Computational fluid dynamic modeling of 100ml and scaled-down 10ml stirred suspension bioreactors enables prediction of embryonic stem cell characteristics
January 15-19, 2017
There is a growing necessity for cell cultivation using bioreactors to translate laboratory based culture protocols into reproducible, scalable, and robust bioprocesses. Stirred suspension bioreactors offer several advantages over planar static cultures, including: reduced labour and operating costs, reduced space requirements, greater cellular homogeneity, and increased cell density per volume . An important consideration when using stirred suspension bioreactors is mechanical stimulation. Fluid shear at the fluid-cell interface triggers cellular responses through mechanotransduction and can modulate stem cell proliferation and differentiation. However, if the shear stress caused by the impeller exceeds the tolerance limit of the cells, it causes cell damage and death, resulting in a lower quality and yield of cells. The shear rate distribution depends on bioreactor geometry, impeller agitation rate, cell density, and cell media viscosity . Current scale-up protocols to predict agitation rates rely on maximum values of hydrodynamic variables, which occur only at the impeller tip. The volume averaged shear stress and maximum shear stress differ greatly, and cells dispersed within the liquid experience different local and global forces. This makes it difficult to predict how cells will respond to changes in bioreactor geometries and sizes. Profiling distributed and average forces in the bioreactor is critical to ensure quality and yield in cell manufacturing. Hydrodynamics, specifically velocities, shear rates, and energy dissipation rates, can be studied using computational fluid dynamic (CFD) modeling.
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Breanna S. Borys, An Le, Michael S. Kallos, Charlie Yu-Ming Hsu, Derrick E. Rancourt, and Ian D. Gates, "Computational fluid dynamic modeling of 100ml and scaled-down 10ml stirred suspension bioreactors enables prediction of embryonic stem cell characteristics" in "Scale-up and Manufacturing of Cell-based Therapies V", Tom Brieva, Celgene Cellular Therapeutics William Miller, Northwestern University Chris Mason, University College London Eds, ECI Symposium Series, (2017). https://dc.engconfintl.org/cellbasedtherapies_v/63