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Abstract

Biological systems have an additional level of complexity compared to other chemical systems because of the effects of metabolic regulation. Such regulation in the form of control of enzyme synthesis and activity leads to nonlinear behavior in bioreactors. Mathematical models that take into account these control mechanisms can be very successful in capturing the peculiarities of bioreactors such as multiple steady states and periodic phenomena. Cybernetic models, which are extremely suitable for this task model expression and activation of enzymes by the use of cybernetic control variables and have been used to explain multiplicities in hybridoma reactors. In particular, the cybernetic model of Namjoshi et al. (2002) has been able to predict the transition from batch and fed-batch to continuous culture in hybridoma experiments of Europa et al. The multiple steady states that result, vary widely in the concentration of cell mass and waste metabolites. The model captures the multiplicity of steady states for the hybridoma reactors. The bifurcation analysis of such models reveals the steady state behavior under a range of operating conditions and can be used to plan bioreactor operation to get the desired staedy states for maximum productivity.