National Research Council of Canada. NRC Biotechnology Research Institute
4th International Conference on Engineering Applications and Computational Algorithms (DCDIS Conference 2005), July 27-29, 2005, Guelph, Ontario, Canada
A main problem in controlling bioprocesses is the lack of manipulated variables. Batch and fed-batch processes do not allow the bioreactor to be drained of the (often) toxic waste substances produced by the biomass. A chemostat (CSTR) only has the dilution rate as the manipulated variable, which allows a certain control over the biomass concentration with a risk, however, of instability if the dilution rate gets higher than the maximum growth rate. Perfusion processes with full biomass retention are somewhat similar to batches, as no steady-state is really obtained until biomass growth is stopped by nutrient limitations. Cell bleed is often used in perfusion processes to improve viability and prevent accumulation of dead cells. However, the idea of using the cell bleed stream as a manipulated variable for control has not previously been studied for perfusion systems. We propose here a control strategy with three degrees of freedom that can be used to control the reactor level, biomass concentration, and a metabolite concentration. In the end, we shall address that controlling these concentrations could be the key to metabolic flux-based optimizations in bioreactors.
Dynamics of Continuous, Discrete and Impulsive Systems, Series B: Applications & Algorithms (2005): 663–667.