CN214572044U - Fixed bed type bioreactor - Google Patents
Fixed bed type bioreactor Download PDFInfo
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- CN214572044U CN214572044U CN202120053945.5U CN202120053945U CN214572044U CN 214572044 U CN214572044 U CN 214572044U CN 202120053945 U CN202120053945 U CN 202120053945U CN 214572044 U CN214572044 U CN 214572044U
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- carrier
- fixed bed
- bioreactor
- column
- culture medium
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- 239000007788 liquid Substances 0.000 claims abstract description 28
- 239000001963 growth medium Substances 0.000 claims abstract description 24
- 238000003760 magnetic stirring Methods 0.000 claims abstract description 22
- 238000003756 stirring Methods 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 230000002572 peristaltic effect Effects 0.000 claims description 12
- 238000007789 sealing Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 5
- 239000012530 fluid Substances 0.000 claims description 5
- 230000009471 action Effects 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000006052 feed supplement Substances 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 239000000725 suspension Substances 0.000 abstract description 4
- 102000004169 proteins and genes Human genes 0.000 abstract description 3
- 108090000623 proteins and genes Proteins 0.000 abstract description 3
- 230000007547 defect Effects 0.000 abstract description 2
- 239000002574 poison Substances 0.000 abstract description 2
- 231100000614 poison Toxicity 0.000 abstract description 2
- 238000005070 sampling Methods 0.000 description 5
- 235000015097 nutrients Nutrition 0.000 description 4
- 238000010008 shearing Methods 0.000 description 4
- 230000001464 adherent effect Effects 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 2
- 238000007599 discharging Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000013019 agitation Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 238000012007 large scale cell culture Methods 0.000 description 1
- 238000009630 liquid culture Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
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- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The utility model relates to a bioreactor technical field of adherence cell and suspension cell is cultivateed to low shear force, concretely relates to fixed bed formula bioreactor. The fixed bed bioreactor comprises a tank body and a carrier column, wherein the upper part of the tank body is hermetically connected with a tank cover, a magnetic stirring base is arranged below the tank body, the bottom of the magnetic stirring base is provided with a drainage hole, a magnetic stirrer for rotationally stirring water is arranged in the magnetic stirring base, the carrier column is detachably arranged above the magnetic stirring base, and a plurality of fibrous carrier sheets are filled in the carrier column; magnetic stirrers stir through the rotation, and the drive culture medium flows in from the drainage hole of bottom, passes the inside carrier piece of carrier post, flows out from the carrier post top at last, gets back to jar in the body, forms the liquid flow direction of a culture medium inner loop. The utility model solves the problems that partial cells are difficult to grow in the bioreactor and partial suspended cells produce poison or the protein expression is low in the common STR reactor aiming at the defects of the prior art.
Description
Technical Field
The patent of the utility model relates to a bioreactor technical field of adherent cell and suspension cell is cultivateed to low shear force, concretely relates to fixed bed formula bioreactor.
Background
In the traditional large-scale cell culture, an STR reactor (STR) is mostly adopted, i.e. cells are attached to microcarriers and fiber carrier sheets or are completely suspended, and are suspended and grown in a bioreactor under the stirring of a bioreactor stirring paddle. However, the shear force caused by this form of agitation can cause damage or death of the cells. Part of adherent cells which are already used for production are difficult to grow on the traditional STR reactor, only the traditional standing culture mode can be adopted, and the requirement of large-scale culture is difficult to adapt. Some of the fully suspended cells can grow, but the protein expression level is low under the action of shear force. Although the prior basket reactor has relatively fixed cells and liquid flows through the cells under the condition of self weight, the problem of larger shearing force is solved, but the flow rate is not easy to control, so that the cells are not uniformly distributed in the whole carrier cavity, and great difficulty is brought to process control.
SUMMERY OF THE UTILITY MODEL
The utility model provides a fixed bed bioreactor with reliable performance to the not enough of prior art, solved that some cells are difficult to grow in bioreactor and some suspension cells produce the poison or the protein expression is low problem in ordinary STR reactor.
