CN112457986A - Bioreactor for human erythropoietin injection CHO cell fermentation - Google Patents

Bioreactor for human erythropoietin injection CHO cell fermentation Download PDF

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Publication number
CN112457986A
CN112457986A CN202110019455.8A CN202110019455A CN112457986A CN 112457986 A CN112457986 A CN 112457986A CN 202110019455 A CN202110019455 A CN 202110019455A CN 112457986 A CN112457986 A CN 112457986A
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bioreactor
control system
cell fermentation
human erythropoietin
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姜栋
解福生
郝向慧
庞甲佩
马晓英
秦绪才
吴化斌
赵玉松
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Huarun Onde Biopharmaceutical Co ltd
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Huarun Onde Biopharmaceutical Co ltd
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    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/38Caps; Covers; Plugs; Pouring means
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    • C12M27/00Means for mixing, agitating or circulating fluids in the vessel
    • C12M27/02Stirrer or mobile mixing elements
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    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/12Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
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    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/44Means for regulation, monitoring, measurement or control, e.g. flow regulation of volume or liquid level
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/48Automatic or computerized control

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Abstract

The invention discloses a bioreactor for CHO cell fermentation of human erythropoietin injection, which comprises a bottom plate, wherein a 360-degree control system host is arranged on the right side of the upper end surface of the bottom plate, a display screen is arranged on the upper end of the front side surface of the 360-degree control system host, an operation panel is arranged at the lower end of the display screen, a peristaltic pump is arranged on the left side of the front end of the 360-degree control system host at the lower end of the operation panel, a peristaltic pump mode switch is connected onto the 360-degree control system host on the right side of the peristaltic pump, a main power switch is arranged on the lower side of the front end surface of the 360-degree control system host, and a. The bioreactor for the human erythropoietin injection CHO cell fermentation can be used for automatically adjusting the biological environment in the reaction tank body, so that the working intensity of workers is reduced, the quality of the human erythropoietin injection CHO cell fermentation is improved, and the data in the cell fermentation culture process can be automatically recorded and read conveniently.

