CN202297606U - Stirring, aerating and cell filtering integrated bioreactor - Google Patents
Stirring, aerating and cell filtering integrated bioreactor Download PDFInfo
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- CN202297606U CN202297606U CN 201120331457 CN201120331457U CN202297606U CN 202297606 U CN202297606 U CN 202297606U CN 201120331457 CN201120331457 CN 201120331457 CN 201120331457 U CN201120331457 U CN 201120331457U CN 202297606 U CN202297606 U CN 202297606U
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- 238000003756 stirring Methods 0.000 title claims abstract description 55
- 238000001914 filtration Methods 0.000 title claims abstract description 30
- 238000004113 cell culture Methods 0.000 claims abstract description 21
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- 239000007788 liquid Substances 0.000 claims description 30
- 238000009423 ventilation Methods 0.000 claims description 24
- 238000009826 distribution Methods 0.000 claims description 15
- 229910001220 stainless steel Inorganic materials 0.000 claims description 10
- 239000010935 stainless steel Substances 0.000 claims description 10
- 238000003466 welding Methods 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 abstract description 43
- 238000000034 method Methods 0.000 abstract description 9
- 230000008569 process Effects 0.000 abstract description 8
- 238000004114 suspension culture Methods 0.000 abstract description 8
- 230000006378 damage Effects 0.000 abstract description 7
- 210000004102 animal cell Anatomy 0.000 abstract description 6
- 230000008859 change Effects 0.000 abstract description 5
- 238000004140 cleaning Methods 0.000 abstract description 5
- 230000029087 digestion Effects 0.000 abstract description 5
- 230000001954 sterilising effect Effects 0.000 abstract description 4
- 238000004659 sterilization and disinfection Methods 0.000 abstract description 4
- 238000005273 aeration Methods 0.000 abstract 3
- 238000011112 process operation Methods 0.000 abstract 1
- 239000007789 gas Substances 0.000 description 20
- 235000015097 nutrients Nutrition 0.000 description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
- 239000001301 oxygen Substances 0.000 description 9
- 229910052760 oxygen Inorganic materials 0.000 description 9
- 239000012228 culture supernatant Substances 0.000 description 8
- 238000011534 incubation Methods 0.000 description 5
- 238000012258 culturing Methods 0.000 description 4
- 230000010412 perfusion Effects 0.000 description 4
- 238000010008 shearing Methods 0.000 description 4
- 239000012737 fresh medium Substances 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 229920001296 polysiloxane Polymers 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- 238000011017 operating method Methods 0.000 description 2
- 230000002572 peristaltic effect Effects 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 241001135989 Porcine reproductive and respiratory syndrome virus Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000006052 feed supplement Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000005475 siliconizing Methods 0.000 description 1
- 229910000679 solder Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
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- 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
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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
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/34—Internal compartments or partitions
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- 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
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/38—Caps; Covers; Plugs; Pouring means
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- 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
- C12M33/14—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus with filters, sieves or membranes
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Abstract
本实用新型涉及一种适用于动物细胞的自悬浮培养或者是微载体悬浮培养的生物反应器。为了找到一种搅拌、通气及细胞过滤一体化生物反应器，从而消除搅拌式生物反应器中搅拌桨和深层通气对所培养的动物细胞造成的剪切伤害，同时无需外接设备，就可以方便的完成培养过程中的换液、清洗、消化。本实用新型公开了一种搅拌、通气及细胞过滤一体化生物反应器，包括反应容器、反应器顶盖、反应器搅拌轴，还包括有一个带孔过滤套筒，所述过滤套管悬置于反应容器中，将反应容器区分为搅拌、通气、过滤一体化腔室及细胞培养腔室。从而将搅拌、通气及培养物过滤三方面工艺操作合为一体，且位于生物反应器内部，统一整体灭菌，无外接设备，操作简单，安全高效。
The utility model relates to a bioreactor suitable for self-suspension culture of animal cells or microcarrier suspension culture. In order to find a bioreactor integrated with stirring, aeration and cell filtration, so as to eliminate the shear damage caused by the stirring paddle and deep aeration in the stirred bioreactor to the cultured animal cells, and without external equipment, it can be conveniently Complete the medium change, cleaning, and digestion during the cultivation process. The utility model discloses a bioreactor integrated with stirring, ventilating and cell filtration, which comprises a reaction vessel, a top cover of the reactor, a stirring shaft of the reactor, and a filter sleeve with holes, and the filter sleeve is suspended In the reaction vessel, the reaction vessel is divided into a stirring, ventilating and filtering integrated chamber and a cell culture chamber. In this way, the three process operations of stirring, aeration and culture filtration are integrated, and it is located inside the bioreactor for unified overall sterilization, no external equipment, simple operation, safe and efficient.
