Periodic Reporting for period 1 - GASTRIC (Gastrointestinal Tract on Chip - An automated microfluidics-based modular device for complete simulation of the processes of digestion and absorption of orally ingested bioactive compounds)
Reporting period: 2020-10-16 to 2022-10-15
The overarching goal of the GASTRIC project was to develop and fabricate the first automated microfluidics-based device for complete simulation of the processes of digestion and intestinal absorption of orally ingested bioactive compounds. The device should offer the possibility to study minute sample amounts, with high resolution and with the potential for high-throughput analysis, which is key for its adoption by large pharmaceutical and food industries with high economic and social impact.
As main conclusions, the GASTRIC project resulted in 2 alternative designs that could effectively simulate human intestinal digestion in a miniaturised manner. The second device iteration is fully automated and sensorised with pH and temperature sensors allowing to control both parameters using a closed feedback loop. The output of the Digestion devices could then be studied in another cell-laden device that simulates intestinal absorption under dynamic fluid flow conditions - the GASTRIC Gut Chip, which integrates sensors for real-time TEER monitoring. In addition, primary human colon samples were used to derive intestinal organoids with the aim of integrating these cultures in the Gut Chip to add physiological relevance and potentiate personalised patient-specific studies. Finally, important studies with primary gut microbiota samples delineated culture conditions for including gut commensal bacteria in the Gut Chip model.
Another device was designed to study intestinal absorption. This was equally fabricated using an elastomer and consisted of two parallel superimposed channels separated by a semi-permeable membrane. Human intestinal cells were cultured on the membrane to form an intestinal epithelium barrier. The device worked under continuous flow and cell differentiation was fully achieved just after 7 days. Importantly, we were able to study the intestinal absorption of samples digested in our devices following a simple treatment to avoid cytotoxicity derived from serine proteases present in the digestion fluids. Our Gut-Chip yielded permeability values that were in line with those reported for ex vivo studies using primary human samples.
In addition, we studied the effect of short-chain fatty acids derived from the fermentation products of primary human faecal bacteria on the same epithelium barrier that we used on-chip. This will be important to inform on the parameters to be used when co-culture gut microbiota with human cells on-chip.
Finally, we optimised within our lab the isolation, culture and expansion of human intestinal organoids derived from primary colon samples obtained from patients undergoing cancer resection surgeries. The use of primary intestinal organoids within our Gut Chips will be pivotal to create disease models and patient-specific tissues for personalised medicine.
The work done within the GASTRIC project has resulted in the publication of 3 articles (1 review and 2 original rsearch) in international peer-reviewed journals, with another 3 publications planned for the following months. In addition, the fellow has presented his work at Nanobiotech Montreux 2021 and EMBL Microfluidics 2022 where he delivered two oral presentations, and as an invited keynote speaker at two national conferences. The work was also disseminated to the general public through the participation in outreach events including the European Researcher’s Night (2021 and 2022) and the Scale Travels programme, which connects art with science to bring it to a wider audience.