CN205347443U - Chip carrier and bioreactor for cell culture - Google Patents
Chip carrier and bioreactor for cell culture Download PDFInfo
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- CN205347443U CN205347443U CN201520920664.XU CN201520920664U CN205347443U CN 205347443 U CN205347443 U CN 205347443U CN 201520920664 U CN201520920664 U CN 201520920664U CN 205347443 U CN205347443 U CN 205347443U
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- chip carrier
- bioreactor
- upper plate
- shell
- lower plate
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Abstract
The utility model relates to a chip carrier and bioreactor for cell culture. The chip carrier contains the 3 -10 piece and connects at same epaxial page or leaf piece, and the page or leaf piece outwards opens. Bioreactor include the shell with the chip carrier. The utility model discloses a carrier bed and the novel combination mode of stirring rake, be favorable to reducing the shearing force, improve the liquid flux, increase the dissolved oxygen effect, accomplish simultaneously that a reactor is under the condition of simply changing the stirring rake for multiple cultivation mode.
Description
The divisional application of utility model that this utility model is application number is 201520576425.7, the applying date is on August 3rd, 2015, denomination of invention is " air guide and bioreactor ".
Technical field
This utility model belongs to field of cell culture, is specifically related to cell cultivation chip carrier and bioreactor.
Background technology
It is a requisite process that cell is cultivated for biotechnology.Cell type, according to whether invest the characteristic of growth on holder, is divided into attaching type and floating type.Cell attachment grows in support surface, only relies on and attaches the cell that could grow and be called attaching type cell.Floating type cell does not then attach on the support.Most animals cell has the custom of adherent growth, and therefore isolated culture conventional glass, plastics etc. are as holder.
Bioreactor is by the reaction unit that biological product produce, and is the capital equipment of bioprocesses, plays central role in bioprocesses.Bioreactor has multiple pattern: fixing bed, fluid bed, gas-lifting type, stirring paddle.Fixed-bed bioreactor can be divided into again packed bed reactor, trickle bed reactor and solid fermentation device.Bed transfixion in fixed-bed bioreactor, fluid is reacted by bed.
Summary of the invention
This utility model provides a kind of cell cultivation chip carrier, and this chip carrier connects hinge on the same axis containing 3-10 sheet, and hinge is flared out.
In a detailed description of the invention, this chip carrier is containing 3-8 sheet hinge.
In a detailed description of the invention, hinge is made up of polyester fiber.
In a detailed description of the invention, hinge length 4～30mm, wide 2～20mm, thick 0.1～1mm.
In a detailed description of the invention, hinge length 4～15mm, wide 2～8mm, thick 0.1～0.5mm.
This utility model also provides for a kind of air guide, this air guide front view is I-shaped, guide shell including the described upper plate of upper plate, lower plate and connection and lower plate, wherein, described guide shell both ends open is separately positioned in described upper plate and lower plate, and is provided with multiple through hole on described upper plate and lower plate.
In a detailed description of the invention, the area of described through hole is 0.5～2cm2。
In a detailed description of the invention, described through hole is circular, square or triangle.
In a detailed description of the invention, upper plate and in lower plate the density of through hole be 20～150 hole/square decimeters.
In a detailed description of the invention, upper plate and/or lower plate (are such as riveted) removably with guide shell and are connected with guide shell.
In a detailed description of the invention, upper plate and one of lower plate or both be connected in non-removable mode (such as welding) with guide shell, form an entirety.
This utility model also provides for a kind of bioreactor, and described bioreactor includes:
(1) shell；With
(2) air guide；
Wherein, described air guide is placed in described enclosure, and front view is I-shaped, guide shell including the described upper plate of upper plate, lower plate and connection and lower plate, wherein, described guide shell both ends open is separately positioned in described upper plate and lower plate, and is provided with multiple through hole on described upper plate and lower plate.
In a detailed description of the invention, described bioreactor also includes agitator, is used for driving fluid to flow downward along guide shell.
In a detailed description of the invention, described agitator includes stirring screw or tilting stirring paddle.
In a detailed description of the invention, stirring paddle is set and is positioned at guide shell.
In a detailed description of the invention, described bioreactor also includes chip carrier, and this chip carrier connects hinge on the same axis containing 3-10 sheet, and hinge is flared out.
