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A compartmentalized microfluidic chip with crisscross microgrooves and electrophysiological electrodes for modeling the blood-retinal barrier

Abstract

The interconnection of different tissue-tissue interfaces may extend organ-on-chips to a new generation of sophisticated models capable of recapitulating more complex organ-level functions. Single interfaces are largely recreated in organ-on-chips by culturing the cells on opposite sides of a porous membrane that splits a chamber in two or by connecting the cells of two adjacent compartments through microchannels. However, it is difficult to interconnect more than one interface using these approaches. To address this challenge, we present a novel microfluidic device where cells are arranged in parallel compartments and highly interconnected through a grid of microgrooves, which facilitates paracrine signaling and heterotypic cell-cell contact between multiple tissues. In addition, the device includes electrodes on the substrate for the measurement of transepithelial electrical resistance (TEER) and the recording of extracellular field potential. Unlike conventional methods for measuring the TEER where electrodes are on each side of the cell barrier, a method with only electrodes on the substrate has been validated. Herein, we demonstrate its utility as a microfluidic blood-retinal barrier (µBRB) model using a co-culture of primary human retinal endothelial cells (HREC), a human neuroblastoma cell line (SH-SY5Y), and a human retinal pigment epithelial cell line (ARPE-19). Cell barrier formations in the µBRB were confirmed by a permeability assay, TEER measurements, and ZO-1 expression. This places the µBRB model as a promising in vitro tool for studying pathologies affecting blood-retinal barrier (BRB) integrity and the neurovascular coupling.

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Publication details

The article was received on 28 Jul 2017, accepted on 11 Nov 2017 and first published on 14 Nov 2017


Article type: Paper
DOI: 10.1039/C7LC00795G
Citation: Lab Chip, 2017, Accepted Manuscript
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    A compartmentalized microfluidic chip with crisscross microgrooves and electrophysiological electrodes for modeling the blood-retinal barrier

    J. Yeste, M. Garcia Ramirez, A. Guimerà Brunet, C. Hernández, X. Illa, R. Simó Canonge and R. Villa, Lab Chip, 2017, Accepted Manuscript , DOI: 10.1039/C7LC00795G

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