Bioprocesses control

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. 

Measurements and control of the fermentation conditions are very important for bioprocess control as they provide knowledge and hence a better understanding of the operation. 

Always based on the use of IR spectrophotometry, a novel attenuated total reflection-Fourier-transform infrared (ATR-FTIR) sensor [42] was proposed for the on-line monitoring of a dechlorination process. Organohalogenated compounds such as trichloroethylene (TCE), tetrachloroethylene (PCE) and carbon tetrachloride (CT) were detected with a limit of a few milligrams per litre, after extraction on the ATR internal-reflection element coated with a hydro-phobic polymer. As for all IR techniques, partial least squares (PLS) calibration models are needed. As previously, this system is promising for bioprocess control and optimization. 

J.V. TWORK and A.M. YACYNYCH (Eds) "Sensors in Bioprocess Control", Marcel Dekker, New York, 1990. 

R. RENNEBERG, A. WARSINKE and G. KAISER, "Amperometric immunosensors for bioprocess control" in "Biosensors Fundamentals, Technologies and Applications", GBF monographs, vol. 17, VCH Publishers, Weinheim, 1992, p. 25. 

Keywords. In-situ, Non-invasive monitoring. Fluorescence, Optical sensor, Bioprocess control... 

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. 

These data are utilized for process control, improvement of product quality, the saving of raw material and energy, and an assurance of safety. In this section, we focus on the measurement of process variables as the basis of bioprocess control. 

Furthermore, using the primary measurements to obtain the secondary process variables (so-called gateway sensor ) is a form of bioprocess control. For example, the measurement of optical density (primary measurement) can be used for the estimation of cell concentration, and, subsequently, the time course of cell concentration can be employed for the estimation of specific growth rate (secondary... 

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. 

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. 

A closed-loop system with feedback, which is illustrated in Figure 13.2, is the central feature of a control system in bioprocess control, as well as in other processing industries. First, a set-point is established for a process variable. Then, the process variable measured in a bioreactor is compared with the set-point value to determine a deviation e. Based on the deviation, a controller uses an algorithm to calculate an output signal O that determines a control action to manipulate a control variable. By repeating this cycle during operation, successful process control is performed. The controller can be the operator when manual control is being employed. 

There are two frequently used algorithms to determine the control action in a feedback control system for bioprocess control, an on-off (two-positioned) control, and a PID (proportional-integral-derivative) control. 

The on-off control is a simple and cheap algorithm for manipulating a control variable, and, therefore, it has been apphed to bioprocess controls such as temperature control and pH control. 

To overcome these difficulties, various advanced control methods specialized in bioprocess control have been developed. 

Application of Artificial Intelligence (Al) Technology to Bioprocess Control... 

Bioprocessing Controlled pore glass Protein A, gelatin, lysine... 

The undelayed evaluation of state of a culture by using software sensors and computers, based on the quantitative analytical information provided by hardware sensors and intelligent analytical subsystems, constitutes an excellent basis for targeted process control. Experts - either human or computer - have the data and the deterministic knowledge to trace observed behavior back to the physical, chemical and physiological roots thereby gaining a qualitative improvement of bioprocess control, a quantum leap process control can act on the causes of effects rather than just cure symptoms. A simple standard operating procedure [398] has proven useful, namely ... 

While these examples illustrate the role of flow cytometry in bioprocess monitoring, the analyses have been conducted off-line thus making their use in bioprocess control impractical. Recently, a portable flow cytometer - the Microcyte - [148] has been described, which due to its small size and lower cost (compared to conventional machines) allows flow cytometry to be used as an at-line technique [149]. Ronning showed that this instrument had a role to play in the determination of viability of starter cultures and during fermentation. The physiological status of each individual cell is likely to be an important factor in the overall productivity of the culture and is therefore a key parameter in optimising production conditions. 

Research in bioprocess control aims at the maximum performance of the process, which depends mostly on the performance of the living organism used as the biocatalyst. The data for setting the optimal or at least permissive environment for performance of the organism is delivered by the monitoring equip-... 

Hundeck HG, Hiibner U, Liibbert A, Scheper T, Schmidt J, Weifl M, Schubert F (1992) Development and application of a four-channel enzyme thermistor system for bioprocess control. 

Flow-injection analysis (FIA) has gained tremendous importance for bioprocess control during the last few years [23-27], Although this is not an in situ or a real on-line analytical technique, it can be automated and operated at very high analysis cycle frequencies (quasi online). One of the most important advantages of FIA is the use of very small sample volumes. 

Several ion-selective electrodes are of interest for bioprocess control [11-13, 44] (see also Chapter 10.1). Only a few of them can be sterilized, and thus they have to be used in FIA or autoanalyzer systems. A PCO2 electrode that is sterilizable in situ is offered by Ingold MeBtechnik. This sensor is based on a pH electrode and can be recalibrated in situ. 

The application of autoanalyzers and FIA systems for bioprocess control has gained more and more importance Several wet chemical or biochemical assays can be run automatically... 

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