Description

Bioreactor for human erythropoietin injection CHO cell fermentation
Technical Field
The invention relates to the technical field of bioreactors, in particular to a bioreactor for human erythropoietin injection CHO cell fermentation.
Background
The bioreactor is a device system for carrying out biochemical reaction in vitro by utilizing the biological function of enzyme or organism, is a biological function simulator, has important application in the aspects of wine, medicine production, organic pollutant degradation and the like, and is used for human erythropoietin injection CHO cell fermentation in the medicine field.
However, the existing bioreactor usually adopts manual feeding and mixed gas filling to the reaction tank body, and the manual operation is easy to generate large errors, so that the cell fermentation effect of human erythropoietin injection CHO is poor, and the existing bioreactor is inconvenient for automatically recording and reading data in the cell fermentation culture process, so that the observation of the conditions in the cell fermentation culture process and the research work of later cell fermentation culture are inconvenient for workers, therefore, a bioreactor for human erythropoietin injection CHO cell fermentation is needed to solve the problems.
Disclosure of Invention
The invention aims to provide a bioreactor for human erythropoietin injection CHO cell fermentation, which aims to solve the problems that the existing bioreactor is inconvenient to automatically feed materials into a reaction tank body and fill proper mixed gas, and is inconvenient to automatically record and read data in the cell fermentation culture process.
In order to achieve the purpose, the invention provides the following technical scheme: a bioreactor for CHO cell fermentation of human erythropoietin injection comprises a bottom plate, wherein a 360-degree control system host is arranged on the right side of the upper end face of the bottom plate, a display screen is arranged on the upper end of the front side face of the 360-degree control system host, a control panel is arranged at the lower end of the display screen, a peristaltic pump is arranged on the left side of the front end of the 360-degree control system host at the lower end of the control panel, a peristaltic pump mode switch is connected onto the 360-degree control system host on the right side of the peristaltic pump, a main power switch is arranged on the lower side of the front end face of the 360-degree control system host, a sensor connecting panel is arranged on the left side face of the 360-degree control system host, a signal connecting panel is arranged on the lower side of the rear end face of the 360-degree control system host, an aeration auxiliary panel is arranged on the, an air inlet mode switch is arranged on the ventilation auxiliary panel on one side of the rotor flow meter, an automatic control valve is connected to the upper end of the rear end face of the ventilation auxiliary panel, a mixer is arranged at the lower end of the automatic control valve, a heat preservation cover is arranged on a bottom plate on the left side of the ventilation auxiliary panel, an electric cabinet is connected to the right side of the heat preservation cover, a lamp tube power switch is arranged on the front end face of the electric cabinet, a support frame is arranged in the heat preservation cover, a tank body is connected to the inside of the support frame, a tank cover is fixedly connected to the upper end of the tank body through a fixing block, a shaft sleeve is fixedly connected to the middle of the upper end face of the tank cover, a stirring shaft is connected to the inside of the shaft sleeve through a bearing, a stirring blade is connected to the side face of the, the PH gel electrode is connected with on the cover of tee bend feed supplement pipe rear side, and is connected with the temperature electrode on the cover of tee bend feed supplement pipe front side, be connected with dissolved oxygen electrode on the cover of air inlet rear side, and be connected with the liquid level electrode on the cover of air inlet front side to be provided with standard reserve mouthful on the cover.
Preferably, the number of the peristaltic pumps is 4, the peristaltic pumps adopt Watson Marlow experiment type peristaltic pump heads with the speed of 4rpm, and the peristaltic pumps are each provided with three modes of automatic control, closing and manual filling.
Preferably, the number of the rotameters is set to 4, and the lower ends of the rotameters are provided with flow adjusting knobs.
Preferably, the structure shape of the heat preservation cover is a hexagonal prism shape, and a heating lamp is arranged on each side face inside the heat preservation cover.
Preferably, the tank cover is fixed on the tank body through a flange opening in a sealing mode, and a rubber sealing ring is arranged between the tank cover and the tank body.
Preferably, the standard spare ports are 12 in number, and the standard spare port interfaces are all standard ports with diameters of 6.35mm or 12 mm.
Preferably, the part of the tank body contacting with the culture solution is made of 316L stainless steel, and the inner surface of the tank body is treated by polishing with 0.4 RA.
Preferably, 6 rectangular blocks are arranged on the side face of the stirring blade, and the middle part of the stirring blade is fixedly connected with the stirring shaft.
Compared with the prior art, the invention has the beneficial effects that: the bioreactor for the human erythropoietin injection CHO cell fermentation can be convenient for automatically adjusting the biological environment in a reaction tank, thereby lightening the working strength of workers and improving the quality of the human erythropoietin injection CHO cell fermentation, and being convenient for automatically recording and reading the data in the cell fermentation culture process:
1. the environmental data in the tank body is monitored through a 360-degree control system host, the material is supplemented, appropriate mixed gas is introduced and heating operation is carried out in the tank body according to parameters set by workers, the optimal fermentation environment of biological cells is guaranteed, and therefore the biological environment in the reaction tank body can be automatically adjusted conveniently, the working strength of the workers is relieved, and the fermentation quality of human erythropoietin injection CHO cells is improved;
