CN108004122B - Fixed bed type cell bioreactor - Google Patents
Fixed bed type cell bioreactor Download PDFInfo
- Publication number
- CN108004122B CN108004122B CN201711318653.4A CN201711318653A CN108004122B CN 108004122 B CN108004122 B CN 108004122B CN 201711318653 A CN201711318653 A CN 201711318653A CN 108004122 B CN108004122 B CN 108004122B
- Authority
- CN
- China
- Prior art keywords
- cylinder shell
- ring cylinder
- tank body
- cover plate
- flow guide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
- C12M25/16—Particles; Beads; Granular material; Encapsulation
- C12M25/18—Fixed or packed bed
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/02—Stirrer or mobile mixing elements
- C12M27/08—Stirrer or mobile mixing elements with different stirrer shapes in one shaft or axis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/06—Nozzles; Sprayers; Spargers; Diffusers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
- C12M29/20—Degassing; Venting; Bubble traps
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
- C12M41/18—Heat exchange systems, e.g. heat jackets or outer envelopes
- C12M41/22—Heat exchange systems, e.g. heat jackets or outer envelopes in contact with the bioreactor walls
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/48—Automatic or computerized control
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Sustainable Development (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Thermal Sciences (AREA)
- Computer Hardware Design (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The invention discloses a fixed bed type cell bioreactor, which comprises a stirring device, a ventilation device, an exhaust device, a feed supplement device, a fixed bed device, a water jacket interlayer and a controller, wherein the fixed bed device consists of an outer ring cylinder shell, a middle ring cylinder shell, an inner ring cylinder shell, a hollow cylinder type flow guide pipe, an upper cover plate, a lower cover plate and a hollow flow guide thin pipe; the invention overcomes the defects of the prior fixed bed cell bioreactor in cell density and mass transfer efficiency, can be suitable for adherent cell culture mode, better provides the mass transfer efficiency of culture solution and oxygen, and achieves higher cell density and product concentration.
Description
Technical Field
The invention relates to the field of biological pharmacy, in particular to a fixed bed type cell bioreactor.
Background
In recent decades, as the demand for biological products such as growth hormones, interferons, monoclonal antibodies, vaccines and interleukins has increased dramatically, cell culture by large scale in vitro culture techniques has become an effective method for producing biological products. The cell mass culture technique is a technique for culturing a large amount of animal cells in a bioreactor at a high density under artificial conditions (setting pH, temperature, dissolved oxygen, etc.) to produce a biological product. At present, animal cells which can be cultured in a large scale comprise a plurality of primary cells such as chick embryos, pig kidneys, monkey kidneys and hamster kidneys, human diploid cells, Vero cells and the like, and products such as rabies vaccines, hepatitis A vaccines, hepatitis B vaccines, erythropoietin and monoclonal antibodies are successfully produced.
The bioreactor provides a suitable and controllable growth environment for cell growth, can enlarge the production scale, meets the production requirement of biological products, and makes the industrial large-scale culture of animal cells possible. The application of the bioreactor has great superiority in the production of biological products, and can continuously improve the productivity, further reduce the cost and enhance the competitiveness. The bioreactor is a key device in the whole culture process, whether the animal cell culture technology can be industrialized and commercialized in a large scale or not is crucial in designing a proper animal cell culture bioreactor.
The fixed bed bioreactor filled with various carriers can better realize the high-density continuous culture of adherent cells, and is widely used for cell culture to develop and produce various biological products. Especially, the method is widely applied in the fields of development and production of Chinese vaccines and genetic engineering medicines.
The fixed bed bioreactor is a container for assembling fixed carriers in the bioreactor, the container is filled with carriers, and the carriers are usually solid or porous balls or flaky fiber samples with the diameter of 2-6 mm. The culture solution circulates through the fixed bed, and the culture medium continuously flows through the packing to transfer nutrients and oxygen. The fixed bed culture mode has high cell culture density and no mechanical damage. However, because only the upper cover plate and the lower cover plate are adopted to tightly press the carrier, metabolic products and dead cells of the cells are difficult to discharge, and because the carriers are stacked together, the culture solution flows unevenly, so that the nutrition distribution is uneven, and the growth speed of the cells is inconsistent.
