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Figure 29. Continuous culture system. (A) Small glass vessel (Wilson, et at., 1976). (B) Pilot plant for continuous cultures with 20 kl bioreactor (Azechi, et al., 1983).

Figure 30. Immobilized plant cell cultures. (Prenosil and Pederson 1983).

3.11 Scale-up Problems

Scale-up techniques for plant cell cultures are not well understood. Some attempts have been made using tobacco cells and applying essentially the same parameters as those for the scale-up of microbial cultures (Azechi, 1985).[33] The results showed that Jq^a values are useful as scale-up parameters, however, the situation for secondary metabolite production is quite different. The productivity of the metabolites decreased as the culture volume increased. An example of this is the productivity of the indole alkaloid, a serpentine which declined significantly as the culture volume increased from 0.1 to 80 1 (Fowler, 1987).1341 Possible reasons for the loss of product on scale-up are the following: (i) altered and inadequate mixing of the nutrient and cells at the high reactor volumes and (ii) lowered dissolved oxygen level (Breuling et al, 1985).[35) Fujita and Tabata (1987)[1] used the scale-up of suspension cultures of Lithospermum erythrorhizon cells for their ability to produce shikonins as the criterion for comparing the aeration-agitation type bioreactor with a modified paddle impeller and the rotary drum type bioreactor. When the aeration-agitation type bioreactor was scaled up to a volume of 1000 1, the shikonin productivity decreased, but when the rotary drum bioreactor was scaled up to 10001, there was no decrease in the yield of shikonins (Fig. 31). Thus, in an industrial pilot plant for secondary metabolite production, mild agitation and oxygen supply will be important variables.

Agitation Type Tank with a Modified Paddle Impeller

TANK VOLUME (I)

Figure31. Scale up of suspension cultures for Lithospermum erythrorhizon cells. (Fujita and Tabata, 1987).

TANK VOLUME (I)

Figure31. Scale up of suspension cultures for Lithospermum erythrorhizon cells. (Fujita and Tabata, 1987).

3.12 Bioprocess Measurement and Control

Bioprocess Measurement and Control in Large Scale Culture.

Measurement and control systems used in the bioreactor for plants are essentially the same as those for microbial or animal cell cultures, but, in special cases, where the mineral components influence the productivity of secondary metabolites, the kind of salts used for the electrode must be taken into consideration.

Mass balance. The mass balance equation (Eq. 4) is generally used for heterotrophic organisms. Pareilleus and Chaubet (1980)I36] have applied the equation to apple cell cultures:

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