CN108048323A - A kind of bioreactor mends alkali device and method - Google Patents
A kind of bioreactor mends alkali device and method Download PDFInfo
- Publication number
- CN108048323A CN108048323A CN201810073816.5A CN201810073816A CN108048323A CN 108048323 A CN108048323 A CN 108048323A CN 201810073816 A CN201810073816 A CN 201810073816A CN 108048323 A CN108048323 A CN 108048323A
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- lye
- agitating
- alkali
- bioreactor
- agitating paddle
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- 239000003513 alkali Substances 0.000 title claims abstract description 43
- 238000000034 method Methods 0.000 title claims abstract description 17
- 238000003756 stirring Methods 0.000 claims abstract description 11
- 239000007788 liquid Substances 0.000 claims description 14
- 239000000243 solution Substances 0.000 claims description 14
- 239000013589 supplement Substances 0.000 claims description 14
- 239000007921 spray Substances 0.000 claims description 4
- 239000012530 fluid Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 17
- 229910052760 oxygen Inorganic materials 0.000 abstract description 17
- 239000001301 oxygen Substances 0.000 abstract description 17
- 238000004113 cell culture Methods 0.000 abstract description 6
- 230000006378 damage Effects 0.000 abstract description 4
- 230000030833 cell death Effects 0.000 abstract description 3
- 210000004102 animal cell Anatomy 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 8
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 8
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
- 238000013019 agitation Methods 0.000 description 5
- 230000008901 benefit Effects 0.000 description 4
- 239000004310 lactic acid Substances 0.000 description 4
- 235000014655 lactic acid Nutrition 0.000 description 4
- 239000002699 waste material Substances 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 239000012930 cell culture fluid Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000000739 chaotic effect Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000790917 Dioxys <bee> Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000007667 floating Methods 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
- C12M21/00—Bioreactors or fermenters specially adapted for specific uses
- C12M21/08—Bioreactors or fermenters specially adapted for specific uses for producing artificial tissue or for ex-vivo cultivation of tissue
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Sustainable Development (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The present invention relates to animal cell culture technology fields, and alkali device and method are mended in particular to a kind of bioreactor；The equipment includes tank body；The tank interior is provided with agitating device；Lye injector head is provided with above the tank skin of the tank body, the lye injector head is connected by valve with storage alkali container.The present invention is by using the lye additional way of pulsed, the agitating device and baffle especially set of arranging in pairs or groups, the generation of turbulent flow, quick mixing lye when can effectively reduce stirring, so as to reduce the cell death caused by mechanical damage and local concentration of lye are excessively high.In addition, surprisingly, unique agitating paddle rotation mode can also extend the residence time of oxygen, so as to effectively reduce the consumption of oxygen.
Description
Technical field
The present invention relates to animal cell culture technology field, in particular to a kind of bioreactor mend alkali equipment and
Method.
Background technology
Cell culture starts from the beginning of this century, starts to expand to scale in 1962, and being developed so far has become in biology, medicine
Widely used technology in research and application utilizes enzyme, growth factor, vaccine of the cell culture production with important medical value
With monoclonal antibody etc., have become the pith of medical biotechnology industry.
The accumulation of metabolic waste is cytostatic principal element in cellular environment, these metabolic wastes include dioxy
Change carbon, lactic acid and ammonia.Wherein, carbon dioxide and lactic acid are most important acidic metabolic wastes in culture medium, with cell culture
The increase of scale and density, carbon dioxide and lactic acid are built up in cell culture medium, and the normal physiological function of cell is produced
It is raw to inhibit even toxic action.
In the prior art mainly by adding alkaline matter (such as NaHCO into cell culture fluid3Solution) it neutralizes
Lactic acid is added in tank (as shown in Figure 1) using the method that no pressure is added dropwise along tank skin stream.This fed-batch mode is not only slow, but also
It cannot rapidly dissolve and come after being added drop-wise in tank, and cause the cell total loss of lye surrounding and dead, the waste of lye
Also it is very big.
In view of this, it is special to propose the present invention.