Disclosure of Invention
The present invention is directed to a fixed-bed cell bioreactor, which solves the above problems of the prior art.
In order to achieve the purpose, the invention provides the following technical scheme:
a fixed bed type cell bioreactor comprises a stirring device, a ventilation device, an exhaust device, a feeding device, a fixed bed device, a water jacket interlayer and a controller.
Further: the tank body is made of stainless steel 316L, the tank body is cylindrical, the bottom of the tank body is arranged as the bottom of the tank body and is a dish-shaped shallow bottom, the top of the tank body is a flat opening, and a tank top cover is covered on the tank body; the ratio of the height of the tank body to the diameter of the tank body is 1.2-2.
Further: the fixed bed device consists of an outer ring cylinder shell, a middle ring cylinder shell, an inner ring cylinder shell, a hollow cylinder type flow guide pipe, an upper cover plate, a lower cover plate and a hollow flow guide thin pipe, wherein the outer ring cylinder shell, the middle ring cylinder shell, the inner ring cylinder shell and the hollow cylinder type flow guide pipe are sequentially arranged in a concentric circle from outside to inside, the outer ring cylinder shell, the middle ring cylinder shell, the inner ring cylinder shell and the hollow cylinder type flow guide pipe are all in a cylinder shape, the lower ends of the outer ring cylinder shell, the middle ring cylinder shell, the inner ring cylinder shell and the hollow cylinder type flow guide pipe are fixedly welded on the lower cover plate, no hole is formed in the cylinder wall of the outer ring cylinder shell, and small holes with; the upper cover plate and the lower cover plate are disc-shaped, corresponding large holes are formed in the circle centers of the upper cover plate and the lower cover plate, the hole diameter of each large hole is equal to the diameter of the hollow cylindrical flow guide pipe, and O-shaped rings made of soft materials are arranged at the edges of the upper cover plate and the lower cover plate; the hollow flow guide thin tubes are arranged in a plurality of numbers, are uniformly distributed on the middle ring cylinder shell and the inner ring cylinder shell and are welded together, are in a thin tube shape, small holes with the aperture of 0.5-2mm are uniformly formed in the tube wall, and the bottoms of the hollow flow guide thin tubes are fixedly connected with the lower cover plate and are welded together.
Further: the ventilation device comprises a ventilation port, an air injection device and a ventilation pipeline, the ventilation pipeline is communicated with the air injection device and the ventilation port, the air injection device is a circular pipeline, the diameter of the circular pipeline is 10-20mm, and a plurality of small holes with the downward diameter of 0.5-1mm are formed in the lower side of the air injection device; the air injection device is positioned in the center of the tank body and below the tank body.
Further: the stirring device comprises a stirring shaft, stirring blades, a motor, a coupler and a motor, wherein the stirring shaft, the stirring blades, the motor and the motor are fixed at the bottom of the tank body, an output shaft of the motor is connected with the stirring shaft through the coupler, the stirring blades are fixedly installed on the stirring shaft, and the stirring blades are a plurality of inclined stirring blades and vertical blades.
Further: the exhaust device comprises a tail gas heater and an exhaust pipeline, the tail gas heater is sleeved on the exhaust pipeline, and the tail gas heater is communicated with a first connector and a second connector.
Further: the water jacket interlayer is sleeved on the outer side of the tank body.
Further: the controller comprises a control cabinet, a touch screen, a PLC, an emergency button, a circuit board and an electric element. Automation of all operations is accomplished by automation software.
Compared with the prior art, the invention has the beneficial effects that: the invention overcomes the defects of the prior fixed bed cell bioreactor in cell density and mass transfer efficiency, can be suitable for adherent cell culture mode, better provides the mass transfer efficiency of culture solution and oxygen, and achieves higher cell density and product concentration.
Drawings
FIG. 1 is a schematic diagram of an elevation structure in a fixed-bed cell bioreactor.
FIG. 2 is a schematic top view of a fixed bed apparatus in a fixed bed type cell bioreactor.
