(8b) Enhanced Mixing and Oxygen Transfer in a Continuous Bioreactor with Optimized Spiroid

Oxygen transfer is a key issue when culturing cells in a bioreactor. Conventional bioreactors are operated in batch mode and can employ impellers for increased mixing and mass transfer which results in shear stress. The high shear stress from mechanical impellers typically results in greater cell death, especially for mammalian cells. Researchers in bioprocess and pharmaceutical industries are focusing on developing methods to increase mixing and maintain shear stress at optimal levels for cells to survive and proliferate in the reactor. A reactor environment that best provides low shear and high oxygen transfer along with controlled growth conditions will be suitable for cell cultures at a larger scale.

A novel rotating continuous bioreactor with an internal spiroid can provide enhanced mixing and oxygen transfer for improved cell viability. The spiroid is embedded in the cylindrical wall of the bioreactor to enhance oxygen transfer to the liquid phase which fills two-thirds of the bioreactor. The bioreactor is a horizontal cylinder rotated on a roller bed. The rotation rate of the reactor can be adjusted to control the flow of gas and liquid in the spiroid. When the partially-filled reactor is rotating, the spiroid picks up slugs of gas and liquid near the reactor exit and delivers them to the reactor entrance. Thus, the spiroid increases the gas-liquid contact areas within the reactor to increase oxygen mass transfer. The bioreactor is produced using rapid prototyping and can be operated in either batch or continuous modes with inlet flows via rotary unions available to provide medium and oxygen and outlet flows for waste and in-line analysis. Computational fluid dynamic simulations were utilized to model flow and oxygen transfer in the spiroid at various operating conditions. The rotational rate of the reactor and the diameter and length of the spiroid were key parameters explored for optimization of the spiroid. Models were generated using CFD studies for calculating the exact value of volumetric oxygen transfer in the spiroid. Cell culture experiments using Saccharomyces cerevisiae were conducted under various conditions to optimize the spiroid and reactor productivity. The amount of oxygen transfer with and without the spiroid was calculated for these cells and compared to published values. Based on these observations, changes to reactor design for better efficiency and performance were also made.