Packed bed bioreactor with porous ceramic beads for animal cell culture

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Abstract
A packed bed bioreactor was investigated as means for the cultivation of mammalian cells. The packed bed is comprised of porous ceramic particles with pores sufficiently large for cell immobilization as well as for intraparticle convective flow. In this way, the transport of limiting nutrients such as oxygen can be significantly enhanced, allowing maintenance of cell viability and productivity in an environment protective of adverse shear effects. The extent of intraparticle convective medium flow was experimentally quantified relative to the reactor operating conditions, and was found to be the dominant mechanism of nutrient transport to cells immobilized in the particle interior. An approximate linear relationship was obtained between overall reactor productivity and the extent of intraparticle convection. As the latter can be controlled at the single‐particle level through total flow rate control, this relationship is a useful scale‐up tool for the design of bioreactors. The high cell densities and the high volumetric productivities achieved by using small lab‐scale reactors underline the potential of this simple bioreactor configuration for large‐scale cell culture applications. © 1993 John Wiley & Sons, Inc.