(174o) Extensional Versus Shear Flow Dynamics and Cell Properties in High Density Cell Cultures

As the production of human biologics rapidly grows and matures, the productivities of large scale, animal cell cultures correspondingly continue to increase. This increased productivity involves several factors including increased specific cell productivity, higher cell densities, and longer culture time (product production time).

A number of recent publications have focused on the biophysics of animal/human cells have confirmed a long-suspected hypothesis that cells exhibit viscoelastic properties. Further very high densities of CHO cultures exhibit non-Newtonian properties.

Our lab, as well as numerous others, have focused on relating the hydrodynamic sensitivity of cells to specific energy dissipation rates, EDR. EDR can be further characterized with two distinct fluid stresses: shear stress and extensional stress. Shear stress acts perpendicular to the flow direction, while extensional stress applies parallel to it.

In this study, a simulation based on finite element methods was employed to design a “second generation” flow contraction device (i.e. torture chamber) which predominately creates extensional forces on the cells. We will present results on comparing the “old” torture chamber to this second-generation device which produces predominately extensional stress and compare the corresponding EDR and cell damage. We will begin to consider the concept of modeling the cell as a viscoelastic fluid with respect to cell damage in bioprocess equipment.