CN219792981U - Gas control system of bioreactor - Google Patents
Gas control system of bioreactor Download PDFInfo
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- CN219792981U CN219792981U CN202320801929.9U CN202320801929U CN219792981U CN 219792981 U CN219792981 U CN 219792981U CN 202320801929 U CN202320801929 U CN 202320801929U CN 219792981 U CN219792981 U CN 219792981U
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- bioreactor
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- control system
- tank
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- 239000007789 gas Substances 0.000 claims abstract description 87
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims abstract description 80
- 229910002092 carbon dioxide Inorganic materials 0.000 claims abstract description 40
- 238000009423 ventilation Methods 0.000 claims abstract description 30
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 29
- 239000001301 oxygen Substances 0.000 claims abstract description 29
- 239000002344 surface layer Substances 0.000 claims abstract description 21
- 239000001569 carbon dioxide Substances 0.000 claims abstract description 20
- 230000001954 sterilising effect Effects 0.000 claims description 25
- 239000011148 porous material Substances 0.000 claims description 8
- 239000010865 sewage Substances 0.000 claims description 8
- UBAZGMLMVVQSCD-UHFFFAOYSA-N carbon dioxide;molecular oxygen Chemical compound O=O.O=C=O UBAZGMLMVVQSCD-UHFFFAOYSA-N 0.000 abstract description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 abstract description 2
- 238000005273 aeration Methods 0.000 description 9
- 230000001105 regulatory effect Effects 0.000 description 7
- 230000001276 controlling effect Effects 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 238000000855 fermentation Methods 0.000 description 4
- 230000004151 fermentation Effects 0.000 description 4
- 210000004962 mammalian cell Anatomy 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Abstract
The utility model discloses a gas control system of a bioreactor, which comprises: a large bubble introducing device, a micro bubble introducing device, a sensor and a PID controller. The utility model is provided with the large bubble introducing device and the micro bubble introducing device, oxygen, carbon dioxide and compressed air can enter the bioreactor from different ventilating devices, and the ventilating devices are fully automatically controlled by the PID controller by combining dissolved oxygen and carbon dioxide partial pressure data acquired by the sensors in the tank, so that the concentration of oxygen or carbon dioxide in the biological culture solution is accurately controlled, and the culture environment is greatly optimized. In addition, the gas control system of the bioreactor can be also provided with a surface layer ventilation device, gas can be introduced above the culture solution in the bioreactor tank to increase the air pressure, and a tail gas exhaust pipeline is arranged at the same time, and the introduction and the discharge of the gas are controlled by a PID controller to control the pressure in the tank.
Description
Technical Field
The utility model relates to a gas control system of a bioreactor, and belongs to the technical field of biological fermentation devices.
Background
For microbial fermentation, it is indeed possible to control the dissolved oxygen in the desired concentration range more effectively by increasing the rotational speed or increasing the aeration rate. Since the tolerance of microorganisms such as E.coli or yeast to shear forces is relatively high, the concentration of dissolved oxygen can be increased by increasing the rotational speed or increasing the ventilation. In the case of aeration, the aeration rate of microbial fermentation can reach 3vvm, while the aeration rate of mammalian cell culture process is not more than 0.1vvm at the highest.
Because the increasing aeration rate for mammalian cell culture process can continue to increase oxygen mass transfer in the culture solution, but at the same time, greater shear forces are involved, and mammalian cells cannot tolerate the greater shear forces caused by bubble collapse. In the same way, the stirring speed must not be too high, which would also lead to greater shear forces than the cells are tolerant to, for mammalian cells.
In addition, not only oxygen, but also partial pressure and dissolved concentration of carbon dioxide have great influence on the reaction process in the course of biological reaction. CO2 is produced by cell metabolism, is dissolved in the culture solution after being discharged outside, is continuously transferred to the bubbles through the liquid, and is then discharged outside the bioreactor. The partial pressure of CO2 determines the concentration of dissolved CO2 in the liquid, and too high and too low concentrations of CO2 can adversely affect cell growth and product expression. So if the partial pressure of CO2 can be precisely controlled so that the cell growth is always in the most suitable range of partial pressure of CO2, it will be more advantageous for the growth of the cell and the expression of its products or the formation of better product quality.