The technical scheme of the utility model is realized like this: this fixed bed formula bioreactor, including jar body and carrier post, jar body upper portion sealing connection has a cover, its characterized in that: a magnetic stirring base is arranged below the tank body, the bottom of the magnetic stirring base is provided with a drainage hole, a magnetic stirrer for rotationally stirring water is arranged in the magnetic stirring base, the carrier column is detachably inserted into a drainage cavity above the magnetic stirring base, and a plurality of fibrous carrier sheets are filled in the carrier column; magnetic stirrers stirs through the rotation, and the drive culture medium flows in the drainage chamber from the drainage hole of bottom, passes the inside carrier piece of carrier post, flows out from the carrier post top at last, gets back to jar body in, forms the liquid flow direction of a culture medium inner loop.
The carrier column comprises a cylindrical shell, a sealing ring and a clamping plate which is connected with the drainage cavity in a clamping manner are arranged below the side wall of the shell, a spoiler, a turbulent flow plate and a top baffle plate are sequentially nested in the shell from bottom to top, the spoiler is a circular thin plate, three turbulent flow grooves for enabling liquid to flow to be divided are uniformly distributed on the circumference of the spoiler, the lower turbulent flow plate is a circular thin plate with honeycomb turbulent flow holes, and fluid can uniformly and horizontally enter the column through the turbulent flow holes to prevent the formation of a central edge effect; the carrier sheet is filled between the turbulence plate and the top baffle.
The cover is provided with a GL45 sampling port for sampling and observing, a feed supplement port for adding culture medium, and a medium-length discharge pipe for controlling the liquid level of the culture medium.
The medium-length discharge pipe is externally connected with a peristaltic pump, and excess culture medium liquid is pumped out outwards under the action of the peristaltic pump or air pressure so as to ensure that the volume of the liquid in the tank is unchanged.
The tank body and the tank cover are connected in a sealing mode through the flange plate and the silica gel gasket.
The rotating speed of the magnetic stirrer is adjustable, and the fixed bed bioreactor accurately controls the linear flow rate of liquid passing through the carrier column and culture process parameters by adjusting the rotating speed of the magnetic stirrer.
The utility model provides an existing defect among the background art, have following beneficial effect:
the utility model discloses structural design scientific and reasonable has solved STR reactor shearing force too big problem, forces controllable liquid flow rate to have solved the inhomogeneous problem of cell adherence in the current basket reactor, lets the adherent cell that is difficult to suspension culture also can carry out bioreactor extensive culture. The utility model discloses a magnetic stirrers rotation driving liquid medium flows in from the bottom drainage hole of magnetic stirrers base, passes the inside carrier piece of carrier post, flows from the carrier capital portion at last, gets back to the reactor jar body in, forms the liquid flow direction of a culture medium inner loop. Meanwhile, the linear flow velocity of the liquid passing through the carrier column can be accurately controlled by adjusting the rotating speed of the magnetic stirrer, so that the cell suspension is forced to rapidly pass through the carrier pieces when the high flow velocity is realized, and the cells can be uniformly attached to each carrier piece in the carrier column; and after the adherence is finished, the solution is passed through the carrier plate at a low flow rate, so that the fresh culture medium continuously flows through the cells under the condition of extremely low shearing force, and necessary nutrient substances are provided for the growth of the cells. The flow rate required by culture strategies such as circulation or perfusion and the like can be accurately controlled by the peristaltic pump connected with the medium-length discharge pipe. By arranging the spoilers and the turbulent plates on the carrier columns, fluid can uniformly and horizontally enter the columns, so that the central edge effect is prevented from being formed, and cells are further uniformly attached to each carrier sheet.
