Stochastic Models To Study the Impact of Mixing on a Fed-Batch Culture of Saccharomyces cerevisiae

Abstract

The mechanisms of interaction between microorganisms and their environment in a stirred bioreactor can be modeled by a stochastic approach. The procedure comprises two submodels: a classical stochastic model for the microbial cell circulation and a Markov chain model for the concentration gradient calculus. The advantage lies in the fact that the core of each submodel, i.e., the transition matrix (which contains the probabilities to shift from a perfectly mixed compartment to another in the bioreactor representation), is identical for the two cases. That means that both the particle circulation and fluid mixing process can be analyzed by use of the same modeling basis. This assumption has been validated by performing inert tracer (NaCl) and stained yeast cells dispersion experiments that have shown good agreement with simulation results. The stochastic model has been used to define a characteristic concentration profile experienced by the microorganisms during a fermentation test performed in a scale-down reactor. The concentration profiles obtained in this way can explain the scale-down effect in the case of a Saccharomyces cerevisiae fed-batch process. The simulation results are analyzed in order to give some explanations about the effect of the substrate fluctuation dynamics on S. cerevisiae.

Influence of bioreactor hydraulic characteristics on a Saccharomyces cerevisiae fed-batch culture: hydrodynamic modelling and scale-down investigations

“…In order to calculate accurately the dextrose concentration gradient, the intermittent behaviour of the pump must be considered [33]. Therefore, a pulse matrix was used to represent the discontinuous behaviour of the pump, in which the number of columns corresponded to the number of transitions, and the number of rows to the number of states.…”

“…The deterministic method is based on the consideration of differential equations that define the flows between the compartments, while the stochastic approach allows the inclusion of the probabilistic nature of the mixing process and the circulation of particles in the reactor to be traced [32]. The advantage of such a model is that both representation of the circulation of the microorganisms and fluid mixing can be performed using the same structure [33].…”

Applicability of GFP Microbial Whole Cell Biosensors to Bioreactor Operations - Mathematical Modeling and Related Experimental Tools

“…Indeed, tracer test involving particulate dye instead of soluble dye has been recently recognized as more relevant to describe the transport of microbial cells (Asraf-Snir, 2011). We have also use this method previously for the characterization of the transport of fluorescently labeled microbial cells in scale-down reactors (Delvigne, 2006b). Our methodology has been improved in the present work, mainly at the level of the method used to detect fluorescent particles.…”

Investigation of the effect of different extracellular factors on the lipase production by Yarrowia lipolityca on the basis of a scale-down approach

“…However, previous hydrodynamic results have shown that the passage of the cells from mixed to non-mixed part of the P-SDR is strongly stochastic [13]. In order to take this important feature into account, a second air valve control algorithm has been elaborated on the basis of a two-compartment stochastic hydrodynamic model developed in our laboratory [14]. Samples of the two controlling schemes are shown at Fig.…”