CN114276927B - Folding carrier column for bioreactor - Google Patents
Folding carrier column for bioreactor Download PDFInfo
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- CN114276927B CN114276927B CN202111636965.6A CN202111636965A CN114276927B CN 114276927 B CN114276927 B CN 114276927B CN 202111636965 A CN202111636965 A CN 202111636965A CN 114276927 B CN114276927 B CN 114276927B
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- 239000001963 growth medium Substances 0.000 claims description 8
- 239000000969 carrier Substances 0.000 claims description 5
- 239000000463 material Substances 0.000 claims description 3
- 239000004745 nonwoven fabric Substances 0.000 claims description 2
- 238000004113 cell culture Methods 0.000 abstract description 13
- 210000004102 animal cell Anatomy 0.000 abstract description 4
- 230000030833 cell death Effects 0.000 abstract description 2
- 239000007788 liquid Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 238000005192 partition Methods 0.000 description 4
- 239000006143 cell culture medium Substances 0.000 description 3
- 230000008093 supporting effect Effects 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000001503 joint Anatomy 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 238000005273 aeration Methods 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000012930 cell culture fluid Substances 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
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- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The invention discloses a folding carrier column for a bioreactor, which comprises a folding carrier column unit, wherein the folding carrier column unit comprises a first cylinder body and a second cylinder body which are sleeved with each other, a first window is arranged on the side wall of the first cylinder body, a culture solution filled in the first cylinder body from the lower end of an opening flows unidirectionally and is filled in a first cavity sealed between the first cylinder body and the second cylinder body under the action of pressure, a second window is arranged on the side wall of the second cylinder body, the culture solution filled in the first cavity flows unidirectionally and is further filled in a second cavity between the second cylinder body and the inner wall of the reactor under the action of pressure, the second cavity is filled in the first cylinder body again through the lower end of the first cylinder body to form circulation, and a folding carrier with a plurality of folding surfaces is arranged in the first cavity. The invention can take the carrier out of the reactor integrally, can prevent cell death caused by extracting the cell culture solution, obviously improves the surface area of the carrier, and can realize large-scale culture of various animal cells.
Description
Technical Field
The invention relates to the technical field of biological pharmaceutical equipment, in particular to a folding carrier column for a bioreactor.
Background
Cell growth vectors come in a wide variety of forms, but fall broadly into two broad categories, microcarriers and sheet-like carriers from the GE company.
At present, whether microcarriers or sheet-like carriers are distributed in an irregular manner on the bottom of the bioreactor when being put into use. The capacity of the bioreactor is greatly difficult to amplify due to the influence of the metabolism of cells and the distribution of cell culture fluid.
In particular, in the fluidized bed reactor, the cell culture medium is extracted together with the cell culture medium during the extraction of the cell culture medium, which makes the operation difficult.
Meanwhile, the granular cell culture carrier is difficult to repeatedly treat after cell culture is completed, and the use efficiency of the bioreactor is affected.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a folding carrier column for a bioreactor.
The technical scheme for achieving the aim is as follows:
a folding carrier column for a bioreactor, comprising:
The folding carrier column unit comprises a first cylinder body and a second cylinder body which are mutually sleeved and longitudinally suspended in the reactor, the upper end of the first cylinder body is closed, a first window is arranged on the side wall of the first cylinder body and used for enabling culture solution filled in the first cylinder body from the lower end of an opening to flow unidirectionally under the action of pressure and to be filled in a first cavity sealed between the first cylinder body and the second cylinder body through the first window, a second window is arranged on the side wall of the second cylinder body and used for enabling the culture solution filled in the first cavity to flow unidirectionally and further to be filled in a second cavity between the second cylinder body and the inner wall of the reactor under the action of pressure through the second window, the second cavity is filled in the first cylinder body again through the lower end of the first cylinder body to form circulation, and a folding carrier with a plurality of folding surfaces is arranged in the first cavity.
Further, the number of the folding carrier column units is one to a plurality, and when the number of the folding carrier column units is a plurality, each folding carrier column unit is suspended in the reactor in a surrounding manner.
