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利用阻抗谱技术在器官芯片上无创感测跨上皮屏障功能和组织分化。

Non-invasive sensing of transepithelial barrier function and tissue differentiation in organs-on-chips using impedance spectroscopy.

机构信息

BIOS Lab on a Chip group, MESA+ Institute for Nanotechnology, MIRA Institute for Biomedical Technology and Technical Medicine and Max Planck Center for Complex Fluid Dynamics, University of Twente, P. O. Box 217, 7500 AE Enschede, The Netherlands.

出版信息

Lab Chip. 2019 Jan 29;19(3):452-463. doi: 10.1039/c8lc00129d.

DOI:10.1039/c8lc00129d
PMID:30632575
Abstract

Here, we describe methods for combining impedance spectroscopy measurements with electrical simulation to reveal transepithelial barrier function and tissue structure of human intestinal epithelium cultured inside an organ-on-chip microfluidic culture device. When performing impedance spectroscopy measurements, electrical simulation enabled normalization of cell layer resistance of epithelium cultured statically in a gut-on-a-chip, which enabled determination of transepithelial electrical resistance (TEER) values that can be compared across device platforms. During culture under dynamic flow, the formation of intestinal villi was accompanied by characteristic changes in impedance spectra both measured experimentally and verified with simulation, and we demonstrate that changes in cell layer capacitance may serve as measures of villi differentiation. This method for combining impedance spectroscopy with simulation can be adapted to better monitor cell layer characteristics within any organ-on-chip in vitro and to enable direct quantitative TEER comparisons between organ-on-chip platforms which should help to advance research on organ function.

摘要

在这里,我们描述了将阻抗谱测量与电路模拟相结合的方法,以揭示在器官芯片微流控培养装置内培养的人肠道上皮的跨上皮屏障功能和组织结构。在进行阻抗谱测量时,电路模拟使静态培养在肠道芯片中的上皮细胞层电阻归一化,从而能够确定可在不同设备平台上进行比较的跨上皮电阻 (TEER) 值。在动态流动条件下培养时,肠绒毛的形成伴随着阻抗谱的特征变化,这些变化可以通过实验测量和模拟验证,我们证明细胞层电容的变化可以作为绒毛分化的测量指标。这种将阻抗谱与模拟相结合的方法可以适应于更好地监测任何器官芯片内的细胞层特征,并实现器官芯片平台之间直接的定量 TEER 比较,这应该有助于推进器官功能的研究。

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