CN108410734A - A kind of biological reactor for cell culture - Google Patents

A kind of biological reactor for cell culture Download PDF

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Publication number
CN108410734A
CN108410734A CN201810475273.XA CN201810475273A CN108410734A CN 108410734 A CN108410734 A CN 108410734A CN 201810475273 A CN201810475273 A CN 201810475273A CN 108410734 A CN108410734 A CN 108410734A
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CN
China
Prior art keywords
ring
cell culture
agitating shaft
tank body
biological reactor
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.)
Pending
Application number
CN201810475273.XA
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Chinese (zh)
Inventor
虞永胜
张剑
陈伟
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Jiangsu Flory Biological Engineering Equipment Co Ltd
Original Assignee
Jiangsu Flory Biological Engineering Equipment Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Jiangsu Flory Biological Engineering Equipment Co Ltd filed Critical Jiangsu Flory Biological Engineering Equipment Co Ltd
Priority to CN201810475273.XA priority Critical patent/CN108410734A/en
Publication of CN108410734A publication Critical patent/CN108410734A/en
Pending legal-status Critical Current

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M27/00Means for mixing, agitating or circulating fluids in the vessel
    • C12M27/02Stirrer or mobile mixing elements
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/06Nozzles; Sprayers; Spargers; Diffusers

Abstract

The present invention provides a kind of biological reactor for cell culture, belong to technical field of cell culture, including tank body, the top of tank body is equipped with enterprising gas port, and lower section is equipped with lower air inlet, and tank base center is equipped with magnetic agitation mechanism, magnetic agitation mechanism is connected with the agitating shaft positioned at tank interior, the top of agitating shaft is equipped with upper blade, and agitating shaft is equipped with the first rabbling mechanism and the second rabbling mechanism to distribute alternately successively from top to bottom, and the length of the second rabbling mechanism is longer than the length of the first rabbling mechanism;Microvesicle ring is equipped with below agitating shaft, microvesicle ring includes the first air intake lever that hollow point of ring of the gradually smaller at least two of diameter and connection divide ring from top to bottom, it is connected with the second air intake lever between first air intake lever and lower air inlet, the lower surface of ring is divided to be equipped with several equally distributed stomatas.Present invention ventilation is uniform and efficient, and cell and nutriment are uniformly mixed, and disclosure satisfy that big volume tank body production, yield is high and product quality is uniform.

