Fermentation is the term used by microbiologists to describe any process for the production of a product by means of the mass culture of a microorganism . The product can either be: i) The cell itself: referred to as biomass production. ii) A microorganism's own metabolite: referred to as a product from a natural or genetically improved strain. iii) A microorganism foreign product: referred to as a product from recombinant DNA technology or genetically engineered strain.
There are three types of fermentation processes existing: batch, continuous and fed-batch processes. In the first case, all ingredients used in the bioreaction are fed to the processing vessel at the beginning of the operation and no addition and withdrawal of materials take place during the entire batch fermentation. In the second case, an open system is set up. Nutrient solution is added to the bioreactor continuously and an equivalent amount of converted nutrient solution with microorganisms is simultaneously taken out of the system. In the fed-batch fermentation, substrate is added according to a predetermined feeding profile as the fermentation progresses. In this book, we focus on the fed-batch operation mode, since it offers a great opportunity for process control when manipulating the feed rate profile affects the productivity and the yield of the desired product . A picture of laboratory bench-scale fermentors is shown in Figure 1.1. The schematic diagram of the fed-batch fermentor and its control setup is illustrated in Figure 1.2.
Fermentation processes have been around for many millennia, probably since the beginning of human civilization. Cooking, bread making, and wine making are some of the fermentation processes that humans rely upon for survival and pleasure. Though they link strongly to human daily life, fermentation processes did not receive much attention in biotechnology and bioengineering research activities until the second half of the twentieth century .
An important and successful application of fermentation process in history is the production of penicillin . In 1941, only a low penicillin productivity of
L. Z. Chen et al.: Modelling and Optimization of Biotechnological Processes, Studies in Computational Intelligence (SCI) 15, 1-16 (2006)
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Sampling a o_n n n n
-pH Agitation control - Aeration jul j!lj!lj
Acid control Base control Antifoam control
Bioflo-3000 Control unit
Fig. 1.2. Schematic diagram of the computer-controlled fed-batch fermentation.
about 0.001 g/L could be obtained by surface culturing techniques, even when high-yielding strains were used. The demand for penicillin at that time exceeded the amount that could be produced. In 1970, the productivity was dramatically increased to over 50 g/L by well-controlled large-scale, submerged and aerated fermentation. As a result, more human's lives were saved by using penicillin. Since then, a large number of innovative products, such as specialty chemicals, materials for microelectronics, and particularly, biophar-maceuticals, have been manufactured using fermentation processes and have been making a significant contribution in improving health and the quality of life . The twenty first century is thus regarded as "the biotechnology century".
Although fermentation operations are abundant and important in industries and academia which touch many human lives, high costs associated with many fermentation processes have become the bottleneck for further development and application of the products. Developing an economically and environmentally sound optimal cultivation method becomes the primary objective of fermentation process research nowadays . The goal is to control the process at its optimal state and to reach its maximum productivity with minimum development and production cost, in the mean time, the product quality should be maintained. A fermentation process may not be operated optimally for various reasons. For instance, an inappropriate nutrient feeding policy will result in a low production yield, even though the level of feed rate is very high. An optimally controlled fermentation process offers the realization of high standards of product purity, operational safety, environmental regulations, and reduction in costs .
Though many attempts have been made in improving the control strategies, the optimization of fermentation processes is still a challenging task , mainly because:
• The inherent nonlinear and time-varying (dynamic) nature make the process extremely complex.
• Accurate process models are rarely available due to the complexity of the underlying biochemical processes.
• Responses of the process, in particular for cell and metabolic concentrations, are very slow, and model parameters vary in an unpredictable manner.
• Reliable on-line sensors which can accurately detect the important state variables are rarely available.
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