(741f) A Scale-up Methodology for Continuous Bioreactor Systems Utilizing an Optimal Design Under Optimal Control Constraint Framework
This work proposes a method for the scale-up of continuous pharmaceutical systems utilizing a framework that pairs the optimal design and optimal control of the reactor to guarantee feasibility. The development of reliable bio-kinetic models is extended to the design of a continuous bioreactor that uses a multi-feed configuration allowing for the ability to use flow rate and substrate concentration of the feed stream as independent manipulated variables. The design problem for the bioreactor is formulated as a nonlinear program (NLP) for which the optimal control problem governing the dilution rate and substrate concentration and the transport and consumption of oxygen and nutrients are used as constraints. From this algorithm the optimal bioreactor geometry is determined for any bioreactor volume as well as the optimal control policy necessary to maximize the reactor productivity. A beta-carotene production process with kinetic models describing the glucose consumption and metabolic product formation and depletion in the Saccharomyces cerevisiaestrain mutant SM14 is utilized as a case study for the described algorithm.
- Garcia-Ochoa, F. and Gomez, E. Bioreactor scale-up and oxygen transfer rate in microbial processes: An overview. Biotechnology Advances 27, 153â??176 (2009).
- Puthli, M. S., Rathod, V. K. and Pandit, A. B. Gasâ??liquid mass transfer studies with triple impeller system on a laboratory scale bioreactor. Biochemical Engineering Journal 23, 25â??30 (2005).
- Wutz, J., Lapin, A., Siebler, F., SchÃ¤fer, J., Wucherpfennig, T., Berger, M. and Takors, R. Predictability of kLa in stirred tank reactors under multiple operating conditions using an Euler-Lagrange approach. Eng. Life Sci. (2016). doi:10.1002/elsc.201500135
- Shuler, M.L and Kargi, F. Bioprocess Engineering: basic concepts. NJ: Prentice Hall PTR. (2002)