CN106635797A - Bioreactor - Google Patents
Bioreactor Download PDFInfo
- Publication number
- CN106635797A CN106635797A CN201710163572.5A CN201710163572A CN106635797A CN 106635797 A CN106635797 A CN 106635797A CN 201710163572 A CN201710163572 A CN 201710163572A CN 106635797 A CN106635797 A CN 106635797A
- Authority
- CN
- China
- Prior art keywords
- cell culture
- fixed plate
- tank body
- guide shell
- plate
- 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
Links
- 238000004113 cell culture Methods 0.000 claims abstract description 79
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000001301 oxygen Substances 0.000 claims abstract description 31
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 31
- 239000007789 gas Substances 0.000 claims abstract description 26
- 230000002093 peripheral effect Effects 0.000 claims abstract description 21
- 239000013598 vector Substances 0.000 claims description 33
- 239000000945 filler Substances 0.000 claims description 28
- 238000003756 stirring Methods 0.000 claims description 22
- 239000006052 feed supplement Substances 0.000 claims description 10
- 238000005070 sampling Methods 0.000 claims description 6
- 238000007789 sealing Methods 0.000 claims description 6
- 239000000835 fiber Substances 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- 238000013022 venting Methods 0.000 abstract 5
- 210000004027 cell Anatomy 0.000 description 27
- 239000012930 cell culture fluid Substances 0.000 description 23
- 238000000034 method Methods 0.000 description 9
- 238000012549 training Methods 0.000 description 9
- 239000000443 aerosol Substances 0.000 description 7
- 230000010261 cell growth Effects 0.000 description 6
- 235000015097 nutrients Nutrition 0.000 description 6
- 239000012530 fluid Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 239000003513 alkali Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000005465 channeling Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 235000016709 nutrition Nutrition 0.000 description 3
- 230000035764 nutrition Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000001802 infusion Methods 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000009434 installation Methods 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 238000004062 sedimentation Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000012611 container material Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 238000005243 fluidization Methods 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000021049 nutrient content Nutrition 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 210000000717 sertoli cell Anatomy 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000010008 shearing Methods 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000009423 ventilation Methods 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
- C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
- C12M25/16—Particles; Beads; Granular material; Encapsulation
- C12M25/18—Fixed or packed bed
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
- C12M25/16—Particles; Beads; Granular material; Encapsulation
- C12M25/20—Fluidized bed
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/02—Stirrer or mobile mixing elements
-
- 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
- C12M27/18—Flow directing inserts
- C12M27/24—Draft tube
-
- 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
Abstract
The invention discloses a bioreactor in the field of medical equipment. The bioreactor comprises a tank body, a flow guide barrel, a multistage speed regulation stirrer, an upper fixed plate and a lower fixed plate, wherein the upper fixed plate and the lower fixed plate are horizontally arranged in the tank body, the flow guide barrel vertically penetrates through the upper fixed plate and the lower fixed plate at the center of the tank body, the upper fixed plate and the lower fixed plate are both perforated plates, and cell culture beds are formed among the tank body, the flow guide barrel, the upper fixed plate and the lower fixed plate; venting pipes which are vertically arranged are fixed to the inner peripheral wall of the flow guide barrel, the top ends of the venting pipes are higher than the top end of the flow guide barrel, the bottom ends of the venting pipes are communicated with one other and are as high as the fixed plate, the outer peripheries of the venting pipes are tightly attached to an annular gas distributor at the inner periphery of the flow guide barrel, the annular gas distributor is an annular pipe which is horizontally arranged, a plurality of oxygen supply venting holes are evenly distributed in the periphery of the annular gas distributor, and the multistage speed regulation stirrer vertically extends into the bottom of the flow guide barrel.
Description
Technical field
The present invention relates to a kind of bioreactor of medical device field.
