bioreactor studies of heterologous protein production by ...

1.4. Immo bilized-Cell Bioreactors
Most previous studies relating to immobiltration of recombinant celis are concerned
mauily with the efféct of immobiliraton on genetic stability. They did not address
bioprocess development of irnmobilized ncornbinant œll systems. Immobilized cd
bioreactor design is a key to immobiüzaton bioprocess developmenL Three-phase (Gas-
liquid-soüd) bioreactors are nwsary for systems involving immobilized cek Gaseous
reactants (oxygen) must be absorbed into the iiquid phase and then transfened to the
surface of the immobiüzed ceiis. At the same tirne, dissolved nacmts are transported to
the surface of the biocatalysts. Finally the biochemical reactions to producu occur in the
immobilited ce&. Ali such three-phase biopmcesses involve seps of gas-iiquid, liquid-
solid. inmoiid phase mas transfer and biochemicai reactions. The relative importance of
these individual steps depends on the type of contact and interaction of the three phases.
Therefore the choice of bioreactor is important for optimum performance.
Traditional immoùilized cell bioreactors are usuaüy packcd-bed or trickle-bed
configurations. In these bioreactor systems, overgrowth of the biornass could block the
bed which could cause operational instability. The most critical problem in these
bioreactor configurations is oxygen transfer limitation. Thus. they may be suitable for
anaerobic fermentation such as ethanol production, but they are not suitable for aerobic
recombinant fermentation. In recent years, pneumatic type three-phase airlift slurry
bioreactors have been receiving increasing attention for imrnobiliPd ceIi culture ( Cm
1988). However. the density of irnrnobiüzed ceii puticles is mdy very close to that of
.