Description
Technical field
The present invention relates to zooblast bio-reactor engineering, relate in particular to a kind of bio-reactor that is applicable to zooblast from suspension culture or microcarrier suspension culture.
Background technology
At present; Mostly the reactor drum that is used for the animal cell large-scale cultivation is the mechanical agitation type bio-reactor; The production technique of FDA approval also basically all is that batch-type, the stream of stirring reactor adds formula, filling type culture process, is the mainstream technology that current animal cell large-scale is cultivated and biomedical product is produced.Stirring reactor is through stir distribution nutrition, gas (oxygen etc.) and the heat of continuing of stirring rake, for zooblast provides metastable growing environment.
But still there are some shortcomings in stirring type bioreactor in actual motion:
1) in the culturing process, the agitating vane of continued running has the shearing force damage that can not eliminate to institute's cultured animals cell, and general rotating speed is big more, and the shearing force damage is big more.Along with the raising of cell density, organism may directly cause cell because of the high shear mass mortality to the increase in demand of oxygen thereby use the strategy that improves mixing speed raising oxygen transfer rate.
2) air, oxygen and carbonic acid gas are being regulated dissolved oxygen and two important parameters of pH in the animal cell culture process.The dissolving of gas in nutrient solution needs stirring rake to carry out effective dispersed with stirring, increases the conduction surface (air pocket breaks and is dispersed into some small bubbles) of gas and liquid.But each bubble breaking, disperseing in the traveling process in nutrient solution can be caused irreversible injury to the zooblast of initial incubation.
3) be accompanied by technological operations such as changing liquid, cleaning, digestion, perfusion in the animal cell large-scale culturing process usually; Two kinds of operating method are arranged at present: 1. adopt a jar interior spin-filter to remove culture supernatant; But the minimum operation excessive height of spin-filter; Change liquid measure and be merely and cultivate 1/3～1/2 of TV, it is not thorough to change liquid, operations such as subsequently cleaning of influence, digestion.The operating altitude of spin-filter will directly restrict the volume of perfusion culture and cultivate usefulness simultaneously.2. adopt external equipment; Like the outer cell retention device of jar, sound wave cell retention device or the like; With culture with nutrient solution takes out in the lump and under the effect of relevant device, hold back culture (cell or the long microcarrier that cell is arranged); Culture supernatant is removed, and in blowback jar, can continuously carry out again by this process for culture.But these equipment mostly belong to the high-end product of overseas enterprise, and price is extremely expensive.And these equipment are external equipments of reactor drum, transmit operation and more or less all have Pollution risk.
This shows; Develop a kind of can effectively reducing and stir the damage of breaking of shearing force, bubble; Can guarantee simultaneously required nutrition, gas, the heat uniform distribution of cell growth again, and it is imperative to have an integrated apparatus of effective isolated cell culture and culture supernatant.
Summary of the invention
The purpose of this invention is to provide a kind of stirring, ventilation and cell filtration integrated bioreactor; Thereby the shearing injury that stirring rake and deep ventilation cause institute's cultured animals cell in the elimination stirring type bioreactor; This bio-reactor also need possess the filtering function of culture (microcarrier/cell) simultaneously; Need not external equipment; Just can accomplish easily and change liquid, cleaning, digestion in the culturing process, thereby be adapted to that feed supplement is cultivated, circulation is cultivated and technological operations such as perfusion culture, safe and reliable.