Drawings
Fig. 1 is a schematic structural view of the present invention;
FIG. 2 is a schematic structural view of the magnetic stirring base of FIG. 1;
FIG. 3 is a schematic cross-sectional view of the magnetic stirring base of FIG. 2;
FIG. 4 is a schematic structural view of the support column of FIG. 1;
FIG. 5 is a schematic structural diagram of the spoiler shown in FIG. 4;
FIG. 6 is a schematic structural view of the turbulator of FIG. 4;
in the figure: 1-tank body, 2-tank cover, 3-carrier column, 4-magnetic stirring base, 5-feeding port, 6-middle-long discharging pipe, 7-GL45 sampling port, 8-magnetic stirrer, 9-culture medium, 10-buckle, 11-drainage hole, 12-drainage cavity, 31-shell, 32-spoiler, 33-spoiler, 34-top baffle, 35-buckle plate, 321-spoiler groove and 331-turbulence hole.
Detailed Description
The technical solutions in the embodiments of the present invention will be described clearly and completely with reference to the accompanying drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments in the present invention, all other embodiments obtained by a person skilled in the art without creative efforts belong to the protection scope of the present invention.
Referring to the embodiment of the fixed bed bioreactor shown in fig. 1 to 6, the fixed bed bioreactor comprises a tank body 1 and a carrier column 3, wherein the upper part of the tank body 1 is hermetically connected with a tank cover 2, a magnetic stirring base 4 is arranged below the inside of the tank body 1, the bottom of the magnetic stirring base 4 is provided with a drainage hole 11, a magnetic stirrer 8 for rotationally stirring water is arranged in the magnetic stirring base, the carrier column 3 is detachably inserted in a drainage cavity 12 above the magnetic stirring base, and a plurality of fibrous carrier sheets are filled in the carrier column 3; the magnetic stirrer 8 drives the culture medium 9 to flow into the drainage cavity 12 from the drainage hole 11 at the bottom through the drainage holes by rotating and stirring, passes through the carrier sheets in the carrier column 3, finally flows out from the top of the carrier column 3 and returns to the tank body, and a liquid flow direction circulating in the culture medium 9 is formed. The rotating speed of the magnetic stirrer 8 is adjustable, and the fixed bed bioreactor accurately controls the linear flow rate of liquid passing through the carrier column 3 and culture process parameters by adjusting the rotating speed of the magnetic stirrer 8. The carrier column 3 comprises a cylindrical shell 31, a sealing ring and a buckle plate 35 connected with the buckle 10 in the drainage cavity 12 are arranged below the side wall of the shell 31, a spoiler 32, a turbulence plate 33 and a top baffle 34 are sequentially nested in the shell 31 from bottom to top, the spoiler 32 is a circular thin plate, three spoiler grooves 321 for enabling liquid to flow and split are uniformly distributed on the circumference of the spoiler, the lower turbulence plate 33 is a circular thin plate provided with honeycomb turbulence holes 331, and the turbulence holes can enable the fluid to uniformly and horizontally enter the column to prevent the formation of a central edge effect; the carrier sheet is filled between the turbulence plate 33 and the top baffle 34. The cover 2 is provided with a GL45 sampling port 7 for sampling and observation, a feed supplement port 5 for adding a culture medium 9, and a medium-length discharge pipe 6 for controlling the liquid level of the culture medium 9. The medium-length discharge pipe 6 is externally connected with a peristaltic pump, and excess liquid is pumped out through the action of the peristaltic pump or air pressure so as to ensure that the volume of the solution in the tank is unchanged. The tank body 1 and the tank cover 2 are hermetically connected through a flange plate and a silica gel gasket.
