478
Chapter 11
Figure 11.1. Schematic representation of analysis steps in scale-up
necessary since the costs for the medium used in the lab may be prohibitive for a large-scale
operation. These additional economic restraints should be kept in mind, although we will restrict
the discussion to the engineering aspects of scale-up.
The phenomena that need to be taken into account during scale-up of a fermentation process can
be divided into physical processes (transport phenomena) and metabolic processes (microbial
kinetics). These need to be combined in order to properly model the reactor and allow scale-up
as schematically shown in Fig 11.1. The physical processes are typically described by classical
mechanical or chemical engineering, and there are mathematical models of varying complexity
available to describe these phenomena. The metabolic phenomena, on the other hand, are not
per
se
scale-dependent. However, as a consequence of scale dependent transport phenomena, the
local environment surrounding the cell will be different in a large-scale bioreactor than in a
small-scale, typically well-mixed reactor. This changed environment may in turn cause
metabolic changes. The consequences of these are sometimes difficult to predict, mainly due to
insufficient experimental data. An important task during scale-up is therefore to identify
potential gaps in knowledge, and take proper actions to acquire the missing information. If no
uncertainties can be accepted, there is always the option of scaling-up by simply multiplying lab-
scale production units. This, however, is expensive, and scale-up will therefore normally involve
a substantial increase in reactor size.
11.2 Bioreactors
11.2.1. Basic requirements and reactor types
In the bioreactor a high product yield, a high productivity and a high reproducibility of the
desired fermentation process should be achieved These overall tasks can be decomposed into a
number of subfunctions (Kossen, 1985, Liden, 2001), and such a list of basic tasks is given in
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