In a detailed description of the invention, described chip carrier is set and is arranged in the inner space that air guide upper plate, lower plate, guide shell and bioreactor shell limit.
In a detailed description of the invention, in inner space, the amount of chip carrier is 25～45 g/l.
In a detailed description of the invention, described bioreactor is provided between upper plate and reactor head and leaves space between lower plate and reactor bottom, to allow fluid to flow downward along guide shell, enter described inner space through lower plate through hole, be upward through upper plate through hole, then flow down from guide shell.
In a specific embodiment, the bioreactor of the present invention includes:
Shell；
It is placed in this utility model air guide in described shell；With
Agitator；
Wherein, described agitator includes screw stirring paddle or tilting stirring paddle, and described screw stirring paddle or tilting stirring paddle are positioned at the middle and upper part of the guide shell of air guide, and exceed the upper plate of air guide；
Described bioreactor is provided between the upper plate of air guide and reactor head and leaves space between lower plate and the reactor bottom of air guide, after allowing fluid to flow downward along the guide shell of air guide, it is upward through lower plate through hole and enters in the inner space that air guide upper plate, lower plate, guide shell and bioreactor shell limit, and be upward through upper plate through hole, then flow down from guide shell；
With optional, described bioreactor also includes the chip carrier described in the utility model being filled in described inner space.
Accompanying drawing explanation
Fig. 1 shows the schematic diagram of one chip carrier of this utility model.
Fig. 2 shows an example of the stirring paddle being applicable to bioreactor of the present utility model.
Fig. 3 shows another example of the stirring paddle being applicable to bioreactor of the present utility model.
Fig. 4 shows an example of this utility model air guide.
Fig. 5 shows an example of this utility model bioreactor.
Fig. 6 shows the example that this utility model bioreactor is specifically used.
The curve of sugar/ventilation/dissolved oxygen stream dosage after the inoculation of Fig. 7 showed cell.
After the virus that shows Fig. 8 accesses the 3rd day starts virus titer curve.
Detailed description of the invention
This utility model provides a kind of cell cultivation chip carrier, for the air guide in bioreactor, and the bioreactor containing air guide.
Chip carrier
Chip carrier of the present utility model, containing 3～10 hinges being connected on same axle, is flared out.Distance between hinge and hinge is not fixed, and can change according to ambient pressure.
In a detailed description of the invention, chip carrier is containing 3～8 hinges.
Chip carrier especially its hinge can be made up of various polyester fibers well known in the art.Axle both can be made up of polyester fiber, it is possible to adopts other material to make, but generally adopts polyester fiber to make, and namely hinge and axle have identical material to make, with lamellar all-in-one-piece structure.
Generally, hinge length (namely axle 101 is long) 4～30mm, wide 2～20mm, thick 0.1～1mm.
In certain embodiments, hinge length 4～20mm, wide 2～12mm, thick 0.1～0.8mm.
In other embodiments, hinge length 4～15mm, wide 2～8mm, thick 0.1～0.5mm.
Chip carrier of the present utility model is applicable to the cultivation of the anchorage-dependent cell such as mammalian cell, insect cell, in order to produce the product such as secreted protein and virus.It is suitable for carrying out cultured cells with chip carrier of the present utility model and includes but not limited to VERO, CHO, BHK, MDCK, ST, MARC-145, MRC-5, SF9, HEK293,123A, 127A, GAMMA and primary cell etc..
Chip carrier of the present utility model can use in the bioreactors such as packed bed bioreactor, disposable bioreactor, culture vessel, SPINNER, and the growth for cell provides sufficient surface area.
Fig. 1 shows example, i.e. chip carrier 100 of this utility model chip carrier.This chip carrier 100 comprises hinge, such as 102 and 103.In Fig. 1, chip carrier 100 is containing 5 hinges.All hinges are centripetal to be connected on identical axle 101, is flared out.
Air guide
Air guide of the present utility model is I-shaped, and including the guide shell of upper plate, lower plate and connection upper plate and lower plate, described guide shell is opened in upper plate and lower plate.