Description

A kind of biological reactor for cell culture
Technical field
The invention belongs to technical field of cell culture, and in particular to a kind of biological reactor for cell culture.
Background technology
Bioreactor is the core equipment of mass cell suspension culture, can effectively increase cell-unit volume Culture density is the mainstay of such product large-scale production.China be world's vaccine product largest production state and Maximum uses state, and with annual 15% speed increase;In recent years, the development of antibody drug and the market demand also increase substantially. To improve production efficiency and product quality, production cost is effectively reduced, is changed with the backwardness production technology of spinner culture cell, it is anxious Need the animal cell culture reactor of the above production scale of kilolitre grade.
Existing cell culture reactor volume is generally less than normal, predominantly stays in 3000L at present hereinafter, low output, energy consumption Height, labour demand is big, product quality is inhomogenous, pollution is difficult to control, therefore comprehensive performance and production efficiency is not high.
It is anti-that existing application for a patent for invention cell reactor (application No. is CN201710482335.5) discloses a kind of cell Device is answered, its key points of the technical solution are that including tank body, the blender being set in tank body, the driving machine for driving the blender Structure, the snorkel being provided on the tank body inside and outside connection tank body, the outer end of the snorkel is connected to air source, the snorkel One end in tank body is connected with closed fibre pipe, and the fibre pipe is connected to the snorkel.The invention solves existing Some cell reactors cause cellular damage due to ventilation leads to the problem of bubble, to achieve the effect that improve cell density, But ventilation lack of homogeneity and efficiency it is low, cannot be satisfied the bioreactor of big volume.
Therefore it is uniform and efficient to be badly in need of a kind of ventilation, cell and nutriment are uniformly mixed, and disclosure satisfy that big volume tank Body produces, the biological reactor for cell culture that yield is high and product quality is uniform.
Invention content
The object of the present invention is to provide a kind of biological reactor for cell culture, ventilate uniform and efficient, cell and nutrition Material mixing is uniform, disclosure satisfy that big volume tank body production, yield is high and product quality is uniform.
The present invention provides the following technical solutions:
The top of a kind of biological reactor for cell culture, including tank body, the tank body is equipped with enterprising gas port, and lower section is equipped with down Air inlet, the tank base center are equipped with magnetic agitation mechanism, and the magnetic agitation mechanism is connected in the tank body The agitating shaft in portion, the top of the agitating shaft are equipped with upper blade, and the agitating shaft is equipped with the to distribute alternately successively from top to bottom One rabbling mechanism and the second rabbling mechanism;
First rabbling mechanism includes the fixed ring for being fixed on the agitating shaft, and the fixed ring is connected with several first Horizontal axis, the first horizontal the tip of the axis are equipped with the first blade;Second rabbling mechanism includes affixed with the agitating shaft Two horizontal axis, the second horizontal the tip of the axis are equipped with transverse slat, and the transverse slat is connected with the second blade, and the length of second horizontal axis is long In the length of first horizontal axis;
Microvesicle ring is equipped with below the agitating shaft, the microvesicle ring includes gradually smaller at least two of diameter from top to bottom The first air intake lever for dividing ring described in hollow point of ring and connection, with the second air inlet between first air intake lever and the lower air inlet Bar is connected, and the lower surface for dividing ring is equipped with several equally distributed stomatas.
Preferably, described that ring is divided to be with circular rings jaggy, two ends for being divided to ring are equipped with removably Plug, convenient for dividing the cleaning and maintenance of ring.
Preferably, the plug divides the end of ring to be to be threadedly coupled with described, convenient disassembly.
Preferably, it is connected with silk mouth nut between first air intake lever and second air intake lever, convenient disassembly;Described One air intake lever is in 30 degree of angles with interplanar, and effect is that microvesicle ring is placed in below rabbling mechanism, and does not have with rabbling mechanism Scraping collision.
Preferably, the distance of a diameter of 0.1 millimeter of the stomata, the two neighboring stomata is 1 centimetre.
Preferably, the height of the enterprising gas port ensures surface layer air inlet not higher than 50 centimetres of liquid level in the tank body Directly in piping and druming to cell culture liquid, more foam is prevented.
Preferably, the magnetic agitation mechanism includes the motor being sequentially connected, outer transmission shaft and intermediate solid drive shaft, the unofficial biography Opposite outer magnetic assembly and interior magnetic assembly, the bottom of the intermediate solid drive shaft and the agitating shaft are equipped between moving axis and the intermediate solid drive shaft End is connected, and power transmits the electromagnetic force for fully relying on magnet steel generation, and mixing effect is good, and is not easy microbiological contamination.
Preferably, the magnetic agitation mechanism and the joint of the tank body are equipped with separation sleeve, advantageously ensure that in tank body Gnotobasis.
Preferably, the inner wall of the tank body is equipped with baffle, is matched with rabbling mechanism, realizes the height of low-shearing force off field Imitate the uniform mixing of oxygen transfer, cell and nutriment.
The beneficial effects of the invention are as follows:
(1) the first rabbling mechanism and the second rabbling mechanism that agitating shaft of the invention is equipped with upper blade and distributes alternately, Upper blade can be stirred the liquid above tank body, and the first rabbling mechanism can be stirred the liquid at tank body center, and second Rabbling mechanism can be stirred the liquid near inner tank wall, to realize in tank body the uniform of cell everywhere and nutriment Mixing.
(2) present invention is equipped with microvesicle ring, and microvesicle ring includes the gradually smaller several hollow point of rings of diameter from top to bottom, can It ventilates from different height and all directions to the cell of tank body, stomata is set to the lower surface for dividing ring, and cell can be prevented broken Air-hole blockage can be met the cell culture of 7500L large volume tank bodies by piece, to greatly improve yield, also be improved Product quality.
