Implementation of a dynamic intestinal gut-on-a-chip barrier model for transport studies of lipophilic dioxin congeners

Kornphimol Kulthong , Loes Duivenvoorde , Barbara Mizera , Deborah Rijkers , Guillaume ten Dam , Gerlof Oegema , Tomasz Puzyn , Hans Bouwmeester , Meike van der Zande


Novel microfluidic technologies allow the manufacture of in vitro organ-on-a-chip systems that hold great promise to adequately recapitulate the biophysical and functional complexity of organs found in vivo. In this study, a gut-on-a-chip model was developed aiming to study the potential cellular association and transport of food contaminants. Intestinal epithelial cells (Caco-2) were cultured on a porous polyester membrane that was tightly clamped between two glass slides to form two separate flow chambers. Glass syringes, polytetrafluoroethylene tubing and glass microfluidic chips were selected to minimize surface adsorption of the studied compounds (i.e. highly lipophilic dioxins), during the transport studies. Confocal microscopy studies revealed that, upon culturing under constant flow for 7 days, Caco-2 cells formed complete and polarized monolayers as observed after culturing for 21 days under static conditions in Transwells. We exposed Caco-2 monolayers in the chip and Transwell to a mixture of 17 dioxin congeners (7 polychlorinated dibenzo-p-dioxins and 10 polychlorinated dibenzofurans) for 24 h. Gas chromatography-high resolution mass spectrometry was used to assess the cellular association and transport of individual dioxin congeners across the Caco-2 cell monolayers. After 24 h, the amount of transported dioxin mixture was similar in both the dynamic gut-on-a-chip model and the static Transwell model. The transport of individual congeners corresponded with their number of chlorine atoms and substitution patterns as revealed by quantitative structure–property relationship modelling. These results show that the gut-on-a-chip model can be used, as well as the traditional static Transwell system, to study the cellular association and transport of lipophilic compounds like dioxins.
Author Kornphimol Kulthong
Kornphimol Kulthong,,
, Loes Duivenvoorde
Loes Duivenvoorde,,
, Barbara Mizera (FCh / DEChR / LECh)
Barbara Mizera,,
- Laboratory of Environmental Chemometrics
, Deborah Rijkers
Deborah Rijkers,,
, Guillaume ten Dam
Guillaume ten Dam,,
, Gerlof Oegema
Gerlof Oegema,,
, Tomasz Puzyn (FCh / DEChR / LECh)
Tomasz Puzyn,,
- Laboratory of Environmental Chemometrics
, Hans Bouwmeester
Hans Bouwmeester,,
, Meike van der Zande
Meike van der Zande,,
Journal seriesRSC Advances, ISSN 2046-2069, (A 35 pkt)
Issue year2018
Publication size in sheets0.65
ASJC Classification1500 General Chemical Engineering; 1600 General Chemistry
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa - Użycie Niekomercyjne (CC-BY-NC); with publication
Score (nominal)35
ScoreMinisterial score = 30.0, ArticleFromJournal
Ministerial score (2013-2016) = 35.0, ArticleFromJournal
Publication indicators WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2017 = 0.736; WoS Impact Factor: 2017 = 2.936 (2) - 2017=3.096 (5)
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