Design, modeling, and validation of an apical flow Transwell insert for small intestinal models

Abstract

This thesis presents the design, modeling and experimental validation of a device that allows for apical flow over an in 'vitro small intestine model. The device is designed to interface with commercially available hanging Transwells. Design considerations and specifications are discussed, based on user considerations, mechanical requirements, and biological requirements. To create a more informed design, multiple phenomena are modeled and results are used to modify design characteristics and give insight into viable operating parameters, such as apical flow rate. Within the device, velocity profiles of media flow as well as oxygen transport and cellular oxygen consumption are modeled. External to the device, heat transfer from a warm incubator into room temperature tubing containing media is modeled to ensure proper media warming. Experimental validation of the flow models is done by tracking dye flow through the insert, and preliminary flow experiments appear to be in agreement with modeling results. The design, modeling, and experimental results discussed in this thesis present a promising step toward a device capable of maintaining oxygen gradients that recapitulate specific aspects of the complex, dynamic environment within the small intestine.