Developing an In-Vitro dynamic model of the stomach and small intestine for milk products : first prototype

摘要

The aim of this study has been to design and develop the first prototype, of a dynamic in-vitro model of the digestive system through the stomach and the small intestine. This has been part of a project initiated by a group of researchers from NMBU, which will use this model to replicate the physical and mechanical processes of digesting milk through the human gastrointestinal tract.Several conditions was set for the design of the in-vitro model, in order to make it able to keep the physical and chemical environment as similar to the in-vivo system as possible. In addition to these conditions, the initial limitation of the limited volume, set the framework for the development process. In the approach to design this model, the fluid flow through vital parts of the system, like through the small intestine, was analysed. To achieve this, the CFD analysis tool “Flow Simulations” by the 3D CAD software SolidWorks, was actively used throughout the design and prototyping processes. The finished apparatus, consists of several components, each with its own purpose. First, the rheometer (Physica UDS200, Germany) function as the “heart” of the operation. It continuously monitors the rheological characteristics of the digestive fluid, in addition to serving as the main container where the different circuits is attached, and to keep one of the physical conditions (the temperature) constant. The different fluid circuits in the system is first the stomach circuit, which consists of milk, saliva and gastric juices in its volume of approximately 15 ml. The second circuit, which is the one circulating the small intestine, consist of the stomach volume added to duodenal juices, which doubles the volume. The third circuit is the buffer volume, where the components from the digested milk should diffuse to, through the membrane. A peristaltic pump (Reclo ICC) controls the circulation of fluid through the entire system, in addition to contributing to the content’s mixing. The chemical condition (the pH-value) is monitored and controlled through a titrator (Compact Titrator G20) apparatus, which is attached to the system. The small intestine device has been one of the primary focuses in this thesis. This device should function as a dialyzer, where different components in the milk is subtracted from the digestive fluid flowing inside the membrane. For this first prototype, an artificial membrane with an ordinary inner diameter was chosen. However, a goal for the further development is to be able to use an intestine from for example a fish to get a more realistic simulation. The finished small intestine device (excluded the membrane) was made successfully by glassblowers from UiO. However, the function of the device mentioned above, has not been successfully developed. Several test were done to test the system’s capability to create diffusion through the membrane, which were unsuccessful. This is a crucial function of the dynamic model, which should be prioritized in further development of this system. The overall dynamic model’s first prototype has been design and developed, keeping the initial conditions intact. A mathematical model to estimate the simplified fluid environment locally at different running conditions, is also presented in this thesis.