In order to realize the object of the invention; The invention discloses a kind of stirring, ventilation and cell filtration integrated bioreactor, comprise reaction vessel, reactor head, reactor drum stir shaft, also include a perforated filter sleeve; Its aperture is less than actual culture; Said filter sleeve inwall is fixed with the gas distribution tube and the liquid flowing tube of band sparger, and is installed on reactor head through gas distribution tube and liquid flowing tube, and said reactor drum stir shaft is positioned at and filters the sleeve pipe axis; Said filtration sleeve pipe is suspended in the reaction vessel, and reaction vessel is divided into stirring, ventilation, filtering integral chamber and cell cultures chamber.Specifically, filter sleeve is installed on the top cover of stirring type bioreactor through gas distribution tube and liquid flowing tube, gets final product with fixing gas distribution tube and the liquid flowing tube that sees through top cover of threaded screw.Wherein gas distribution tube is used for feeding aseptic gas to nutrient solution, and liquid flowing tube is used to connect silicone tube and pipettes the nutrient solution that does not contain culture.Other chamber is meant and is positioned at filter sleeve inner stirring, ventilation, filtering integral chamber, and is positioned at the cell cultures chamber between reactor wall and filter sleeve.Utilize this device that mechanical stirring oar, deep ventilation are separated with cell culture, can effectively reduce the damage of agitating vane and bubble pair cell culture in the culturing process.The stainless steel filter sleeve possesses filtering function simultaneously; Its inner liquid flowing tube only pipettes nutrient solution when getting liquid; And cell culture still is retained in the cell cultures chamber; Fast and effectively nutrient solution and culture are separated, be reduced at operating procedures such as changing liquid, cleaning, digestion, feeding culture, circulation cultivation, perfusion culture in the bio-reactor greatly.
Because reaction vessel is divided into stirring, ventilation, filtering integral chamber and cell cultures chamber; Receive the restriction in aperture on the filter sleeve so must guarantee cell or the carrier cultivated therein, can not in two chambers, move freely, so the aperture is less than actual culture; Microcarrier suspension culture for zooblast; The aperture is typically chosen in about 100 μ m, for zooblast from suspension culture, the aperture is typically chosen in 10 μ m～15 μ m.
Owing to the diameter ratio of filter sleeve with reaction vessel; Directly have influence on the space size of cell cultures chamber; So the invention discloses reaction vessel and filter sleeve diameter than being the technical scheme of 2:1 ~ 3:1, thereby guarantee that the space size of cell cultures chamber can satisfy the cultivation value-added speed of cell.
Simultaneously, the present invention also further discloses said filter sleeve apart from reaction vessel bottom 3 ~ 5cm, makes the cell cultures chamber still be one and is communicated with cavity, can be divided into two independent culture space by the filter sleeve that the centre adds.
As further improvement, the invention discloses said reactor drum stir shaft two or more stirring rake is installed, thereby form axial flow and radial flow, realize the annularly flow up and down of liquid.
As a kind of optimal way of stirring rake, the invention discloses said reactor drum stir shaft turbine propulsion oar and in line six leaf oars are installed simultaneously, thereby help the formation of axial flow and radial flow more, annularly flow property up and down is better.
Simultaneously, the present invention also further discloses the optimal way of sparger, and said sparger is circle distributor or microvesicle sparger.
Because gas distribution tube and liquid flowing tube itself play the fixed action to filter sleeve; So the invention also discloses the technical scheme that said gas distribution tube and liquid flowing tube are symmetrically fixed on the filter sleeve inwall; Just make that so fixing of filter sleeve is more reasonable; Bed knife is more even, and the hub of filter sleeve also is mapped with the physics axis, and product is more stable at work.
Preferred as a kind of fixed form the invention discloses said gas distribution tube and the filter sleeve inwall is fixed in liquid flowing tube spot welding, and be not only fixed, and solder joint is little, and the influence that pair cell is cultivated is little.