The content of the invention
The present invention relates to a kind of bioreactors to mend alkali equipment, including tank body；
The tank interior is provided with agitating device；
Lye injector head is provided with above the tank skin of the tank body, the lye injector head is by valve with storing up alkali container phase
Even.
Device provided by the present invention can ensure that the stirring of lye prestissimo is opened, so as to reduce the death toll of cell
Amount.
The invention further relates to a kind of bioreactor alkali supplement methods, carry out mending alkali operation using equipment as described above
When, it is intermittent to open the valve so that the lye injector head pulsed sprays lye, open simultaneously the agitating device with
So that mixing is complete rapidly for the lye of supplement.
Description of the drawings
It, below will be to specific in order to illustrate more clearly of the specific embodiment of the invention or technical solution of the prior art
Embodiment or attached drawing needed to be used in the description of the prior art are briefly described, it should be apparent that, in describing below
Attached drawing is some embodiments of the present invention, for those of ordinary skill in the art, before not making the creative labor
It puts, can also be obtained according to these attached drawings other attached drawings.
Fig. 1 is the benefit alkali equipment principle schematic diagram of the prior art；
Fig. 2 is benefit alkali equipment principle schematic diagram of the present invention；
Fig. 3 is the structure diagram of the benefit alkali equipment employed in one embodiment of the invention；
Fig. 4 is the schematic top plan view of the benefit alkali equipment employed in one embodiment of the invention.
Reference numeral：
Tank body A；
Microvesicle air-breather 1
Agitating device 2；Agitating shaft 201；Agitating paddle 202；
Power set 3；
Baffle 4；
Lye injector head 5；Valve 501.
Specific embodiment
Technical scheme is clearly and completely described below in conjunction with the drawings and specific embodiments, but
It is it will be understood to those of skill in the art that following described embodiment is part of the embodiment of the present invention rather than whole
Embodiment is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.Based on the embodiments of the present invention, ability
Domain those of ordinary skill all other embodiments obtained without making creative work, belong to guarantor of the present invention
The scope of shield.The person that is not specified actual conditions in embodiment, the condition suggested according to normal condition or manufacturer carry out.Agents useful for same
Or production firm person is not specified in instrument, is the conventional products that can be obtained by commercially available purchase.
In the description of the present invention, it is necessary to explanation, term " " center ", " on ", " under ", "left", "right", " vertical ",
The orientation or position relationship of the instructions such as " level ", " interior ", " outer " be based on orientation shown in the drawings or position relationship, merely to
Convenient for the description present invention and simplify description rather than instruction or imply signified device or element must have specific orientation,
With specific azimuth configuration and operation, therefore it is not considered as limiting the invention.In addition, term " first ", " second ",
" the 3rd " is only used for description purpose, and it is not intended that instruction or hint relative importance.
In the description of the present invention, it is necessary to illustrate, unless otherwise clearly defined and limited, term " installation ", " phase
Even ", " connection " should be interpreted broadly, for example, it may be being fixedly connected or being detachably connected or be integrally connected；It can
To be mechanical connection or be electrically connected；It can be directly connected, can also be indirectly connected by intermediary, Ke Yishi
Connection inside two elements.For the ordinary skill in the art, with concrete condition above-mentioned term can be understood at this
Concrete meaning in invention.
The present invention relates to a kind of bioreactors to mend alkali equipment, as shown in figure 3, the equipment includes tank body A；
The tank body A is internally provided with agitating device 2；
Lye injector head 5 is provided with above the tank skin of the tank body A, the lye injector head 5 passes through valve 501 and storage alkali
Container is connected.
The principle of the equipment is as shown in Fig. 2, lye is spurted into the culture medium of tank body with pulsed by lye injector head 5
It is interior, quickly stirred and evenly mixed in agitating device 2, can to avoid local pH it is excessively high caused by cellular damage.
Preferably, the bioreactor is mended in alkali equipment and is additionally provided with pH meter.
