A numerical study of the fluid dynamics of novel stem cell bioreactors

Over the last decade especially, the promise of stem cell technology to cure a multitude of genetic disorders and diseases has been at the forefront of medical research. To meet the large supply of these cells needed for clinical applications, three-dimensional modes of culture in combination with differing bioreactor designs will most likely be necessary, optimised relative to the particular cell or tissue sought. Stress upon cells or tissues, oxygen concentration, and mixing capacity are all important factors that influence the culture outcome. As such, the optimisation of bioreactor designs should include the fluid dynamic perspective. Within this thesis two novel bioreactors are investigated numerically primarily from the fluid dynamic perspective, providing insight into the effect that control and geometry parameters have on these factors. The first bioreactor studied was a Radial Aerial Disk Bioreactor (RADB), consisting of a layer of culture medium, within a shallow cylindrical vessel, beneath a layer of air. The flow within the fluid medium is driven by a disk rotating in the air layer. Three steady-state flow states within the medium were found, as the rotating speed of the impeller and the bioreactor geometry were varied. Additionally, metastability of these states was also identified. Importantly the stress distributions and oxygen concentrations within each state differed significantly, even at the same Reynolds number. The second bioreactor studied was an Inclined Disk Bioreactor (IDB), consisting of a cylindrical vessel full of fluid, again also beneath a layer of air, although in this instance the flow within the medium was directly driven at the bottom by a rotating end disk. The vortex breakdown bubble that occurs within this configuration was primarily investigated with regard to its structure as the control parameters, Reynolds number and tilt angle of the cylinder with the vertical axis, were varied. An open structure was found, with the degree of modification to the structure quantified as the parameters were varied. Overall, this thesis provides flow field, concentration, and stress characteristics for the bioreactors as a function of flow and geometrical parameters. It is hoped that this information will provide guidance to optimal bioreactor design and operation when combined with further biological focused studies conducted within Monash University and elsewhere