Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0197101
Title: A multi-chamber microfluidic intestinal barrier model using Caco-2 cells for drug transport studies
Authors: Tan H.-Y. 
Trier S.
Rahbek U.L.
Dufva M.
Kutter J.P.
Andresen T.L.
Keywords: aminopeptidase
dextran
insulin
mannitol
multidrug resistance protein 1
politef
rhodamine 123
tight junction protein
ABC transporter subfamily B
ABCB1 protein, human
dextran
insulin
maltose
mannitol
rhodamine 123
tetradecyl maltoside
Article
biocompatibility
biological model
Caco-2 cell line
cell differentiation
cell growth
controlled study
drug transport
electric resistance
enzyme activity
human
human cell
hydrophilicity
immunocytochemistry
intestine
melting point
microfluidics
monolayer culture
mucus
permeability barrier
analogs and derivatives
Caco-2 cell line
cytology
devices
drug effect
intestine absorption
intestine mucosa
lab on a chip
metabolism
microfluidic analysis
procedures
ATP Binding Cassette Transporter, Sub-Family B
Caco-2 Cells
Dextrans
Humans
Insulin
Intestinal Absorption
Intestinal Mucosa
Lab-On-A-Chip Devices
Maltose
Mannitol
Microfluidic Analytical Techniques
Rhodamine 123
Issue Date: 2018
Citation: Tan H.-Y., Trier S., Rahbek U.L., Dufva M., Kutter J.P., Andresen T.L. (2018). A multi-chamber microfluidic intestinal barrier model using Caco-2 cells for drug transport studies. PLoS ONE 13 (5) : e0197101. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0197101
Rights: Attribution 4.0 International
Abstract: This paper presents the design and fabrication of a multi-layer and multi-chamber microchip system using thiol-ene ‘click chemistry’ aimed for drug transport studies across tissue barrier models. The fabrication process enables rapid prototyping of multi-layer microfluidic chips using different thiol-ene polymer mixtures, where porous Teflon membranes for cell monolayer growth were incorporated by masked sandwiching thiol-ene-based fluid layers. Electrodes for trans-epithelial electrical resistance (TEER) measurements were incorporated using low-melting soldering wires in combination with platinum wires, enabling parallel real-time monitoring of barrier integrity for the eight chambers. Additionally, the translucent porous Teflon membrane enabled optical monitoring of cell monolayers. The device was developed and tested with the Caco-2 intestinal model, and compared to the conventional Transwell system. Cell monolayer differentiation was assessed via in situ immunocyto-chemistry of tight junction and mucus proteins, P-glycoprotein 1 (P-gp) mediated efflux of Rhodamine 123, and brush border aminopeptidase activity. Monolayer tightness and relevance for drug delivery research was evaluated through permeability studies of mannitol, dextran and insulin, alone or in combination with the absorption enhancer tetradecylmaltoside (TDM). The thiol-ene-based microchip material and electrodes were highly compatible with cell growth. In fact, Caco-2 cells cultured in the device displayed differentiation, mucus production, directional transport and aminopeptidase activity within 9–10 days of cell culture, indicating robust barrier formation at a faster rate than in conventional Transwell models. The cell monolayer displayed high TEER and tightness towards hydrophilic compounds, whereas co-administration of an absorption enhancer elicited TEER-decrease and increased permeability similar to the Transwell cultures. The presented cell barrier microde-vice constitutes a relevant tissue barrier model, enabling transport studies of drugs and chemicals under real-time optical and functional monitoring in eight parallel chambers, thereby increasing the throughput compared to previously reported microdevices. © 2018 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161229
ISSN: 19326203
DOI: 10.1371/journal.pone.0197101
Rights: Attribution 4.0 International
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