A structured-segregated approach for modeling the dynamics of microbial populations in the three-dimensional turbulent field of a stirred-tank bioreactor
Special Symposium - Biotechnology
Invited Session on Biotechnology: Honoring Prof. John Villadsen (S-3)
Keywords: Cellular systems, bioproduction processes, bioreactor modelling
A structured-segregated approach for modeling the dynamics of microbial populations in the three-dimensional turbulent field of a stirred-tank bioreactor – travelling along the lifelines of single cells
Matthias Reuss and Alexei Lapin (keynote lecture)
The physiological state of cellular systems and its related behaviour with respect to growth and product formation is the result of the complex interplay between the extracellular environment and the cellular machinery. Functionality of a biosystem for the purpose of bioproduction processes is therefore determined by the cooperative actions of the extracellular stimuli and dynamic responses inside the biological phase. Optimal engineering of bioreactors in which living cells function as the factories is further complicated because of the dynamic variations of the extracellular environment. This in turn may result in drastic changes in metabolism and final outcome of the process. A quantitative description of these phenomena should consequently rest upon the two interwoven aspects of structured bioreactor modelling:
(1) Complex interactions between the functional units of the cells, including the mathematical formulation of the dynamics of metabolism and the key regulation of this network in response to changes in the environment.
(2) Structure of the abiotic phases of the bioreactor to analyse mixing and other transport phenomena between the phases causing gradients in the concentrations of various substrates and products.
The contribution aims at introducing an Euler-Lagrange approach to characterize the behaviour of the heterogeneous cell population in a stirred-tank bioreactor with non-ideal mixing. The approach allows one to describe population behaviour at the outcome of the interaction between the intracellular state of the individual cell and the turbulent flow field in the reactor. The modelling approach and the numerical method employed are based on an Euler-Lagrange formulation of the system combined with a fractional-step method to allow for a stable, accurate, and numerically efficient solution of the underlying equations. This strategy permits one to account for the heterogeneity present in real reactors in both the abiotic and biotic phases. The example of sugar uptake (phosphotransferase system, PTS) of Escherichia coli cells growing in a fed-batch culture is used to illustrate the application of the approach. The activity of the uptake system depends on the local concentration of glucose as well as the ratio of the intracellular concentrations of phosphoenolpyruvate and pyruvate, which in turn is a function of the history of the individual cell. The simulation results point to distinct differences in the viability of the cells at different scale of operation.
Presented Wednesday 19, 15:30 to 16:00, in session Invited Session on Biotechnology: Honoring Prof. John Villadsen (S-3).
