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Scale-down

Scale-down

Production scale

Laboratory scale Sca|e-Up

Figure 35. Schematic representation of the scale-down method. Adapted from Oosterhuis (177).

the downcomer may become very relevant. This was shown by MacNeil and Kristiansen (180,186) for the scale-up of an external-loop ALR for the production of Aureobasidium pullulans. The poor oxygen supply in the downcomer was reflected on the level of product synthesis, as shown in Figure 36. The smaller residence times lead to higher A. pul-lulans production.

An analysis of the time constants required for the design of an ALR for plant cell culture has recently been presented (187). Figure 37 shows the reported values of the time constants calculated for an external-loop ALR for mixing, mass transfer, and oxygen consumption at two different cell concentrations: 5 and 30 kg/m3. These graphs exemplify the changes in the controlling mechanism that may take place as the physical properties of the broth change in the course of the bioprocess.

Details on bioreactor scale-up may be found in the recent review of Sola (180). It should be remembered, however, that the reliability of a scale-up will always be limited by the quality of the predictions of gas holdup, liquid velocity, and mass transfer rate.

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