In the figure: 1-a first interface, 2-a tail gas heater, 3-an exhaust pipeline, 4-a second interface, 5-a tank top cover, 6-an air vent, 7-a tank body, 11-a material supplementing device, 12-an upper cover plate, 13-a water jacket interlayer, 14-a lower cover plate, 21-a diversion tubule, 23-a hollow cylindrical diversion pipe, 26-a stirring shaft, 27-an inclined stirring blade, 28-a vertical blade, 30-an air injection device, 32-a motor, 33-an air vent pipeline, 35-a tank body bottom, 36-a coupler, 41-an outer annular cylinder shell, 42-an intermediate annular cylinder shell and 43-an inner annular cylinder shell.
Detailed Description
Referring to the drawings, in the embodiment of the present invention, a fixed bed type cell bioreactor includes a stirring device, a ventilating device, an exhausting device, a feeding device 11, a fixed bed device, a water jacket interlayer 13 and a controller;
the tank body 7 is made of stainless steel 316L, the overall design meets the requirements of ASME-BPE, and the tank is easy to clean and free of dead angles. The tank body 7 is designed into a cylindrical shape, and the volume utilization rate is maximized. The bottom of the tank body 7 is set as a tank body bottom 35 which is designed as a dish-shaped shallow bottom and is beneficial to flowing and uniformly mixing culture solution; the top of the tank body 7 is in a flat opening design, and a tank top cover 5 is covered on the tank body, so that the tank can be detached, lifted and lowered, and the fixed bed device assembly is convenient to maintain and replace; the proportion of the height of the tank body 7 and the diameter of the tank body 7 is 1.2-2, the cell culture requirement is met, a water jacket interlayer 13 is sleeved on the outer side of the tank body 7, the tank body is heated and cooled, the tank body 7 is provided with a heat insulation layer, and operators are protected from being injured.
The fixed bed device is composed of an outer ring cylinder shell 41, a middle ring cylinder shell 42, an inner ring cylinder shell 43, a hollow cylinder type draft tube 23, an upper cover plate 12, a lower cover plate 14 and a hollow draft tubule 21, and all components in the fixed bed device are made of stainless steel materials.
The outer ring cylinder shell 41, the middle ring cylinder shell 42, the inner ring cylinder shell 43 and the hollow cylinder type draft tube 23 are sequentially arranged in a concentric circle from outside to inside.
The outer ring cylinder shell 41 is cylindrical, no opening is formed in the cylinder wall, and the bottom of the outer ring cylinder shell 41 is connected with the edge of the lower cover plate 14 and welded together to form a fixed structure.
The middle ring cylinder shell 42 is cylindrical, small holes with the aperture of 2-4mm are uniformly distributed on the cylinder wall, and the bottom of the middle ring cylinder shell 42 is connected with the lower cover plate 14 and welded together to form a fixed structure.
The inner ring cylinder shell 43 is cylindrical, and small holes with the aperture of 2-4mm are uniformly distributed on the cylinder wall. The bottom of the inner ring cylinder shell 43 is connected with the lower cover plate 14 and welded together, and is a fixed structure.
The hollow cylinder type draft tube 23 is cylindrical, and small holes with the aperture of 2-4mm are uniformly distributed on the cylinder wall. The bottom of the hollow cylindrical draft tube 23 is connected with the lower cover plate 14 and welded together, and the hollow cylindrical draft tube is of a fixed structure.
The lower cover plate 14 is disc-shaped, a large hole is formed in the center of the circle of the lower cover plate 14, the diameter of the hole is equal to that of the hollow cylindrical flow guide pipe 23, and the edge of the hole is connected with the bottom of the hollow cylindrical flow guide pipe 23 and welded together to form a fixed structure. Small holes with the aperture of 2-4mm are uniformly distributed on the lower cover plate 14; the edge of the disk of the lower cover plate 14 is provided with an O-shaped ring made of soft material, so that the disorder of the tank wall caused by the direct contact of the lower cover plate 14 and the inner wall of the tank body can be avoided, and the sealing function can be realized.
