Low-cost microphysiological systems: Feasibility study of a tape-based barrier-on-chip system for small intestine modeling

Abstract

We see affordability as a key challenge in making organs-on-chips accessible to a wider range of users, particularly outside the highest-resource environments. Here, we present an approach to barrier-on-a-chip fabrication based on double-sided pressure-sensitive adhesive tape and off-the-shelf polycarbonate. Besides a low materials cost, common also to PDMS or thermoplastics, it requires minimal (€ 100) investment in laboratory equipment, yet at the same time is suitable for upscaling to industrial roll-to-roll manufacture. We evaluate our microhpysiological system with an epithelial (C2BBe1) barrier model of the small intestine, studying the biological effects of permeable support pore size, as well as stimulation with a common food compound (chili pepper-derived capsaicinoids). The cells form tight and continuous barrier layers inside our systems, with comparable permeability but superior epithelial polarization compared to Transwell culture, in line with other perfused microphysiological models. Permeable support pore size is shown to weakly impact barrier layer integrity as well as the metabolic cell profile. Capsaicinoid response proves distinct between culture systems, but we show that impacted metabolic pathways are partly conserved, and that cytoskeletal changes align with previous studies. Overall, our tape-based microphysiolgical system proves to be a robust and reproducible approach to studying physiological barriers, in spite of its low cost.

Towards the Development of Delivery Systems of Bioactive Compounds With Eyes Set on Pharmacokinetics

“…Permeation of caffeine and other compounds over mucus barriers was described and tested with porcine intestinal mucus, deserving further pharmacological validation (Elberskirch et al, 2019). Other barrier-on-chip system was fabricated for small intestine modelling with an epithelial cell layer responsive to capsaicinoids (Winkler et al, 2020). A farther elaborated system combining different organ chips fluidically linked (Table 1) was proposed to mimic absorption-metabolism-excretiontoxicity and predict PK/pharmacodynamics of drugs (Herland et al, 2020).…”