Further, the plurality of folding carrier column units are suspended in the reactor in a manner of abutting joint of the upper ends and the lower ends of the first cylinder bodies respectively, wherein the first cylinder bodies of the folding carrier column units are communicated with each other, the upper end of the first cylinder body of the uppermost folding carrier column unit is closed, and the lower end of the first cylinder body of the lowermost folding carrier column unit is provided with an opening for filling culture solution into the first cylinder body Fang Gesuo.
Further, the plurality of folding carrier column units are suspended in the reactor in a manner of butt joint of the upper ends and the lower ends of the first cylinder bodies in sequence to form a folding carrier column unit group, in the folding carrier column unit group, the first cylinder bodies of the folding carrier column units are mutually communicated, the upper end of the first cylinder body of the uppermost folding carrier column unit is closed, the lower end of the first cylinder body of the lowermost folding carrier column unit is provided with an opening, the upper end of the first cylinder body is used for filling culture solution into the first cylinder body Fang Gesuo, the folding carrier column unit group is a plurality of folding carrier column unit groups, and the folding carrier column unit groups are suspended in the reactor in a surrounding manner.
Further, the carrier comprises a folding carrier with a plurality of folding surfaces which takes the first cylinder body as a center and is radially distributed towards the second cylinder body.
Further, the carrier comprises a first carrier and a second carrier which are arranged in the first cavity in a stacked manner; the number of the radial folding surfaces on the first carrier is larger than that of the radial folding surfaces on the second carrier, and/or the height of the first carrier is smaller than that of the second carrier.
Further, the carrier material comprises a nonwoven fabric.
Further, a grid and a mesh are arranged on the side wall of the second cylinder in a surrounding mode, and the mesh serves as the second window.
Further, the folding carrier column unit is configured to rotate and revolve in the reactor, the culture liquid is pumped up into the first cylinder from the open lower end of the first cylinder, flows unidirectionally through the first window and fills the first cavity under the combined action of pressure and centrifugal force, and further flows unidirectionally through the second window and fills the second cavity under the combined action of pressure and centrifugal force.
Further, the upper end of the first cavity is closed by an end cover, the carrier is fixed in the first cavity through a filter screen arranged between the upper end of the carrier and the end cover, and rotary interfaces are respectively arranged at the upper end and the lower end of the first cylinder.
Compared with the prior art, the invention has the following advantages:
(1) The whole flaky folding carrier replaces the traditional small granular carrier, breaks through the traditional technical mode, greatly reduces labor cost and reduces carrier loss.
(2) The folding carrier is arranged in the folding carrier column unit and can be integrally taken out along with the carrier column, so that the defect of the traditional manual net bag for taking is overcome, and the situation that the cell culture carrier is also extracted together when the cell culture liquid is extracted in the past to cause cell death is perfectly solved.
(3) By designing the folding carrier with a plurality of folding surfaces in radial distribution, not only a good supporting surface for cell growth is provided, but also the surface area of the cell culture carrier is remarkably increased, and a large-scale effective culture of various animal cells can be realized.
(4) Through scientific design carrier column structure, successfully establish the unidirectional circulation route of culture solution between carrier column inside (first cavity) and reactor inside (second cavity and third cavity) to the circulation effect of culture solution has been improved.
(5) By arranging a plurality of carrier column units and different combination forms between the carrier column units, the capacity of the bioreactor can be amplified, and the productivity is obviously improved.
(6) The carriers are layered in the carrier column unit in a vertically stacking mode, so that the structural strength of the carriers in the carrier column is improved, and the problem of small carrier bearing capacity is successfully solved.
(7) By arranging the culture solution flowing window on the side surface of the carrier column unit, the rotation and revolution of the carrier column in the reactor can be utilized, so that the culture solution can flow and circulate under the combined action of pressure and centrifugal force, the proportion of dissolved oxygen is obviously improved, and the cell growth is effectively promoted.
Drawings
FIGS. 1-3 are schematic views of a folding support column for a bioreactor according to a preferred embodiment of the present invention.