The existing bioreactor has no function of precisely controlling gases such as oxygen, carbon dioxide and the like, so how to provide a bioreactor capable of controlling partial pressure of CO2 and dissolved oxygen concentration is a problem to be solved in the field.
Disclosure of Invention
In order to solve the above problems, the present utility model provides a gas control system of a bioreactor, comprising: a large bubble introducing device, a micro bubble introducing device, a sensor and a PID controller;
the microbubble introducing device comprises: the micro-bubble vent pipe is arranged at the bottom of the bioreactor tank body and is connected with an external gas generating device through a micro-bubble air inlet pipe; the micro-bubble vent pipe is distributed with a micro-pore structure, and the pore diameter is several micrometers to tens of micrometers;
the large bubble introducing device comprises: the large bubble vent pipe is arranged at the bottom of the bioreactor tank body and is connected with an external gas generating device through a large bubble air inlet pipe; the large bubble vent pipe is provided with openings distributed on the large bubble vent pipe, and the aperture range is 0.1-10 mm;
the sensor is used for collecting the gas concentration in the culture solution in the tank and sending the gas concentration to the PID controller;
and the PID controller controls the microbubble introducing device and the large bubble introducing device to introduce gas into the tank body through concentration parameters.
In one embodiment, the micro-bubble vent pipe is sequentially connected with a sterilizing filter, a pneumatic valve, a check valve, a float flowmeter, a mass flowmeter and an external gas generating device from the tank body;
a sewage outlet is arranged below the sterilizing filter, a pneumatic valve is connected to the sewage outlet, and a pressure gauge is connected to the top of the sterilizing filter;
and two ends of the mass flowmeter are connected with a pipeline in a bridging way, a manual valve is arranged on the pipeline, and when the mass flowmeter is blocked, the pipeline is connected in a bridging way through the manual valve, and the float flowmeter is used for metering.
In one implementation mode, the large bubble vent pipe is sequentially connected with a sterilizing filter and a pneumatic valve from the tank body, and the pneumatic valve is connected with two paths of air inlet pipelines;
each air inlet pipeline is sequentially connected with a check valve, a float flowmeter, a mass flowmeter and an external gas generating device, two ends of the mass flowmeter are connected with one pipeline in a bridging mode, a manual valve is arranged on the pipeline, and when the mass flowmeter is blocked, the manual valve is used for opening the bridging pipeline to measure by the float flowmeter; the external gas generating device connected with one path of air inlet pipeline is as follows: compressed air generating device.
In one embodiment, the bioreactor further comprises: the surface layer ventilation device, the pressure transmitter and the tail gas exhaust pipeline;
the vent pipe of the surface layer ventilation device penetrates through the side wall of the bioreactor tank body to ventilate the tank; the surface layer breather pipe is sequentially connected with a sterilizing filter, a pneumatic valve, a check valve, a float flowmeter, a mass flowmeter and an external gas generating device from the tank body;
the surface layer ventilation device, the pressure transmitter and the tail gas exhaust pipeline are all connected with the PID controller, the pressure transmitter is used for measuring the air pressure in the tank, and the PID controller controls the surface layer ventilation device and the tail gas exhaust pipeline to be introduced into or exhausted from the gas in the tank according to the air pressure in the tank.
In one embodiment, the external gas generating apparatus includes: oxygen generating device, carbon dioxide generating device and compressed air generating device.
In one embodiment, the sensor is: an oxygen dissolving electrode.
In one embodiment, the sensor is a carbon dioxide partial pressure electrode.