The utility model discloses a working process is: the carrier sheet is desirably loaded between the turbulence plate 33 and the top baffle 34 to ensure that the carrier sheet is present in a certain density in the column of the carrier, and then the lower turbulence plate 32 is installed and all the components are packaged and formed at once. When the carrier column 3 is used, the end part of the sealing ring is inserted into the magnetic stirring base 4 at the bottom of the tank body 1, and the clamping plate 35 and the upper clamping buckle 10 of the stirring base are clamped in an aligning manner in a rotating manner. And carrying out pressure maintaining test after the installation is finished, and ensuring the sealing of the bioreactor. After high-pressure sterilization, the bioreactor is connected with a bioreactor control cabinet or connected with a corresponding electrode transmitter for cell culture. The magnetic stirrer 8 is powered by a magnetic stirrer motor to rotate. Thereby drive liquid culture medium 9 and flow into in drainage chamber 12 from the bottom drainage hole 11 of magnetic stirring base 4, pass the inside carrier piece of carrier post, flow out from carrier post 3 top at last, get back to the reactor jar body in, flow down again to the bottom of magnetic stirring base 4, 3 in the reentrant carrier post, form the liquid flow direction of a culture medium 9 inner loop. The cell culture mode is high-density culture, consumed nutrient substances need to be continuously supplemented in the culture process, in order to ensure that the total volume of nutrient solution in a tank body is unchanged, a medium-length discharging pipe 6 is arranged on a tank cover and is connected with a peristaltic pump through a silicone tube, the solution is pumped outwards all the time, and when the liquid level of a culture medium 9 is lower than the pipe orifice, the solution cannot be pumped out, so that the volume of the solution in the tank body is unchanged. The volume of culture medium ensures that the flow rate of liquid through the carrier sheet is constant when the magnetic stirrer is externally driven at a particular rotational speed. The flow rate of liquid through the support column 3 is accurately adjustable while ensuring this volume of medium. The flow rate is increased during the cell adherence process, and the cell suspension is forced to rapidly pass through the carrier plates, so that the cells can be uniformly attached to each carrier plate in the carrier column 3. After the adherence is finished or the suspension cells are positioned, the flow velocity can be adjusted to be low, so that the solution passes through the carrier sheet at a very low flow velocity, and the cells are continuously flowed through by fresh culture medium under the condition of very low shearing force, thereby providing necessary nutrient substances for the growth of the cells. Therefore, different culture modes such as circulation, perfusion and the like can be simply realized by setting the rotating speed of the peristaltic pump connected with the peristaltic pump to be slightly greater than that of the peristaltic pump with the feeding port so as to meet the requirements of different cell growth. The flow rate required by culture strategies such as circulation or perfusion and the like can be accurately controlled by the peristaltic pump connected with the medium-length discharge pipe 6. Meanwhile, the linear flow velocity of the liquid passing through the carrier column can be accurately controlled by adjusting the rotating speed of the magnetic stirrer 8, so that the culture process parameters can be conveniently controlled. The utility model has the advantages that the cell suspension flow direction can enter the carrier column 3 from a plurality of directions from the circumferential edge of the carrier column 3 by arranging the spoiler 32 and evenly distributing the three spoiler grooves 321 on the circumference; the honeycomb-shaped turbulence holes 331 of the turbulence plate 33 allow the fluid to uniformly and horizontally enter the column, preventing the formation of the center-edge effect, thereby uniformly attaching the cells to each carrier sheet. The low shear force allows the suspensible cells to grow and express on the carrier sheet with high efficiency. Meanwhile, the fibrous carrier sheet filled in the carrier column can provide a great culture area, so that high-density culture of cells is realized.
The above description is only a preferred embodiment of the present invention, and should not be taken as limiting the invention, and any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (6)
1. The utility model provides a fixed bed formula bioreactor, includes jar body (1) and carrier column (3), jar body (1) upper portion sealing connection has cover (2), its characterized in that: a magnetic stirring base (4) is arranged below the tank body (1), a drainage hole (11) is formed in the bottom of the magnetic stirring base (4), a magnetic stirrer (8) for rotationally stirring water is arranged in the magnetic stirring base, the carrier column (3) is detachably inserted into a drainage cavity (12) above the magnetic stirring base, and a plurality of fibrous carrier sheets are filled in the carrier column (3); the magnetic stirrer (8) drives the culture medium (9) to flow into the drainage cavity (12) from the drainage hole (11) at the bottom through rotary stirring, pass through the carrier sheets in the carrier column (3), finally flow out from the top of the carrier column (3) and return to the tank body (1) to form a liquid flow direction of the internal circulation of the culture medium (9).