Fig. 4 is a schematic view showing a transverse arrangement structure of a carrier in a folding carrier column unit according to a preferred embodiment of the present invention.
Fig. 5 is a schematic view showing a longitudinal arrangement structure of a carrier in a folding carrier column unit according to a preferred embodiment of the present invention.
Fig. 6 is a schematic diagram showing the combined structure of a folding type carrier column unit according to a preferred embodiment of the present invention.
FIG. 7 is a schematic diagram showing a structure of a folding carrier column for a bioreactor according to a preferred embodiment of the present invention applied to a bioreactor.
Detailed Description
In order to better understand the technical scheme of the present invention, the present invention will be described in detail by means of specific embodiments.
Please refer to fig. 1. A folding carrier column for a bioreactor of the present invention comprises one or more folding carrier column units 14. Wherein the folding carrier column unit 14 includes a first cylinder 141 and a second cylinder 142; the first cylinder 141 and the second cylinder 142 are nested with each other in a parallel manner and can be suspended in the reactor in a longitudinal direction.
In a preferred embodiment, the first cylinder 141 and the second cylinder 142 comprise cylindrical cylinders, and the cylindrical cylinders of the first cylinder 141 and the cylindrical cylinder of the second cylinder 142 are coaxially sleeved with each other.
Please refer to fig. 1. In use, the upper end of the first cylinder 141 is a closed end, and the lower end of the first cylinder 141 is an open end. Further, a closed space is formed between the upper end of the first cylinder 141 and the upper end of the second cylinder 142, and a closed space is also formed between the lower end of the first cylinder 141 and the lower end of the second cylinder 142, so that a closed first cavity 146 is formed between the side wall of the first cylinder 141 and the side wall of the second cylinder 142 (refer to fig. 4).
The first cavity 146 is internally provided with a carrier 143 providing a cell growth support surface. The invention adopts the folding carrier 143 with a plurality of folding surfaces arranged in the first cavity 146, which is used for providing the carrier 143 with larger surface area for cell culture and improving the productivity and the efficiency of cell culture.
Please refer to fig. 2. A first window 1411 is provided on a sidewall of the first cylinder 141, and a second window 1421 is provided on a sidewall of the second cylinder 142. The first window 1411 and the second window 1421 are communicated through the first cavity 146 such that the carrier 143 disposed in the first cavity 146 is communicated with the inside of the first cylinder 141 through the first window 1411 and is communicated with the outside of the folding carrier column unit 14 through the second window 1421.
In this way, the culture liquid 13 can be filled into the first cylinder 141 from the open lower end of the first cylinder 141 by the pressure applied to the culture liquid 13. Since the upper end of the first cylinder 141 is in a closed state, the culture solution 13 introduced into the inside of the first cylinder 141 flows unidirectionally into the first cavity 146 through the first window 1411 under pressure, and fills the first cavity 146, so that the carrier 143 in the first cavity 146 is immersed in the culture solution 13, and cells adhered to the surface of the carrier 143 are cultured.
Meanwhile, since the second window 1421 is further provided on the side wall of the second cylinder 142, the culture solution 13 in the first cavity 146 continues to flow through the second window 1421 in one direction through the carrier 143 into the second cavity 11 between the second cylinder 142 and the inner wall of the reactor, i.e., into the chamber of the reactor 10 between the folded carrier column unit 14 and the inner wall of the reactor 10, and can flow back from the second cavity 11, under pressure, is refilled into the first cylinder 141 through the lower end of the first cylinder 141, thereby forming dynamic circulation of the culture solution 13, as shown in fig. 7.
In a preferred embodiment, the first window 1411 and the second window 1421 may be laterally disposed strip-shaped windows, i.e., the lateral length of the first window 1411 and the second window 1421 is greater than the vertical height of the first window 1411 and the second window 1421.
Also, the first and second windows 1411 and 1421 may be provided in plurality on the sidewalls of the first and second cylinders 141 and 142, respectively, such that a plurality of folding surfaces of the carrier 143 can be exposed through each of the first and second windows 1411 and 1421.