2. carry out real-time monitoring and regular automatic recording and store the hard disk to the internal environmental data of jar through 360 control system host computers, and can derive fast to can be convenient for automatic recording and read the data of cell fermentation culture in-process, the staff of being convenient for observes the condition of cell fermentation culture in-process and the cell fermentation culture research work in later stage.
Drawings
FIG. 1 is a front perspective view of the present invention;
FIG. 2 is a schematic front view of the present invention;
FIG. 3 is a rear view of the present invention;
FIG. 4 is a schematic top view of the present invention;
FIG. 5 is a schematic top view of the cross-sectional structure of the present invention;
FIG. 6 is a schematic rear view of the cross-sectional structure of the present invention;
fig. 7 is a schematic rear perspective internal structure of the present invention.
In the figure: 1. a base plate; 2. 360 control the system host; 3. a display screen; 4. a control panel; 5. a peristaltic pump; 6. a peristaltic pump mode switch; 7. a main power switch; 8. a ventilation assistance panel; 9. a vent interface; 10. a rotameter; 11. an air intake mode switch; 12. a heat-preserving cover; 13. an electric cabinet; 14. a lamp tube power switch; 15. a can lid; 16. a fixed block; 17. a motor; 18. a shaft sleeve; 19. a sensor connection panel; 20. a signal connection panel; 21. an automatic control valve; 22. a mixer; 23. a tee material supplementing pipe; 24. a standard standby port; 25. an air inlet; 26. a PH gel electrode; 27. a dissolved oxygen electrode; 28. a temperature electrode; 29. a liquid level electrode; 30. a tank body; 31. stirring blades; 32. a support frame; 33. a heating lamp; 34. a stirring shaft; 35. an air inlet pipe.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Referring to fig. 1-7, the present invention provides a technical solution: a bioreactor for CHO cell fermentation of human erythropoietin injection comprises a bottom plate 1, a 360 control system host 2, a display screen 3, an operation panel 4, a peristaltic pump 5, a peristaltic pump mode switch 6, a main power switch 7, an auxiliary ventilation panel 8, a ventilation interface 9, a rotor flow meter 10, an air inlet mode switch 11, a heat preservation cover 12, an electric cabinet 13, a lamp tube power switch 14, a tank cover 15, a fixed block 16, a motor 17, a shaft sleeve 18, a sensor connecting panel 19, a signal connecting panel 20, an automatic control valve 21, a mixer 22, a three-way material supplementing pipe 23, a standard standby port 24, an air inlet 25, a PH gel electrode 26, an oxygen dissolving electrode 27, a temperature electrode 28, a liquid level electrode 29, a tank body 30, a stirring blade 31, a support frame 32, a heating lamp 33, a stirring shaft 34 and a stirring shaft 35, wherein the air inlet pipe 2 of the 360 control system host is arranged on the right side of the upper end face of the bottom plate 1, the 360 control, the lower end of the display screen 3 is provided with a control panel 4, the left side of the front end of a 360-degree control system host 2 at the lower end of the control panel 4 is provided with a peristaltic pump 5, the 360-degree control system host 2 at the right side of the peristaltic pump 5 is connected with a peristaltic pump mode switch 6, the lower side of the front end face of the 360-degree control system host 2 is provided with a main power switch 7, the left side face of the 360-degree control system host 2 is provided with a sensor connecting panel 19, the lower side of the rear end face of the 360-degree control system host 2 is provided with a signal connecting panel 20, the left bottom plate 1 of the 360-degree control system host 2 is provided with an aeration auxiliary panel 8, the lower end of the front end face of the aeration auxiliary panel 8 is connected with an aeration interface 9, the aeration auxiliary panel 8 at the upper end of the aeration interface 9 is connected with, the lower end of an automatic control valve 21 is provided with a mixer 22, a heat preservation cover 12 is arranged on a bottom plate 1 at the left side of a ventilation auxiliary panel 8, the right side surface of the heat preservation cover 12 is connected with an electric cabinet 13, the front end surface of the electric cabinet 13 is provided with a lamp tube power switch 14, a support frame 32 is arranged inside the heat preservation cover 12, a tank body 30 is connected inside the support frame 32, the upper end of the tank body 30 is fixedly connected with a tank cover 15 through a fixed block 16, the middle part of the upper end surface of the tank cover 15 is fixedly connected with a shaft sleeve 18, a stirring shaft 34 is connected inside the shaft sleeve 18 through a bearing, the side surface of the stirring shaft 34 is connected with a stirring blade 31, the upper end of the stirring shaft 34 is connected with a motor 17, the left side of the upper end surface of the tank cover 15 is connected with a three-way material supplementing, and the tank cover 15 at the front side of the three-way material supplementing pipe 23 is connected with a temperature electrode 28, the tank cover 15 at the rear side of the air inlet 25 is connected with a dissolved oxygen electrode 27, the tank cover 15 at the front side of the air inlet 25 is connected with a liquid level electrode 29, and the tank cover 15 is provided with a standard standby port 24.
The quantity of peristaltic pump 5 sets up to 4, and peristaltic pump 5 adopts the Watson Marlow experiment type peristaltic pump 5 of 4rpm, and peristaltic pump 5 every all is provided with automatic control, three kinds of modes are closed and manual filling, can be convenient for set up to 4 through the quantity of peristaltic pump 5 and make bioreactor can supply jar body 30 to 4 kinds of nutrient solutions simultaneously in, and can be convenient for adjust the mode of operation of peristaltic pump 5 through peristaltic pump mode switch 6 of 5 sides of peristaltic pump, thereby can realize automatic and manual switching, satisfy the special user demand of staff.