Background technology
The bioreactor of cell culture is carried out at present, is broadly divided into fluidized bed aerosol generator and fixed bed biological respinse
Device.Fixed-bed bioreactor is filled with cell culture vector to carry out filling out for cell culture in the middle of a fixed container
Material.Described filler is made up of cell culture vector, and the cell culture vector is typically diameter 2-6mm particulate vectors, many
The balloon borne body in hole or sheet-like fiber carrier.Cell culture fluid cycles through cell culture vector, and cell culture fluid relies on agitator
The negative pressure produced in stirring constantly flows in fixed-bed bioreactor, to carry out the transmission of nutrient content and/or oxygen.Just
On the surface of the cell culture vector, as cell is bred, cell begins to fill with the cell culture to the cell growth of inoculation
Space between carrier.Fixed-bed bioreactor inner cell nutrient solution flowing velocity is big, and cell density is high, can reduce without blood
The consumption of albumen during clear culture, it is adaptable to breed suspension cell, and cell mechanical is damaged, but, due to described filler
Compressed by upper mounted plate and bottom plate, the metabolite and dead cell of cell are difficult to discharge, while cell culture fluid is uneven
Flowing and cause channeling and nutrient distribution uneven, vitro growth rates uniformity is poor.
Fluidized bed aerosol generator includes tank body, agitator, and the filler being made up of cell culture vector etc., by institute
State agitator and swirling flow upwards is produced in the tank body, make the cell culture fluid that sertoli cell grows in fluidization, and in making
Cell culture vector in the described filler of portion's filling is stirred up and down, and a large amount of cells for depending on the cell culture vector growth exist
Grow under suspended state.In fluidized bed aerosol generator, the good fluidity of cell culture fluid, the nutrition needed for the growth of cell exists
It is evenly distributed in fluidized bed aerosol generator, cell growth uniformity is good, but cell and cell culture vector are easily gone out, while
With increasing for cell, cell suspended state in fluidized bed aerosol generator is deteriorated.While the scale of fluidized bed aerosol generator
Cannot amplify, the depth of existing fluidized bed aerosol generator is only 2m or so to the maximum, and cross-sectional area maximum-norm is only 1m3。
The content of the invention
The invention aims to overcome the deficiencies in the prior art, there is provided a kind of bioreactor, it contributes to right
Cell culture bed is carried out before deep layer oxygen supply, realizes the separation of dissolved oxygen and oxygen bubble, prevents oxygen bubble from entering cell culture
Bed, bubble is damaged so as to prevent oxygen bubble from rupturing.
Realizing a kind of technical scheme of above-mentioned purpose is：A kind of bioreactor, including tank body, guide shell, multistep speed regulation
Agitator, and the upper mounted plate and bottom plate being horizontally placed in the tank body, the guide shell is at the center of the tank body
Vertically porous plate is through fixed plate and the bottom plate, fixed plate and the bottom plate, it is described
Tank body, forms cell culture bed between the guide shell, fixed plate and the bottom plate；
The breather pipe being vertically arranged is fixed with the inner peripheral wall of the guide shell, the top of the breather pipe is higher than described
The top of guide shell, the bottom connection of the breather pipe is contour with the bottom plate, and excircle is close to the guide shell inner circle
The annular gas distributor in week, the annular gas distributor is a horizontally disposed ring pipe, the annular gas distribution
Uniform multiple oxygen supply passages on the circumference of device, the multistep speed regulation agitator vertically stretches into the bottom of the guide shell.
The multistep speed regulation agitator vertically stretches into the bottom of the guide shell.
Further, the guide shell is divided into from top to bottom that successively with one heart the vertical draft tube of connection, internal diameter are up-small and down-big
Bell-mouth structure of air, and vertical stirring room, the vertical draft tube is through fixed plate and solid with fixed plate
Fixed, the top of the bell-mouth structure of air connects with one heart the bottom of the vertical draft tube, the bottom of the bell-mouth structure of air and institute
State bottom plate to fix, the top of the vertical stirring room connect with one heart the bottom of the bell-mouth structure of air and with the lower fixation
Plate is fixed；The annular gas distributor is contour with the bottom plate and is close to the inner peripheral wall of the bell-mouth structure of air, institute
State multistep speed regulation agitator and stretch into vertical stirring room from the bottom of the tank body, the blowdown pipe be close to the vertical draft tube and
The inner peripheral wall of the bell-mouth structure of air.
Further, the inner peripheral wall of the vertical draft tube is fixed with the feed supplement pipe being vertically arranged, the feed supplement pipe
Top higher than the guide shell top and be less than the top of the breather pipe, bottom and bottom of the vertical draft tube etc.
It is high.
Further, the height that the multistep speed regulation agitator stretches into vertical stirring room part is the multistage tune
The a quarter of fast agitator total height is to 1/3rd.