In a preferred embodiment, any two adjacent first windows 1411 and any two adjacent second windows 1421 may be arranged in a staggered manner in the vertical direction, for example, a pattern may be formed between the first windows 1411 in the delta shape, and a pattern may be formed between the second windows 1421 in the delta shape, as shown in fig. 2.
Further, in the horizontal direction, each (each layer) of the first windows 1411 may be located at the same vertical level as one (one layer) of the second windows 1421 on the opposite side. Or the first window 1411 and the second window 1421 on the opposite side may be staggered in the vertical direction. Still further, the number and layer number of the first windows 1411 provided on the first cylinder 141 may be the same as or different from the number and layer number of the second windows 1421 provided on the second cylinder 142.
In a preferred embodiment, the sidewalls of the first window 1411 and the second window 1421 have an inclination angle toward the outside, respectively, such that the first window 1411 and the second window 1421 are wide-angle windows opened toward the outside.
Please refer to fig. 3. In a preferred embodiment, the side wall of the second cylinder 142 is uniformly provided with grids and meshes around the side wall of the second cylinder 142, wherein the meshes serve as the second windows 1421, so as to promote the flow circulation of the culture solution 13 to the greatest extent. The folding carrier column unit 14 can maintain the stability of the overall structure by virtue of the supporting action of the first cylinder 141.
The first window 1411 and the second window 1421 function as inlets and outlets, respectively, for flow renewal of the culture broth 13 disposed on the closed first cavity 146.
Please refer to fig. 4. In a preferred embodiment, the carrier 143 may be a folded carrier 143 radially disposed about the axis of the first cylinder 141 and toward the side wall of the second cylinder 142 when viewed in a vertical direction, the folded carrier 143 having a plurality of folding surfaces formed in a repeatedly folded manner, each folding surface being connected end to end and surrounding the periphery of the first cylinder 141 to form a vertical cylindrical structure having a radial folding surface profile with a relatively larger surface area for providing a cell culture support surface.
Please refer to fig. 5. In a preferred embodiment, the carrier 143 may include a first carrier 1431 and a second carrier 1432 as viewed in a horizontal direction; and, the first carrier 1431 and the second carrier 1432 are disposed in the first cavity 146 in a stacked manner.
In a preferred embodiment, the number of folds of the radial fold surface on the upper first carrier 1431 is set to be greater than the number of folds of the radial fold surface on the lower second carrier 1432.
In a preferred embodiment, the vertical height of the first carrier 1431 may be set smaller than the vertical height of the second carrier 1432.
In this way, the second carrier 1432 with relatively fewer folds and relatively higher height can be used as the supporting structure of the first carrier 1431 with relatively more folds and relatively lower height, so that the problem of structural collapse caused by the increase of weight of the carrier 143 after the growing cells are fully loaded due to softer material can be eliminated, and the convective capacity of the culture solution 13 in the first cavity 146 can be promoted by using the structural independence between the first carrier 1431 and the second carrier 1432.
In a preferred embodiment, the carrier 143 material may comprise a nonwoven. But the present invention is not limited thereto.
Please refer to fig. 6-7. In a preferred embodiment, when there are a plurality of folding carrier column units 14, each folding carrier column unit 14 may be suspended in a surrounding manner in the reactor 10 (the second cavity 11). For example, six folding carrier column units 14 are shown, which are uniformly suspended in the reactor 10 in such a manner as to surround the center (guide cylinder 12) of the reactor 10, so that the volume of the reactor 10 can be enlarged by correspondingly enlarging the area of the reactor 10, the yield of cell culture can be significantly increased, and large-scale effective cultivation of various animal cells can be realized.
In a preferred embodiment, when there are a plurality of folding carrier column units 14, each folding carrier column unit 14 may be suspended in the reactor 10 in a manner of abutting the upper and lower ends of the respective first cylinder 141. The first cylinders 141 of the respective folding carrier column units 14 are connected to each other with their upper ends and lower ends in butt joint, the upper end of the first cylinder 141 of the uppermost folding carrier column unit 14 is closed, and the lower end of the first cylinder 141 of the lowermost folding carrier column unit 14 is opened for filling the culture medium 13 into the first cylinders 141. Thereby the volume of the reactor 10 can be enlarged by correspondingly increasing the height of the reactor 10, and the output of cell culture can be obviously increased, so that various animal cells can be effectively cultured on a large scale.