2. The fixed bed bioreactor as set forth in claim 1, wherein: the carrier column (3) comprises a cylindrical shell (31), a sealing ring and a clamping plate (35) connected with a clamp (10) in the drainage cavity (12) are arranged below the side wall of the shell (31), a spoiler (32), a turbulence plate (33) and a top baffle (34) are sequentially nested in the shell (31) from bottom to top, the spoiler (32) is a circular thin plate, three spoiler grooves (321) for shunting liquid flow are uniformly distributed on the circumference of the spoiler (32), the turbulence plate (33) is a circular thin plate provided with honeycomb turbulence holes (331), and the turbulence holes can enable fluid to uniformly and horizontally enter the column to prevent the formation of a central edge effect; the carrier sheet is filled between the turbulence plate (33) and the top baffle (34).
3. The fixed bed bioreactor as claimed in claim 1 or 2, wherein: be equipped with on cover (2) and be used for the sample and observe GL45 thief hatch (7), add feed supplement mouth (5) of culture medium (9), be used for medium-length discharge pipe (6) of culture medium (9) liquid level control.
4. The fixed bed bioreactor as set forth in claim 3, wherein: the medium-length discharge pipe (6) is externally connected with a peristaltic pump, and excess culture medium (9) liquid is pumped out through the action of the peristaltic pump or air pressure so as to ensure that the volume of the liquid in the tank is unchanged.
5. The fixed bed bioreactor as set forth in claim 1, wherein: the tank body (1) and the tank cover (2) are connected in a sealing mode through the flange plate and the silica gel gasket.
6. The fixed bed bioreactor as set forth in claim 1, wherein: the rotating speed of the magnetic stirrer (8) is adjustable, and the fixed bed bioreactor accurately controls the linear flow rate of liquid passing through the carrier column (3) and culture process parameters by adjusting the rotating speed of the magnetic stirrer (8).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202120053945.5U CN214572044U (en) | 2021-01-11 | 2021-01-11 | Fixed bed type bioreactor |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202120053945.5U CN214572044U (en) | 2021-01-11 | 2021-01-11 | Fixed bed type bioreactor |
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| CN214572044U true CN214572044U (en) | 2021-11-02 |
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| CN202120053945.5U Active CN214572044U (en) | 2021-01-11 | 2021-01-11 | Fixed bed type bioreactor |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112708562A (en) * | 2021-01-11 | 2021-04-27 | 昆明柏特生物科技有限公司 | Fixed bed type bioreactor |
| CN118185765A (en) * | 2024-05-17 | 2024-06-14 | 同腾新创(苏州)科技有限公司 | Fixed bed type bioreactor |
-
2021
- 2021-01-11 CN CN202120053945.5U patent/CN214572044U/en active Active
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112708562A (en) * | 2021-01-11 | 2021-04-27 | 昆明柏特生物科技有限公司 | Fixed bed type bioreactor |
| CN118185765A (en) * | 2024-05-17 | 2024-06-14 | 同腾新创(苏州)科技有限公司 | Fixed bed type bioreactor |
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Effective date of registration: 20240708 Address after: Room 1805, Building 6, Yunnan Yingxiang City Park Plaza, Platinum Avenue, Panlong District, Kunming City, Yunnan Province, 650000 Patentee after: Kunming chaotai economic and Trade Co.,Ltd. Country or region after: China Address before: No. 1609, Siji apartment, Jiangdong Commercial Plaza, Panlong District, Kunming, Yunnan 650051 Patentee before: Kunming Baite Biotechnology Co.,Ltd. Country or region before: China |