The invention discloses a kind of preferred material of filter sleeve at last, said filter sleeve is a stainless steel, more preferably the stainless steel of 316L label.Make that whole device is more ageing-resistant, corrosion-resistant, in order further to improve this performance, can also carry out siliconizing certainly on the surface of device.
In sum, adopt technical scheme disclosed by the invention after, can stirring, ventilation and culture be filtered three aspect technological operations and be integrated, and be positioned at bio-reactor inside, unified whole sterilization, no external equipment, simple to operate, safe and efficient.
Description of drawings
Fig. 1 stirring, ventilation and cell filtration integrated bioreactor synoptic diagram;
Wherein 1 is gas distributor tube, and 2 is liquid flowing tube, and 3 is reactor head, and 4 is the reactor drum stir shaft; 5 is filter sleeve, and 6 are stirring, ventilation, filtering integral chamber, and 7 is the cell cultures chamber; 8 is reaction vessel, and 9 is in line six leaf oars, and 10 are the turbine propulsion oar.
Embodiment
Below in conjunction with description of drawings embodiment of the present invention.But what need specifically note is, only the following specifically describes for the purpose of description, should not be taken the qualification to the scope of the invention.According to description of the invention, the change mode of the equivalence that the professional and technical personnel derives ought to be encompassed within the scope of the present invention.
Embodiment 1
, in suspension culture, single unit system disclosed by the invention is installed in the 5L zooblast reaction vessel 8 at BHK21, as shown in Figure 1; Stainless steel filter sleeve 5 highly is 32cm; Diameter is 6cm, is installed on reactor head 3 times, and gas distributor tube 1 is passed through top cover with liquid flowing tube 2; Fixing with threaded screw and reactor head 3, guarantee that the hub of filter sleeve 5 overlaps with reactor drum stir shaft 4 fully.The pore size filter of stainless steel filter sleeve 5 is selected 10 μ m for use, guarantees to hold back the BHK21 cell of single suspension growth.Single unit system is with the whole simultaneously sterilization of reaction vessel 8, and cooling and aseptic detection back pressurize are for use.
When cultivating beginning, the BHK21 seed cell is with every milliliter 3.5 * 10
5The density of individual cell is inoculated in the cell cultures chamber 7, and adds nutrient solution, and maximum volume of culture is 3.8L.The liquid level of nutrient solution is lower than the top of stainless steel filter sleeve 5 all the time; Promptly this device effectively with the BHK21 cell retention in cell cultures chamber 7, culture parameters pH is set at 7.2, DO is set at 40%, to be set at 37 ℃, speed setting be 35～55rpm to temperature.Along with the rotation of reactor drum stir shaft 4, the turbine propulsion oar 10 and the in line six leaf oars 9 that are mounted thereon rotate together, form transverse flow and radial flow, thereby have formed annularly flow system up and down.Along with the passing of incubation time, cell density progressively raises.Cultivate that cell density reaches every milliliter 1.1 * 10 after 3 days
6Individual cell, the metabolic by-prods lactic acid concn that detects in the culture supernatant is 15.7mmol/L, ammonia concentration is 4.9mmol/L, changes the liquid operation.Act on the silicone tube that be connected liquid flowing tube 2 on peristaltic pump this moment, directly from stirring, ventilation, the integrated chamber 6 of filtering chamber, fully draws culture supernatant, and the culture supernatant volume of removal is roughly 3.0～3.5L.Adding fresh medium continues to cultivate.Further rising along with cell density; Can suitably improve the cultivation rotating speed, progressively be increased to 60rpm, even can reach 75rpm from 35rpm; Thereby the gas (comprising air and oxygen) that fully disperses release from gas distribution pipeline 1; And diffuse to again in the cell cultures chamber 7 through filter sleeve 5, effectively improved oxygen supply speed, help the further raising of cell density and keep higher cell viability.Through repeating the above-mentioned liquid operation of changing, the maximum cell density of final BHK21 can reach every milliliter 4.8 * 10
6Individual cell, cell survival rate is higher than 95%, and culture cycle can extend to 9 days.
