Advances and challenges in bioreactor design for the production of chemicals from plant tissue culture

Plant cells can be grown in an undifferentiated state as cell suspensions, or as differentiated tissues including transformed root culture. This paper summarizes the highlights of our efforts over the past 10 years in the design and operation of these reactor systems. The following assertions are presented: 1) Plant cell suspensions can be grown in virtually any bioreactor configuration; the important issue is the operational strategy - not the specifics of the bioreactor design. This conclusion is substantiated by pilot-scale stirred tank studies and with recent results for high-density culture in a low-cost plastic-lined bioreactor at a scale of 100 L working volume. Future improvements in biomass productivity will come from refinements in monitoring and control; future improvements in reduced volumetric cost could come from reduced capital investment bioreactors. 2) Root culture can be scaled up in various configurations, with liquid mixing limiting submerged culture systems (tissue < 25% working volume), and trickle-bed bioreactors providing high-density culture (25-75% working volume). Ongoing studies of gas flow and mixing in packed beds of fibers as well as the inhibitory role of root hairs on mixing are briefly described. Studies of mixing and trickle-bed pressure drop highlight the application of a control strategy based on mass-balance principles and simple media measurements (refractive index, electrical conductivity and osmotic pressure). Future research is needed to adapt existing and develop new principles for scale-up in dense matrices.