CN112430540A - Compact reactor capable of being placed in biological incubator - Google Patents
Compact reactor capable of being placed in biological incubator Download PDFInfo
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- CN112430540A CN112430540A CN202011129274.2A CN202011129274A CN112430540A CN 112430540 A CN112430540 A CN 112430540A CN 202011129274 A CN202011129274 A CN 202011129274A CN 112430540 A CN112430540 A CN 112430540A
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- end cover
- glass tank
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- compact reactor
- sampling port
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- 239000007788 liquid Substances 0.000 claims abstract description 52
- 239000011521 glass Substances 0.000 claims abstract description 30
- 238000005070 sampling Methods 0.000 claims abstract description 20
- 229920001296 polysiloxane Polymers 0.000 claims description 13
- 230000002572 peristaltic effect Effects 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 238000004113 cell culture Methods 0.000 abstract description 5
- 241000700605 Viruses Species 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 31
- 239000007789 gas Substances 0.000 description 4
- 238000010008 shearing Methods 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000005054 agglomeration Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
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- 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
-
- 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
- C12M29/04—Filters; Permeable or porous membranes or plates, e.g. dialysis
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- 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
- C12M29/18—External loop; Means for reintroduction of fermented biomass or liquid percolate
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- 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
- C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
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- 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
- C12M37/00—Means for sterilizing, maintaining sterile conditions or avoiding chemical or biological contamination
- C12M37/04—Seals
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- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
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Abstract
The invention relates to the technical field of cell culture, in particular to a compact reactor capable of being arranged in a biological incubator, which comprises a glass tank, wherein a lower end cover is sleeved on the outer wall of the glass tank and is close to a port of the glass tank, the lower end cover is connected with an upper end cover through a bolt, an O-shaped ring mounting groove is formed in the end surface of the glass tank, an O-shaped ring is arranged inside the O-shaped ring mounting groove, and an air inlet hole, an air outlet hole, a liquid inlet, a liquid outlet and a cell liquid filling and sampling port are respectively arranged on the end surface of the upper end cover The yield of products such as target antibodies, target viruses and the like is more suitable for the development stage.
Description
Technical Field
The invention relates to the technical field of cell culture, in particular to a compact reactor which can be arranged in a biological incubator.
Background
In the cell culture production process, the requirements of the growth of some cells on the environment are strict, the growth of the cells can be influenced by shearing force, temperature change, pH value and dissolved oxygen supply, and the shearing force generated by a reactor with paddles on the market is larger, so that the growth of some cells is not facilitated. And the traditional reactor needs to be provided with special gas filtering, ventilating and adjusting units such as O2 and CO2, needs a special sensor module, has a complex structure and high purchasing and using cost, the traditional manual mode adopts a shake flask to culture cells and can generate small shearing force, but the volume of the cultured cells is small, the time cost is greatly increased, and when the cell density is high, the cells cultured by the shake flask are easy to agglomerate, so that a large number of cells die.
In view of the above, the present invention solves the existing problems by designing a compact reactor that can be placed inside a biological incubator.
Disclosure of Invention
The object of the present invention is to provide a compact reactor that can be placed inside a biological incubator, in order to solve the problems set out in the background art mentioned above.
In order to achieve the purpose, the invention provides the following technical scheme:
the utility model provides a can arrange compact reactor in biological incubator in, includes the glass jar, the outer wall of glass jar and the port that is close to the glass jar cup joints the lower extreme cover, the lower extreme cover has the upper end cover through bolted connection, O type circle mounting groove has been seted up on the glass jar terminal surface, the internally mounted of O type circle mounting groove has O type circle, be provided with inlet port, exhaust hole, inlet, liquid outlet and cell liquid filling sample connection on the terminal surface of upper end cover respectively, be provided with air cleaner on the inlet port, air cleaner is last to be connected on the vacuum pump through the silicone tube, the liquid outlet passes through the silicone tube and connects on the peristaltic pump, the inlet passes through the silicone tube and connects on the peristaltic pump, be connected with aseptic joint on the cell liquid filling sample connection.
Preferably, the glass tank, the lower end cover, the upper end cover and the O-shaped ring form a reaction tank body.