Upper plate and lower plate have multiple through hole, to allow fluid to flow through.Hole is generally circular but it also may be other shape, such as square, triangle etc..The area in hole is generally at 0.5～2cm2Left and right.On every block of plate, the quantity in hole is not limit, and density is not limit, and can determine according to the size of bioreactor, purposes etc..Such as, in upper plate and lower plate, the density in hole may be configured as 20～150 hole/square decimeters.For the distance between Kong Yukong also without particular restriction, it is generally equidistant.Size between Kong Yukong also can be different, but usual porose area is all the same.The quantity in the hole in the quantity in the hole on upper plate, size and lower plate, size may be the same or different.
The diameter of upper plate and lower plate is typically smaller than the internal diameter equal to bioreactor shell.To the thickness of upper plate and lower plate also without particular/special requirement.
The diameter of guide shell, length are also not particularly limited, can determine according to the size etc. of the size of bioreactor, stirring paddle.Guide shell is generally circular, naturally it is also possible to be the shape that other is suitable, as long as it can be taken agitator in and allow fluid from.
Air guide generally adopts rustless steel to make, and certainly may be used without other material, for instance glass or plastics are made.
In air guide, upper plate and/or lower plate can be connected with guide shell removably with guide shell in (such as riveted joint), or, upper plate and one of lower plate or both be connected in non-removable mode (such as welding) with guide shell, form an entirety.
Fig. 4 illustrates example, i.e. air guide 400 of air guide.Air guide 400 includes upper plate 401, lower plate 403, guide shell 402 and hole 404 and 405 etc..
Bioreactor
This utility model includes bioreactor, and this bioreactor includes shell and is placed in the air guide within shell.Generally, air guide is coaxial with shell.Air guide generally takes up more than the 1/2 of bioreactor body height, at most can be consistent with body height.The main body of bioreactor refers to that shell of reactor does not include the part that upper and lower reduces.Such as, in the reactor shown in Fig. 5, its main body refers to that shell is cylindrical part.
Bioreactor may also include opening, is usually located at shell two ends.Available lid is by the top of reactor and sealed bottom.Lid can have corresponding opening and closure mechanism.
Fig. 5 illustrates an example of this utility model bioreactor.In Fig. 5, bioreactor 500 has shell 501, opening 502 and 503 and be placed in the air guide 400 within shell 501.
To the shell shape of bioreactor without particular restriction.Generally its main body is cylindrical.The lower interior portion of bioreactor can include the holder (not shown) protruded, in order to support air guide.Certainly, (as seen Fig. 5 and 6) in the diminishing situation of bioreactor lower body part, holder can be not provided with.In the case, air guide can be placed in this bioreactor naturally without falling.Generally, enough distances are left between air guide lower plate and reactor bottom, to allow fluid to flow out from the guide shell of air guide, and it is upward through in the inner space that through hole enters air guide upper plate, the shell of lower plate and guide shell and reactor limits of lower plate.As it can be seen in figures 5 and 6, this inner space is used for filling chip carrier of the present utility model.
Bioreactor may also include agitator.Agitator generally includes stirring paddle and drives the motor of stirring paddle running.Generally, stirring paddle is set in air guide, flows from the top down in guide shell in order to control fluid, after reserving air guide, flowed up by the hole of air guide lower plate, and flowed out by the hole of air guide upper plate, then flow downward from the guide shell of air guide again.Generally stirring paddle is arranged on the middle and upper part of guide shell, and slightly above upper plate, for instance exceed 0.5～5cm.
Include but not limited to adopt the screw stirring paddle of upper stirring or tilting stirring paddle suitable in stirring paddle of the present utility model.Fig. 2 illustrates an example suitable in stirring paddle of the present utility model, for screw stirring paddle 200.Fig. 3 illustrates an example suitable in stirring paddle of the present utility model, for tilting stirring paddle 300.Stirring paddle can be driven (see Fig. 6) by the motor being placed in outside bioreactor.
Bioreactor of the present utility model may also include chip carrier of the present utility model.As it was previously stated, described chip carrier is arranged in the inner space that the shell of air guide upper plate, lower plate and guide shell and reactor limits.
Can according to the size of bioreactor, treat that the factors such as cultured cells arrange the quantity of chip carrier in described inner space.Generally, the amount of the chip carrier of filling is 25～45 g/l, and multilamellar can be divided to fill.