Embodiment 2
In the Marc-145 cell microcarrier suspension culture, in single unit system installation disclosed by the invention and 5L zooblast reactor drum 8, as shown in Figure 1; Device highly is 32cm; Assembly dia is 6cm, is installed on reactor head 3 times, and gas distributor tube 1 is passed through top cover with liquid flowing tube 2; Fix with threaded screw and top cover, guarantee that the hub of this device overlaps with reactor drum mixing center axle 4 fully.The pore size filter of stainless steel filter sleeve 5 is selected 120um for use, guarantees to hold back microcarrier culture (adhering to the Marc-145 cell of growth on microcarrier cytodex1 and the microcarrier).All device is followed the whole simultaneously sterilization of reactor drum, and cooling and aseptic detection back pressurize are for use.
When cultivating beginning, the Marc-145 seed cell is with every milliliter 3 * 10
5The cytodex1 that the density of individual cell and pre-treatment finish (working concentration is 5g/L) is inoculated in the cell cultures chamber 7, and adds nutrient solution, and the initial incubation volume is 1.5L.Initial incubation parameter p H is set at 7.2, DO is set at 40%, to be set at 37 ℃, speed setting be 30pm to temperature; Rotation along with reactor drum stir shaft 4; The turbine propulsion oar 10 and the in line six leaf oars 9 that are mounted thereon rotate together; Form transverse flow and radial flow, thereby formed annularly flow system up and down.After the initial incubation 12 hours; Suitably increase the nutrient solution volume; But the liquid level of nutrient solution is lower than the top of stainless steel filter sleeve 5 all the time; Promptly this device effectively is trapped in the microcarrier culture of Marc-145 cell in the cell cultures chamber 7, continue to cultivate, and parameter p H is set at 7.2, DO is set at 40%, to be set at 37 ℃, speed setting be 45～65rpm to temperature.Cultivate after 24 hours, the adhesion situation of Marc-145 cell on the microcarrier is observed in sampling, accounts for the ball rate and reaches more than 95% basically.Beginning to carry out circumfusion immediately cultivates; Act on the silicone tube that is connected on the liquid flowing tube 2 with peristaltic pump and directly from stirring, ventilation, the integrated chamber 6 of filtering chamber, draw culture supernatant with certain speed this moment, adds fresh medium with identical speed simultaneously.Along with the further rising of cell density, can suitably improve the speed of drawing culture supernatant and adding fresh medium, i.e. circumfusion speed is to satisfy the needs of cell to nutritive substance.Cultivate rotating speed and progressively be increased to 75rpm from 35rpm; The gas (air and oxygen) that can fully disperse release from gas distribution pipeline 1; And diffuse to again in the cell cultures chamber 7 through filter sleeve 5; Effectively improved oxygen supply speed, helped the further raising of cell density and keep higher cell viability.Through repeating the operation of above-mentioned circumfusion, the Marc-145 cell has promptly reached every milliliter 5.4 * 10 of maximum cell density cultivating in 5 days
6Individual cell, cell survival rate is higher than 95%, can be used for the propagation of high-pathogenicity porcine reproductive and respiratory syndrome virus.
Claims (10)
1. stirring, ventilation and cell filtration integrated bioreactor; Comprise reaction vessel, reactor head, reactor drum stir shaft; It is characterized in that: also include a perforated filter sleeve, its aperture is less than actual culture, and said filter sleeve inwall is fixed with the gas distribution tube and the liquid flowing tube of band sparger; And be installed on reactor head through gas distribution tube and liquid flowing tube; Said reactor drum stir shaft is positioned at and filters the sleeve pipe axis, and said filtration sleeve pipe is suspended in the reaction vessel, and reaction vessel is divided into stirring, ventilation, filtering integral chamber and cell cultures chamber.
2. stirring according to claim 1, ventilation and cell filtration integrated bioreactor is characterized in that: said reaction vessel is 2:1 ~ 3:1 with filter sleeve diameter ratio.