The upper cover plate 12 is disc-shaped, the center of the circle of the upper cover plate 12 is provided with a large hole, the diameter of the large hole is equal to that of the hollow cylinder type draft tube 23, the edge of the position of the large hole is matched with the edge of the top of the hollow cylinder type draft tube 23, the edge of the disc of the upper cover plate 12 is matched with the outer cylinder shell 41, and small holes with the diameter of 2-4mm are uniformly distributed on the upper cover plate 12; the edge of the disc of the upper cover plate 12 is added with an O-shaped ring made of soft material, so that the phenomenon that the upper cover plate 12 is in direct contact with the inner wall of the tank body 7 to cause disorder of the tank wall can be avoided, and a sealing effect can be achieved.
The utility model discloses a novel water conservancy diversion tubule 21, including well ring shell 42, inner ring shell 43, cavity water conservancy diversion tubule 21, the pipe wall is evenly opened to have the aperture to be 0.5-2mm, cavity water conservancy diversion tubule 21 adopts equilateral octagon or other structure, and the bottom of cavity water conservancy diversion tubule 21 is in the same place with lower apron 14 fixed connection and welding, is fixed knot structure, and evenly distributed is in the same place on well ring shell 42, inner ring shell 43.
The ventilation device comprises a ventilation opening 6, an air injection device 30 and a ventilation pipeline 33, wherein the ventilation pipeline 33 is communicated with the air injection device 30 and the ventilation opening 6, the air injection device 30 is a circular pipeline, the diameter of the circular structure is 10-20mm, a plurality of small holes with the downward diameter of 0.5-1mm are formed in the lower side of the air injection device 30, and specifically, one small hole is formed at each interval of 10 mm; the air injection device 30 is positioned in the center of the tank 7 and below the tank 14.
The stirring device comprises a stirring shaft 26, stirring blades, a motor 32, a coupler 36 and a motor 32 which are fixed at the bottom of the tank body 7, wherein an output shaft of the motor 32 is connected with the stirring shaft 26 through the coupler 36, the stirring blades are fixedly arranged on the stirring shaft 26 and are inclined stirring blades 27 or vertical blades 28, and the stirring blades are formed by combining a plurality of components.
Exhaust apparatus is including tail gas heater 2 and exhaust pipe way 3, and 2 covers of tail gas heater are on exhaust pipe way 3, and the first interface 1 of intercommunication and second interface 4 on the tail gas heater 2 let in industrial steam from interface 4, follow interface 1 outflow steam, the gas that produces among the process of cultivateing is discharged through exhaust pipe way 3, and through tail gas heater 2, gas is heated the drying, can not soak the exhaust filter core, can guarantee to cultivate the in-process and need not change the exhaust filter core.
The water jacket interlayer 13 is heated and cooled in a double-plate mode. The water jacket interlayer 13 of the tank body 7 is filled with purified water during operation, and water circulation is kept through an internal pump. When the temperature is raised, industrial steam is introduced into the heating plate, heat is exchanged into the jacket reclaimed water, and the water in the jacket transfers the heat to the liquid in the culture tank body through circulation to complete the temperature rise. When the temperature is reduced, cooling water is introduced into the heating plate, the cold energy is exchanged into the jacket reclaimed water, and the water in the jacket transfers the cold energy to the liquid in the culture tank body through circulation to finish the temperature reduction.
The controller comprises a control cabinet, a touch screen, a PLC, an emergency button, a circuit board and an electric element. Automation of all operations is accomplished by automation software.