Preferably, bioreactor as described above mends alkali equipment, and the 5 front end endoporus aperture of lye injector head is 1mm
~3mm；More preferably 2mm.
Preferably, bioreactor as described above mends alkali equipment, and the agitating device 2 includes agitating shaft 201 and stirring
Paddle 202；
The agitating shaft 201 is perpendicular to horizontal plane and is fixed on tank bottom, and the agitating paddle 202 is arranged at the agitating shaft
On 201, the bottom of the agitating shaft 201 is connected with power set 3；
Preferably, the equipment further includes microvesicle air-breather 1, and the microvesicle air-breather 1 is arranged at the agitating paddle
202 underface.
Microvesicle air-breather 1 can be commercial product in the present invention, can be to cell oxygen supply/CO2.
Preferably, bioreactor as described above mends alkali equipment, and there are three the agitating paddles 202, from the agitating shaft
From top to bottom it is followed successively by the first agitating paddle, the second agitating paddle and the 3rd agitating paddle；The second agitating paddle agitated liquid is by upper
It moves downward；The first and third agitating paddle agitated liquid moves from bottom to top；
By above-mentioned set-up mode, the oxygen discharged in microvesicle air-breather 1 can be confined between first and third agitating paddle
(it is considered that spiral liquid stream is formd between three agitating paddles), it is resident in culture solution so as to extend bubbles of oxygen
Time increases the utilization rate of oxygen.
Preferably, the agitating paddle 202 is turbine type agitating paddle or pusher agitating paddle；
It is furthermore preferred that the agitating paddle 202 is four leaf push type agitating paddles.
Preferably, the rake angle degree of the agitating paddle is 40 °~60 °；More preferably 50 °；Since each agitating paddle makes
The direction of motion of liquid stream is different, thus the preferably deflection of the deflection angle of second agitating paddle and first and third agitating paddle
Angle mirror symmetry.
Preferably, the ratio of the paddle footpath of the agitating paddle and tank diameter is 0.2~0.7, more preferably 0.3~0.5.
Preferably, the rotating speed of the agitating paddle is 30~70rpm.
Preferably, bioreactor as described above mends alkali equipment, and baffle 4 is additionally provided with inside the tank skin of the tank body,
The baffle 4 is perpendicular to horizontal plane；
Preferably, the baffle 4 has 3~5, more preferably 4, and be uniformly distributed on the tank skin of the tank body；
Preferably, as shown in figure 4, the baffle 4 deviate its with 30 ° of Grain lines where the tank body A tie points~
40 °, and each baffle deflection direction is consistent；
Preferably, the width of the baffle is 1/13~1/10 tank diameter.
It is furthermore preferred that each baffle deflection direction is consistent with the direction of rotation of agitating paddle；Such as the direction of rotation of agitating paddle is
Counterclockwise, then the deflection direction of the baffle 4 just as shown in figure 4, being deflected in obtuse angle along current counterclockwise.
Due to second agitating paddle and first and third agitating paddle by the direction of aqueous agitation on the contrary, culture solution into
During row agitation liquid flow direction can than three agitating paddles equidirectional (upwards agitation) it is more chaotic, therefore, this agitation mode
Although dissolved oxygen amount can be greatly increased, it is also easier to, because the chaotic impact of liquid stream forms turbulent flow, in turn result in cell and break simultaneously
Broken death.Based on this reason, the present invention is provided with baffle 4, and its deflection angle is consistent with the direction of rotation of agitating paddle, baffle 4
Can play the role of water conservancy diversion, due to cell culture fluid bioreactor to close at tank skin flow velocity maximum, thus on tank skin
Baffle 4 can slow down flow rate of liquid, guiding liquid flow direction, and then effectively avoid the generation of turbulent flow herein.
The invention further relates to a kind of bioreactor alkali supplement methods, carry out mending alkali operation using equipment as described above
When, it is intermittent to open the valve 501 so that 5 pulsed of lye injector head sprays lye, opens simultaneously the stirring dress
2 are put so that the lye of supplement mixes rapidly completely.
