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See detailL'extrapolation des bioréacteurs : un problème de génie des procédés ou de physiologie microbienne ?
Delvigne, Frank ULg; Destain, Jacqueline ULg; Brognaux, Alison ULg et al

in Chimie Nouvelle (2010), 104

Bioreactor scale-up often pose a serious issue during the industrial development of a bioprocess considering the numerous physical and biological phenomena occurring in the reacting volume. The basic ... [more ▼]

Bioreactor scale-up often pose a serious issue during the industrial development of a bioprocess considering the numerous physical and biological phenomena occurring in the reacting volume. The basic principles of scale-up coming from the traditional chemical and process engineering approaches will be first reviewed and will be then compared to a new one involving recent development at the level of microbial strain manipulation. This "physiological" approach of scale-up involves directly a biological component of the system (by comparison with the traditional approach for scaling-up involving physical parameters indirectly linked to the physiological phenomena occurring in the bioreactor), i.e. the synthesis of a reporter fluorescent protein when microbial cells are exposed to stress. It will be shown how this principle can be used for a better understanding of the relationship between bioreactor hydrodynamics and microbial stress. [less ▲]

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See detailInfluence of bioreactor hydraulic characteristics on a Saccharomyces cerevisiae fed-batch culture: hydrodynamic modelling and scale-down investigations.
Lejeune, Annick ULg; Delvigne, Frank ULg; Thonart, Philippe ULg

in Journal of Industrial Microbiology & Biotechnology (2010), 37

Yeast is a widely used microorganism at the industrial level because of its biomass and metabolite production capabilities. However, due to its sensitivity to the glucose effect, problems occur during ... [more ▼]

Yeast is a widely used microorganism at the industrial level because of its biomass and metabolite production capabilities. However, due to its sensitivity to the glucose effect, problems occur during scale-up to the industrial scale. Hydrodynamic conditions are not ideal in large-scale bioreactors, and glucose concentration gradients can arise when these bioreactors are operating in fed-batch mode. We have studied the effects of such gradients in a scale-down reactor, which consists of a mixed part linked to a non-mixed part by a recirculation pump, in order to mimic the hydrodynamic conditions encountered at the large scale. During the fermentation tests in the scale-down reactor, there was a drop in both biomass yield (ratio between the biomass produced and the glucose added) and trehalose production and an increase in both fermentation time (time between inoculation and beginning of stationary phase) and ethanol production. We have developed a stochastic model which explains these effects as the result of an induction process determined mainly by the hydrodynamic conditions. The concentration profiles experienced by the microorganisms during the scale-down tests were expressed and linked to the biomass yields of the scale-down tests. [less ▲]

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See detailTrehalose as a stress marker of the physiological impact of mixing on yeast production: scale-down reactors and mini-bioreactors investigations
Lejeune, Annick ULg; Delvigne, Frank ULg; Thonart, Philippe ULg

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment [=BASE] (2010), 14

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See detailStochastic models to study the impact of mixing on a fed-batch culture of Saccharomyces cerevisiae.
Delvigne, Frank ULg; Lejeune, Annick ULg; Destain, Jacqueline ULg et al

in Biotechnology Progress (2006), 22(1), 259-69

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 ... [more ▼]

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. [less ▲]

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