|An automated modular microsystem for enzymatic digestion with gut-on-a-chip applications
Haan, P. de; Ianovska, M.A. ; Mathwig, K. ; Bouwmeester, H. ; Verpoorte, E. - \ 2020
In: 21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2017. - Chemical and Biological Microsystems Society (21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2017 ) - ISBN 9780692941836 - p. 1593 - 1594.
Digestion - Enzyme kinetics - Gut-on-a-chip - Organ-on-a-chip
Gut-on-a-chip models have gained attention as replacements for other cell-based assays or animal studies in drug development or toxicological studies. These models aim to provide a more accurate representation of the in vivo situation in form and function; however, no digestive processes have been included in these systems so far. This work describes a miniaturized digestive system based on artificial digestive juices that digest liquid samples in a series of three microreactors. After optimization of the pH value of juices and mixtures, samples leading to fluorescent products were digested to demonstrate enzyme functionality and to determine kinetic parameters.
Digestion-on-a-chip: A continuous-flow modular microsystem recreating enzymatic digestion in the gastrointestinal tract
Haan, Pim De; Ianovska, Margaryta A. ; Mathwig, Klaus ; Lieshout, Glenn A.A. Van; Triantis, Vassilis ; Bouwmeester, Hans ; Verpoorte, Elisabeth - \ 2019
Lab on a Chip 19 (2019)9. - ISSN 1473-0197 - p. 1599 - 1609.
In vitro digestions are essential for determining the bioavailability of compounds, such as nutrients. We have developed a cell-free, miniaturized enzymatic digestive system, employing three micromixers connected in series to mimic the digestive functions of the mouth, stomach and small intestine. This system continuously processes samples, e.g. containing nutrients, to provide a constant flow of digested materials which may be presented to a subsequent gut-on-a-chip absorption module, containing living human intestinal cells. Our system incorporates three-compartment enzymatic digestion, one of the key functions of the gastrointestinal tract. In each of these compartments, we modify the chemical environment, including pH, buffer, and mineral composition, to closely mimic the local physiological environment and create optimal conditions for digestive processes to take place. It will therefore provide an excellent addition to existing gut-on-a-chip systems, providing the next step in determining the bio-availability of orally administered compounds in a fast and continuous-flow ex vivo system. In this paper, we demonstrate enzymatic digestion in each separate compartment using compounds, starch and casein, as model nutrients. The use of transparent, microfluidic micromixers based on chaotic advection, which can be probed directly with a microscope, enabled enzyme kinetics to be monitored from the very start of a reaction. Furthermore, we have digested lactoferrin in our system, demonstrating complete digestion of this milk protein in much shorter times than achievable with standard in vitro digestions using batch reactors.