WhY Use a Packed Bed Bioreactor System?
Adherent cells are traditionally attached to treated plastic surfaces such as T-flasks or roller bottles, or to micro-carriers or macro-porous non-woven fibers. A gentle mechanical agitation, wave motion, or rotating/shaking motion is then applied to facilitate the mixing and oxygenation. Nonetheless, MA systems are ideal for all cell cultures and are commonly used in the industry for good reason. There are however limitations and drawbacks: (1) limitation of cell density for high productivity; (2) lack of reliable scheme to separate cells from medium for perfusion culture or medium exchange at minimal or no cost; (3) relatively high shear rate even with low shear agitator. Packed bed systems were therefore developed to resolve these limitations. Carriers are packed as a bed to adhere or entrap the cells and utilize the mechanical agitation, circulation pump, or pneumatic means to circulate the media through the bed to replenish nutrients, including oxygen. With cells immobilized in this manner, cell density is significantly increased and can be naturally separated from the medium. With cells confined inside the matrix the shear force applied on each cell is also significantly reduced compared to cells that are freely exposed in the medium. The packed bed bioreactor with cells immobilized in the bed can now easily perform high cell density culture, readily replace the fresh medium or recover the product secreted in the medium; and can perform perfusion culture for higher productivity. This is the reason why a packed bed bioreactor systems have gained a great interest in the industry.