Preferably, the tank body A is 3000L~6000L volumes；
Preferably, bioreactor alkali supplement method as described above, the lye are 0.8mol/L~1.2mol/L's
NaHCO3Solution；The more preferably NaHCO of 1mol/L3Solution.
Preferably, bioreactor alkali supplement method as described above, the valve 501 open one at interval of 4.5s~5.5s
It is secondary, 50ms~200ms is opened every time；It is furthermore preferred that the valve 501 at interval of 5s open once, every time open 100ms~
150ms。
Preferably, bioreactor alkali supplement method as described above, when spraying lye, the liquid in the lye injector head 5
Body pressure is 0.08MPa~0.12MPa；It is furthermore preferred that the fluid pressure in the lye injector head 5 is 0.10MPa.
Preferably, bioreactor alkali supplement method as described above, when carrying out mending alkali operation, the agitating device 2
Rotating speed is 30rpm~70rpm；It is furthermore preferred that the rotating speed of the agitating device 2 is 50rpm.
The switch time of concentration of lye, valve, pressure (the cooperation injection in the rotating speed of agitating device and lye injector head
The outlet diameter of head, what is actually limited is the lye amount sprayed every time) it is the bioreactor that applicant combines the present invention
Alkali device structure is mended especially to set, to can quick mixing lye, to reduce its injury to cell.
Wherein, the opening and closing of the valve, the rotating speed of agitating device can be controlled by an electronic control unit, control dress
It puts by reading pH meter data and analyzing, and then controls the operating of above device.
Embodiment
In the present embodiment, bioreactor tank body is 6000L tank bodies, cultivates floating type mdck cell.Above tank skin
Lye injector head is provided with, lye injector head passes through valve and storage 1.0mol/LNaHCO3The container of solution is connected, and valve is every
It is spaced 5s to open once, opens 120ms every time.When spraying lye, the fluid pressure in the lye injector head is 1.0MPa, alkali
The a diameter of 2mm of jet port of liquid injector head.Bottom is provided with microvesicle air-breather for leading to oxygen in tank, and bottom is also set up in tank
There is agitating device, the agitating device includes agitating shaft and agitating paddle, and the agitating shaft is perpendicular to horizontal plane and is fixed on tank bottom,
The agitating paddle is arranged on the agitating shaft, and the bottom of the agitating shaft is connected with power set；Three are set on agitating shaft
Agitating paddle is from top to bottom followed successively by the first agitating paddle, the second agitating paddle and the 3rd agitating paddle, is to rotate clockwise；Described
Two agitating paddle agitated liquids move from top to bottom；The first and third agitating paddle agitated liquid moves from bottom to top.The paddle of agitating paddle
Leaf angle of inclination is 50 °, and the ratio of paddle footpath and tank diameter is 0.4.When lye is added dropwise, rotating speed of agitator is 50 turns/min；Normally
When culture cell leads to oxygen, rotating speed of agitator is 40 turns/min.Four baffles are set on tank skin, and the deflection direction of baffle is up time
Pin deviates itself and 35 ° of Grain lines where the tank body tie point, and the width of baffle is 1/12 tank diameter.This embodiment is arranged to
Experimental group sets comparative example on this basis.
Comparative example 1：It is differed only in experimental group, removes baffle.
Comparative example 2：Lye injector head is removed, add alkaline methods replace with side wall of the prior art and formula is added dropwise；Agitating paddle
Rotating speed is always 40 turns/min.
Comparative example 3：It is differed only in experimental group, baffle is set perpendicular to tank body.
Comparative example 4：It is differed only in experimental group, three agitating paddles stir culture solution upwards, and remove baffle.
