| Biotechnology is widely used in industries such as energy, chemical, medicine, food, healthcare and so on. However, due to the lack of knowledge of key scale-up factors, optimized technologies in laboratory always cannot be industrialized. The most common method is to research the flow fluid, mass transfer, mixing characteristics of the bioreactor by computational fluid dynamics (CFD) method and to validate the results by appropriate experimental method, and then instruct the scale-up of bioprocess.First, in this thesis, the CFD method of rotational bioreactor was set up and fluid dynamics characteristics were compared between different microwell plates. The results showed that the fluid shape in 48-microwell plate was most irregular, resulting in a bigger mass transfer area and shear rate. Because the 96-microwell plate was too narrow, the fluid in it cannot flow sufficiently and the mass transfer and shear properties were bad. With the increase of bioreactor volume, turbulence dynamic energy and volumetric power consumption were increased. Mass transfer capacity in 24 and 48-microwell plates can reach the flask level. For the microwell plate, the contributions of kL and a to kLa were the same, while for the flask, the contributions of kL to kLa was much bigger than a. The shear rate in 24 and 48-microwell plates is fairly to the flask.Based on the above CFD model, the complicated unsteady-state turbulent flow field formed in normal and baffled flasks was studied. The baffled flask showed advantages both in mass transfer capacity and in shear formation in comparison with normal flasks. Detailed investigations were carried out in baffled flasks under different shaking frequencies and filling volumes. The results showed that the specific power input and specific interface area were both greatly influenced by shaking frequency and filling volume. For the positive effect of shaking frequency on both mass transfer coefficient (kL) and specific interface area (a), the volumetric mass transfer coefficient (kLa) increased greatly with shaking frequency. Results also showed that filling volume had no significant effect on kL but negative effect on specific interface area. Shear force formed in baffled flask showed great dependent on shaking frequency, but it was insensitive to the filling volume. Finally, cultivations of filamentous fungus conducted in normal and baffled flasks validated the simulating results.Then, PBM model was used to study the flow field, gas-liquid distribution and engineering parameters under four different impeller combinations condition in a 50L bioreactor. The result showed that for the 3RT combination, the gas dispersion performance was best, while the mixing time was longest, and shear rate and power consumption were biggest. For the 2WHu combination, the gas dispersion performance was worst, while the mixing time was shortest, and shear rate and power consumption were least. The gas hold performance of BTD-2WHd combination was best, leading the biggest gas hold-up and mass transfer capacity. The experiment results validated the simulation results.Finally, the CFD method was used to solve the problems in industrial bioprocess. By CFD study, two solutions were provided for the optimization of a 500mL mammal cell bioreactor fermentation process, and key technical parameters were provided for the scale-up of 30L-1000L mammal cell fermentation process, and some guidance were made for the improvement of 50t large scale bioreactor. By studying the flow field and engineering parameters in plant scale bioreactors, the solution can be provided for solve the similar problems related to bioreactor structure. |
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