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微流控体外平台用于(纳米)安全性和(纳米)药物效率筛选。

Microfluidic In Vitro Platform for (Nano)Safety and (Nano)Drug Efficiency Screening.

机构信息

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.

出版信息

Small. 2021 Apr;17(15):e2006012. doi: 10.1002/smll.202006012. Epub 2021 Jan 18.

Abstract

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.

摘要

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。

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