In a preferred embodiment, a plurality of folding carrier column units 14 are suspended in the reactor 10 in a manner of abutting the upper and lower ends of the respective first cylinders 141 in sequence to form a folding carrier column unit group. In each folding carrier column unit group, the first cylinder bodies 141 of the folding carrier column units 14 are mutually communicated, the upper end of the first cylinder body 141 of the uppermost folding carrier column unit 14 is closed, and the lower end of the first cylinder body 141 of the lowermost folding carrier column unit 14 is provided with an opening for filling the culture solution 13 into each first cylinder body 141. And, a plurality of folding type carrier column unit groups are provided so that each folding type carrier column unit group is suspended in the reactor 10 in a surrounding manner. Thus, a larger scale cell culture can be achieved by further expanding the volume of the reactor 10 by increasing both the area and the height of the reactor 10.
Please refer to fig. 7. In a preferred embodiment, the folding carrier column unit 14 may be configured to spin in the reactor 10 and revolve around the center of the reactor 10. The advantage of this arrangement is that when the culture medium 13 is pumped up into the first cylinder 141 from the open lower end of the first cylinder 141 by the stirring pump 16, it smoothly flows unidirectionally through the first window 1411 and fills the first cavity 146 under the combined action of the pumping pressure and the rotational centrifugal force, and further smoothly flows unidirectionally through the second window 1421 and fills the second cavity 11 under the combined action of the pressure and the centrifugal force. Meanwhile, by using the rotation and revolution arrangement of the folding type carrier column unit 14, a certain stirring effect can be exerted on the culture liquid 13 in the reactor 10 (the second cavity 11), so that the Dissolved Oxygen (DO) content can be further improved, thereby improving the cell culture efficiency.
Please refer to fig. 1. In a preferred embodiment, the lower end of the first cavity 146 may be closed by a bottom plate 145.
In an example, the lower end of the first cylinder 141 may be exposed to the lower end surface of the second cylinder 142, and the bottom plate 145 may be provided with a mounting hole corresponding to the outer diameter of the first cylinder 141. The bottom plate 145 is sleeved on the first cylinder 141 from the lower end of the first cylinder 141 through the mounting hole, and the inner edge and the outer edge of the bottom plate 145 are respectively fixed with the side wall of the lower end of the first cylinder 141 and the end face of the lower end of the second cylinder 142, so that the lower end of the first cavity 146 is closed.
In a preferred embodiment, an external rotation port may be provided on the end surface of the lower end of the first cylinder 141 exposed to the bottom plate 145, for screwing with the bottom surface of the second cavity 11 of the reactor 10, or for screwing with the internal rotation port of the upper end of the first cylinder 141 of another folding carrier column unit 14 to be stacked below. Thus, when the cultivation is completed, the folding carrier column unit 14 can be disengaged from the bottom surface of the second cavity 11 of the reactor 10 by rotating the folding carrier column unit 14, so that the folding carrier column unit 14 can be conveniently lifted out of the reactor 10.
A plurality of connected folding carrier column units 14 can also be conveniently separated.
In a preferred embodiment, the upper end of the first cavity 146 may be closed by a removable end cap 144.
In an example, the upper end of the first cylinder 141 may be flush with or near the upper end of the second cylinder 142, and the end cap 144 may be configured in a flange shape, such that the flange of the end cap 144 corresponds to the upper port diameter of the first cylinder 141. Wherein, an inner rotary interface is provided on the inner wall of the flange opening of the end cover 144, and is used for being matched with the sealing cover to seal the upper end of the first cylinder 141 in a screwing way, or is communicated with the outer rotary interface of the lower end of the first cylinder 141 of another folding carrier column unit 14 which needs to be stacked above in a screwing way.