The quantity of rotameter 10 sets up to 4, and the 10 lower extremes of rotameter all is provided with flow control knob, can be convenient for monitor the flow of nitrogen gas, oxygen, carbon dioxide and air respectively through 4 rotameter 10, and can all be convenient for carry out manual regulation to the flow of nitrogen gas, oxygen, carbon dioxide and air through rotameter 10 lower extreme, and can be convenient for adjust the mode of admitting air through mode switch 11 that admits air.
The structural shape of the heat preservation cover 12 is hexagonal prism shape, and all be provided with the heat lamp 33 on every side of the inside of heat preservation cover 12, can be convenient for keep warm the nutrient solution of jar body 30 through the heat preservation cover 12 parcel with jar body 30 in, and can be convenient for all be provided with the heat lamp 33 on every side of the inside of heat preservation cover 12 and heat the nutrient solution of jar body 30, thereby make jar body 30 each face be heated evenly, thereby make jar body 30 inside nutrient solution heat more evenly.
The cover 15 is through the sealed fixed jar of body 30 of flange mouth, and is provided with rubber seal between the cover 15 and the jar body 30, can be convenient for through the flange mouth on the cover 15 and the fixed block 16 that its up end edge equidistance set up with the inseparable connection of cover 15 on the jar body 30, and can be convenient for make through the rubber seal who sets up between cover 15 and the jar body 30 to seal between cover 15 and the jar body 30, thereby prevent that external environment from leading to the fact the pollution to jar body 30 is inside.
The number of the standard spare ports 24 is 12, and the interfaces of the standard spare ports 24 are standard ports with the diameter of 6.35mm or 12mm, so that other related equipment can be conveniently connected in the tank body 30 through the standard spare ports 24, and the expanding applicability of the bioreactor can be conveniently improved.
The contact part of the tank body 30 and the culture solution adopts 316L stainless steel materials, and the inner surface of the tank body 30 is polished by 0.4RA, so that the tank body 30 has certain strength and high temperature resistance by adopting the 316L stainless steel materials in the contact part of the tank body 30 and the culture solution, and the inner surface of the tank body 30 is polished by 0.4RA to make the inner part of the tank body 30 smoother.
Stirring leaf 31 side is provided with 6 rectangular blocks, and stirring leaf 31 middle part and (mixing) shaft 34 fixed connection, can be convenient for drive (mixing) shaft 34 through starter motor 17 and rotate, and (mixing) shaft 34 rotates and drives and rotates rather than fixed connection's stirring leaf 31, and can be convenient for stir the nutrient solution through 6 rectangular blocks that stirring leaf 31 side set up to make various nutrient solution misce bene.
The working principle is as follows: when the human erythropoietin injection CHO cells are required to be fermented, firstly, each air supply pipe is connected to the ventilation interface 9, and the air outlet end of the mixer 22 is connected to the air inlet 25 on the tank cover 15 through the air pipe;
the PH gel electrode 26, the dissolved oxygen electrode 27, the temperature electrode 28 and the liquid level electrode 29 on the tank cover 15 are connected with the interfaces on the sensor connecting panel 19 on the side of the 360-degree control system main machine 2 through cables;
the automatic control valve 21 and the mixer 22 on the rear side of the ventilation auxiliary panel 8 are connected with the interface on the signal connection panel 20 on the rear side of the 360 control system main unit 2 by using signal lines;
the bioreactor is started through a main power switch 7, parameters are displayed through a display screen 3 on a 360-degree control system host 2, and equipment parameters can be adjusted through a control panel 4;
culture nutrient solution can be added into the tank body 30 through the three-way material supplementing pipe 23 on the tank cover 15, and the peristaltic pump mode switch 6 and the air inlet mode switch 11 are both set to be in an automatic mode;
during the process of cell fermentation culture, the bioreactor monitors the PH value, the oxygen content, the temperature and the liquid level in a tank 30 through a PH gel electrode 26, a dissolved oxygen electrode 27, a temperature electrode 28 and a liquid level electrode 29;
the peristaltic pump 5 is controlled by the 360-degree control system host 2, so that the material can be automatically supplemented in the tank body 30, and the 360-degree control system host 2 controls the automatic control valve 21 and the mixer 22, so that the flow of various gases is controlled;
the heating lamp 33 in the heat-insulating cover 12 is controlled through the 360-degree control system host machine 2, so that the temperature in the tank body 30 is controlled;
the 360-degree control system host 2 processes and records the monitored data, and performs material supplementing, appropriate mixed gas introducing and heating operations on the tank body 30 according to parameters set by workers, so that the optimal fermentation environment of biological cells is ensured;
in the process of cell fermentation culture, the 360-degree control system host 2 regularly controls the motor 17 to rotate, the motor 17 drives the stirring shaft 34 to rotate, so that the stirring shaft 34 drives the stirring blade 31 to stir the nutrient solution in the tank 30, and the nutrient solution in the tank 30 is mixed more uniformly.
It is to be understood that the terms "central," "longitudinal," "lateral," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," and the like are used in the orientations and positional relationships indicated in the drawings for the purpose of convenience and simplicity of description, and do not indicate or imply that the referenced devices or components must be in a particular orientation, constructed and operated in a particular orientation, and are not to be considered limiting of the scope of the present invention.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.