It is cultivated by cell culture density for 1,800,000/ml with batch mdck cell 5 days, by the way that alkali is added to maintain, pH is constant to be
6.8-7.2 detects following data：
It was found from comparative example 1 and 2, mode is added dropwise in different lye has large effect to Cell viability.It is adherent that drop is added dropwise
The mode added is also continuous, and it is excessive to often result in concentration of lye at dropwise addition, thus can cause more cell death.If accelerate
Rotating speed then also results in the increase that mechanical damage causes cell mortality；Also can not in addition, dosage is added dropwise in adherent dropwise addition every time
Control, can not precisely adjust pH.It was found from comparative example 1 and 3, baffle plate setting mode is incorrect or removes baffle, although can reduce
Flow of oxygen, but more violent turbulent flow can be formed, Cell viability is caused to be greatly lowered.From comparative example 4, three stirrings
When paddle stirs culture solution upwards, it is resident and is shortened in culture solution due to oxygen, thus oxygen utilization rate declines, oxygen consumption total amount
It is soaring apparent；It is uniformly dispersed in addition, the change of aqueous agitation mode is also unfavorable for oxygen, since the present invention is using the life of big volume
Object reactor, the mixing difficulty of oxygen are consequently increased, it is possible to cause the decline of local oxygen concentration, Cell viability is caused to drop
It is low.
In conclusion lye additional way of the present invention by using pulsed, arrange in pairs or groups the agitating device that especially sets and
Baffle, can effectively less stirring when the generation of turbulent flow, quick mixing lye, so as to reduce because mechanical damage and local lye are dense
Cell death caused by spending height.In addition, surprisingly, unique agitating paddle rotation mode can also extend staying for oxygen
The time is stayed, so as to effectively reduce the consumption of oxygen.
Finally it should be noted that：The above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations；To the greatest extent
Pipe is described in detail the present invention with reference to foregoing embodiments, but it will be understood by those of ordinary skill in the art that：Its
It can still modify to the technical solution recorded in foregoing embodiments either to which part or all technical characteristic
Carry out equivalent substitution；And these modifications or replacement, the essence of appropriate technical solution is not made to depart from various embodiments of the present invention skill
The scope of art scheme.
Claims (10)
1. a kind of bioreactor mends alkali equipment, which is characterized in that including tank body；
The tank interior is provided with agitating device；
Lye injector head is provided with above the tank skin of the tank body, the lye injector head is connected by valve with storage alkali container.
2. bioreactor according to claim 1 mends alkali equipment, which is characterized in that the lye injector head front end endoporus
Aperture is 1mm~3mm.
3. bioreactor according to claim 1 mends alkali equipment, which is characterized in that the agitating device includes agitating shaft
And agitating paddle；
The agitating shaft is perpendicular to horizontal plane and is fixed on tank bottom, and the agitating paddle is arranged on the agitating shaft, the stirring
The bottom of axis is connected with power set；
Preferably, the equipment further includes microvesicle air-breather, the microvesicle air-breather be arranged at the agitating paddle just under
Side.
4. bioreactor according to claim 3 mends alkali equipment, which is characterized in that there are three the agitating paddles, from institute
It states agitating shaft and is from top to bottom followed successively by the first agitating paddle, the second agitating paddle and the 3rd agitating paddle；The second stirring paddle stirring
Liquid moves from top to bottom；The first and third agitating paddle agitated liquid moves from bottom to top；
Preferably, the agitating paddle is turbine type agitating paddle or pusher agitating paddle；
It is furthermore preferred that the agitating paddle is four leaf push type agitating paddles.
5. alkali equipment is mended according to Claims 1 to 4 any one of them bioreactor, which is characterized in that the tank of the tank body
Pars intramuralis is additionally provided with baffle, and the baffle is perpendicular to horizontal plane；
Preferably, the baffle has 3~5, more preferably 4, and be uniformly distributed on the tank skin of the tank body；
Preferably, the baffle deviates itself and 30 °~40 ° of Grain lines where the tank body tie point, and each baffle deflects
Direction is consistent.
6. a kind of bioreactor alkali supplement method, which is characterized in that usage right require 1~5 any one of them equipment into
It is intermittent to open the valve when row mends alkali operation so that the lye injector head pulsed sprays lye, opens simultaneously described
Agitating device is so that the lye of supplement mixes rapidly completely；
Preferably, the tank body is 3000L~6000L volumes.