Preferably, the air inlet hole, the air exhaust hole, the liquid inlet, the liquid outlet and the cell sap filling and sampling port are respectively welded on the upper end cover and are of an integral structure, and the air inlet hole, the air exhaust hole, the liquid inlet, the liquid outlet and the cell sap filling and sampling port are respectively of a communicating structure with the inside of the glass tank
Preferably, air filters are arranged on the exhaust hole and the air inlet hole.
Preferably, the liquid inlet penetrates through the upper end cover and extends to the inside of the glass tank, the bottom of the liquid inlet is in contact with the bottom of the inside of the glass tank, and the bottom of the liquid inlet is a slope cut.
Preferably, the liquid outlet penetrates through the upper end cover and extends to the inside of the glass jar, and the bottom of the liquid outlet is in a horn shape.
Preferably, the cell sap filling and sampling port comprises a sampling port and a cell sap filling port, the sampling port and the cell sap filling port are made of the same pipe, and the CPC sterile connector is made of a connector with a stop valve female head.
Compared with the prior art, the invention has the beneficial effects that:
1. according to the invention, by designing the compact reactor which can be placed in a biological incubator, the temperature and humidity in the incubator are constant, the temperature is uniform, the gas supply proportion is uniform, the pH value is in a normal range, and the cell can be cultured more efficiently under low shear force.
Drawings
FIG. 1 is a schematic view of the overall structure of the present invention;
FIG. 2 is a schematic view of the structure of a tank of the reactor of the present invention;
FIG. 3 is a schematic left side sectional view of a reactor tank according to the present invention;
FIG. 4 is a schematic right side sectional view of a reactor tank according to the present invention;
fig. 5 is an enlarged schematic view of the structure of the present invention a.
In the figure: 1-glass jar, 2-lower end cover, 3-upper end cover, 4-O-shaped ring mounting groove, 5-O-shaped ring, 6-air inlet hole, 7-air outlet hole, 8-liquid inlet hole, 9-liquid outlet hole, 10-cell sap filling and sampling hole, 11-air filter, 12-silicone tube, 13-vacuum pump, 14-peristaltic pump, 15-CPC aseptic joint.
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 embodiments, and all other embodiments obtained by a person of ordinary skill in the art without creative efforts based on the embodiments of the present invention belong to the protection scope of the present invention.
Referring to fig. 1-5, the present invention provides a technical solution:
the utility model provides a can arrange compact reactor in biological incubator in, including glass jar 1, the outer wall of glass jar 1 and the port that is close to glass jar 1 cup joints lower end cover 2, lower end cover 2 has upper end cover 3 through bolted connection, O type circle mounting groove 4 has been seted up on the 1 terminal surface of glass jar, the internally mounted of O type circle mounting groove 4 has O type circle 5, be provided with inlet port 6 on the terminal surface of upper end cover 3 respectively, exhaust hole 7, inlet 8, liquid outlet 9 and cell liquid filling sample connection 10, be provided with air cleaner 11 on the inlet port 6, connect on vacuum pump 13 through silicone tube 12 on air cleaner 11, liquid outlet 9 passes through silicone tube 12 and connects on peristaltic pump 14, inlet 8 passes through silicone tube 12 and connects on peristaltic pump 14, be connected with CPC aseptic joint 15 on cell liquid filling sample connection 10.
