Scale‐up of bioreactors for fermentation of mammalian cell cultures with special reference to oxygen supply and microcarrier mixing

Abstract

AbstractThe increasing demand for products from mammalian cells has prompted the authors to develop a new type of bioreactor. Its significant features include the supply of oxygen, homogeneous distribution of microcarrier suspensions and process control. Media with high protein contents, required for mammalian cell cultures tend to generate foam. This causes the flotation of solid particles. The reactor was equipped with a system of porous hydrophobic Accurel hollow fibre membranes in order to prevent the formation of bubbles. The membrane is coiled in the form of a basket, or fixed on several carriers. If the liquid pressure is higher than that of the gas phase inside the membrane, a bubble ‐ free oxygen supply to the culture broth can be achieved. The problem of axial mixing of microcarier suspensions was solved by the use of a spiral agitator, attached underneath the aeration system at the bottom of the reactor. The combined aeration and mixing system, which is driven by an eccentric motor, undergoes a tumbling motion. Sufficiently homogeneous suspensions are produced in this system at low membrane velocities, i.e. in presence of low shear forces.