芯片上器官平台与集成的丝网印刷电极阵列用于实时监测跨上皮屏障和气泡形成。

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

机构信息

School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907, United States.

Birck Nanotechnology Center, Purdue University, West Lafayette, Indiana 47907, United States.

出版信息

ACS Biomater Sci Eng. 2023 Mar 13;9(3):1620-1628. doi: 10.1021/acsbiomaterials.2c00494. Epub 2023 Feb 10.

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.

摘要

细胞紧密连接在调节上皮和内皮组织中不同溶质的选择性通过方面,在建立身体不同隔室之间的屏障方面起着关键作用。在过去的十年中,人们已经做出了巨大的努力来开发更具临床相关性的“芯片上器官”模型,这些模型具有集成的跨上皮电阻(TEER)监测系统,以帮助更好地理解上皮组织在暴露于不同物质时的基本生理基础。然而,这些平台中的大多数都需要使用昂贵且耗时的光刻工艺,这限制了它们在临床研究中的可扩展性和实际应用。为了解决这一需求,我们开发了一种具有集成电极阵列的低成本微流控平台,该平台可通过使用可扩展的制造技术(如丝网印刷和激光处理)来连续实时监测 TEER 和微流系统中气泡形成的风险。集成的印刷电极阵列即使在长期暴露于复杂培养基后,也表现出出色的稳定性(电阻变化小于约 0.02 Ω)。作为概念验证,使用 HMT3522 S1 上皮细胞对完全集成的平台进行了测试,通过 TEER 测量评估紧密屏障连接的形成,并通过针对封闭蛋白-1 (Zonula occludens-1 protein)的标准免疫染色程序进行了验证。该平台可被视为制造具有集成传感器的一次性和低成本器官和组织芯片模型的垫脚石,以促进在更接近生理的条件下研究上皮组织对不同物质的动态响应。

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