Fraunhofer Institute for Biomedical Engineering IBMT, Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V., Joseph-von-Fraunhofer-Weg 1, Sulzbach, 66280, Germany.
Tyndall National Institute, University College Cork, Dyke Parade, Cork, T12 R5CP, Ireland.
Small. 2021 Apr;17(15):e2006012. doi: 10.1002/smll.202006012. Epub 2021 Jan 18.
Microfluidic technology is a valuable tool for realizing more in vitro models capturing cellular and organ level responses for rapid and animal-free risk assessment of new chemicals and drugs. Microfluidic cell-based devices allow high-throughput screening and flexible automation while lowering costs and reagent consumption due to their miniaturization. There is a growing need for faster and animal-free approaches for drug development and safety assessment of chemicals (Registration, Evaluation, Authorisation and Restriction of Chemical Substances, REACH). The work presented describes a microfluidic platform for in vivo-like in vitro cell cultivation. It is equipped with a wafer-based silicon chip including integrated electrodes and a microcavity. A proof-of-concept using different relevant cell models shows its suitability for label-free assessment of cytotoxic effects. A miniaturized microscope within each module monitors cell morphology and proliferation. Electrodes integrated in the microfluidic channels allow the noninvasive monitoring of barrier integrity followed by a label-free assessment of cytotoxic effects. Each microfluidic cell cultivation module can be operated individually or be interconnected in a flexible way. The interconnection of the different modules aims at simulation of the whole-body exposure and response and can contribute to the replacement of animal testing in risk assessment studies in compliance with the 3Rs to replace, reduce, and refine animal experiments.
微流控技术是一种非常有价值的工具，可用于实现更接近细胞和器官水平的体外模型，从而快速、无需动物即可对新型化学品和药物进行风险评估。由于其微型化，微流控细胞基设备允许进行高通量筛选和灵活的自动化，同时降低成本和试剂消耗。人们越来越需要更快、无需动物的方法来开发药物和对化学品进行安全评估（化学品注册、评估、授权和限制，REACH）。本文介绍了一种用于类似体内的体外细胞培养的微流控平台。它配备了基于晶圆的硅芯片，包括集成电极和微腔。使用不同的相关细胞模型进行的概念验证表明，它适合用于无标记评估细胞毒性作用。每个模块内的小型化显微镜可监测细胞形态和增殖。集成在微流控通道中的电极允许对屏障完整性进行非侵入式监测，随后对细胞毒性作用进行无标记评估。每个微流控细胞培养模块可以单独操作或灵活地相互连接。不同模块的互连旨在模拟全身暴露和反应，有助于符合 3R 原则（替代、减少和优化动物实验），在风险评估研究中替代动物试验。
