Understanding the impact of shear stresses on different cell lines in the Allegro STR system

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The first part of the project will aim to quantify maximum and average Reynolds stresses in the Allegro system at different operating conditions. This can be achieved by (i) designing an accurate scale down device able to reproduce the geometry, environment and flow dynamics characteristics of the large scale reactor and/or (ii) adapting the Allegro reactor in order to be optically accessible by experimental flow dynamics techniques and thus directly measuring stresses in the system. A second step will involve the selection of three representative cell lines and the use of existing or new USD tools to better understand cell response to the range of stresses previously measured in the Allegro STR. Analytical information will be collected at different stages of the cell culture step (metabolic profiles, cell counting, particle size distribution, Scanning Electron Microscopy among others) to quantify the extent of cell damage. The combination of the experimental results obtained in the two stages will provide a thorough and complete insight of the interaction between the bioreactor geometry, the operating conditions and the resulting stresses, in addition to the challenges faced at large scale and potential bottlenecks.The experimental work could be combined with a modelling approach to provide better understanding of the relationship between gas flow rate/gas distribution patterns, which are experimentally challenging to measure, and cell damage under different operating conditions. This part of the project will result in predictive correlations, able to inform future scale-down model design and support the validation of scaling correlations and identification of optimal operating conditions at the large scale.