The working principle of the invention is as follows: when cell culture is performed, a fixed bed is packed with an adherence vehicle. The culture solution is added, and the culture solution surface submerges the upper cover plate 12. The motor 32 drives the stirring shaft 26 to drive the blades to rotate, the stirring blades are inclined blade stirring blades, and the liquid in the hollow cylindrical guide pipe 23 is driven to flow from the top to the bottom of the hollow cylindrical guide pipe 23; part of the liquid in the hollow cylindrical draft tube 23 is pushed by the vertical blades 28 to enter the fixed bed device through the small holes on the wall of the hollow cylindrical draft tube 23 so as to provide nutrient substances for cell growth; part of the liquid in the hollow cylinder type draft tube 23 flows out of the bottom of the hollow cylinder type draft tube 23, the liquid flows through the gas injection device 30, when gas is introduced into the gas injection device 30, a large amount of bubbles are generated, and the bubbles and the culture liquid are mixed in a gas-liquid mode at the bottom 35 of the tank body; part of the mixed culture solution enters the fixed bed through the small holes on the lower cover plate 14 to transfer nutrient substances and oxygen required by cell growth, flows through the carriers stacked layer by layer, and then flows out through the small holes on the upper cover plate 12; part of the mixed culture solution flows through the hollow diversion tubule 21 and enters the fixed bed through the small hole on the hollow diversion tubule 21 to transfer nutrient substances and oxygen required by cell growth; after the multi-path fluid above the upper cover plate 12 is converged, the multi-path fluid returns to the top of the hollow cylindrical draft tube 23, and the culture solution and the oxygen are distributed and transmitted to the inside of the fixed bed through continuous and repeated circulation.
A suitable volume of support is introduced into the fixed bed apparatus, and the upper cover plate 12 is covered and fixed. And installing other components of the bioreactor. After the completion, the bioreactor tank body is sterilized by a solid tank, namely the tank body is filled with a certain volume of buffer solution and treated carriers. After sterilization, the buffer in the tank should be emptied. The various nutrients and supplementary materials required in the culture process should be sterilized in advance by high temperature and high pressure or sterile filtration, and filled into suitable sterile containers with suitable sterile pipelines and connectors.
And the container filled with the supplementary material liquid is connected with the bioreactor after the sterilization through a four-valve group connector, and pure steam is introduced again for aseptic treatment. And after the sterilization is finished, closing the steam and drain valve, and opening the material supplementing valve. And (4) placing the silicone tube in the material supplementing pipeline into the peristaltic pump, and fixing. And operating automatic control software in a touch screen of the control cabinet, and operating a specified peristaltic pump to operate the material supplementing. The operation can be manual or automatic, and is stopped when the specified volume of liquid is replenished. The liquid to be supplemented includes cell culture solution, alkali solution, etc.
Introducing a sufficient number of said adherent cells into a culture tank body. In the automatic control software, parameters such as temperature, stirring speed, pH, DO and the like are set, and the operation is automatically controlled. In addition, the pH module is associated with an alkali liquor feeding pipeline, and the DO module is associated with a deep ventilation pipeline. The pH adjustment can be carried out by monitoring on line through a pH sensor and automatically controlling the alkali liquor feeding peristaltic pump. DO regulation can be monitored on-line by a DO sensor, automatically controlling a gas flow meter and feeding gas through a valve.
The carrier is fixed in a fixed bed, and adherent cells are gradually attached to the carrier in the fixed bed through fluid circulation. The culture parameters are stable. Adherent cells will adsorb to the microcarriers and gradually expand in a short time. After most adherent cells are attached to the microcarriers, the speed of a feed supplement pump is set, and nutrient substances are continuously supplemented into the tank body; setting the harvesting pump speed (which is consistent with the feed supplement pump speed) through an interception device; ensure that new nutrient substances continuously enter the tank body, metabolic products are continuously discharged, and the volume of liquid in the tank body is kept unchanged.
When the cells enter the equilibrium phase, the cell density reaches a higher level. Can be inoculated with virus seeds to infect cells. The feeding strategy remained unchanged. Can follow jar internal sampling daily, detect the target product concentration in the sample, record data draws the target product concentration curve.
And finishing the culture when the number and the activity of the whole suspension cells are reduced and the concentration of the target product is reduced. And harvesting the liquid in the tank body in an aseptic mode. And (4) performing downstream purification treatment on the harvest liquid to obtain a corresponding product.
Furthermore, it should be understood that although the present description refers to embodiments, not every embodiment may contain only a single embodiment, and such description is for clarity only, and those skilled in the art should integrate the description, and the embodiments may be combined as appropriate to form other embodiments understood by those skilled in the art.