The utility model has the advantages that:
the gas control system of the bioreactor is provided with the large bubble introducing device and the micro bubble introducing device, oxygen, carbon dioxide and compressed air can enter the bioreactor from different ventilating devices, and the ventilating devices are fully automatically controlled through the PID controller by combining dissolved oxygen and carbon dioxide partial pressure data acquired by the sensors in the tank, so that the concentration of oxygen or carbon dioxide in biological culture solution is accurately controlled, and the culture environment is greatly optimized.
In addition, the gas control system of the bioreactor can be provided with a surface layer ventilation device, gas can be introduced above the culture solution in the bioreactor, the gas pressure is increased, meanwhile, a tail gas exhaust pipeline is arranged, the gas pressure in the tank is measured in real time through a pressure sensor (pressure transmitter) during use, and the introduction and the discharge of the gas are controlled by a PID controller according to the gas pressure, so that the pressure in the tank is controlled.
Drawings
FIG. 1 is a diagram showing the overall construction of a gas control system of a bioreactor according to an embodiment of the present utility model; wherein, 1: a bioreactor tank; 2: surface layer ventilation, microbubble ventilation and large bubble ventilation pipelines and gas generating devices; 3: an exhaust gas discharge pipe.
FIG. 2 is a block diagram of a bioreactor tank according to an embodiment of the present utility model.
Fig. 3 is a block diagram of a superficial gas vent pipe, a micro-bubble gas vent pipe, and a macro-bubble gas vent pipe of a bioreactor according to an embodiment of the present utility model.
FIG. 4 is a block diagram of a bioreactor gas sterilizing filter in accordance with an embodiment of the present utility model.
Fig. 5 is a structural diagram of an exhaust gas discharge pipe according to an embodiment of the present utility model.
Detailed Description
The present utility model will be described in detail below.
Example 1:
the present embodiment provides a bioreactor gas control system capable of controlling the concentration of dissolved oxygen, as shown in fig. 1, which is a schematic diagram of the bioreactor gas control system of the present embodiment, and includes: a large bubble introducing device, a micro bubble introducing device, an oxygen dissolving electrode and a PID controller;
the microbubble aeration device includes: the micro-bubble vent pipe is arranged at the inner bottom of the bioreactor tank body and is connected with an external gas generating device through a micro-bubble air inlet pipe; the micro bubble vent pipe is distributed with a micro pore structure, and the pore diameter is from a few micrometers to tens micrometers;
the micro-bubble vent pipe is sequentially connected with a sterilizing filter, a pneumatic valve, a check valve, a float flowmeter, a mass flowmeter and an oxygen generating device from the tank body;
a sewage outlet is arranged below the sterilizing filter, a pneumatic valve is connected to the sewage outlet, and a pressure gauge is connected to the top of the sterilizing filter;
two ends of the mass flowmeter are connected with a pipeline in a bridging way, a manual valve is arranged on the pipeline, and when the mass flowmeter is blocked, the pipeline is connected with a float flowmeter in a bridging way through the manual valve for metering.
The large bubble introducing device comprises: the large bubble vent pipe is arranged at the bottom of the bioreactor tank body and is connected with an external gas generating device through a large bubble air inlet pipe; the large bubble vent pipe is provided with openings with the aperture range of 0.1-10 mm;
the big bubble breather pipe is connected with a sterilizing filter and a pneumatic valve in sequence from the tank body, and the pneumatic valve is connected with two paths of air inlet pipelines.
The first air inlet pipeline is sequentially connected with a check valve, a float flowmeter, a mass flowmeter and an oxygen generating device, two ends of the mass flowmeter are connected with a pipeline in a bridging mode, a manual valve is arranged on the pipeline, when the mass flowmeter is blocked, the pipeline is opened by the manual valve to measure through the float flowmeter, oxygen needed by the bioreactor is continuously introduced, then a pressure reducing valve is connected, and finally the oxygen is connected.