Further, fixed by O-ring between fixed plate and the guide shell, the bottom plate with it is described
It is welded and fixed between guide shell, it is described by being socketed between the inner peripheral wall of the excircle of fixed plate and the tank body
Flange on upper mounted plate excircle and the washer sealing being socketed on the flange excircle week, the bottom plate it is cylindrical
By the flange that is socketed on the bottom plate excircle and it is socketed in described between the inner peripheral wall of all and tank body
Washer sealing on flange excircle week.
Further, the bottom of the tank body is inserted with sampling valve, and the sampling valve includes a valve rod, and the valve rod is from institute
State the bottom insertion cell culture bed of bottom plate.
Further, filler is filled with the cell culture bed, described filler is made up of cell culture vector, described to fill out
The height of material is 4th/2nd to five/3rds of the cell culture bed height, the cell culture vector with diameter greater than institute
State the aperture of institute's upper mounted plate and the bottom plate.
Further, the cell culture vector is sheet-like fiber cell culture vector.
Further, bubble output hole is provided with the top of the tank body, the bubble output hole is connected with condenser.
Further, the blade of the multistep speed regulation agitator is Ping Ye or propeller shape blade.
Employ a kind of technical scheme of bioreactor of the present invention, including the stirring of tank body, guide shell, multistep speed regulation
Device, and the upper mounted plate and bottom plate being horizontally placed in the tank body, center vertical of the guide shell in the tank body
Through fixed plate and the bottom plate, fixed plate and the bottom plate are porous plate, the tank body,
Cell culture bed is formed between the guide shell, fixed plate and the bottom plate；The inner peripheral wall of the guide shell
On be fixed with the breather pipe being vertically arranged, the top of the breather pipe higher than the guide shell top, the bottom of the breather pipe
End connection is contour with the bottom plate, and excircle is close to the annular gas distributor of the guide shell inner periphery, the annular
Gas distributor is a horizontally disposed ring pipe, uniform multiple oxygen supply ventilations on the circumference of the annular gas distributor
Hole, the multistep speed regulation agitator vertically stretches into the bottom of the guide shell.It has the technical effect that：It contributes to training cell
Foster bed is carried out before deep layer oxygen supply, realizes the separation of dissolved oxygen and oxygen bubble, prevents oxygen bubble from entering cell culture bed, so as to
Prevent oxygen bubble from rupturing and damage bubble.
Description of the drawings
Fig. 1 is a kind of structural representation of bioreactor of the present invention.
Fig. 2 is the structural representation of a kind of bioreactor Center Vent tube of the present invention and annular gas distributor.
Fig. 3 is the top view of annular gas distributor in a kind of bioreactor of the invention.
Specific embodiment
Fig. 1 is referred to, the present inventor is led to below in order to be able to preferably understand technical scheme
Specifically embodiment is crossed, and combines accompanying drawing and be described in detail：
Fig. 1 is referred to, a kind of bioreactor of the present invention belongs to a kind of fixed-bed bioreactor, including：Including tank
Body 1, guide shell 18, feed supplement pipe 11, breather pipe 9, annular gas distributor 10, multistep speed regulation agitator 8, upper mounted plate 15 and under
Fixed plate 17.
Wherein, the top of tank body 1 sets bubble output hole 2 and condenser mouth (figure is not marked), bubble output hole 2 and condenser mouth with it is cold
Condenser (figure is not marked) connection, the cell culture fluid in bioreactor enters the condenser from bubble output hole, and by described
Cyclone hydraulic separators in condenser carries out gas-liquid separation, is returned by the condenser mouth through the cell culture fluid of gas-liquid separation
In tank body 1, gas is discharged through the tail gas filter core and proportioning valve of the condenser.
The circumferential wall of tank body 1 is provided with four fluid infusion mouths, and liquid outlet and electrode ports.The fluid infusion mouth is used for tank body
The alkali lye of addition cell culture fluid and regulation pH value in 1.
Upper mounted plate 15 and bottom plate 17 are horizontally placed in tank body 1 and are arranged concentrically.The excircle of upper mounted plate 15
On the packing ring that is socketed with flange and is socketed on flange excircle week, for realizing the excircle and tank body 1 of upper mounted plate 15
Inner peripheral wall between sealing.Flange is socketed with the excircle of bottom plate 17 and is socketed on the flange excircle week
Packing ring, for realizing the sealing between bottom plate 17 and the inner peripheral wall of tank body 1.Guide shell 18 is located at the center of tank body 1, leads
The Upper vertical of flow cartridge 18 extends upward through upper mounted plate 15, and the lower vertical of guide shell 18 is downward through bottom plate 17.Also
The excircle for being the excircle and bottom plate 17 of saying fixed plate 15 is detached with the inner peripheral wall of tank body 1, therefore is easy to
The installation and removal of bioreactor.
