Control of bioprocesses

The goal of bioprocess control is to maintain important process variables in a bioreactor at a desired level regardless of time-dependent environmental changes. Process control will be performed by the following two steps based on the information obtained through the instrumentation. 

1) A check of the deviation between the set point and the measured process variable. 

Process control can be done manually or automatically. Needless to say, current refinery and petrochemical process plants are fully automated however, it should be noted that manual control by experienced operators still occupies an important portion of bioprocess control due to the difficulties, as previously described. 

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D. Dochain and M. Perrier. Advanced Instrumentation, Data Interpretation, and Control of Biotechnological Processes, chapter Monitoring and Adaptive Control of Bioprocesses, pages 347-400. Kluwer Academic Publishers, 1998. 

There are several barriers to the successful control of bioprocesses due to particular circumstances that are related to their characteristics the complexities of microbial metabolisms, the nonlinearity of microbial reactions, the frequent use of batch and fed-batch operations, and the limited availability of sterihzable online sensors for important process variables such as cell and product concentrations. Furthermore, it is difficult to construct mathematical models that can predict the entire range of batch or fed-batch operations that many fermentation processes require. 

To overcome this difficulty, many challenges have been met in the fields of bioprocess control. In this chapter, the basic principles of the instrumentation and control of bioprocess are explained. 

Yamane, T. and Shioya, S. (1997) Intelligent Control of Bioprocesses, Kyoritsu Shuppan Co., Ltd. (in Japanses). 

Schiigerl K (2001), Progress in monitoring, modeling and control of bioprocesses during the last 20 years, J. Biotechnol. 85 149-173. 

Axelsson JP, Munch T, Sonnleitner B (1992) In Karim N (ed) Computer applications in fermentation technology - modelling and control of bioprocesses. Pergamon, p 383... 

Enzymatically coupled FETs have reached the stage of development where their application to practical sensing problems in various analytical fields is possible. Applications in the field of medical diagnostics are most frequent, although a few are used for the control of bioprocesses, for example, a fermentation bioreactor (12, 49). 

At BPEC, the Engineering Research Center of Excellence at MIT, advanced computer control of bioprocesses is being researched with an eye... 

Chapters 9-16 cover the application of optical and biosensor methods for on-line monitoring and control of bioprocesses. Topics include the use of expert systems for controlling flow injection analysis systems and hybrid process modeling for bioprocess control. 

In this chapter, the integrated design and control of bioprocesses was considered as a multi-objective optimization problem subject to non-linear differential-algebraic constraints. This formulation has a number of advantages over the traditional sequential approach, not only because it takes into account the process dynamics associated to a particular design, but also it provides a set of possible solutions from which the engineer can choose the most appropriate to his/her requirements. However, these problems are usually challenging to solve due to their non-convexity, which causes the failure of procedures based on local (e.g. SQP) NLP solvers. 

Schiigerl, K., Progress in Monitoring, Modeling and Control of Bioprocesses during the Last 20 Years, /. BiotechnoL, 85,149 (2001). 

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