Applications of Computer Control in Fermentation Process

Applications of Computers in Fermentation 

The fermentation process is an extremely complex biochemical reaction process. In the early days, manual manipulation based on practical experience has long been unable to meet the requirements of the new process. The products lack competitiveness in the international market, and cannot achieve scientific, reasonable, and efficient supervision in production and management. With the development of various technologies of computer control system, the automatic control system of biological fermentation process is more and more widely used in the pharmaceutical industry. 

Computer Control of Fermentation Process

  • The application of computer automatic control technology in large-scale production in the fermentation industry basically began in the middle and late 1960s. After that, with the continuous development of computer technology, sensor technology, and actuator technology.
  • It can be said that the improvement of the fermentation process or the demand for new processes is an important internal factor for the application of computer automatic control technology in the production process, and this internal factor is still the driving force behind the continuous advancement of computer integrated technology in the application of fermentation production.
  • When the fermentation system is under the direct control of the computer system, it is known as Direct Digital Control. It is an automated control of the fermentation system by the computers.
  • Fermentation Conditions can be optimized by computer monitoring technology to obtain the maximum yield.
  • Parameters such as temperature, pH, foam formation, etc can be measured by the sensors which produce a signal which is detectable by a computer system.

History of Computer Control in Fermentation Technology: 

  • The initial use of computers in fermentation technology was discovered by Yamashita and Murao in the 1960s for the production of glutamic acid and penicillin.
  • Nyiri in 1972 recognized the functions of computers in distinct areas. There were three areas: Logging of process data, Data analysis or reduction of logged data, and process control.
  • The logging of process data is data acquisition with software and hardware components. It is an interface between the sensors and the computer.
  • Aiba et al. in 1973 described the Gateway Sensors. Some of the gateway sensors are pH, DO Sensors, Gas-flow rate, Feed rate, Sugar-level, Carbon dioxide evolution rate, oxygen in exit gas sensors.

List of Parameters Control by Computer

  1. Sterilization temperature, 
  2. pH value of fermentation broth
  3. Airflow, 
  4. Dissolved oxygen content (DO), 
  5. Fermentation broth volume (weighing), 
  6. Tail gas carbon dioxide and tail gas oxygen content, 
  7. Stirring speed, Motor speed.
  8. Motor current, 
  9. Foam Location, seeding amount, humidity.
  10. Steam temperature, steam pressure, steam flow (accumulated).
  11. Coldwater inlet temperature, pressure,  Coldwater outlet temperature, bromine 
  12. Inlet and outlet temperature of circulating water, fermentation temperature.
  13. Defoaming and refueling, ventilation, tank top pressure, continuous consumption control, etc.

Computer Application in Fermentation Technology

Fermentation Temperature Control
  • Temperature is one of the most basic and important conditions in the fermentation process. 
  • The increase in temperature can enhance the activity of enzymes and affect the growth rate of microorganisms. 
  • Generally, for every 10°C increase in temperature, the growth rate approximately doubles. If the growth temperature is higher than the optimum temperature, the growth rate decreases rapidly with the increase of temperature, if the maximum temperature is exceeded, the microorganisms will die in a short time. 
  • If the growth temperature is lower than the optimum temperature, the growth rate is slowed down. 
  • Too high or too low temperature will reduce or lose the activity of a certain enzyme in the cell.
  • To monitor the fermentation temperature; temperature sensors are provided at the cooling water inlet and outlet respectively. 
  • The non-electrical type, electric type, radiation types sensors are usually used to measure temperature in fermenters.

Nutrients such as carbon sources:
  • When the concentration of fermented glucose is moderately low, the growth of microorganisms and the generation of metabolites are limited by the initial glucose content, and it is impossible to obtain higher metabolite yields. 
  • The solution is to initially The glucose content in the medium is medium or low, and the concentrated glucose is supplemented by a fed-feed method in the middle of the fermentation so that the glucose content is maintained in the most suitable range and the final product reaches the optimum value. To control the feeding of various nutrients, it is necessary to measure the amount of fermentation liquid, which can be manually input into the control computer before the fermentation starts, or the method of measuring the liquid level (weighing) of the fermentation tank can be used to realize the measurement.

Foam-Control:
  • The persistent existence of foam will affect the filling amount of the fermenter, make the bacteria float up, hinder the discharge of carbon dioxide, and is not conducive to the normal operation of metabolic activities; in severe cases, it will affect ventilation, stirring, and hinder the dissolution of oxygen, resulting in abnormal metabolism, resulting in product yield. 
  • To eliminate the influence of foam on fermentation, antifoaming is used in fermentation production. 
  • The mechanical antifoam devices are devices, Propellers, Brushes, or Hollow cones. They are used for the mechanical breaking of foam. Load cells are used for determining the weight of the fermenter vessel.
  • In fermentation production, to prevent the continued existence of a large amount of foam to affect the fermentation progress and reduce the fermentation level, it is necessary to reduce the generation of foam.

pH Control
  • In the process of antibiotic fermentation, microorganisms decompose and utilize various nutrients, produce various decomposition products, and rapidly change the PH value of the fermentation broth. 
  • For most antibiotics, the most suitable pH value for mycelial growth and antibiotic synthesis should be close to neutral. 
  • When the pH is too acidic or too basic, on the one hand, the synthesis pathway of antibiotics is disturbed, and the synthesis of antibiotics is inhibited. 
  • On the one hand, the fermentation broth that is too acidic or too basic will cause some antibiotics to degrade, resulting in the inactivation of antibiotics. 
  • The pH value sensor is used to detect the pH value in the fermentation process. 
  • This sensor must be able to withstand the high-temperature sterilization of the fermenter, and can accurately and continuously measure the change of pH value in the fermenter.
  • The galvanic electrode is used in the measurement of dissolved oxygen. Whereas, glass electrodes, silver electrodes, combined electrodes are used in the measurement of the pH of a solution.

Pressure Control 
  • The main purpose of maintaining a certain positive pressure in the fermentation tank is to prevent outside air from entering the fermentation tank and causing pollution; 
  • Another purpose is to increase the partial pressure of oxygen and increase the solubility of oxygen. 
  • The tank pressure uses a pressure transmitter to convert the pressure of the fermenter into an electrical signal and connect it to the control system.
  • The safety valves are used for controlling pressure. It must be incorporated into every vessel which is subjected to pressure to ensure pressure does not exceed over safe limit recommended by the manufacturer.
  • The devices used for the measurement of pressure are diaphragm gauge, strain gauge, pressure bellows, piezoelectric transducer, etc.
  
Rotation speed Control: stirring speed and stirring power
  • For the fermenter with a frequency conversion system, the parameters such as rotation speed, motor current, and stirring power can be obtained from the frequency converter through standard signals or communication.
  • For the fermenter without a frequency conversion system, the speed and current and stirring power are measured by independent sensors.
  
Other factors:
  • The total air temperature and humidity have a great influence on the efficiency of the air filter and the fermentation level, and it is necessary to detect and control them.

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