Further, the outer periphery of the end cover 144 is further provided with external threads, and the inner wall of the upper end of the second cylinder 142 is correspondingly provided with internal threads. After the carrier 143 is put into the first cavity 146, when the first cavity 146 is closed, the flange opening of the end cover 144 is aligned with the upper end of the first cylinder 141, the internal rotation opening on the inner wall of the flange opening of the end cover 144 is utilized to be matched with the external threads arranged on the outer side of the upper end of the first cylinder 141, and meanwhile, the end cover 144 is screwed on the upper ends of the first cylinder 141 and the second cylinder 142 simultaneously by utilizing the external threads on the periphery of the end cover 144 and the internal threads on the inner wall of the upper end of the second cylinder 142, so that the first cavity 146 is closed, and the stability of the structure of the folding carrier column unit 14 is realized.
In an alternative embodiment, the end cap 144 and the flap may be integral.
In a preferred embodiment, a screen may also be disposed in the first cavity 146 below the end cap 144, and the carrier 143 may be secured in the first cavity 146 by a screen disposed between its upper end and the end cap 144. The screen may function to prevent cells on the carrier 143 from adsorbing on the inner surface of the end cap 144.
Please refer to fig. 7. A folded carrier column for a bioreactor of the present invention may be used in a bioreactor such as that of fig. 7. The interior of the reactor 10 is divided into a second cavity 11 located above and a third cavity 15 located below the second cavity 11.
The guide shell 12 is arranged in the second cavity 11. The upper end of the guide cylinder 12 is provided with an opening, and the lower end of the guide cylinder 12 is communicated with the third cavity 15.
A stirrer pump 16 is provided in the third cavity 15 below the open lower end of the guide cylinder 12. Blades 161 of the stirring pump 16 may be disposed toward the open lower end of the guide cylinder 12.
A chamber cover 111 may be provided on the upper end of the reactor 10; the chamber cover 111 may be provided with a plurality of inlet valves 112. The aeration pipe 121 provided in the guide tube 12 may be ventilated by the introduction valve 112, and the culture solution 13 may be added to the reactor 10. A support bracket 17 may also be provided at the lower end of the reactor 10. A discharge valve communicating with the second chamber may be provided at the lower end of the reactor 10, and may be used for replacing the culture solution 13 or the like.
The second cavity 11 and the third cavity 15 may be separated by a partition 18, and the partition 18 may be horizontally and fixedly installed on the inner wall of the reactor 10. Wherein, the baffle 18 is provided with a first diversion port and a second diversion port; the lower end of the guide cylinder 12 may be connected to the third cavity 15 through a first guide port on the partition 18, and the lower end of the first cylinder 141 on each folded carrier column unit 14 may be connected to the third cavity 15 by screwing with a corresponding second guide port on the partition 18.
By turning on the stirring pump 16, the culture medium 13 flowing downward from the second cavity 11 into the third cavity 15 through the open upper end of the guide tube 12 is stirred and pressurized, whereby the culture medium 13 is fed from the open lower end of the first cylinder 141 into the first cylinder 141. Since the upper end of the first cylinder 141 is in a closed state, the culture solution 13 introduced into the inside of the first cylinder 141 flows unidirectionally into the first cavity 146 through the first window 1411 under pressure, and fills the first cavity 146, so that the carrier 143 in the first cavity 146 is immersed in the culture solution 13, and cells adhered to the surface of the carrier 143 are cultured.
Meanwhile, since the side wall of the second cylinder 142 is further provided with the second window 1421, the culture solution 13 in the first cavity 146 continuously passes through the second window 1421 through the carrier 143 under the pressure, and further flows unidirectionally to fill the second cavity 11. By setting the liquid level of the culture solution 13 in the second cavity 11 to be higher than the upper end of the opening of the guide cylinder 12, the culture solution 13 can flow back into the third cavity 15 downwards from the upper end of the opening of the guide cylinder 12 through the overflow of the culture solution 13, and under the action of the pressure applied by the stirring pump 16, the culture solution 13 is pumped and filled into the first cylinder 141 again through the lower end of the first cylinder 141, so that the dynamic circulation of the culture solution 13 is formed. In which the level of the culture medium 13 in the second cavity 11 is higher than the open upper end of the guide cylinder 12 in a stable dynamic circulation state, so that the guide cylinder 12, the third cavity 15 and the folding carrier column unit 14 are all filled with the culture medium 13.