The second air inlet pipeline is sequentially connected with a check valve, a float flowmeter, a mass flowmeter and a compressed air generating device, two ends of the mass flowmeter are connected with a pipeline in a bridging mode, a manual valve is arranged on the pipeline, when the mass flowmeter is blocked, the pipeline is opened by the manual valve to measure by the float flowmeter, compressed air needed by the bioreactor is continuously introduced, then a pressure reducing valve is connected, and finally compressed air is connected.
The bioreactor gas control system of this embodiment further comprises: the surface layer ventilation device, the pressure transmitter and the tail gas exhaust pipeline;
the ventilation pipe of the surface ventilation device penetrates through the side wall of the tank body of the bioreactor to ventilate the tank; the surface layer breather pipe is sequentially connected with a pneumatic valve and a sterilizing filter from the tank body, a drain outlet is arranged below the filter, the drain outlet is connected with the pneumatic valve, then is connected with a tail gas regulating valve, and finally is connected to a discharge pipeline or a discharge point.
The dissolved oxygen electrode, the pressure transmitter, the pneumatic valve, the mass flowmeter and the tail gas regulating valve are all connected to the PID controller. The control system comprises an underlying I/O module, a PLC, a server, a human-computer interface and the like.
The working principle of the embodiment is as follows:
1. a step of increasing the oxygen partial pressure by the ratio of oxygen to compressed air:
1. if compressed air is only introduced through the large bubble, the compressed air passes through a pressure reducing valve, a manual valve, a mass flowmeter and a float flowmeter, a check valve, a pneumatic valve, a gas sterilization filter and a large bubble vent pipe to enter the bottom of the embarrassing tank.
2. If oxygen needs to be introduced through the big bubble, the oxygen enters the bottom of the bioreactor through a pressure reducing valve, a manual valve, a mass flowmeter, a float flowmeter, a check valve, a pneumatic valve, a gas sterilization filter and a big bubble vent pipe.
3. In the process, the pneumatic valves of the mass flowmeter are controlled by a PID controller. The oxygen supply from the microbubbles can also be controlled by a PID controller if desired. Or a certain amount of compressed air and a certain amount of oxygen are introduced, and the control system can fully automatically control the air after setting the air and the oxygen through the control system.
2. The pressure is controlled by the tail gas as follows:
1. the pressure of the surface layer of the bioreactor to be controlled and the flow rate of the compressed air to be introduced in the ventilation of the top surface layer are set on a PID controller.
The PID controller can open a pneumatic valve on the surface layer ventilation pipeline to open a compression ventilation channel, and simultaneously control the mass flowmeter to flow compressed air with a set flow value.
And 3, the PID controller automatically adjusts the tail gas regulating valve in a PID mode according to the value of the pressure gauge at the top of the tank so as to maintain the pressure in the bioreactor tank.
4. In the pressure control process, compressed air flows through a pressure reducing valve, a manual valve, a mass flowmeter, a float flowmeter, a check valve, a pneumatic valve and a gas sterilization filter to enter the tank. The gas which is generated in the tank and is not utilized by cells and is introduced into the gas inlet pipeline is discharged out of the fermentation system through the pneumatic valve, the gas sterilization filter and the tail gas regulating valve of the tail gas pipeline.
Example 2:
the present embodiment provides a bioreactor gas control system capable of controlling partial pressure of carbon dioxide, comprising: a large bubble introducing device, a micro bubble introducing device, a carbon dioxide partial pressure electrode and a PID controller;
the gas control system of the present embodiment can also refer to fig. 1, and is different from embodiment 1 in that the present embodiment adopts a carbon dioxide partial pressure electrode to collect the carbon dioxide concentration, and the oxygen generating device is replaced by a carbon dioxide generating device accordingly.
