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摘要
Orbitally shaken bioreactors, OSRs, are commonly employed in the pharmaceutical industry at the drug development and screening stage, because they provide a high throughput solution where several cell cultures can be run in parallel. In general cell-culture media used in bioprocessing exhibit a viscosity close to water, but this hypothesis is less valid when high density cell cultures are considered, such as in continuous fermentations, where cells are retained in the bioreactor at large densities and the drug-product is continuously removed and fed to the downstream capture steps of the process. In this context the viscosity of the culture media increases with culture time and with the amount of biomass present in the reactor. In this frame of work two sets of measurements, based on DIMST and pLIF, were carried out to further study the mixing dynamics in a orbitally shaken cylindrical reactor when fluids of viscosity higher than water are considered. These data allowed to identify different flow transitions, which have not been previously observed in the PIV experiments of Ducci and Weheliye (2014). The mixing time measurements highlighted the presence of a poor mixing region for all the flow regimes considered, irrespective of the vortical structure present in the flow, and an attempt was made to quantify the diffusion process occurring at the edges of this region. A more detailed understanding of the flow and deformation dynamics occurring at small scales can be gained from the pLIF measurements. These allowed to visualise the lamellar structures induced by the flow deformation occurring over several orbital cycles. The growth rate of the material lines was estimated and compared to models commonly employed in the literature to assess mixing dynamics. These information are relevant for micro-mixing models, when the mixing process is limited by the growth of the interfacial area rather than the reaction time.
- 出版日期2018-4