Fig. 5 show schematically show this utility model chip carrier 100 and stirring paddle 200 that contain in bioreactor 500.Should be understood that in Fig. 5, the position of stirring paddle 200 is merely schematic.As it was previously stated, generally stirring paddle to be arranged on the middle and upper part of guide shell, and slightly above upper plate, for instance exceed 0.5～5cm.
Reactor may also include other for the opening with external connection, in order to measure the pH of reactant in such as reactor, temperature, DO value etc..
Fig. 6 illustrates after being filled in bioreactor of the present utility model by the chip carrier of this utility model carrier, and this reactor is connected to the schematic diagram in actual production circuit.
In Fig. 6, under the driving of stirring paddle, fluid, for instance cell culture fluid flows downward along air guide under the propelling of stirring paddle, then pass through the bed being filled with chip carrier, for the cells with nutrient composition of growth.Arrow indication is the flow direction of fluid.
Advantage of the present utility model
The carrier bed of this utility model employing and the novel combination of stirring paddle, be conducive to reducing shearing force, improve liquid flux, increase dissolved oxygen effect, accomplish that a reactor is when providing for simple replacement of stirring paddle, for multiple training method simultaneously.
Additionally, when using bioreactor of the present utility model to carry out cell cultivation, also have the advantage that
(1) culture medium flows through carrier layer, and stirring shearing force does not produce impact with ventilation bubble cell growth；
(2) energy isolation medium efficient, simple and cell, results product is cultivated with realizing tank stream；
(3) high area to volume ratio, cell density is high；
(4) tension structure of multilamellar, it is ensured that culture medium and cell are fully contacted, favourable Growth of Cells；
(5) Growth of Cells is being similar to the resting state of rolling bottle, and incubation is simple, easy to control；With
(6) highdensity cell can be reached cultivate, be used for producing the biological product such as virus, albumen.
Hereafter will set forth the present invention in the way of specific embodiment.Should be understood that these specific embodiments are only illustrative, what do not limit the present invention comprises scope.In embodiment, the method for employing, reagent, cell etc. are all the conventional method of this area, reagent and cell.
Embodiment 1, cell density detection test
Cleaning up the solid fluidized bed bioreactor of 10L, connect each joint and filter, pipeline, load chip carrier 250 grams, inject PBS, sterilizing, after cooling, the DMEM culture medium of the serum with 10% replaces PBS, preculture at least 24 hours.
Recovery VERO cell, is expanded to and turns 3L bottle, and cell state is good, and quantity is at 1.5 hundred million to 2.0 hundred million/bottles.By working volume 8L, access cell and make cell density 1.0～2.5 × 105Individual/milliliter, controls pH 7.2, DO 35～50%, and mixing speed, at 100～150RPM, started perfusion after 8 hours and cultivates, control residual sugar between 0.5～1.5.After cultivating 120 hours, stop cultivating.Taking 3 points at random the upper, middle and lower of bed is each respectively, each point takes 32, peptic cell, the quantity of counting cells.
Carrier cell density test data such as table 1 below:
Table 1
Embodiment 2, the test of cultivation SAD vaccine on cell BSR
Clean up the solid fluidized bed bioreactor of 30L, connect each joint and filter, pipeline, carrier loaded 1000 grams, inject PBS, after sterilizing, cooling, the DMEM culture medium displacement PBS of the serum with 10%, preculture at least 24 hours.
Recovery bsr cell, is expanded to and turns 3L bottle, and cell state is good, and quantity is at 1.5 hundred million to 2.0 hundred million/bottles.By working volume 30L, access cell and make cell density 1.0～2.5 × 105Individual/milliliter, control pH 7.2, DO is 35～50%, mixing speed, at 100～150RPM, started perfusion after 8 hours and cultivates, control residual sugar between 0.5～1.5, after cultivating 120 hours, change the DMEM of serum-free into, and access pseudorabies SAD strain, started the virus in perfusion harvest liquid is detected after the 3rd day.
Relevant parameter in perfusion culture fluid is detected by incubation, to monitor the state of Growth of Cells.
After SAD virus accesses, the value of detection relevant parameter, monitoring virus production.
