Various Approaches To Scale Up And Scale Down Methods

The scale-up of air-lift reactors

Bubble columns and air-lift vessels tend to be scaled-up on the basis of geometric similarity and constant gas velocity (Scragg, 1991). Under these conditions the KLa and shear rate in the two scales will be similar. The major difference will be the height of the vessels resulting in increased pressure at the base of the larger vessel. This would result in higher oxygen and carbon dioxide solubility which would give a higher KLa but might result in carbon dioxide inhibition. The other problem in the scale-up of air-lift systems is that the organism is exposed to extremes of oxygen levels in the riser and downcomer and the effects of these conditions should be investigated on the laboratory scale.

Scale-down methods

Scale-down is the situation where laboratory- or pilot-scale experiments are conducted under conditions which mimic the industrial-scale conditions. This approach is important in both the development of a new product and the improvement of an existing full-scale fermentation. The procedure has been reviewed by Jem (1989). Frequently, conditions achievable on a laboratory scale are impractical on an industrial scale, which means that if inappropriate conditions have been used in the laboratory unrealistic yield objectives may be set for the scaled-up process. The aspects to consider in the design of laboratory- or pilot-plant experiments in the context of scale-down may be summarized as follows:

(i) Medium design. Media relevant to the industrial situation should be used in development experiments.

(ii) Medium sterilization. If the medium is to be batch sterilized on the large scale its exposure time at a high temperature will be much greater than that experienced in the laboratory or pilot plant. Thus, the sterilization times on the smaller scales should be increased to mimic the industrial situation. Alternatively, medium sterilized in the production fermenter may be used in the laboratory and pilot plant. This highlights the advantage of continuous sterilization where little loss of medium quality occurs. Furthermore, the same continuous sterilizer may be used for both full-scale and pilot scale vessels.

(iii) Inoculation procedures. Due to a range of cir cumstances, it may not always be possible to inoculate every production fermentation with inoculum in optimum condition. The scale down approach can be used to predict the consequences of such events by mimicking these situations in the laboratory, for example by storing inoculum or using inocula of different ages.

(iv) Number of generations. An industrial scale fermentation requires a greater number of generations than does a laboratory one; this may place more severe stability criteria on the process strain than may have been appreciated on the small scale. The industrial situation may be modelled in the laboratory by using serial sub-culture to ensure that the strain is sufficiently stable. This approach is particularly pertinent in the development of recombinant fermentations.

(v) Mixing. As indicated in the previous section it is almost inevitable that the degree of mixing will decrease with an increase in scale. Thus, it is possible to model inadequate mixing in the laboratory by subjecting the organism to pulse medium feeds or fluctuating process conditions such as oxygen concentration, pH and temperature. Such scaled-down experiments then allow predictions to be made about the suitability of new strains for industrial exploitation.

(vi) Oxygen transfer rate. Far higher oxygen transfer rates can be achieved in laboratory fermenters than in industrial-scale ones. Thus, unrealistic demands may be made of a fermentation plant if the development work has been done at very high oxygen-transfer rates. Therefore, the laboratory and pilot fermenters should reflect the oxygen transfer rates achievable in the full-scale fermenters.

The adoption of these simple approaches to small scale experimentation can prevent many scale-up problems before they even occur!

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