7. bioreactor alkali supplement method according to claim 6, which is characterized in that the lye for 0.8mol/L~
The NaHCO of 1.2mol/L3Solution.
8. bioreactor alkali supplement method according to claim 6, which is characterized in that the valve at interval of 4.5s~
5.5s is opened once, opens 50ms~200ms every time.
9. bioreactor alkali supplement method according to claim 6, which is characterized in that during injection lye, the lye spray
The fluid pressure penetrated in head is 0.08MPa~0.12MPa.
10. bioreactor alkali supplement method according to claim 6, which is characterized in that described when carrying out mending alkali operation
The rotating speed of agitating device is 30rpm~70rpm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810073816.5A CN108048323B (en) | 2018-01-25 | 2018-01-25 | Alkali supplementing equipment and method for bioreactor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810073816.5A CN108048323B (en) | 2018-01-25 | 2018-01-25 | Alkali supplementing equipment and method for bioreactor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108048323A true CN108048323A (en) | 2018-05-18 |
| CN108048323B CN108048323B (en) | 2024-02-06 |
Family
ID=62124850
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810073816.5A Active CN108048323B (en) | 2018-01-25 | 2018-01-25 | Alkali supplementing equipment and method for bioreactor |
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| CN (1) | CN108048323B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118165806A (en) * | 2024-05-15 | 2024-06-11 | 上海数郜机电有限公司 | Biological fermentation tank |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1398072A1 (en) * | 1999-03-11 | 2004-03-17 | Cobra Biologics Limited | A vessel for mixing a cell lysate |
| WO2006101074A1 (en) * | 2005-03-22 | 2006-09-28 | Suntory Limited | Ventilating/stirring culture tank |
| CN206783683U (en) * | 2017-05-17 | 2017-12-22 | 潢川县鹏升畜产品有限公司 | Auxiliary material feeds controllable enzymolysis device |
| CN107557299A (en) * | 2017-10-30 | 2018-01-09 | 黄山市中新生物科技有限公司 | A kind of liquid atomization system for cell culture |
| CN107619777A (en) * | 2016-12-09 | 2018-01-23 | 济南航晨生物科技有限公司 | A kind of high-viscosity products dedicated liquid fermentation tank |
| CN207958395U (en) * | 2018-01-25 | 2018-10-12 | 吉林冠界生物技术有限公司 | A kind of bioreactor benefit alkali equipment |
-
2018
- 2018-01-25 CN CN201810073816.5A patent/CN108048323B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1398072A1 (en) * | 1999-03-11 | 2004-03-17 | Cobra Biologics Limited | A vessel for mixing a cell lysate |
| WO2006101074A1 (en) * | 2005-03-22 | 2006-09-28 | Suntory Limited | Ventilating/stirring culture tank |
| CN107619777A (en) * | 2016-12-09 | 2018-01-23 | 济南航晨生物科技有限公司 | A kind of high-viscosity products dedicated liquid fermentation tank |
| CN206783683U (en) * | 2017-05-17 | 2017-12-22 | 潢川县鹏升畜产品有限公司 | Auxiliary material feeds controllable enzymolysis device |
| CN107557299A (en) * | 2017-10-30 | 2018-01-09 | 黄山市中新生物科技有限公司 | A kind of liquid atomization system for cell culture |
| CN207958395U (en) * | 2018-01-25 | 2018-10-12 | 吉林冠界生物技术有限公司 | A kind of bioreactor benefit alkali equipment |
Non-Patent Citations (3)
| Title |
|---|
| A. KLOKE等: "A versatile miniature bioreactor and its application to bioelectrochemistry studies" * |
| 韩今依等: "搅拌反应器内相际传质行为 2.反应器结构特性研究" * |
| 颜旭等: "适用于动物细胞培养的搅拌桨及其数值模拟" * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118165806A (en) * | 2024-05-15 | 2024-06-11 | 上海数郜机电有限公司 | Biological fermentation tank |
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| CN108048323B (en) | 2024-02-06 |
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