Working Principles of Bioprocess Technology

Based on the strategy of systematic process development, an engineering approach to bioprocessing includes several stages, as illustrated in the scheme of Fig. 2.14. As already stated in Fig. 1.4, the concepts of a rate-determining step (rds) and of the quasi-steady-state (qss) are very useful (see Sect. 2.4.1). Some basic principles play an important role to simplify, to quantify, to separate, to model, and to recombine the separated phenomena to form a total process model. 

The engineer responsible for planning must always strike a balance between involved complications and practicality in addition every model will be characterized by the number of variables and the measuring techniques used for them. The predictive power of the model will thus be limited. 

According to Fig. 2.3, microbial cells suspended in the liquid phase of the bioreactor are treated as black boxes this does not mean that they are neglected. Their macroscopic behavior, manifested in the changes of the concentrations in the liquid phase, is taken into consideration. As a consequence of this approach, the bioreactor itself is not treated as a black box. The core of the formal macroapproach is that formal analogies are used (see Sect. 2.4.3). The utility of the principle of simplification can also be demonstrated in the case of modeling the dynamics of bioprocesses (see Sects. 3.5.3 and 5.7). 

Separation deals with the accurate design of experiments for obtaining data on biological and physical phenomena in circumstances where the rates of the biological and physical processes are independent of one another. Macroconversion (macrokinetics) is an ill-defined basis for scale-up, and efforts must be made to avoid the appearance of such data. This is done with the aid of the test of pseudohomogeneity (see Sect. 4.3) and of regime analysis in general (see Sect. 4.2). 

In connection with the problem of pseudohomogeneity, it is clear that a reaction occurring inside a solid phase is not directly measurable. The internal flux of a metabolic reaction can thus only be checked by measuring the external fluxes in the liquid medium by means of computer simulation. Bar-ford and Hall (1979) found that an external overall flux does not reflect, even in an approximate manner, the internal fluxes. Moreover, in vitro examination of an isolated section of metabolism is inadequate for quantification of the coordinated and integrated biochemical control of an intact living system due to in vivo interactions between different parts of the metabolism. 

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