Monitoring bioprocesses

As seen previously for some specific applications such as wastewater treatment plants, software sensors can be envisaged to provide on-line estimation of non-measurable variables, model parameters or to overcome measurement delays [81-83]. Software sensors have been developed mainly for monitoring bioprocesses because the control system design of bioreactors is not straightforward due to [84] significant model uncertainty, lack of reliable on-line sensors, the non-linear and time-varying nature of the system or slow response of the process. 

Similarly, in a paper by Sonnleitner,29 many of the instruments available for monitoring bioprocesses are described. He discusses various conventional and nonconventional monitoring instruments and evaluates them for usefulness and benefits, also discussing their pitfalls. 

Monitoring Bioprocesses Using Raman Vibrational Spectroscopy. . 92... 

Park, B. G., Lee, W. G., Chang, Y. K., Chang, H. N. (1999). Long-term operation of continuous high cell density culture of Saccharomyces cerevisiae with membrane filtration and on-line cell concentration monitoring. Bioprocess Engineering, 21, 97—100. 

There are several methods to monitor the off-gas analysis. Online gas chromatography is commonly used. The daily operation for inlet and outlet gases is balanced to project growth in the bioprocess. High operating cost is the disadvantage of the online system. 

Continuous and detailed knowledge of process conditions is necessary for the control and optimization of bioprocessing operations. Because of containment and contamination problems, this knowledge must often be obtained without sampling the process stream. At present, conditions such as temperatme, pressure, and acidity (pH) can be measured rapidly and accurately. It is more difficult to monitor the concentrations of the chemical species in the reaction medium, to say nothing of monitoring the cell density and intracellular concentrations of hundreds of compounds. 

Heinzle, E., and Saner, U. (1991) Methodology for Process Control in Research and Development. In Bioprocess Monitoring and Control, Ed. Pons, M.N., Hanser, Munich, p. 223-304. 

Marose S., Lindemann C., Scheper T., Two-Dimensional Fluorescence Spectroscopy A New Tool for On-Line Bioprocess Monitoring, Biotechnol. Prog., 1998 14 63-74. 

Taking all these prerequisites into account, the use of chemical and physical sensors within household appliances is considerably restricted, and only a few applications are already on the market. In the field of bioanalytics, sensors are already used for bioprocess-monitoring and biomedical applications. In this area highly specific recognition processes can be used in sensors that only require a short lifespan, due to operating conditions etc. [64]. 

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. 

Add to these new instruments the breakthroughs in computers (more power, speed, and the ability to go wireless) and software (e.g., chemometrics packages), and the capacity to monitor and affect bioprocesses in real time is more than possible it is almost commonplace. 

In a review paper devoted to the chemometrics discussed in previous citations, Shaw et al.28 go into details of the many applications of advanced chemometrics to bioprocess monitoring. Multivariate methods and numerous algorithms are explored in this work. 

Some of the earliest work on NIR of bioprocesses was performed on the nutrients and metabolites in a fermentation broth. A classic paper (if 1996 is antiquity) was written by Hall et al.30 on the determination of acetate, ammonia, biomass, and glycerol in E. coli fermentations. This early paper used NIR to simultaneously monitor all the above-mentioned parameters. The correlation coefficients were all better than 0.985 with variable SEPs acetate, 0.7 g/1 ammonia, 7 mM glycerol, 0.7 g/1 and biomass, 1.4 g/1. While later work with more modem equipment has attained better results, this remains as one of the first. The work was performed at line in a cuvette, but rapidly enough to be considered a process measurement. 

Hagman and Sivertsson discussed the work performed at Pharmacia and Upjohn52 on monitoring and controlling bioprocesses. They followed the protein production-derived form Chinese hamster cells (CHO-cells) in a 500-1 reactor over a 3-month period. The diagrams of the flow cell and pumping/NIR system are displayed, and the logic behind the work outlined. External and on-line calibrations were performed. 

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