Vessel temperature control
The temperature of the vessel affects the rate of enzyme reaction and the solubility of oxygen in the culture broth during the fermentation process, which is closely related to the growth of bacteria, antibiotic synthesis and dissolved oxygen.
Vessel temperature control mainly includes controlling the heating and cooling amount. Among them, the heating amount is calculated by the process; the cooling amount is the cooling amount needed after heating or sterilization and under the specified cooling time.
The cooling quantity is derived by calculating the required cooling quantity at the specified cooling time, and the heating quantity is derived by calculating the required heating quantity at the specified heating time. In the vessel temperature control that takes into account both culture and sterilization, PID automatic control is used, and the fluctuation control range of its culture temperature is ±0.1℃.
Sterilization control cleans, disinfects or sterilizes fermentation equipment in accordance with process and GMP requirements. The usual sterilization method used for fermentation vessels is moist heat sterilization. In the sterilization temperature control, the temperature fluctuation cycle in the temperature rise curve should be considered, which is usually set to 1min after reaching the set temperature before the formal timing to meet the F0 value requirement of wet heat sterilization.
Maintaining positive pressure in the fermenter can not only eliminate the contamination caused by the vessel pressure of 0, but also increase the solubility of oxygen in the culture solution, which is conducive to the growth and synthesis of bacteria.
Both the vessel and the pipeline need a certain pressure control during the fermentation process. During the fermentation and culture period, the pressure inside the vessel can be basically kept constant. However, in the process of sterilization and cooling, a certain amount of air needs to be introduced to keep the pressure in order to avoid the negative pressure from inhaling non-clean air from the environment and the possibility of damaging the vessel by the negative pressure. In this case, the pressure influence during the cooling process is a non-control parameter, which is controlled by an air inlet valve.
Air flow and mixing speed control
Air flow role: Air is an important source of oxygen supply to aerobic bacteria.
Stirring speed role: increasing the stirring speed can increase the dissolution rate of oxygen.
Calibration of DO value
The DO value of fermentation broth directly affects the enzyme activity, metabolic pathway and product yield of microorganisms, so the DO calibration is very important. In the process of sterilization and warming, when the temperature reaches 120 ℃, the calibration value of DO electrode zero point is the zero point value of dissolved oxygen calibration; the calibration of DO electrode 100% full value is to set the initial temperature of fermentation, stirring speed (the highest), aeration and tank pressure before the formal fermentation, and use the dissolved oxygen in this initial state as the dissolved oxygen calibration.
（HOLVES HF-Control fermenter system control interface）
The HF-Control second generation fermentation control system developed by HOLVES uses a dashboard design language that allows users to see key data during the fermentation process at a glance by observing the dynamic digital dials, so they can accurately grasp the parameters and quickly make subsequent operations. The system is based on HOLVES' unique patented technology, and the automation function module developed by the system brings the fermentation work into an intelligent platform, which greatly improves the efficiency and time cost of users' experiments.
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