Result shows in figures 7 and 8.
Claims (6)
1. a cell cultivation chip carrier, it is characterised in that described chip carrier connects hinge on the same axis containing 3-10 sheet, and hinge is flared out.
2. cell cultivation chip carrier as claimed in claim 1, it is characterised in that described chip carrier is containing 3-8 sheet hinge.
3. cell cultivation chip carrier as claimed in claim 1 or 2, it is characterised in that described hinge is made up of polyester fiber.
4. cell cultivation chip carrier as claimed in claim 1 or 2, it is characterised in that described hinge length 4～30mm, wide 2～20mm, thick 0.1～1mm.
5. cell cultivation chip carrier as claimed in claim 4, it is characterised in that described hinge length 4～15mm, wide 2～8mm, thick 0.1～0.5mm.
6. a bioreactor, it is characterised in that described bioreactor includes:
Shell；
It is placed in the air guide in described shell；
Agitator；With
Chip carrier according to any one of claim 1-5；
Wherein, described agitator comprises screw stirring paddle or tilting stirring paddle, and described screw stirring paddle or tilting stirring paddle are positioned at the middle and upper part of the guide shell of air guide, and exceed the upper plate of air guide；
Described air guide front view is I-shaped, and including the guide shell of the described upper plate of upper plate, lower plate and connection and lower plate, wherein, described guide shell both ends open is separately positioned in described upper plate and lower plate, and is provided with multiple through hole on described upper plate and lower plate；The area of described through hole is 0.5～2cm2, for circular, square or triangle；On upper plate and lower plate, the density of through hole is 20～150 hole/square decimeters；And upper plate and/or lower plate are connected with guide shell in detachable or non-removable mode with guide shell；
Described bioreactor is provided between the upper plate of air guide and reactor head and leaves space between lower plate and the reactor bottom of air guide, after allowing fluid to flow downward along the guide shell of air guide, it is upward through lower plate through hole and enters in the inner space that air guide upper plate, lower plate, guide shell and bioreactor shell limit, and be upward through upper plate through hole, then flow down from guide shell；With
Described chip carrier is filled in described inner space.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201520920664.XU CN205347443U (en) | 2015-08-03 | 2015-08-03 | Chip carrier and bioreactor for cell culture |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201520920664.XU CN205347443U (en) | 2015-08-03 | 2015-08-03 | Chip carrier and bioreactor for cell culture |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201520576425.7U Division CN205062084U (en) | 2015-08-03 | 2015-08-03 | Air guide and bioreactor |
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| Publication Number | Publication Date |
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| CN205347443U true CN205347443U (en) | 2016-06-29 |
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| Application Number | Title | Priority Date | Filing Date |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN109182123A (en) * | 2018-07-27 | 2019-01-11 | 安徽细胞之星生物科技有限公司 | A kind of cell culture bed for bioreactor |
-
2015
- 2015-08-03 CN CN201520920664.XU patent/CN205347443U/en active Active
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN109182123A (en) * | 2018-07-27 | 2019-01-11 | 安徽细胞之星生物科技有限公司 | A kind of cell culture bed for bioreactor |
| CN109182123B (en) * | 2018-07-27 | 2021-06-22 | 安徽细胞之星生物科技有限公司 | Cell culture bed for bioreactor |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Chen Ling Inventor after: Liang Hongyang Inventor before: Chen Ling |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20200123 Address after: 101111 No.6, boxing 2nd Road, economic and Technological Development Zone, Daxing District, Beijing Patentee after: Beijing Biological Products Research Institute Co., Ltd. Address before: 201114 room 232, no.1266, Pujin Road, Minhang District, Shanghai Patentee before: SHANGHAI CHUKUN BIOLOGICAL TECHNOLOGY CO., LTD. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20200309 Address after: 201419 No.31, Lane 9688, Puxing Road, Fengxian District, Shanghai Co-patentee after: Beijing Biological Products Research Institute Co., Ltd. Patentee after: SHANGHAI CHUKUN BIOLOGICAL TECHNOLOGY CO., LTD. Address before: 101111 No.6, boxing 2nd Road, economic and Technological Development Zone, Daxing District, Beijing Patentee before: Beijing Biological Products Research Institute Co., Ltd. |