Guide shell 18 is divided into from top to bottom the up-small and down-big horn mouth knot of the vertical draft tube 12, internal diameter for connecting with one heart successively
Structure 13 and vertical stirring room 14.Vertical draft tube 12 vertically runs through upper mounted plate 15.The top of vertical draft tube 12 is higher than upper solid
The top surface of fixed board 15, bottom is connected with the top of bell-mouth structure of air 13.Pass through O shapes between vertical draft tube 12 and upper mounted plate 15
Circle is fixed, and O-ring is connected in the draw-in groove of the inner periphery of upper mounted plate 15.That is, the inner periphery of upper mounted plate 15 with
Guide shell 15 is detached, therefore is easy to the installation and removal of bioreactor.
Because the bioreactor is easily installed dismounting, therefore can repeatedly use, this for research work, pole
The earth reduces cost.
The bottom of bell-mouth structure of air 13 is welded and fixed with the top of bottom plate 17 and vertical stirring room 14, vertical stirring
The bottom of the top of room 14 and bell-mouth structure of air 13 and bottom plate 17 are welded and fixed, so that bottom plate 17 and horn mouth
The position of structure 13 and the connection of vertical stirring room 14 is welded and fixed.The excircle of bell-mouth structure of air 13 is a conical surface.
The middle part of guide shell 18 arranges the up-small and down-big bell-mouth structure of air 13 of internal diameter, beneficial to cell culture fluid in biological respinse
Circulation in device.The back cavity formed below 7 of bottom plate 17, bottom plate 17, upper mounted plate 15, tank body 1 and guide shell
Cell culture bed is formed between 18, the bottom surface of upper mounted plate 15 is the cell culture bed top surface, and the top surface of bottom plate 17 is the cell
Culture bed bottom surface.Multistep speed regulation agitator 8 stretches into vertical stirring room 14, the i.e. bottom of guide shell 18 from the bottom of tank body 1.It is many
Level speed-adjustable stir device 8 stretches into a quarters of the height h2 for total height h1 of multistep speed regulation agitator 8 of the part of vertical stirring room 14
To 1/3rd, and the top of the blade of multistep speed regulation agitator 8 is less than annular gas distributor 10.
Fill in cell culture bed between the bottom surface of upper mounted plate 15 and the top surface of bottom plate 17 and carried by cell culture
The filler 5 of body composition, cell culture vector generally uses sheet-like fiber carrier.It is upper mounted plate 15, lower solid in the present embodiment
Fixed board 17 is all porous plate, is made from porous stainless steel plate.The hole of the porous plate that upper mounted plate 15, bottom plate 17 are adopted
Footpath, it is necessary to less than the diameter of cell culture vector in filler 5, play the iris action to cell culture vector in filler 5, also prevent
The cell for causing to be cultivated in cell culture vector in vertical stirring room 14 is only entered in filler 5 by multistep speed regulation agitator 8
The effect of shearing force.The height d of filler 5 is 4th/2nd to five/3rds of cell culture bed height h.
The bottom of tank body 1 is provided with outlet valve 6 and sampling valve 4, and sampling valve 4 includes a valve rod, and the valve rod is from lower fixation
The bottom insertion cell culture bed of plate 17, is sampled to the cell in cell culture bed.
In tank body 1, cell culture fluid is flowed to be formed in the bottom of tank body 1, guide shell 18 from guide shell 18 and flowed downward
Swirling flow, the swirling flow that this flows downward gone out into the bottom of tank body 1 from the bottom of the vertical stirring room 14 of the bottom of guide shell 18
Back cavity 7.The swirling flow for flowing downward, in the presence of multistep speed regulation agitator 8, multistep speed regulation agitator 8 is formed when rotating
Centrifugal force cell culture fluid is got rid of into lower section to multistep speed regulation agitator 8, cell culture fluid rebounds after the diapire of tank body 1 is encountered
Upwards dispersion transfers to define the swirling flow for flowing up in back cavity 7.Due to upper mounted plate 15 and bottom plate 17 be it is many
Orifice plate, the swirling flow that this is flowed up enters filler 5 from the bottom of bottom plate 17, is thin in cell culture vector in filler 5
Born of the same parents provide nutrition and dissolved oxygen.The swirling flow for flowing up continues up flowing, through upper mounted plate 15, simultaneously as multistage
The effect of the centrifugal force of speed-adjustable stir device 8, forms negative pressure at multistep speed regulation agitator 8, the inner cell nutrient solution of tank body 1 is just from top Jing
The internal reflux of guide shell 18 is to back cavity 7, then bounce-back rises after the rotation of multistep speed regulation agitator 8 is downward, so as to reach
The purpose of tank interior circulation.Cell culture vector so in cell culture bed is settled downwards, and cell culture bed inner cell culture
In the case that the speed that liquid flows up tends to balance with the speed of cell culture bed inner cell culture carrier sedimentation, realize that cell is trained
The suspension of foster carrier.Another purpose of back cavity 7 is to reduce the circulation dead angle in cell culture fluid cyclic process.
