Fermentations control systems

Ferreira L S, de Souza M B, Folly ROM (2001). Development of an alcohol fermentation control system based on biosensor measurements interpreted by neural networks. Sens. Act B Chem. 75 166-171. 

An industrial fermentor of capacity up to several hundred kiloliters equipped with aeration and stirring devices, as well as other automatic control systems, is used. The cultures must be sterilized and aseptic air must be used owing to the high sensitivity to bacterial contamination of L-glutamic acid fermentation. 

Fermentation. The term fermentation arose from the misconception that black tea production is a microbial process (73). The conversion of green leaf to black tea was recognized as an oxidative process initiated by tea—enzyme catalysis circa 1901 (74). The process, which starts at the onset of maceration, is allowed to continue under ambient conditions. Leaf temperature is maintained at less than 25—30°C as lower (15—25°C) temperatures improve flavor (75). Temperature control and air diffusion are faciUtated by distributing macerated leaf in layers 5—8 cm deep on the factory floor, but more often on racked trays in a fermentation room maintained at a high rh and at the lowest feasible temperature. Depending on the nature of the leaf, the maceration techniques, the ambient temperature, and the style of tea desired, the fermentation time can vary from 45 min to 3 h. More highly controlled systems depend on the timed conveyance of macerated leaf on mesh belts for forced-air circulation. If the system is enclosed, humidity and temperature control are improved (76). 

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. 

A control system must therefore provide flexibility in such a way that the results are accurate and repeatable. Also, precise control of the fermentation environment is necessary, which includes ... 

Control of Substances Hazardous to Health Regulations (COSHH UK), 14 220 Control rods, nuclear reactor, 17 569 Control room, in plant layout, 10 514—515 Controls, food processing, 12 87-88 Control stations, 20 668 Control strategies, for fermentation, 11 36-40 Control systems... 

Nomura, Y., Iwahara, M., and Hongo, M. 1988. Acetic acid production by an electrodialysis fermentation method with a computerized control system. Appl. Environ. Microb. 54, 137-142. 

The control of a fed-batch alcoholic fermentation process can be obtained by controlling the substrate concentration in the medium by manipulation of the feed flow. The fermentation process presents complicated kinetic mechanisms. In addition, there is the absence of accurate and reliable mathematical models as well as the difficulty of obtaining direct measurements of the process variables owing to a lack of appropriate on-line analyzers and sensors. Control systems are formed by a set of instruments and control mechanisms connected through electrical signals in the... 

As a result of advances made in sensor development, today more so than in the past, it is possible to rely on environmental control in order to gain economical fermentation results. Until recently fermentation control was limited to that of temperature, pH, and aeration. With the development of numerous sensors and inexpensive computing systems, the engineer can think in terms of sophisticated control systems for fermentation processes. Figure 30.5 shows how a highly instrumented fermentor is designed to secure basic information on almost... 

Minekus, M., Smeets-Peter, M., Bernalier, A., Marol-Bonnln, S., Havenaar, R., Marteau, P, Alric, M., Fonty, G., and Huis in t Veld, J. H. J. (1999), A computer-controlled system to simulate conditions of the large intestine with peristaltic mixing, water absorption and absorption of fermentation products, Appl. Microbiol. Biotechnol., 53,108-114. 

We consider that the production of the C3 chiral unit is relatively easy, because a simple synthetic medium can be used. However, we had to reduce the reaction time in order to decrease the production cost, and establish a stable and reliable reaction for the industrial production. Generally, the fermentation process is like a black box making reliable production difficult, but on the other hand, failures should not occur in industrial production. This means that the fermentation reaction must be well known and a control system established. As for the C3 chiral units production, this is a reaction in which either optical isomer is converted by a microorganism. In as far as it multiplies, the microorganism itself acts like a catalyst. As for the status of the reaction, the cell multiplication, and the phase of the fermentation are not constant but vary over time. The cells as catalysts are formed and multiplied by consuming oxygen, DCP or CPD, ammonium sulfate and a trace of inorganic substance. 

The same results were obtained from the 1-2 L scale reaction therefore, different lots of the racemate, water, ratio of the feed, and a new active starter were evaluated. The prediction system was also applied to the C4 chiral production. Even though the C4 chiral production using a static cell is not the same as the C3 chiral production reaction, good reliability was actually obtained. Fermentation is a type of chemical reaction where scale-up is difficult, and reproduction is sometimes not achieved. We thought that this might be difficult before the control system was established, but we do not think so now, as the signals are digitized. The status is evaluated as one number, no matter whether the reaction is a fermentation or a synthesis. 

Figure 7. Configuration of process control system for glutathione fermentation.

Figure 8. Trends of glutathione, reducing sugar, dry cell weight (DCW) and ethanol concentration in the broth during the glutathione fermentation in 120-kl fermenter using the feed-forward/feedback control system.

For each parameter, the pH, DO (dissolved oxygen), ORP (oxidation-reduction potential), temperature, agitation speed, culture volume and pressure can be measured with sensors located in the fermenter. The output of the individual sensors is accepted by the computer for the on-line, continuous and real-time data analysis. Information stored in the computer control system then regulates the gas flow valves and the motors to the feed pumps. A model of a computer control system is shown in Fig. 11. The computer control systems, like the batch systems for mammalian cell culture, seem to level out at a maximum cell density of 10 cells/ml. It may be impossible for the batch culture method to solve the several limiting factors (Table 10) that set into high density culture where the levels are less than 10 cells/ml. 

Figure 11. General control system of batch fermenter.

From the basic chemical industry come raw materials to use in large-scale formulation of the new product. From the vast fermentation vats come antibiotics. In laboratory-like formulation facilities, the mixing, baking, compressing, coating, and other pharmaceutical processes take place, under the watchful eye of quality control inspectors. In the space-age-clean rooms of biological production, virus vaccines are grown, harvested, purified, and endlessly tested. From start to finish, statistical, numerical, procedural, physical, chemical, and analytical control systems attempt to reduce to near-zero the potential error, mixup, distortion, or hazard. 

There are two different ways of operating a continuous stirred-tank fermentor, namely chemostat and turbidostat. In the chemostat, the flow rate of the feed medium and the liquid volume in the fermentor are kept constant. The rate of cell growth will then adjusts itself to the substrate concentration, which depends on the feed rate and substrate consumption by the growing cells. In the turbidostat the liquid volume in the fermentor and the liquid turbidity, which varies with the cell concentration, are kept constant by adjusting the liquid flow rate. Whereas, turbidostat operation requires a device to monitor the cell concentration (e.g., an optical sensor) and a control system for the flow rate, chemostat is much simpler to operate and hence is far more commonly used for continuous fermentation. The characteristics of the continuous stirred-tank fermentor (CSTF), when operated as a chemostat, is discussed in Chapter 12. 

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