array that allows continuous real-time monitoring of TEER and the risk of bubble formation in the microfluidic system by using scalable manufacturing technologies such as screen printing and laser processing. The integrated printed electrode array exhibited excellent stability (with less than ∼0.02 Ω change in resistance) even after long-term exposure to a complex culture medium. As a proof of concept, the fully integrated platform was tested with HMT3522 S1 epithelial cells to evaluate the tight barrier junction formation through TEER measurement and validated with standard immunostaining procedures for Zonula occludens-1 protein. This platform could be regarded as a stepping stone for the fabrication of disposable and low-cost organ and tissue-on-a-chip models with integrated sensors to facilitate studying the dynamic response of epithelial tissues to different substances in more physiologically relevant conditions.