Samenvatting

Microfluidic devices have the potential to adopt more accurate physiological conditions of the human intestine through the use of continuous flow and by producing mechanical stress to the cells. This study evaluated the translocation properties of a microfluidic gut-on-chip device in comparison with conventional static Transwells. The dynamic in vitro model consisted of a microchip with a porous membrane assembled and connected to a syringe pump system. This allowed for constant flows to be streamed through the apical and basolateral side of the membrane, thereby feeding the cells with fresh medium and producing mechanical shear stress. Antipyrine, a highly permeable model drug, was used to investigate the translocation across Caco-2 intestinal cells, together with a low permeability marker, Lucifer Yellow, commonly used to assess the monolayer integrity. The results showed comparable permeability coefficients in the two in vitro models. The translocation of Antipyrine revealed a similar linear transport trend in Transwell inserts and gut-on-chip. The apparent permeability (Papp) was found to be relatively higher in the Transwell inserts when compared to the gut-on-chip, with 17.4 x 10-6 cm s-1 Papp determined under static conditions, and 7.59 x 10-6 cm s-1 in the case of the dynamic microchip. Well-formed tight junctions, characteristic of differentiated Caco-2 cells, were suggested by permeation of Lucifer Yellow, revealing insignificant amounts translocated across the Caco-2 monolayer upon a 24hr exposure time. The Papp values determined for Lucifer Yellow correlated well in the two in vitro models, with 0.94 x 10-6 cm s-1 computed in Transwell inserts, and 0.60 x 10-6 cm s-1 in the gut-on-chip, respectively. These findings support the validity of the gut-on-chip device, indicating consistent permeability results relative to the well-studied Transwell systems. Furthermore, the use of gut-on-chip showed advantages in obtaining more automatised conditions and a minimal consumption of reagents. Nevertheless, further experiments are required for a more detailed picture of the gut-on-chip and its feasibility for translocation studies, given the limited experiments performed on this device, as compared to the static model.