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Integration of multiple flexible electrodes for realtime detection of barrier formation with spatial resolution in a gut-on-chip system

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Microsystems & Nanoengineering 2024年第1期10卷 105-114页

作者： Mara Lucchetti Gabriel Werr Sofia Johansson Laurent Barbe Léa Grandmougin Paul Wilmes maria tenje Luxembourg Centre for Systems Biomedicine(LCSB) University of LuxembourgEsch-sur-Alzette L-4362Luxembourg Division of Biomedical Engineering Department of Materials Science and EngineeringScience for Life LaboratoryUppsala University75121 UppsalaSweden Department of Life Sciences and Medicine Faculty of ScienceTechnology and MedicineUniversity of LuxembourgEsch-sur-Alzette L-4362Luxembourg

In healthy individuals,the intestinal epithelium forms a tight barrier to prevent gut bacteria from reaching blood circulation.To study the effect of probiotics,dietary compounds and drugs on gut barrier formation and disruption,human gut epithelial and bacterial cells can be cocultured in an in vitro model called the human microbial crosstalk(HuMiX)gut-on-a-chip system.Here,we present the design,fabrication and integration of thin-film electrodes into the HuMiX platform to measure transepithelial electrical resistance(TEER)as a direct readout on barrier tightness in realtime.As various aspects of the HuMiX platform have already been set in their design,such as multiple compressible layers,uneven surfaces and nontransparent materials,a novel fabrication method was developed whereby thin-film metal electrodes were first deposited on flexible substrates and sequentially integrated with the HuMiX system via a transfer-tape approach.Moreover,to measure localized TEER along the cell culture chamber,we integrated multiple electrodes that were connected to an impedance analyzer via a multiplexer.We further developed a dynamic normalization method because the active measurement area depends on the measured TEER levels.The fabrication process and system setup can be applicable to other barrier-on-chip systems.As a proof-of-concept,we measured the barrier formation of a cancerous Caco-2 cell line in real-time,which was mapped at four spatially separated positions along the HuMiX culture area.

关键词： barrier system multiple

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