Customizable gut-on-a-chip microsystems with enzymatic digestion for food and drug studies

With our ability to integrate an ever-wider range of physiologically inspired functions into an organ-on-a-chip, we can customize devices to be increasingly fit for purpose. For instance, intestine-on-chip (or gut-on-chip) devices have to date focused on mimicking the in vivo intercellular interactions at the intestinal wall thatcontrol the absorption of compounds over this biological interface.However, the compound of interest arrives at the intestine after having been ingested as a medicine containing excipients or as a foodmatrix. Enzymatic digestion serves to release and change the formof the compound as it passes from the mouth through the stomachto the intestine. Therefore, to study the uptake of novel drugs, toxicants, or food materials, a fit for purpose organ-chip should includean in vitro digestive system in addition to intestinal absorption, toprovide valid information on bioavailability (the fraction of compound that finally reaches the bloodstream).The work described here considers on-chip digestion, a processrequiring multiple functions, for eventual integration with a guton-a-chip. After earlier work that mimicked adult digestive processes [1], we now present a versatile system to emulate the digestion of infants. We translated a static, batch-wise, in vitro digestivesystem for à terme infants [2] into a continuously flowing, infantile, digestive system. Sequentially linked microfluidic micromixers were employed as microreactors to perform specific digestiveprocesses. Artificial digestive juices were prepared at defined compositions and pH, to ensure exact physiological conditions at eachstage (microreactor) of infantile digestion. All of the flows in theon-chip digestive system and the gut-on-a-chip were maintained bya novel flow control system, based on Coriolis mass flow sensorsto maintain exact flow rates irrespective of digestive-juice properties [3]. Operation of the organ-chip was possible for a period of13 days with no replacement of medium reservoirs required. Wedemonstrate the digestion of lactoferrin benchmarked against currently used in vitro digestion models.References[1] de Haan et al. (2019). Lab Chip. doi:10.1039/C8LC01080C[2] Ménard et al. (2018). Food Chem. doi:10.1016/j.foodchem.2017.07.145[3] Sparreboom et al. (2013). Micromachines. doi:10.3390/mi401002