Claims (8)

1. A bioreactor for human erythropoietin injection CHO cell fermentation comprises a bottom plate (1) and is characterized in that: the right side of the upper end face of the bottom plate (1) is provided with a 360-degree control system host (2), the upper end of the front side face of the 360-degree control system host (2) is provided with a display screen (3), the lower end of the display screen (3) is provided with a control panel (4), the left side of the front end of the 360-degree control system host (2) at the lower end of the control panel (4) is provided with a peristaltic pump (5), the 360-degree control system host (2) at the right side of the peristaltic pump (5) is connected with a peristaltic pump mode switch (6), a main power switch (7) is arranged on the lower side of the front end face of the 360-degree control system host (2), the left side face of the 360-degree control system host (2) is provided with a sensor connecting panel (19), a signal connecting panel (20) is arranged on the lower side of the rear end face of the 360-degree control, the lower end of the front end face of the ventilation auxiliary panel (8) is connected with a ventilation interface (9), the ventilation auxiliary panel (8) at the upper end of the ventilation interface (9) is connected with a rotameter (10), the ventilation auxiliary panel (8) at one side of the rotameter (10) is provided with an air inlet mode switch (11), the upper end of the rear end face of the ventilation auxiliary panel (8) is connected with an automatic control valve (21), the lower end of the automatic control valve (21) is provided with a mixer (22), the bottom plate (1) at the left side of the ventilation auxiliary panel (8) is provided with a heat insulation cover (12), the right side face of the heat insulation cover (12) is connected with an electric cabinet (13), the front end face of the electric cabinet (13) is provided with a lamp tube power switch (14), a support frame (32) is arranged in the heat insulation cover (12), and the support frame, and the upper end of the tank body (30) is fixedly connected with a tank cover (15) through a fixing block (16), the middle part of the upper end face of the tank cover (15) is fixedly connected with a shaft sleeve (18), a stirring shaft (34) is connected in the shaft sleeve (18) through a bearing, the side face of the stirring shaft (34) is connected with a stirring blade (31), the upper end of the stirring shaft (34) is connected with a motor (17), the left side of the upper end face of the tank cover (15) is connected with a three-way material supplementing pipe (23), the right side of the upper end face of the tank cover (15) is provided with an air inlet (25), the lower end of the air inlet (25) is connected with an air inlet pipe (35), the tank cover (15) at the rear side of the three-way material supplementing pipe (23) is connected with a PH gel electrode (26), the tank cover (15) at the front side of, and a liquid level electrode (29) is connected to the tank cover (15) at the front side of the air inlet (25), and a standard standby port (24) is arranged on the tank cover (15).
2. The bioreactor for human erythropoietin injection CHO cell fermentation according to claim 1, characterized in that: the number of the peristaltic pumps (5) is set to be 4, the peristaltic pumps (5) adopt Watson Marlow experiment type peristaltic pump heads with the rpm of 4, and the peristaltic pumps (5) are respectively provided with three modes of automatic control, closing and manual filling.
3. The bioreactor for human erythropoietin injection CHO cell fermentation according to claim 1, characterized in that: the number of the rotameters (10) is set to 4, and the lower ends of the rotameters (10) are provided with flow adjusting knobs.
4. The bioreactor for human erythropoietin injection CHO cell fermentation according to claim 1, characterized in that: the structure shape of the heat preservation cover (12) is a hexagonal prism shape, and a heating lamp (33) is arranged on each side face inside the heat preservation cover (12).
5. The bioreactor for human erythropoietin injection CHO cell fermentation according to claim 1, characterized in that: the tank cover (15) is fixedly sealed with the tank body (30) through a flange opening, and a rubber sealing ring is arranged between the tank cover (15) and the tank body (30).
6. The bioreactor for human erythropoietin injection CHO cell fermentation according to claim 1, characterized in that: the number of the standard standby ports (24) is 12, and the interfaces of the standard standby ports (24) are standard ports with the diameter of 6.35mm or 12 mm.
7. The bioreactor for human erythropoietin injection CHO cell fermentation according to claim 1, characterized in that: the contact part of the tank body (30) and the culture solution is made of 316L stainless steel, and the inner surface of the tank body (30) is treated by polishing 0.4 RA.
8. The bioreactor for human erythropoietin injection CHO cell fermentation according to claim 1, characterized in that: the side surface of the stirring blade (31) is provided with 6 rectangular blocks, and the middle part of the stirring blade (31) is fixedly connected with the stirring shaft (34).
CN202110019455.8A 2021-01-07 2021-01-07 Bioreactor for human erythropoietin injection CHO cell fermentation Pending CN112457986A (en)

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CN113025485A (en) * 2021-03-17 2021-06-25 厦门大学 Continuous foam separation coupling fermentation device
CN114561291A (en) * 2022-03-21 2022-05-31 广州齐志生物工程设备有限公司 500ml small-sized one-control multi-cell bioreactor

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Application publication date: 20210309