Bioreactors for Cell Immobilization

Fluidized-bed bioreactors (FBRs). (d) Air-lift bioreactors (ALRs). (e) Hoilow fiber membrane bioreactors (HFMRs). 

One critical issue to consider in running HFMRs is the oxygen supply. Different from the other bioreactors, the ECS in an HFMR cannot be directly aerated. In order to improve oxygen supply, the culture medium has to be circulated in the lumen at high rates. HFMRs have been used for immobilizing bacterial, yeast, and mammalian cells [129]. However, most of the studies were focused on mammalian cell cultures, for example, culture of hybridoma cells for the production of antibodies [130,131]. 

1) Preparation and operation of immobilized cell cultures are often complex and time consuming and incur additional costs, which is an inherent problem that significantly compromises their technical advantages and makes this technology economically unacceptable at large scale. 

2) Most cell immobilized systems suffer from leakages of cells from matrixes, resulting from instability of support matrices, unrestrained cell growth, and/or gas evolution reaction (i.e., the reaction in which Oj or CO2 is produced) bursting the immobilizing matrixes. The released cells then either are lost or contaminate the product. 

3) Diffusion barrier to oxygen and/or other nutrients is possibly created by the immobilization matrixes and by the high cell density. In aerobic systems, oxygen transfer is often the rate-limiting step in free cell cultures, and this problem will be more severe in immobilized cell systems and pose severe limitations on the use of this technology at industrial scale. 

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