In the present embodiment, by the mixing speed for changing multistep speed regulation agitator 8, thus it is possible to vary the swirling flow for flowing up
Movement velocity in the filler 5 upwards.When multistep speed regulation agitator 8 is in zero span, nothing in the back cavity 7 of the bottom of tank body 1
Method forms the swirling flow for flowing up.When the rotary speed of multistep speed regulation agitator 8 is in a grade of lowest speed, this is flowed up
The speed that flows up of swirling flow go out a little less than cell culture vector in filler 5, cell culture vector can be in filler 5
Settle down in cell culture bed, form the training method of similar fixed bed culture.When the rotary speed of multistep speed regulation agitator 8
During one grade in middling speed, there is larger gap in filler 5 between cell culture vector, and be observed that the cell training
Foster carrier carry out it is small rock, this rocking contributes to making cell culture fluid being uniformly distributed in filler 5, than existing
Fixed bed training method is superior.
When the rotary speed of multistep speed regulation agitator 8 continues to rise, i.e., the rotary speed of multistep speed regulation agitator 8 is in most
During the N shelves of high speed, sedimentation speed of the speed that the swirling flow for flowing up is flowed up higher than cell culture vector in filler 5
Degree, make cell culture vector in filler 5 in suspended state, form the training method similar to fluid bed.Due to upper fixation
The porous plate that plate 15 and bottom plate 17 are adopted, its aperture is respectively less than the diameter of cell culture vector in filler 5, in filler 5
Cell culture vector is intercepted, without going out.Such design avoids the uneven flowing of cell culture fluid and makes
It is uneven into channeling and nutrient distribution, ensure that the nutrition needed for cell growth is evenly distributed in cell culture bed,
Cell growth uniformity is good.Thus overcome using solidification bed carry out cell culture when because carrier overstock, cell culture fluid stream
It is dynamic to be obstructed, cause the uneven flowing of cell culture fluid and cause channeling and nutrient distribution uneven, so as to cause cell
The inconsistent defect of the speed of growth.Culture can be amplified to the cell in cell culture bed.
It is fixed with vertical breather pipe 9 on the inner peripheral wall of guide shell 18, the top of the top of breather pipe 9 than guide shell 18
High 3cm, the bottom of breather pipe 9 extends to the bottom of bell-mouth structure of air 13 along the inner peripheral wall of guide shell 18.The bottom of breather pipe 9
Portion's connection is arranged around the bottom inner peripheral wall of bell-mouth structure of air 13, i.e., the diameter of excircle is equal to the bottom inner circle of bell-mouth structure of air 13
The diameter in week, and the annular gas distributor 10 contour with bottom plate 17, annular gas distributor 10 is horizontally disposed for one
Ring pipe, breather pipe 9 is seamlessly connected and connects with annular gas distributor 10, uniform on the circumference of annular gas distributor 10
There are 36 oxygen supply passages 101.The oxygen of external world's input is transported to annular gas distributor 10 by breather pipe 9, and leads to
Cross on annular gas distributor 10 36 keeping passages 101, under the active force of multistep speed regulation agitator 8 fully with
Cell culture fluid mixes, and most of bubble is crushed by multistep speed regulation agitator 8, and oxygen is completely dissolved in cell culture fluid, shape
Into the dissolved oxygen for being dissolved in cell culture fluid, and filler 5 is entered by the bottom of bottom plate 17, to cell culture in filler 5
Carrying the cell of In vivo culture carries out deep layer oxygen supply, and the bubble containing oxygen of some unbroken then Jing guide shells 18 drive in the wrong direction upwards
To at the top of tank body 1, Jing bubble output holes 2 are discharged, and the tension force for being not directly contacted with cell to reduce the bubbles burst is trained to the cell
The damage of foster carrier inner cell.That is, annular gas distributor 10 contribute to extend oxygen before into cell culture fluid
Stroke, before deep layer oxygen supply is carried out to cell culture bed, realize the separation of dissolved oxygen and oxygen bubble, prevent oxygen bubble from entering
Enter cell culture bed, so as to prevent tension force when oxygen bubble ruptures and damaging cells.
