Skin-on-a-Chip: Transepithelial Electrical Resistance and Extracellular Acidification Measurements through an Automated Air-Liquid Interface.

Skin-on-a-Chip: Transepithelial Electrical Resistance and Extracellular Acidification Measurements through an Automated Air-Liquid Interface.
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DOI:
10.3390/genes9020114
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发表时间:
2018-02-21
期刊:
影响因子:
3.5
通讯作者:
Wiest J
Wiest J
中科院分区:
生物学3区
文献类型:
--
作者:
Alexander FA;Eggert S;Wiest J

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皮肤是一个重要的器官,在保护身体内部器官方面起着至关重要的作用。为此,大量的工作已经进入创造表皮的人工模型,用于体外皮肤毒性测试。这些组织模型被称为重建的人类表皮(RhE),被制药,化妆品和环境领域的研究人员用于评估暴露于外源性物质后的皮肤毒性。在这里,我们提出了一种无标签的解决方案,利用智能移动的实验室体外诊断(IMOLA-IVD),一个非侵入性的,基于传感器的平台,监测跨上皮电阻(TEER)的RhE模型和贴壁细胞培养在多孔膜插入。首先将在聚碳酸酯膜上培养的鼠成纤维细胞用作测试模型,以使用定制的BioChip封装设计以及双流体配置来优化程序,用于膜结合培养物的连续和自动灌注。监测膜结合的L929细胞的胞外酸化速率(EAR)和TEER。然后使用开发的方案在48小时内监测MatTek EpiDermTM RhE模型的TEER。TEER和TER测量表明,所设计的系统能够在芯片上保持稳定的培养物,监测代谢参数,并随着时间的推移揭示组织分解。
Skin is a critical organ that plays a crucial role in defending the internal organs of the body. For this reason, extensive work has gone into creating artificial models of the epidermis for in vitro skin toxicity tests. These tissue models, called reconstructed human epidermis (RhE), are used by researchers in the pharmaceutical, cosmetic, and environmental arenas to evaluate skin toxicity upon exposure to xenobiotics. Here, we present a label-free solution that leverages the use of the intelligent mobile lab for in vitro diagnostics (IMOLA-IVD), a noninvasive, sensor-based platform, to monitor the transepithelial electrical resistance (TEER) of RhE models and adherent cells cultured on porous membrane inserts. Murine fibroblasts cultured on polycarbonate membranes were first used as a test model to optimize procedures using a custom BioChip encapsulation design, as well as dual fluidic configurations, for continuous and automated perfusion of membrane-bound cultures. Extracellular acidification rate (EAR) and TEER of membrane-bound L929 cells were monitored. The developed protocol was then used to monitor the TEER of MatTek EpiDermTM RhE models over a period of 48 h. TEER and EAR measurements demonstrated that the designed system is capable of maintaining stable cultures on the chip, monitoring metabolic parameters, and revealing tissue breakdown over time.
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