(3) present invention hits exactly magnetic agitation using bottom, and sealing effect is good, reduces microbiological contamination risk, is conducive to cell Smoothly culture.
Description of the drawings
Attached drawing is used to provide further understanding of the present invention, and a part for constitution instruction, the reality with the present invention It applies example to be used to explain the present invention together, not be construed as limiting the invention.In the accompanying drawings:
Fig. 1 is the structural schematic diagram of the present invention;
Fig. 2 is the structural schematic diagram of the first rabbling mechanism;
Fig. 3 is the main structure diagram of microvesicle ring in embodiment;
Fig. 4 is the present invention looks up structural representation of microvesicle ring in embodiment;
Fig. 5 is the structural schematic diagram of magnetic agitation mechanism.
In figure label for:1, tank body;2, enterprising gas port;3, agitating shaft;4, upper blade;5, the first rabbling mechanism;51, fixed Ring;52, the first horizontal axis;53, the first blade;6, the second horizontal axis;7, transverse slat;8, the second blade;9, baffle;10, lower air inlet; 11, the second air intake lever;12, the first air intake lever;13, upper ring;14, lower ring;15, magnetic agitation mechanism;151, motor;152, unofficial biography Moving axis;153, interior magnetic assembly;154, outer magnetic assembly;155, separation sleeve;156, intermediate solid drive shaft;16, silk mouth nut;17, stomata; 18, plug.
Specific implementation mode
As shown in Figure 1, a kind of biological reactor for cell culture, including tank body 1, the top of tank body 1 are equipped with enterprising gas port 2, Lower section is equipped with lower air inlet 10, and the height of enterprising gas port 2 ensures that surface layer air inlet is not straight higher than 50 centimetres of liquid level in tank body 1 It connects in piping and druming to cell culture liquid, prevents more foam.
As depicted in figs. 1 and 2,1 bottom center of tank body is equipped with magnetic agitation mechanism 15, and magnetic agitation mechanism 15 is connected with position The top of agitating shaft 3 inside tank body 1, agitating shaft 3 is equipped with upper blade 4, and agitating shaft 3 is equipped with distributes alternately from top to bottom successively The first rabbling mechanism 5 and the second rabbling mechanism.First rabbling mechanism 5 includes the fixed ring 51 for being fixed on agitating shaft 3, fixed ring 51 are connected with several first horizontal axis 52, and the end of the first horizontal axis 52 is equipped with the first blade 53;Second rabbling mechanism includes and stirring The end of the second affixed horizontal axis 6 of axis 3, the second horizontal axis 6 is equipped with transverse slat 7, and transverse slat 7 is connected with the second blade 8, the second horizontal axis 6 Length is longer than the length of the first horizontal axis 52.The inner wall of tank body 1 is equipped with baffle 9, is matched with rabbling mechanism, realizes low-shearing force The uniform mixing of efficient oxygen transfer, cell and nutriment off field.
Shown in as shown in Figure 1, Figure 3 and Figure 4,3 lower section of agitating shaft is equipped with microvesicle ring, and microvesicle ring gradually becomes including diameter from top to bottom Hollow point of ring of small at least two, the present embodiment divides the quantity of ring to be 2, including upper ring 13 and lower ring 14, upper ring 13 and lower ring 14 Between with the first air intake lever 12 be connected, the first air intake lever is connected and is connected with the second air intake lever 11 between 12 and lower air inlet 10, upper ring 13 It is equipped with several equally distributed stomatas 17 with the lower surface of lower ring 14, a diameter of 0.1 millimeter of stomata 17, two neighboring stomata 17 distance is 1 centimetre.Upper ring 13 and lower ring 14 are with circular rings jaggy, and two ends are equipped with plug 18, block up First 18 with divide ring end be is threadedly coupled, convenient disassembly, convenient for microvesicle ring cleaning and maintenance.First air intake lever 12 and second It is connected with silk mouth nut 16 between air intake lever 11, convenient disassembly;First air intake lever 12 is in 30 degree angles with interplanar, act on be by Microvesicle ring is placed in below rabbling mechanism, and does not have scraping collision with rabbling mechanism.
As shown in figure 5, magnetic agitation mechanism 15 includes motor 151, outer transmission shaft 152 and the intermediate solid drive shaft being sequentially connected 156, opposite outer magnetic assembly 154 and interior magnetic assembly 153, intermediate solid drive shaft 156 are equipped between outer transmission shaft 152 and intermediate solid drive shaft 156 It is connected with the bottom end of agitating shaft 3, power transmits the electromagnetic force for fully relying on magnet steel generation, and mixing effect is good, and is not easy microbiological contamination. Magnetic agitation mechanism 15 and the joint of tank body 1 are equipped with separation sleeve 155, advantageously ensure that the gnotobasis in tank body 1.
The present invention advantage be:
(1) the first rabbling mechanism and the second rabbling mechanism that agitating shaft of the invention is equipped with upper blade and distributes alternately, Upper blade can be stirred the liquid above tank body, and the first rabbling mechanism can be stirred the liquid at tank body center, and second Rabbling mechanism can be stirred the liquid near inner tank wall, to realize in tank body the uniform of cell everywhere and nutriment Mixing.
(2) present invention is equipped with microvesicle ring, and microvesicle ring includes the gradually smaller several hollow point of rings of diameter from top to bottom, can It ventilates from different height and all directions to the cell of tank body, stomata is set to the lower surface for dividing ring, and cell can be prevented broken Air-hole blockage can be met the cell culture of 7500L large volume tank bodies by piece, to greatly improve yield, also be improved Product quality.
(3) present invention hits exactly magnetic agitation using bottom, and sealing effect is good, reduces microbiological contamination risk, is conducive to cell Smoothly culture.
The foregoing is only a preferred embodiment of the present invention, is not intended to restrict the invention, although with reference to aforementioned reality Applying example, invention is explained in detail, for those skilled in the art, still can be to aforementioned each implementation Technical solution recorded in example is modified or equivalent replacement of some of the technical features.All essences in the present invention With within principle, any modification, equivalent replacement, improvement and so on should all be included in the protection scope of the present invention god.