Meanwhile, the inner peripheral wall of mozzle 12 is fixed with four feed supplement pipes 11 being vertically arranged, and the top of feed supplement pipe 11 is high
In the top of guide shell 18, the i.e. top of vertical draft tube 12, and less than the top of breather pipe 9.The bottom of feed supplement pipe 11 with it is vertical
The bottom of mozzle 12 is contour.The alkali lye of cell culture fluid and regulation pH value is introduced into guide shell 18 and exists by feed supplement pipe 11
Be sufficiently mixed in the presence of multistep speed regulation agitator 8 it is uniform after enter back in cell culture bed, it is to avoid the cell culture added
Liquid and alkali lye are directly entered cell culture bed, cause that the moment of cell culture environment drastically changes and cell growth is caused not
Profit affects.In the present embodiment, than the top of guide shell 18, i.e. the high 2cm in top of vertical draft tube 12 leads to for the top of feed supplement pipe 11
The top of tracheae 9 than guide shell 18 top, i.e. the high 3cm in top of vertical draft tube 12, to ensure depth to cell culture bed
Layer oxygen supply and deep layer are supported, and prevent the generation of bubble during deep layer oxygen supply and deep layer keeping.
In order to ensure the speed governing of multistep speed regulation agitator 8, the blade that multistep speed regulation agitator 8 is adopted is Ping Ye or screw
Shape blade.
The bioreactor culture mode, the rotary speed of multistep speed regulation agitator 8 based on middling speed, interval and briefly
Change the rotary speed of multistep speed regulation agitator 8, make cell culture vector in flour filler 5 in suspended state, form similar
In the training method of fluid bed, cell culture fluid and metabolite in bioreactor is set to homogenize.The bioreactor is excellent
The culture of choosing may be set to：The training method culture 1-3 hours of fixed bed, the training method culture 1-3 minutes of fluid bed, stop
Stirring 0.5-1 minutes, then restart to carry out cell culture using the training method of fixed bed.
The bioreactor is capable of achieving highdensity cell culture, and the cell culture density in the cell culture bed is reachable
3-5×107Individual/more than ml, and the continuous culture of long-time can be carried out, this is to supply cell by the continuous bottom toward tank body 1
Nutrient solution and dissolved oxygen, while the top of tank body 1 exports supernatant to realize.In filler 5, cell is in cell culture vector
Portion grows, and has good population effect, difficult for drop-off.Therefore its amplification potential is good, can realize in the cell culture bed highly dense
The cell culture of degree.The bioreactor is particularly suitable for free serum culture, the continuous perfusion of long-time, long-time harvesting generation
Thank to product.
Those of ordinary skill in the art it should be appreciated that the embodiment of the above be intended merely to explanation the present invention,
And be not used as limitation of the invention, as long as in the spirit of the present invention, the change to embodiment described above
Change, modification all will fall in the range of claims of the present invention.
Claims (10)
1. a kind of bioreactor, including tank body, guide shell, multistep speed regulation agitator, and be horizontally placed in the tank body
Upper mounted plate and bottom plate, the guide shell runs through fixed plate and the lower fixation in the center vertical of the tank body
Plate, fixed plate and the bottom plate are porous plate, the tank body, the guide shell, fixed plate and institute
State formation cell culture bed between bottom plate；It is characterized in that：
The breather pipe being vertically arranged is fixed with the inner peripheral wall of the guide shell, the top of the breather pipe is higher than the water conservancy diversion
The top of cylinder, the bottom connection of the breather pipe is contour with the bottom plate, and excircle is close to the guide shell inner periphery
Annular gas distributor, uniform multiple oxygen supply passages on the circumference of the annular gas distributor, the multistep speed regulation stirring
Device vertically stretches into the bottom of the guide shell.
