The objective of this research study is to be able to scale-up and optimize aerobic fermentation processes via computer simulations. As an example the production of penicillin by P. chrysogenum is studied. In vivo kinetics of the cell can be understood by conducting stimulus response and scale down experiments. These experiments provide dynamic information that can be used to estimate parameters of enzyme kinetic models. The transport phenomena inside the bioreactor can by understood by solving hydrodynamic model using computational fluid dynamics (CFD). Thus, with information from intracellular and extracellular environments, an integrated model is solved using CFD. In these simulations, the multiphase flow and transport phenomena taking place inside the bioreactor are simulated, and integrated with the microbial reaction kinetics. The micro-organisms inside the reactor are followed along their trajectories, where they experience a changing environment. The dynamic response of the cells to this environment dictates the productivity and selectivity of the cells. By simulating both the flow in the reactor and the response of the cells, the entire process inside the bioreactor can be assessed and scaled-up and optimization can be done without the need of costly experiments, both in time and financial resources.@en

The relationship between shear environment and physiological characteristics of plant cells is always a crucial and challenging aspect in the scale up of suspension cultivations. In this work, we propose a quantitative method for evaluating the lethal effects of hydrodynamic on Carthamus tinctorius L. cell with computational fluid dynamic (CFD) technology and online capacitance viable cell detection. The study towards the effect of short term shear force on C. tinctorius L. cells was carried out in 5 L bioreactor under various overall shear intensities (0.02–1.82 w/kg), in which an online capacitance electrode was applied to count the dynamic vital cell. A first order kinetic model was achieved to describe the death rate in a time span of 60 min based on the capacitance. A product of the maximum shear stress and shear frequency (SSF) parameter, which is an evolution of energy dissipation/circulation function, was established to relate cell death rate to the shear environment. A good correlation between cell death kinetics and the SSF parameter was observed in the verification test in a 15 L STR bioreactor. SSF can be used to determine the maximum operating range of hydrodynamic stress, and improve the design and optimization of the of C. tinctorius L. cultivation in scale-up process.@en