Mixing, Mass Transfer and Cell Production in a Continuous Bioreactor
Type of DegreePhD Dissertation
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This research investigated a novel continuous bioreactor which has the advantages of enhanced oxygen transfer, low shear stress, ease of operation and scalability. The bioreactor showed significant improvement in gas-liquid and medium mixing through its unique design, leading to higher cell production. The bioreactor had both an outer shell cylinder and an inner core cylinder, each with adjustable rotational velocities to control the mixing in the reactor. Inlet flows were controlled to provide additional medium and oxygen to the reactor volume. Moreover, a spiroid tube was attached to the wall of the outer cylinder, providing enhanced gas-liquid interfacial area thus improving oxygen transfer. Computational fluid dynamics (CFD) simulations were performed to analyze the resulting hydrodynamic properties (shear stress, velocity distribution, eddy viscosity and turbulence kinetic energy) in the multiphase bioreactor, and the results were used to determine the optimum operating conditions for oxygen transfer experiments. Mathematical models were also developed to simulate the experimental dynamic behaviors of oxygen transfer process and to obtain the volumetric mass transfer coefficients (kLa) in the bioreactor at a variety of operating conditions operating conditions. To increase the potential for cell production, this bioreactor was further scaled up by 9 nine times, from 1.11 x 10-4 m3 to 0.986 x 10-3 m3. Oxygen measurements were conducted to characterize the bioreactor with and without spiroid. The comparisons proved the advantages of using spiroid as a method to improve oxygen transfer performance or adding spiroid to the bioreactor could help reduce the oxygen saturation time by two times. Furthermore, biological tests (using E. coli, K91BlueKan) were used to further verity the potentials in the cellular production of this bioreactor under various operating conditions (batch and continuous modes, different rotational rates and different flow rates). By measuring the cell growth and glucose consumptions for the microorganism in the bioreactor with and without spiroid under different operating conditions, the results not only further demonstrated the advantages of using the spiroid in oxygen delivery (increase 15% cells in the batch and reduced 33% operating time), but also showed great potentials in harvesting cells continuously.