Claims (9)

1. a kind of biological reactor for cell culture, which is characterized in that including tank body, the top of the tank body is equipped with enterprising gas port, Lower section is equipped with lower air inlet, and the tank base center is equipped with magnetic agitation mechanism, and the magnetic agitation mechanism, which is connected with, to be located at The top of the agitating shaft of the tank interior, the agitating shaft is equipped with upper blade, and the agitating shaft is equipped with phase successively from top to bottom Between the first rabbling mechanism and the second rabbling mechanism that are distributed;
First rabbling mechanism includes the fixed ring for being fixed on the agitating shaft, and it is horizontal that the fixed ring is connected with several first Axis, the first horizontal the tip of the axis are equipped with the first blade;Second rabbling mechanism includes affixed with the agitating shaft second Horizontal axis, the second horizontal the tip of the axis are equipped with transverse slat, and the transverse slat is connected with the second blade, and the length of second horizontal axis is longer than The length of first horizontal axis;
Microvesicle ring is equipped with below the agitating shaft, the microvesicle ring is hollow including gradually smaller at least two of diameter from top to bottom Divide the first air intake lever for dividing ring described in ring and connection, with the second air intake lever phase between first air intake lever and the lower air inlet Connection, the lower surface for dividing ring are equipped with several equally distributed stomatas.
2. a kind of biological reactor for cell culture according to claim 1, which is characterized in that described that ring is divided to be with jagged Circular rings, two ends for being divided to ring are equipped with dismountable plug.
3. a kind of biological reactor for cell culture according to claim 2, which is characterized in that the plug divides ring with described End be threadedly coupled.
4. a kind of biological reactor for cell culture according to claim 1, which is characterized in that first air intake lever and institute It states and is connected with silk mouth nut between the second air intake lever, first air intake lever is in 30 degree of angles with interplanar.
5. a kind of biological reactor for cell culture according to claim 1, which is characterized in that the stomata it is a diameter of 0.1 millimeter, the distance of the two neighboring stomata is 1 centimetre.
6. a kind of biological reactor for cell culture according to claim 1, which is characterized in that the height of the enterprising gas port Higher than 50 centimetres of liquid level in the tank body.
7. a kind of biological reactor for cell culture according to claim 1, which is characterized in that magnetic agitation mechanism packet The motor being sequentially connected, outer transmission shaft and intermediate solid drive shaft are included, is equipped between the outer transmission shaft and the intermediate solid drive shaft opposite outer Magnetic assembly and interior magnetic assembly, the intermediate solid drive shaft are connected with the bottom end of the agitating shaft.
8. a kind of biological reactor for cell culture according to claim 1, which is characterized in that the magnetic agitation mechanism with The joint of the tank body is equipped with separation sleeve.
9. a kind of biological reactor for cell culture according to claim 1, which is characterized in that set on the inner wall of the tank body There is baffle.
CN201810475273.XA 2018-05-17 2018-05-17 A kind of biological reactor for cell culture Pending CN108410734A (en)

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Application Number Priority Date Filing Date Title
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110312087A1 (en) * 2009-02-09 2011-12-22 Mohsan Khan Bioreactor for the cultivation of mammalian cells
JP2012044943A (en) * 2010-08-27 2012-03-08 Hitachi Plant Technologies Ltd Culture vessel and culture device for biological cell
US20120070860A1 (en) * 2009-06-05 2012-03-22 Marco Jenzsch Combination stirrer
CN203200277U (en) * 2013-03-27 2013-09-18 南京江辉生物科技有限公司 Biological reactor
CN206396254U (en) * 2016-11-29 2017-08-11 肇庆绿健农业科技有限公司 Asparagus liquid strain culture tank
CN107988074A (en) * 2018-01-25 2018-05-04 吉林冠界生物技术有限公司 The full suspension cell culture reactor of 6000L serum-frees
CN208362367U (en) * 2018-05-17 2019-01-11 江苏弗洛瑞生物工程设备有限公司 A kind of biological reactor for cell culture

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110312087A1 (en) * 2009-02-09 2011-12-22 Mohsan Khan Bioreactor for the cultivation of mammalian cells
US20120070860A1 (en) * 2009-06-05 2012-03-22 Marco Jenzsch Combination stirrer
JP2012044943A (en) * 2010-08-27 2012-03-08 Hitachi Plant Technologies Ltd Culture vessel and culture device for biological cell
CN203200277U (en) * 2013-03-27 2013-09-18 南京江辉生物科技有限公司 Biological reactor
CN206396254U (en) * 2016-11-29 2017-08-11 肇庆绿健农业科技有限公司 Asparagus liquid strain culture tank
CN107988074A (en) * 2018-01-25 2018-05-04 吉林冠界生物技术有限公司 The full suspension cell culture reactor of 6000L serum-frees
CN208362367U (en) * 2018-05-17 2019-01-11 江苏弗洛瑞生物工程设备有限公司 A kind of biological reactor for cell culture

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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

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