The specific implementation case is as follows:
referring to fig. 2-4, the reactor tank body is composed of a glass tank 1, a lower end cover 2, an upper end cover 3 and an O-ring 5, and the upper end cover 2 and the lower end cover 3 tightly press the O-ring with screws to seal;
referring to fig. 2-4, an air inlet hole 6, an air outlet hole 7, a liquid inlet 8, a liquid outlet 9 and a cell sap filling sampling port 10 are welded on an upper end cover 3 to form a whole, so that the pressure in the tank body can be effectively ensured to be stable, and the gas in the incubator can conveniently enter the tank body of the reactor, so that the DO (dissolved oxygen) and PH (potential of Hydrogen) states of the culture medium are ensured to be stable, the air inlet hole 6 and the air outlet hole 7 are both connected with an air filter 11 to avoid pollution, the air in the incubator is pumped in from the air inlet hole 6 of the tank body of the reactor by the vacuum pump 13 under the action that the air filter 11 is connected with the vacuum pump 13 through a silicone tube 12, the surface layer culture solution in the reactor can directly contact with the uniform gas in the;
referring to fig. 1, a liquid outlet 9 is connected to a peristaltic pump 14 through a silicone tube 12, a liquid inlet 8 is connected to the peristaltic pump 14 through the silicone tube 12, the peristaltic pump 14 is used as a power driving member to drive liquid in the silicone tube 12 to flow, the liquid inlet 8 is directly communicated with the bottom of the reactor tank to effectively suck cell solution in the tank, the bottom of the liquid inlet 8 is processed by slope incision, and the bottom of the liquid outlet 9 is horn-shaped, and functions in that the horn-shaped forms a local diffusion vortex, low-shear stirring is performed through the vortex to avoid cell agglomeration, so that cell diffusion can be effectively discharged, cell agglomeration can be prevented, cell death during culture can be avoided, nutrient components in the culture medium can be effectively used for improving the circulation efficiency, and a certain vertical height and horizontal distance are maintained between the liquid inlet 8 and the liquid outlet 9, under the condition that the culture solution in the reactor circulates once within 1-2min, cells and nutrients can be uniformly distributed in the culture solution in the process of pumping the culture solution;
referring to fig. 1-4, the cell sap filling and sampling port 10 comprises a sampling port and a cell sap filling port, the sampling port and the cell sap filling port are made of the same pipe, the CPC aseptic joint 15 is a joint with a stop valve female head, a liquid path is unblocked by connecting a CPC male head and the CPC female head during sampling, and the liquid path is stopped when the CPC male head and the CPC female head are disconnected, so that the pollution risk is effectively avoided;
to sum up arrange the compact reactor of this scheme inside the incubator in to can provide the environment of stable constant temperature and humidity, N2, 02, CO2 gaseous proportion is even, and this process designs a compact reactor that can arrange in the biological incubator when passing through, reaches following effect: 1) the peristaltic pump pumps liquid to ensure that the liquid in the tank flows mildly and uniformly, the generated shearing force is small, the damage to cells is small, and the growth state of the cells under natural conditions in a living body is simulated; 2) the structure is simple, sealing is facilitated, and the cell product generation cost is effectively optimized; 3) compared with a shake flask, the utility model greatly increases the culture volume and saves the cell culture space; 4) cells and nutrients can be uniformly distributed in the culture solution through the bell-mouth-shaped liquid outlet, the high-density cell culture is not easy to agglomerate, and the efficiency of the cells in the growth process is effectively optimized; 5) a CPC (compound parabolic concentrator) stop valve sterile connector is added, so that liquid adding and sampling are facilitated, and pollution risk is avoided; 6) inside whole device placed the incubator in, can provide the environment of stable constant temperature and humidity, N2, 02, CO2 gaseous proportion is even, removes traditional reactor from and needs supporting expensive and complicated environment maintenance unit, 7) increases the vacuum pump, better with gaseous exchange in reactor glass jar and the incubator, environmental parameters such as DO, PH keep in the culture medium with low-cost high efficiency. .
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 (7)
1. A compact reactor that can be placed inside a biological incubator, comprising a glass jar (1), characterized in that: the glass tank is characterized in that the outer wall of the glass tank (1) is connected with a lower end cover (2) through a port close to the glass tank (1), the lower end cover (2) is connected with an upper end cover (3) through a bolt, an O-shaped ring mounting groove (4) is formed in the end face of the glass tank (1), an O-shaped ring (5) is mounted inside the O-shaped ring mounting groove (4), an air inlet hole (6), an exhaust hole (7), a liquid inlet (8), a liquid outlet (9) and a cell liquid filling sampling port (10) are respectively formed in the end face of the upper end cover (3), an air filter (11) is arranged on the air inlet hole (6), the air filter (11) is connected to a vacuum pump (13) through a silicone tube (12), the liquid outlet (9) is connected to a peristaltic pump (14) through a silicone tube (12), the liquid inlet (8) is connected to the peristaltic, the cell sap filling and sampling port (10) is connected with a CPC sterile connector (15).
2. A compact reactor placeable in a biological incubator according to claim 1, characterized in that: the reaction tank body is composed of the glass tank (1), the lower end cover (2), the upper end cover (3) and the O-shaped ring (5).
3. A compact reactor placeable in a biological incubator according to claim 1, characterized in that: the air inlet hole (6), the exhaust hole (7), the liquid inlet (8), the liquid outlet (9) and the cell sap filling sampling port (10) are respectively welded on the upper end cover (3) and form an integral structure, and the air inlet hole (6), the exhaust hole (7), the liquid inlet (8), the liquid outlet (9) and the cell sap filling sampling port (10) are respectively communicated with the inside of the glass tank (1).
