The Challenges Faced at Large Scale in SLF and SSF

The major challenge in the scale-up of aerobic submerged liquid fermentation processes is the transfer of O2 into the liquid at a sufficient rate to obtain high cell densities. Scale-up strategies that address this transfer, which is characterized by the parameter kLa, have long been available in the area of SLF (Kossen and Oosterhuis 1985). Although heat transfer calculations must be done, in order to provide sufficient cooling capacity, heat removal is typically not an overly challenging task. If the outer surface of the bioreactor does not provide a sufficiently large surface area to give the necessary rate of heat removal to the cooling water in a water jacket, then a cooling coil can be incorporated into the design without causing much complication in construction or operation.

On the other hand, in the case of SSF, heat removal is typically the major concern. It is more difficult to remove the waste metabolic heat from a bed of solids in which the inter-particle phase is occupied by air than it is to remove this heat from a continuous aqueous phase. There are two reasons for this:

• the thermal properties of a continuous aqueous phase, namely the thermal conductivity and heat capacity of liquid water, are superior to those of a bed of moist solids with inter-particle air;

• mixing greatly promotes heat removal by bringing the medium into contact with the cooling surfaces within the bioreactor. However, typically mixing must be minimized in SSF bioreactors, for several reasons: Firstly, it requires higher energy inputs to mix the bed of solid particles within an SSF bioreactor than to mix the liquid medium in an SLF bioreactor. Secondly, the presence of internal heat transfer surfaces such as plates or coils within the bioreactor will interfere much more with the mixing of a solid bed than it will with the mixing of a liquid medium. Finally, a liquid medium can be mixed reasonably well without causing undue shear forces, whereas in a bed of solids in an SSF process involving a fungus, even the slightest mixing action will cause significant physical damage to the mycelium growing at the particle surface.

The difficulty of heat removal from large-scale SSF bioreactors has two consequences for bioreactor design:

• evaporation may occur as a result of temperature rises in the bed (see Fig. 4.3.(c)), and in some cases it may in fact be promoted deliberately, given that it is one of the most effective heat removal mechanisms. However, continued evaporation can dry the bed out to water activities low enough to restrict growth. Therefore the maintenance of the water activity of the bed becomes a consideration that guides design and operation.

• given that in many SSF bioreactors the air phase plays a central role in heat removal and that the aeration rates needed in order to remove heat at a reasonable rate are more than sufficient to ensure a reasonable O2 supply to the surface of the particles, O2 supply is typically a minor consideration (except for Group I bioreactors, i.e., static beds without forced aeration).

The following discussion about the general scale-up problem therefore focuses on heat removal as the key scale-up criterion and maintenance of water activity as a related consideration. O2 supply will not be covered in this general discussion, although something will be said about it in Chap. 6, which talks about Group I bioreactors.

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