3. stirring according to claim 1 and 2, ventilation and cell filtration integrated bioreactor is characterized in that: said filter sleeve is apart from reaction vessel bottom 3 ~ 5cm.
4. stirring according to claim 1, ventilation and cell filtration integrated bioreactor is characterized in that: said reactor drum stir shaft is equipped with two or more stirring rake.
5. stirring according to claim 4, ventilation and cell filtration integrated bioreactor is characterized in that: said reactor drum stir shaft is equipped with turbine propulsion oar and in line six leaf oars simultaneously.
6. stirring according to claim 1, ventilation and cell filtration integrated bioreactor is characterized in that: said sparger is circle distributor or microvesicle sparger.
7. stirring according to claim 1, ventilation and cell filtration integrated bioreactor is characterized in that: said gas distribution tube and liquid flowing tube are symmetrically fixed on the filter sleeve inwall.
8. according to claim 1 or 7 described stirrings, ventilation and cell filtration integrated bioreactor, it is characterized in that: the filter sleeve inwall is fixed in said gas distribution tube and liquid flowing tube spot welding.
9. stirring according to claim 1, ventilation and cell filtration integrated bioreactor is characterized in that: said filter sleeve is a stainless steel.
10. stirring according to claim 9, ventilation and cell filtration integrated bioreactor is characterized in that: said filter sleeve is the stainless steel of 316L label more preferably.
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| CN 201120331457 CN202297606U (en) | 2011-09-06 | 2011-09-06 | Stirring, aerating and cell filtering integrated bioreactor |
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Cited By (6)
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| CN106834099A (en) * | 2017-03-29 | 2017-06-13 | 江苏丰泽生物工程设备制造有限公司 | Bioreactor low sheraing hoisting type aeration mixing device |
| CN107603870A (en) * | 2017-11-10 | 2018-01-19 | 上海保兴生物设备工程有限公司 | A kind of digestion filter for micro-carriers cell culture |
| CN107974399A (en) * | 2017-12-27 | 2018-05-01 | 北京科兴生物制品有限公司 | A kind of cell dissociation device |
| CN108441407A (en) * | 2018-04-02 | 2018-08-24 | 天晴干细胞股份有限公司 | Automatic cell purification and cryopreservation device |
| CN108660070A (en) * | 2018-06-27 | 2018-10-16 | 昆山奕盛来环境科技有限公司 | A kind of vertical type columnar microorganism reactor |
| CN115895887A (en) * | 2022-12-13 | 2023-04-04 | 成都康华生物制品股份有限公司 | Influenza vaccine production device and method and influenza vaccine |
-
2011
- 2011-09-06 CN CN 201120331457 patent/CN202297606U/en not_active Expired - Lifetime
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106834099A (en) * | 2017-03-29 | 2017-06-13 | 江苏丰泽生物工程设备制造有限公司 | Bioreactor low sheraing hoisting type aeration mixing device |
| CN107603870A (en) * | 2017-11-10 | 2018-01-19 | 上海保兴生物设备工程有限公司 | A kind of digestion filter for micro-carriers cell culture |
| CN107603870B (en) * | 2017-11-10 | 2023-06-02 | 上海保兴生物设备工程有限公司 | Digestion and filtration device for microcarrier cell culture |
| CN107974399A (en) * | 2017-12-27 | 2018-05-01 | 北京科兴生物制品有限公司 | A kind of cell dissociation device |
| CN108441407A (en) * | 2018-04-02 | 2018-08-24 | 天晴干细胞股份有限公司 | Automatic cell purification and cryopreservation device |
| CN108660070A (en) * | 2018-06-27 | 2018-10-16 | 昆山奕盛来环境科技有限公司 | A kind of vertical type columnar microorganism reactor |
| CN115895887A (en) * | 2022-12-13 | 2023-04-04 | 成都康华生物制品股份有限公司 | Influenza vaccine production device and method and influenza vaccine |
| CN115895887B (en) * | 2022-12-13 | 2023-06-02 | 成都康华生物制品股份有限公司 | Influenza vaccine production device and method and influenza vaccine |
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