Sonically-Intensified Mixing for Enhanced Plant Cell Culture Productivity

NON-TECHNICAL SUMMARY: The market for plant-derived drugs and intermediates is approximately $10 billion in the United States. In addition to market considerations, productive plant cell culture processes offer the potential to accelerate clinical development of plant-derived pharmaceuticals, protect the originating plant species from over-exploitation, and reduce supply fluctuations due to unpredictable climate variables. Due to economic limitations, very few plant cell culture processes have been commercially developed. Low volumetric productivity of plant cell cultures is the primary reason for the lack of economic viability. Conventionally, mechanically-stirred or airlift systems are the two bioreactor choices for plant cell cultures. Mechanically-stirred systems usually provide adequate mass-transport, but often impart unacceptable levels of hydrodynamic shear stress that impairs plant cell growth and/or secondary metabolite production. Airlift systems provide greatly reduced shear stress, but often not enough mass transfer to maintain secondary metabolite production at high densities. In both types of systems, the elevated viscosities of high cell densities significantly impair mass transport. This Phase I project will demonstrate the feasibility of an innovative sonically-intensified bioreactor for the production of secondary metabolites from plant cell culture. The use of this technology may greatly increase the volumetric productivity of high-density plant cell cultures, enabling more processes to reach the level of economic feasibility.