Development of a high throughput 3D perfused liver tissue bioreactor

Abstract

This thesis describes the development of a device designed for culturing liver tissue in a 3D perfused environment. Cells form tissue inside miniature channels of a scaffold, and the tissue is perfused with culture medium to create a culture microenvironment that has previously been described by the Griffith lab. In order to support this microenvironment, the reactor needs a pumping system, reservoirs and a controller. Previously, these have all been stand-alone components. This work focuses on the development of a new, integrated culture system. This system integrates 12 reactor microenvironments, reservoirs and pumping systems onto a single plate with a configuration modeled after standard multi-well plates. Each of the 12 bioreactor units utilize pneumatic pumps driven by a single external controller. This design offers substantial advantages over previous systems as it is far more user-friendly and can be used in a higher throughput capacity. The thesis describes the design and fabrication of the reactor and controller, including several models that were used during the development process. It also offers mechanical and biological characterizations of the device.