It will be appreciated by persons skilled in the art that the above embodiments are provided for illustration only and not for limitation of the invention, and that changes and modifications of the above embodiments are intended to fall within the scope of the claims of the invention as long as they fall within the true spirit of the invention.
Claims (7)
1. A folding carrier column for a bioreactor, comprising:
The folding carrier column unit comprises a first cylinder body and a second cylinder body which are mutually sleeved and longitudinally suspended in the reactor, the upper end of the first cylinder body is sealed, a first window is arranged on the side wall of the first cylinder body and used for enabling culture solution filled from the lower end of an opening in the first cylinder body to flow unidirectionally under the action of pressure and fill into a first cavity sealed between the first cylinder body and the second cylinder body through the first window, a second window is arranged on the side wall of the second cylinder body and used for enabling the culture solution filled into the first cavity to flow unidirectionally further into a second cavity between the second cylinder body and the inner wall of the reactor under the action of pressure through the second window, the second cavity is filled into the first cylinder body again through the lower end of the first cylinder body to form circulation, a folding carrier with a plurality of folding surfaces is arranged in the first cavity,
The number of the folding carrier column units is multiple, the folding carrier column units are suspended in the reactor in a surrounding manner,
The folding carrier column unit is configured to rotate and revolve in the reactor, the culture solution is pumped up into the first cylinder from the open lower end of the first cylinder, flows unidirectionally through the first window and fills the first cavity under the combined action of pressure and centrifugal force, and further flows unidirectionally through the second window and fills the second cavity under the combined action of pressure and centrifugal force,
The carrier comprises a folding carrier with a plurality of folding surfaces, wherein the folding carrier takes the first cylinder as a center and is radially distributed towards the second cylinder.
2. The folding carrier column for a bioreactor according to claim 1, wherein each of the folding carrier column units is suspended in the bioreactor in such a manner that upper and lower ends of the respective first cylinders are sequentially butted, wherein the first cylinders of each of the folding carrier column units are communicated with each other, an upper end of the first cylinder of the uppermost one of the folding carrier column units is closed, and a lower end of the first cylinder of the lowermost one of the folding carrier column units is opened for filling up Fang Gesuo of the first cylinders with a culture medium.
3. The folding carrier column for a bioreactor according to claim 1, wherein a plurality of the folding carrier column units are suspended in the reactor in a manner of abutting upper and lower ends of the respective first cylinders in turn to form a folding carrier column unit group, wherein the first cylinders of the folding carrier column units are communicated with each other, the upper end of the first cylinder of the uppermost one of the folding carrier column units is closed, the lower end of the first cylinder of the lowermost one of the folding carrier column units is opened for filling culture medium into the first cylinder Fang Gesuo, and the folding carrier column unit group is suspended in the reactor in a surrounding manner.
4. The folding carrier column for a bioreactor of claim 1, wherein the carriers comprise a first carrier and a second carrier disposed in the first cavity in a stack one above the other; the number of the radial folding surfaces on the first carrier is larger than that of the radial folding surfaces on the second carrier, and/or the height of the first carrier is smaller than that of the second carrier.
5. The folding support column for a bioreactor according to claim 1 or 4, characterized in that the support material comprises a nonwoven fabric.
6. A folding carrier column for a bioreactor according to claim 1, characterized in that the side wall of the second cylinder is surrounded by a mesh and a net, the net serving as the second window.
7. The folding carrier column for a bioreactor according to claim 1, wherein the upper end of the first cavity is closed by an end cap, the carrier is fixed in the first cavity by a filter screen provided between the upper end and the end cap, and the upper end and the lower end of the first cylinder are provided with rotary interfaces.
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