The microbubble aeration device includes: the micro-bubble vent pipe is arranged at the inner bottom of the bioreactor tank body and is connected with an external gas generating device through a micro-bubble air inlet pipe; the micro bubble vent pipe is distributed with a micro pore structure, and the pore diameter is from a few micrometers to tens micrometers;
the micro-bubble vent pipe is sequentially connected with a sterilizing filter, a pneumatic valve, a check valve, a float flowmeter, a mass flowmeter and a carbon dioxide generating device from the tank body;
a sewage outlet is arranged below the sterilizing filter, a pneumatic valve is connected to the sewage outlet, and a pressure gauge is connected to the top of the sterilizing filter;
two ends of the mass flowmeter are connected with a pipeline in a bridging way, a manual valve is arranged on the pipeline, and when the mass flowmeter is blocked, the pipeline is connected with a float flowmeter in a bridging way through the manual valve for metering.
The large bubble introducing device comprises: the large bubble vent pipe is arranged at the bottom of the bioreactor tank body and is connected with an external gas generating device through a large bubble air inlet pipe; the large bubble vent pipe is provided with openings with the aperture range of 0.1-10 mm;
the big bubble breather pipe is connected with a sterilizing filter and a pneumatic valve in sequence from the tank body, and the pneumatic valve is connected with two paths of air inlet pipelines.
All connect gradually check valve, float flowmeter, mass flowmeter and carbon dioxide generating device on the air intake pipe of first way, the both ends cross-over connection of mass flowmeter has a pipeline, is equipped with manual valve on the pipeline, takes place to block up when mass flowmeter, opens the cross-over connection pipeline through manual valve and measures with the float flowmeter, continues to let in the carbon dioxide that the bioreactor needs, then connects is the relief pressure valve, finally connects carbon dioxide.
The second air inlet pipeline is sequentially connected with a check valve, a float flowmeter, a mass flowmeter and a compressed air generating device, two ends of the mass flowmeter are connected with a pipeline in a bridging mode, a manual valve is arranged on the pipeline, when the mass flowmeter is blocked, the pipeline is opened by the manual valve to measure by the float flowmeter, compressed air needed by the bioreactor is continuously introduced, then a pressure reducing valve is connected, and finally compressed air is connected.
The gas control system of the bioreactor of this embodiment further includes: the surface layer ventilation device, the pressure transmitter and the tail gas exhaust pipeline;
the ventilation pipe of the surface ventilation device penetrates through the side wall of the tank body of the bioreactor to ventilate the tank; the surface layer breather pipe is sequentially connected with a pneumatic valve and a sterilizing filter from the tank body, a drain outlet is arranged below the filter, the drain outlet is connected with the pneumatic valve, then is connected with a tail gas regulating valve, and finally is connected to a discharge pipeline or a discharge point.
The carbon dioxide partial pressure electrode, the pressure transmitter, the pneumatic valve, the mass flowmeter and the tail gas regulating valve are all connected to the control system. The control system comprises an underlying I/O module, a PLC, a server, a human-computer interface and the like.
The working principle of the embodiment is as follows:
1. the partial pressure of CO2 in the culture solution is controlled by controlling the aeration proportion of the large bubbles and the microbubbles, and the strategy is as follows: when carbon dioxide is fed into the bioreactor through microbubbles, compressed air can be introduced into the bioreactor through the large bubbles. When the partial pressure of CO2 is too high, the proportion of large bubbles introduced can be controlled to be increased by using a PID controller so as to bring more CO2; conversely, if the CO2 partial pressure is too low, large bubbles of ventilation may reduce or even stop ventilation.
The large bubble ventilation may be oxygen or compressed air. But the CO2 removal is better when compressed air is used.
2. The PID controller controls the surface aeration device to introduce a certain amount of CO2 to maintain the partial pressure of CO2 in the gas on the top of the bioreactor, so that the concentration of CO2 in the culture solution is improved. If the partial pressure of CO2 is always larger in the cell culture process, the CO2 inlet amount of the surface layer ventilation device can be reduced to 0, namely CO2 is not introduced into the top, so that a better CO2 removal effect is maintained.
3. When only one path of large bubbles is used for ventilation or only one path of micro bubbles is used for ventilation, the CO2 concentration in the culture solution can be controlled and regulated by controlling the ventilation proportion of the compressed air.
