Advances in cell culture technologies and methods in recent years have resulted in increasing solids densities at harvest. This results in a higher number of cell culture harvest processes requiring a centrifugation step at pilot and commercial scale. The traditional scaling approach used for disk stack centrifugation is to use Q/Σ theory to transfer equivalent centrifugal separation conditions between different centrifuges. However, several data sets have been generated showing that this model can be too ideal to be used in practice. Some limitations to Q/Σ theory include that it assumes unbreakable solid spheres are being separated and there is perfectly efficient separation. In practice, disk stack centrifuges vary in efficiency by design and are affected by quality of feed material. Also, for shear sensitive mammalian cell types in particular, when intact cells enter a disk stack centrifuge they are broken down by shear forces into many smaller particles. In an attempt to generate a more realistic model of expected disk stack centrifugation performance, a scale down model using capillary shear constructed of common lab parts was performed. Presented here are the results of the capillary model experiments which successfully demonstrated that sheared broth material had turbidity and particles size distribution profiles more representative of process streams generated by disk stack centrifugation compared to traditional batch centrifuged broth. Additionally, observations on the difference in shear response for PER.C6 and Chinese Hamster Ovary (CHO) mammalian cells will be discussed.

Small scale modeling of disk stack centrifugation with mammalian cell culture capillary shear for a more predictive harvest process transfer

ACS Fall 2020 Virtual Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.