4. A compact reactor placeable in a biological incubator according to claim 1, characterized in that: air filters (11) are arranged on the exhaust holes (7) and the air inlet holes (6).
5. A compact reactor placeable in a biological incubator according to claim 1, characterized in that: the liquid inlet (8) penetrates through the upper end cover (3) and extends to the inside of the glass tank (1), the bottom of the liquid inlet (8) is in contact with the bottom of the inside of the glass tank (1), and the bottom of the liquid inlet (8) is a slope cut.
6. A compact reactor placeable in a biological incubator according to claim 1, characterized in that: the liquid outlet (9) penetrates through the upper end cover (3) and extends into the glass tank (1), and the bottom of the liquid outlet (9) is in a horn shape.
7. A compact reactor placeable in a biological incubator according to claim 1, characterized in that: the cell sap filling and sampling port (10) comprises a sampling port and a cell sap filling port, the sampling port and the cell sap filling port are made of the same pipe, and the CPC sterile joint (15) is made of a joint with a stop valve female head.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011129274.2A CN112430540A (en) | 2020-10-21 | 2020-10-21 | Compact reactor capable of being placed in biological incubator |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011129274.2A CN112430540A (en) | 2020-10-21 | 2020-10-21 | Compact reactor capable of being placed in biological incubator |
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| Publication Number | Publication Date |
|---|---|
| CN112430540A true CN112430540A (en) | 2021-03-02 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011129274.2A Pending CN112430540A (en) | 2020-10-21 | 2020-10-21 | Compact reactor capable of being placed in biological incubator |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116676192A (en) * | 2023-06-07 | 2023-09-01 | 上海多宁生物科技股份有限公司 | Bioreactor convenient for extracting and supplementing materials and used for CHO cell culture and method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011172533A (en) * | 2010-02-25 | 2011-09-08 | Fusao Komada | Method for three-dimensional high-density cell culture using microspace structure |
| CN106282015A (en) * | 2016-09-27 | 2017-01-04 | 惠倪 | Systemic circulation fluid bed bioreactor and the method cultivating zooblast |
| CN106635797A (en) * | 2017-03-15 | 2017-05-10 | 上海戈洛思生物科技有限公司 | Bioreactor |
| US20170204358A1 (en) * | 2014-04-04 | 2017-07-20 | Synthecon, Inc. | Bioreactor system for stem cell expansion |
| WO2017152343A1 (en) * | 2016-03-07 | 2017-09-14 | 浙江大学 | Recirculating perfusion bioreactor device that can realize three-dimensional scaffold recirculating perfusion |
| US20180030398A1 (en) * | 2015-02-09 | 2018-02-01 | Univercells Nv | System, apparatus and method for the production of cells and/or cell products |
-
2020
- 2020-10-21 CN CN202011129274.2A patent/CN112430540A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011172533A (en) * | 2010-02-25 | 2011-09-08 | Fusao Komada | Method for three-dimensional high-density cell culture using microspace structure |
| US20170204358A1 (en) * | 2014-04-04 | 2017-07-20 | Synthecon, Inc. | Bioreactor system for stem cell expansion |
| US20180030398A1 (en) * | 2015-02-09 | 2018-02-01 | Univercells Nv | System, apparatus and method for the production of cells and/or cell products |
| WO2017152343A1 (en) * | 2016-03-07 | 2017-09-14 | 浙江大学 | Recirculating perfusion bioreactor device that can realize three-dimensional scaffold recirculating perfusion |
| CN106282015A (en) * | 2016-09-27 | 2017-01-04 | 惠倪 | Systemic circulation fluid bed bioreactor and the method cultivating zooblast |
| CN106635797A (en) * | 2017-03-15 | 2017-05-10 | 上海戈洛思生物科技有限公司 | Bioreactor |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116676192A (en) * | 2023-06-07 | 2023-09-01 | 上海多宁生物科技股份有限公司 | Bioreactor convenient for extracting and supplementing materials and used for CHO cell culture and method thereof |
| CN116676192B (en) * | 2023-06-07 | 2023-11-14 | 上海多宁生物科技股份有限公司 | Bioreactor convenient for extracting and supplementing materials and used for CHO cell culture and method thereof |
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