2. a kind of bioreactor according to claim 1, it is characterised in that：The guide shell is divided into from top to bottom successively
The up-small and down-big bell-mouth structure of air of the vertical draft tube of connection, internal diameter, and vertical stirring room with one heart, the vertical draft tube is passed through
Wear fixed plate and fix with fixed plate, the top of the bell-mouth structure of air connects with one heart the vertical draft tube
Bottom, the bottom of the bell-mouth structure of air fixes with the bottom plate, and the top of the vertical stirring room connects with one heart institute
State the bottom of bell-mouth structure of air and fix with the bottom plate；The annular gas distributor is contour with the bottom plate simultaneously
It is close to the inner peripheral wall of the bell-mouth structure of air, the multistep speed regulation agitator stretches into vertical stirring from the bottom of the tank body
Room, the blowdown pipe is close to the inner peripheral wall of the vertical draft tube and the bell-mouth structure of air.
3. a kind of bioreactor according to claim 2, it is characterised in that：The inner peripheral wall of the vertical draft tube is consolidated
Surely there are the feed supplement pipe being vertically arranged, the top of the top higher than the guide shell of the feed supplement pipe and the top less than the breather pipe
End, bottom is contour with the bottom of the vertical draft tube.
4. a kind of bioreactor according to claim 2, it is characterised in that：The multistep speed regulation agitator stretches into described
The height of vertical stirring room part is a quarter of the multistep speed regulation agitator total height to 1/3rd.
5. a kind of bioreactor according to claim 2, it is characterised in that：Fixed plate and the guide shell it
Between fixed by O-ring, be welded and fixed between the bottom plate and the guide shell, the excircle of fixed plate and institute
State between the inner peripheral wall of tank body by the flange that is socketed on fixed plate excircle and be socketed in outside the flange
Between the inner peripheral wall of the washer sealing on circumference, the excircle of the bottom plate and the tank body by be socketed in it is described under
Flange on fixed plate excircle and the washer sealing being socketed on the flange excircle week.
6. a kind of bioreactor according to claim 1, it is characterised in that：The bottom of the tank body is inserted with sampling valve,
The sampling valve includes a valve rod, and the valve rod inserts cell culture bed from the bottom of the bottom plate.
7. a kind of bioreactor according to claim 1, it is characterised in that：It is filled with the cell culture bed
Material, described filler is made up of cell culture vector, the height of described filler be the cell culture bed height 2/3rds to
4/5ths, the cell culture vector with diameter greater than institute's upper mounted plate and the aperture of the bottom plate.
8. a kind of bioreactor according to claim 7, it is characterised in that：The cell culture vector is sheet-like fiber
Cell culture vector.
9. a kind of bioreactor according to claim 1, it is characterised in that：Bubble output hole is provided with the top of the tank body,
The bubble output hole is connected with condenser.
10. a kind of bioreactor according to claim 1, it is characterised in that：The blade of the multistep speed regulation agitator
For Ping Ye or propeller shape blade.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710163572.5A CN106635797A (en) | 2017-03-15 | 2017-03-15 | Bioreactor |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710163572.5A CN106635797A (en) | 2017-03-15 | 2017-03-15 | Bioreactor |
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| CN106635797A true CN106635797A (en) | 2017-05-10 |
Family
ID=58847647
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| Application Number | Title | Priority Date | Filing Date |
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| CN201710163572.5A Pending CN106635797A (en) | 2017-03-15 | 2017-03-15 | Bioreactor |
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| CN108004122A (en) * | 2017-12-12 | 2018-05-08 | 黄山市中新生物科技有限公司 | A kind of fixed-bed type bioreactor |
| CN108676716A (en) * | 2018-08-10 | 2018-10-19 | 武汉赛科成科技有限公司 | A kind of 3D Constituent cells culture carrier and bioreactor |
| CN111801410A (en) * | 2017-12-20 | 2020-10-20 | 尤尼沃尔塞尔斯技术股份公司 | Bioreactor and related methods |
| CN112430540A (en) * | 2020-10-21 | 2021-03-02 | 英诺维尔智能科技（苏州）有限公司 | Compact reactor capable of being placed in biological incubator |
| CN114250147A (en) * | 2021-12-29 | 2022-03-29 | 上海日泰医药设备工程有限公司 | Biological reaction device |
| CN114276979A (en) * | 2021-12-29 | 2022-04-05 | 上海日泰医药设备工程有限公司 | Animal cell culture method |
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