While the utility model has been described with reference to the preferred embodiments, it is not limited thereto, and various changes and modifications can be made therein by those skilled in the art without departing from the spirit and scope of the utility model as defined in the appended claims.
Claims (7)
1. A gas control system for a bioreactor, the control system comprising: a large bubble introducing device, a micro bubble introducing device, a sensor and a PID controller;
the microbubble introducing device comprises: the micro-bubble vent pipe is arranged at the inner bottom of the bioreactor tank body and is connected with an external gas generating device through a micro-bubble air inlet pipe; the micro-bubble vent pipe is distributed with a micro-pore structure, and the pore diameter is several micrometers to tens of micrometers;
the large bubble introducing device comprises: the large bubble vent pipe is arranged at the bottom of the bioreactor tank body and is connected with an external gas generating device through a large bubble air inlet pipe; the large bubble vent pipe is provided with openings distributed on the large bubble vent pipe, and the aperture range is 0.1-10 mm;
the sensor is used for collecting the gas concentration in the culture solution in the tank and sending the gas concentration to the PID controller;
and the PID controller controls the microbubble introducing device and the large bubble introducing device to introduce gas into the tank body through concentration parameters.
2. The gas control system of the bioreactor according to claim 1, wherein the micro-bubble vent pipe is sequentially connected with a sterilizing filter, a pneumatic valve, a check valve, a float flowmeter, a mass flowmeter and an external gas generating device from the tank;
a sewage outlet is arranged below the sterilizing filter, a pneumatic valve is connected to the sewage outlet, and a pressure gauge is connected to the top of the sterilizing filter;
and two ends of the mass flowmeter are connected with a pipeline in a bridging way, a manual valve is arranged on the pipeline, and when the mass flowmeter is blocked, the pipeline is connected in a bridging way through the manual valve, and the float flowmeter is used for metering.
3. The gas control system of the bioreactor according to claim 1, wherein the large bubble vent pipe is sequentially connected with a sterilizing filter and a pneumatic valve from the tank body, and the pneumatic valve is connected with two air inlet pipelines;
each air inlet pipeline is sequentially connected with a check valve, a float flowmeter, a mass flowmeter and an external gas generating device, two ends of the mass flowmeter are connected with one pipeline in a bridging mode, a manual valve is arranged on the pipeline, and when the mass flowmeter is blocked, the manual valve is used for opening the bridging pipeline to measure by the float flowmeter; the external gas generating device connected with one path of air inlet pipeline is as follows: compressed air generating device.
4. The gas control system of a bioreactor of claim 1, wherein the bioreactor further comprises: the surface layer ventilation device, the pressure transmitter and the tail gas exhaust pipeline;
the vent pipe of the surface layer ventilation device penetrates through the side wall of the bioreactor tank body to ventilate the tank; the breather pipe of the surface layer breather device is sequentially connected with a sterilizing filter, a pneumatic valve, a check valve, a float flowmeter, a mass flowmeter and an external gas generating device from the tank body;
the surface layer ventilation device, the pressure transmitter and the tail gas exhaust pipeline are all connected with the PID controller, the pressure transmitter is used for measuring the air pressure in the tank, and the PID controller controls the surface layer ventilation device and the tail gas exhaust pipeline to be introduced into or exhausted from the gas in the tank according to the air pressure in the tank.
5. The gas control system of a bioreactor according to any one of claims 1 to 4, wherein the external gas generating means comprises: oxygen generating device, carbon dioxide generating device and compressed air generating device.
6. The gas control system of a bioreactor of any one of claims 1-4, wherein the sensor is: an oxygen dissolving electrode.
7. The gas control system of a bioreactor of any one of claims 1-4, wherein the sensor is: a carbon dioxide partial pressure electrode.
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CN202320801929.9U CN219792981U (en) | 2023-04-12 | 2023-04-12 | Gas control system of bioreactor |
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CN202320801929.9U CN219792981U (en) | 2023-04-12 | 2023-04-12 | Gas control system of bioreactor |
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