The Reason Why Scaleup Is not Simple

Bioreactor design would be simple if all you needed to do was to obtain good performance in a laboratory-scale bioreactor and then simply construct a geometrically-identical larger version of this bioreactor. However, this is impossible to achieve. Recalling the argument presented in Sect. 2.3 (also see Fig. 2.3):

• the aim of the bioreactor is to control the conditions within the bed, such as the temperature and water activity, at the optimum values for growth and product formation;

• however, the growth of the organism causes deviations from the optimum conditions in its immediate surroundings, through the release of waste metabolic heat and the consumption of O2, amongst other processes;

• in operating a bioreactor, we are limited to manipulating external operating variables;

• the effects of the operating variables on the conditions within the bioreactor, such as the bed temperature, are not direct. Between the manipulation that we make in the operating variable (for example, changing the temperature at which the air enters a forcefully aerated bioreactor) and any particular position in the bed, we have various transport phenomena. For example, to arrive at mid-height within a packed-bed bioreactor, the inlet air firstly has to pass through half of the bed, and the temperature of that air will have risen from the inlet value by the time it reaches the middle of the bed, due to the heat transfer that occurred over the intervening distance. This will decrease its ability to cool the middle of the bed (in fact, this phenomenon is the basis of the axial temperature profile shown in Fig. 4.3 for the forced aeration of static beds);

• the importance of these transport phenomena increases as the distance over which transport must occur increases. This distance typically increases as the size of the bioreactor increases.

So transport phenomena are of crucial importance in controlling how the bioreactor operates. Scale-up becomes a challenging task because the underlying physiology of the microorganism is independent of scale. The microorganism will respond in exactly the same way for a given set of conditions that it finds in its local environment, regardless of whether it is located within a bioreactor holding 10 g of substrate or a bioreactor holding many tons of substrate. In other words, in both bioreactors it will give the same rate of growth and heat release for a given combination of O2 concentration, nutrient concentration, pH, temperature, and water activity.

The key question of the scale-up problem then becomes "Is it possible to keep the local environmental conditions at or very near optimal values as scale is increased?" Note that it is relatively easy to control the local environment within small-scale bioreactors. In fact, it is for this reason that thin columns are used for basic kinetic studies (which will be seen in Chap. 15).

It is important to understand that the conditions in the local environment depend on the balance between the changes caused by the microorganism and the transport phenomena that arise to counteract these changes. For example, the local temperature sensed by the organism (and which will affect its growth) depends on the balance between the rate of waste metabolic heat production and the rate of conduction of energy away to regions in which the temperature is lower (Fig. 5.1(a)). If the rate of waste heat production is higher than the rate of conduction, then the local temperature will rise, which of course occurs during the early periods of the fermentation when the growth rate is accelerating (Fig. 5.1(b)).

passing air at Tair continuously removing heat rate of metabolic heat production (a growth rate)

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