Biotechnology process controls

The determination of oxygen partial pressure (p02) is a major task in chemical and biotechnological process control, pharmaceutical screening, medical chemistry and... 

The continuous monitoring of chemical parameters is becoming increasingly important in biotechnology, process control, environmental analysis and medicine. In a limited number of cases, chemical sensors are available that show a sufficient spedfldty for the components to be measured. More oft however, measurement with a chemical sensor can only be carried out after the sample has undergone some form of pretreatment. This is necessary to eliminate the influence of interfering species on sensor response, to obtain the selectivity and sensitivity required for an accurate determination. 

Bioprocess Control An industrial fermenter is a fairly sophisticated device with control of temperature, aeration rate, and perhaps pH, concentration of dissolved oxygen, or some nutrient concentration. There has been a strong trend to automated data collection and analysis. Analog control is stiU very common, but when a computer is available for on-line data collec tion, it makes sense to use it for control as well. More elaborate measurements are performed with research bioreactors, but each new electrode or assay adds more work, additional costs, and potential headaches. Most of the functional relationships in biotechnology are nonlinear, but this may not hinder control when bioprocess operate over a narrow range of conditions. Furthermore, process control is far advanced beyond the days when the main tools for designing control systems were intended for linear systems. 

L. E. S. Brink and J. Tramper, in Modelling and Control of Biotechnological Processes, Pergammon Press, Oxford, 1985, pp. 111-117. 

T. Scheper, T. Lorenz, W. Schmidt, and K. Schugerl, On-line measurement of culture fluorescence for process monitoring and control of biotechnology processes, Ann. NY Acad. Sci. 506, 431—445... 

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. 

D. Dochain and G. Bastin. Modelling and Control of Biotechnological Processes. Pergamont Press, Oxford UK., 1986. 

Rottenbacher, L., Schofiler, M. and Bauer, W., Mathematical modelling of alcoholic fermentation in a gas/solid bioreactor - combined effects of solids mixing and non-steady-state kinetics. Proceedings of the First IFAC Symposium on Modelling and Control of Biotechnological Processes, Noordwijkerhout, 1985b, 151-157. 

The optimum yield of a condensation product is obtained at the pH where Ka has a maximum. For peptide synthesis with serine proteases this coincides with the pH where the enzyme kinetic properties have their maxima. For the synthesis of penicillins with penicillin amidase, or esters with serine proteases or esterases, the pH of maximum product yield is much lower than the pH optimum of the enzymes. For penicillin amidase the pH stability is also markedly reduced at pH 4-5. Thus, in these cases, thermodynamically controlled processes for the synthesis of the condensation products are not favorable. When these enzymes are used as catalysts in thermodynamically controlled hydrolysis reactions an increase in pH increases the product yield. Penicilhn hydrolysis is generally carried out at pH about 8.0, where the enzyme has its optimum. At this pH the equiUbrium yield of hydrolysis product is about 97%. It could be further increased by increasing the pH. Due to the limited stability of the enzyme and the product 6-aminopenicillanic acid at pH>8, a higher pH is not used in the biotechnological process. 

Nakamura, T., Kuratani, T., and Morita, Y. (1985) Fuzzy control application to glutamic acid fermentation. Proceedings of IFAC Modelling and Control of Biotechnology Processes, pp. 211215. 

Photoswitchable enzymes could have an important role in controlling biochemical transformations in bioreactors. Various biotechnological processes generate an inhibitor, or alter the environmental conditions (pH, for example) of the reaction medium. Photochemical activation of enzymes that adjust environmental conditions or deplete the inhibitor to a low concentration may maintain the bioreactor at optimal performance. More specifically, integration of the photoswitchable biocataly-tic matrix with a sensory electrode might yield a feedback mechanism in which the sensor element triggers the light-induced activation/deactivation of the photosensitive biocatalyst. 

In general the quality control procedures for products obtained through biotechnology are very similar to those routinely used with traditional pharmaceutical products in areas such as raw material testing, documentation of process control, and aseptic processing. The fundamental difference is in the type of methods used, so as to determine the product s identity, uniformity, and purity. In the quality control of products obtained through recombinant DNA technology, it is necessary to employ validated tests for the final and intermediary products to ensure the elimination of undesirable impurities. 

Sandmeier EP, Keller J, Heinzle E, Dunn IJ, Bourne JR (1988) Development of an on-line pyrolysis mass spectrometry system for the on-line analysis of fermentations. In Hienzle E, Reuss M (eds). Mass Spectrometry in Biotechnological Process Analysis and Control. Plenum, New York, p 209... 

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