Claims (5)
1. A fixed bed type cell bioreactor is characterized in that: comprises a stirring device, a ventilation device, an exhaust device, a material supplementing device (11), a fixed bed device, a water jacket interlayer (13) and a controller;
the fixed bed device comprises an outer ring cylinder shell (41), a middle ring cylinder shell (42), an inner ring cylinder shell (43), a hollow cylinder type flow guide pipe (23), an upper cover plate (12), a lower cover plate (14) and a hollow flow guide tubule (21), wherein the outer ring cylinder shell (41), the middle ring cylinder shell (42), the inner ring cylinder shell (43) and the hollow cylinder type flow guide pipe (23) are sequentially arranged in a concentric circle from outside to inside, the outer ring cylinder shell (41), the middle ring cylinder shell (42), the inner ring cylinder shell (43) and the hollow cylinder type flow guide pipe (23) are all cylindrical, the lower ends of the outer ring cylinder shell (41) are fixedly welded on the lower cover plate (14), no hole is formed in the cylinder wall of the outer ring cylinder shell (41), and small holes with the aperture of 2-4mm are uniformly distributed in the middle ring cylinder shell (42), the inner ring cylinder shell (43), the hollow cylinder type flow guide pipe; the upper cover plate (12) and the lower cover plate (14) are disc-shaped, corresponding large holes are formed in the centers of circles, the diameter of each large hole is equal to that of the hollow cylindrical flow guide pipe (23), and O-shaped rings made of soft materials are arranged on the edges of the upper cover plate (12) and the lower cover plate (14); the hollow flow guide thin tubes (21) are uniformly distributed on the middle ring cylinder shell (42) and the inner ring cylinder shell (43) and welded together, the hollow flow guide thin tubes (21) are thin tube-shaped, small holes with the aperture of 0.5-2mm are uniformly formed in the tube walls, and the bottoms of the hollow flow guide thin tubes (21) are fixedly connected with the lower cover plate (14) and welded together;
the ventilation device comprises a ventilation opening (6), an air injection device (30) and a ventilation pipeline (33), the ventilation pipeline (33) is communicated with the air injection device (30) and the ventilation opening (6), the air injection device (30) is a circular pipeline, the diameter of the circular structure is 10-20mm, and a plurality of small holes with the downward diameter of 0.5-1mm are formed in the lower side of the air injection device (30); the air injection device (30) is positioned in the center of the tank body (7) and below the tank body (14);
the stirring device comprises a stirring shaft (26), stirring blades, a motor (32) and a coupler (36), wherein the motor (32) is fixed at the bottom of the tank body (7), an output shaft of the motor (32) is connected with the stirring shaft (26) through the coupler (36), the stirring blades are fixedly installed on the stirring shaft (26), and the stirring blades are a plurality of inclined stirring blades (27) and upright blades (28).
2. The fixed-bed cell bioreactor as claimed in claim 1, wherein: the tank body (7) is made of stainless steel 316L, the tank body (7) is cylindrical, the bottom (35) of the tank body is a dish-shaped shallow bottom, the top of the tank body (7) is a flat opening, and a tank top cover (5) is covered on the flat opening; the ratio of the height of the tank body (7) to the diameter of the tank body (7) is 1.2-2.
3. The fixed-bed cell bioreactor as claimed in claim 1, wherein: exhaust apparatus is including tail gas heater (2) and exhaust pipe way (3), and cover on exhaust pipe way (3) tail gas heater (2), first interface (1) and second interface (4) of intercommunication on tail gas heater (2).
4. The fixed-bed cell bioreactor as claimed in claim 1, wherein: the water jacket interlayer (13) is sleeved on the outer side of the tank body (7).
5. The fixed-bed cell bioreactor as claimed in claim 1, wherein: the controller comprises a control cabinet, a touch screen, a PLC, an emergency button, a circuit board and an electric element, and the automation of all operations is completed through automatic control software.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711318653.4A CN108004122B (en) | 2017-12-12 | 2017-12-12 | Fixed bed type cell bioreactor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711318653.4A CN108004122B (en) | 2017-12-12 | 2017-12-12 | Fixed bed type cell bioreactor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108004122A CN108004122A (en) | 2018-05-08 |
| CN108004122B true CN108004122B (en) | 2020-12-01 |
Family
ID=62058086
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711318653.4A Active CN108004122B (en) | 2017-12-12 | 2017-12-12 | Fixed bed type cell bioreactor |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108004122B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG11202003030RA (en) | 2017-10-03 | 2020-04-29 | Abec Inc | Reactor systems |
| CN108641960A (en) * | 2018-05-22 | 2018-10-12 | 黄山市中新生物科技有限公司 | A kind of multipurpose bioreactor |
| CN108865651A (en) * | 2018-06-05 | 2018-11-23 | 李盈贤 | A kind of sealing cultivation algae culturing device and its assemble method |
| CN111849774B (en) * | 2020-08-17 | 2023-07-14 | 陈红 | Wall-attached cell culture fermentation tank |
| CN112375685A (en) * | 2020-12-04 | 2021-02-19 | 山东新华医疗器械股份有限公司 | Fixed bed bioreactor |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5081035A (en) * | 1988-04-18 | 1992-01-14 | The University Of Michigan | Bioreactor system |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN201272799Y (en) * | 2008-09-12 | 2009-07-15 | 广州齐志生物工程设备有限公司 | Biological reactor |
| CN205347443U (en) * | 2015-08-03 | 2016-06-29 | 上海楚鲲生物科技有限公司 | Chip carrier and bioreactor for cell culture |
| CN106635797A (en) * | 2017-03-15 | 2017-05-10 | 上海戈洛思生物科技有限公司 | Bioreactor |
| CN106754366A (en) * | 2017-04-05 | 2017-05-31 | 苏州迪欧益生物科技有限公司 | For the disposable intelligent digester systems of animal cell culture |
-
2017
- 2017-12-12 CN CN201711318653.4A patent/CN108004122B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5081035A (en) * | 1988-04-18 | 1992-01-14 | The University Of Michigan | Bioreactor system |
Non-Patent Citations (1)
| Title |
|---|
| "现代动物细胞培养反应器概述";王洪跃等;《中国医药生物技术》;20100430;第5卷(第2期);第156-157页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108004122A (en) | 2018-05-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108004122B (en) | Fixed bed type cell bioreactor | |
| CN107904169B (en) | Modularized bioreactor suitable for culturing multiple cell types | |
| Xu et al. | Microalgal bioreactors: challenges and opportunities | |
| US11319522B2 (en) | Photobioreactor used for algae cultivation, and algae cultivation system | |
| CN108641960A (en) | A kind of multipurpose bioreactor | |
| CN102199537B (en) | Membrane bioreactor used in microgravity environment and simulated microgravity environment | |
| CN103589638A (en) | Pneumatic self-circulation animal cell culture bioreactor and application method thereof | |
| CN205295351U (en) | Pipeline type microalgae photobioreactor | |
| CN101914431A (en) | Device and method for cultivating microalgae by utilizing all plastic modular photobioreactor system | |
| CN104531521A (en) | Shallow dish type solid fermenting equipment | |
| CN106520552A (en) | Cell culture biological reactor | |
| CN202211050U (en) | Split temporary immersion type cultivation device | |
| CN104073435A (en) | Movable all-weather microalgae light complement bioreaction culture system and culture method | |
| KR101670129B1 (en) | Photoreactive Apparatus and method for culturing microalgae | |
| CN203373351U (en) | Programmed domesticating and screening culture equipment | |
| CN109251847B (en) | Device and method for culturing photosynthetic microorganisms by using sunlight | |
| CN202415569U (en) | Tidal animal cell culture bioreactor | |
| CN204981904U (en) | Pipeline formula cell culture device | |
| CN102703325A (en) | Method for producing chlamydomonas at low cost | |
| CN203159616U (en) | Mist type microalgae illumination reaction device | |
| CN103131627A (en) | Light organism reaction device and application | |
| CN105695313B (en) | A kind of positive conveyance tubular type bioreactor | |
| CN212128171U (en) | Device is banked up with earth to batch formula little algae | |
| CN205590687U (en) | Normal position moves and carries tubular photobioreactor | |
| CN2352538Y (en) | Plant cell, tissue culturing reactor with air floating type periodic submerging and illumination |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |