Modular bioreactor for cell culture
The modularly designed bioreactor solves the problem of parameter instability in traditional reactors when scale changes, achieves consistency and safety of cell culture environment, reduces damage to cells caused by mechanical stirring, and adapts to different scale requirements.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- SHANGHAI OPM BIOSCI CO LTD
- Filing Date
- 2023-04-04
- Publication Date
- 2026-05-15
AI Technical Summary
When traditional bioreactors are scaled up, changes in physical parameters affect cell behavior, making it difficult to maintain constant parameters between reactors of different sizes. In particular, the specific surface area decreases during scale-up, leading to difficulties in heat dissipation. Shear stress generated by mechanical stirring damages cells, and different host cells have different sensitivities to parameters, increasing the complexity of culture scale.
Design a modular bioreactor that forms a cylindrical geometry by splicing multiple reactor bodies. Use track components and connecting components to achieve detachable connection and rotation of the reactor bodies, ensuring a consistent microenvironment inside each module, and reduce cell damage through a sloping structure to adapt to different scale requirements.
It achieves consistency in cell culture environment across different scales, reduces shear stress damage caused by mechanical stirring, adapts to the needs of different scales of culture, and improves the efficiency and safety of cell culture.
Smart Images
Figure CN116478816B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of bioreactor technology, specifically to a modular bioreactor for cell culture. Background Technology
[0002] Animal cells are cultured on a large scale for the production of various therapeutic proteins, vaccines, and antibodies. For cost reasons, cell culture processes are typically developed in small-volume reactors. However, to obtain sufficient quantities of product, the final process requires the application of large-volume reactors.
[0003] When reactor scale changes, many physical parameters (such as volume and surface area) also change due to altered dimensions. These changes affect the chemical environment and influence cell behavior. Maintaining constant parameters across different reactor sizes is challenging as the scale of culture equipment changes. Traditional bioreactors based on geometric similarity scale up maintain the proportionality of reactor geometry, scaling all lengths proportionally. In this approach, the reactor's surface area increases with the square of the length, while the volume increases to the cube. Consequently, the surface area per unit culture volume decreases. In microbial culture, this reduced surface area hinders the removal of heat generated by metabolism and mechanical agitation. In animal cell culture, metabolic heat is relatively low and often overlooked, but animal cells are sensitive to physical damage and may be affected by other variables in reactor scale-up. Furthermore, different host cell species have different sensitivity parameters, and the introduction of target genes can also influence the range of sensitivity parameters. These factors increase the complexity of scale-up. In conclusion, reactor scale-up remains a significant challenge for large-scale culture. Therefore, we propose a modular bioreactor for cell culture. Summary of the Invention
[0004] To overcome the above shortcomings, the present invention provides a modular bioreactor for cell culture.
[0005] The technical solution of this invention is:
[0006] A modular bioreactor for cell culture includes a reactor support frame on which a plurality of reactor bodies are mounted. These reactor bodies are joined together to form a cylindrical geometry. Each reactor body is hollow, and a disposable reaction bag is placed in the hollow portion of each reactor body. The bioreactor also includes:
[0007] A track component is provided along the surface of the reactor outer support and is connected to several reactor bodies. By moving each reactor body, each reactor body can be detached from the reactor outer support.
[0008] A connecting component is provided on each of the reactor bodies, which can be used for connection between two adjacent reactor bodies.
[0009] Preferably, the reactor external support consists of two or more vertical rods.
[0010] Preferably, the track component includes:
[0011] Two rows of vertical rails are mounted on vertical rods. Each row of vertical rails is equipped with a corresponding limiting block. A transverse rail connects the two rows of vertical rails and is located below the limiting blocks. Each row of vertical rails is slidably connected to a bracket, the other end of which is connected to the side wall of the reactor body.
[0012] Preferably, each reactor body is composed of a side plate and a bottom plate. The two ends of the bottom of the side plate are flat and the middle is inclined. A vent pipe is fixedly connected to one side of the side plate. A pressure relief valve and a water stop clamp are connected to the vent pipe. The vent pipe is a telescopic structure.
[0013] Preferably, the structure of the base plate and the bottom of the side plate are adapted to each other, and the middle part of the base plate is a temperature control plate.
[0014] Preferably, the connecting component consists of two connection ports, which are respectively connected to the upper and lower ends of the reactor body, and the two connection ports are inclined and symmetrical.
[0015] Preferably, the structure of the disposable reaction bag is consistent with the structure of the reactor body, and the upper and lower ends of the disposable reaction bag are respectively fixedly connected with connection ports two. The two connection ports two are also inclined and symmetrical, and the two connection ports two are respectively connected to the two connection ports one of the reactor body.
[0016] Preferably, a sampling tube is fixedly connected to one side of the disposable reaction bag. The sampling tube can be tubular, multiple bubble-shaped, or other shapes, and a pressure relief valve and a water-stopping clamp are fixedly connected to the sampling tube.
[0017] Compared with the prior art, the beneficial effects of the present invention are:
[0018] 1. The present invention features a reactor body composed of side plates and a bottom plate, with the side plates and bottom plate being detachable. This facilitates cleaning the inside of the reactor by disassembly. Furthermore, the reactor can rotate along its central axis, which facilitates mixing of the culture medium and reduces damage from shear stress caused by mechanical stirring.
[0019] 2. The bottom plate of the reactor of the present invention has flat ends and a sloping middle, so that the cell fluid cultured in each reactor can flow to the next reactor through the sloping surface, and the sloping surface can buffer the cell fluid, thereby reducing damage to the cells.
[0020] 3. By setting up track components, this invention enables multiple reactor bodies to be spliced together to form a cylindrical geometry. This allows the number of reactor bodies to be increased or decreased according to the actual needs of the cultivation scale. At the same time, with the cooperation of the connecting components, each reactor can not only be used as an independent module for testing culture media or other cultivation conditions, but also be connected to each reactor body when the scale is increased, expanding the volume of the reactor and ensuring that the internal microenvironment of each individual module is consistent, without the parameter changes that occur when the volume of a traditional reactor is increased. Attached Figure Description
[0021] Figure 1 This is a schematic diagram of the overall structure of the present invention;
[0022] Figure 2 This is a schematic diagram of the reactor external support structure of the present invention;
[0023] Figure 3 This is an exploded view of the reactor body of the present invention;
[0024] Figure 4 This is a schematic diagram of the reactor body structure of the present invention;
[0025] Figure 5 This is a schematic diagram of the disposable reaction bag structure of the present invention.
[0026] In the picture:
[0027] 1. Reactor external support; 11. Vertical track; 12. Limiting block; 13. Horizontal track;
[0028] 2. Reactor body; 21. Side plate; 211. Connection port one; 212. Vent pipe; 22. Bottom plate; 23. Disposable reaction bag; 231. Connection port two; 232. Sampling tube. Detailed Implementation
[0029] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0030] In the description of this invention, it should be understood that the terms "center," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," and "counterclockwise," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.
[0031] Please see Figure 1-5 The present invention will describe the above technical solution in detail through the following embodiments:
[0032] A modular bioreactor for cell culture includes an outer support 1, which consists of two or more vertical rods. Several reactor bodies 2 are mounted on the outer support 1, and these reactor bodies 2 are joined together to form a cylindrical geometry. Each reactor body 2 consists of a side plate 21 and a bottom plate 22. The bottom ends of the side plate 21 are flat, and the middle is inclined. A vent pipe 212 is fixedly connected to one side of the side plate 21, and a pressure relief valve with a water stop clamp is connected to the vent pipe 212. The vent pipe 212 is telescopic. The structure of the bottom plate 22 is adapted to the bottom of the side plate 21, and the middle of the bottom plate 22 has a temperature control unit. Each reactor body 2 is hollow inside, and a disposable reaction bag 23 is provided in the hollow part of each reactor body 2. The structure of the disposable reaction bag 23 is the same as that of the reactor body 2. The upper and lower ends of the disposable reaction bag 23 are respectively fixedly connected to the two connection ports 231. The two connection ports 231 are also inclined and symmetrical, and the two connection ports 231 are respectively connected to the two connection ports 211 of the reactor body 2. A sampling tube 232 is fixedly connected to one side of the disposable reaction bag 23. The sampling tube 232 can be tubular, multiple bubble-shaped, or other shapes. A pressure relief valve and water stop clamp 2 are fixedly connected to the sampling tube 232.
[0033] It should be noted that the side plates 21 and bottom plates 22 of each reactor body 2 are also detachably connected.
[0034] In this embodiment, each reactor body 2 is composed of a side plate 21 and a bottom plate 22, and the side plate 21 and the bottom plate 22 are detachable, which not only facilitates the installation of disposable reaction bags 23, but also facilitates the cleaning of the inside of the reactor. The bottom plate 22 and the side plate 21 have the same bottom, with flat ends and a sloping middle. Therefore, the cell culture fluid in each reactor can flow to the next reactor through the sloping surface. The sloping surface forms a buffer for the cell culture fluid, thereby reducing damage to the cells. The bottom plate 22 is a temperature control plate that can control the temperature in each reactor at any time to ensure the culture effect. However, when the culture medium is being prepared, the two connecting ports of each disposable reaction bag 23 can be opened. 31 is connected to the two connection ports 211 of each reactor body 2, so that each disposable reaction bag 23 is placed in the hollow part inside each reactor body 2. Then, the bottom plate 22 and the side plate 21 of each reactor body 2 are connected, thus completing the installation of a single reactor body 2. The culture medium can be injected into the disposable reaction bag 23 from the connection port 211 above the reactor body 2. Then, the pressure relief valve and water stop clamp 2 are opened, so that the culture medium in the disposable reaction bag 23 enters the sampling tube 232. Then, the pressure relief valve and water stop clamp 2 are closed. Finally, the sampling section containing the culture medium can be removed by heating or squeezing the sealed part, thus effectively preventing the reaction medium from being contaminated.
[0035] The track component is arranged along the surface of the reactor outer support 1 and connected to several reactor bodies 2. By moving each reactor body 2, each reactor body 2 can be detached from the reactor outer support 1. The track component includes: two rows of vertical tracks 11, which are arranged on vertical rods. Each of the two rows of vertical tracks 11 is provided with a corresponding limiting block 12. A transverse track 13 is connected between the two rows of vertical tracks 11 and is arranged below the limiting block 12. A bracket is slidably connected to each of the two rows of vertical tracks 11, and the other end of the bracket is connected to the side wall of the reactor body 2.
[0036] It should also be noted that each support and the two side walls of the reactor body are detachably connected.
[0037] In this embodiment, each reactor body 2 is first connected to a support on one of the vertical tracks 11. Then, the single reactor body 2 is moved vertically so that it slides to the limiting block 12 on the vertical track 11. The limiting block 12 fixes the single reactor body 2 to the outer support 1 of the reactor. Then, the above-mentioned sliding reactor body 2 action is repeated so that multiple reactor bodies 2 are spliced together to form a cylindrical geometry and fixed to the outer support 1 of the reactor, which facilitates the flow of cell fluid. However, when it is necessary to disassemble the upper reactor body 2, the upper reactor body 2 can be slid from one of the vertical tracks 11 to the horizontal track 13, and then from the horizontal track 13 to the other vertical track 11, and the support connection is released, thereby completing the disassembly of the upper reactor body 2. The number of reactor bodies 2 can be increased or decreased according to the actual culture requirements, which enhances the ease of use.
[0038] A connecting component is provided on each reactor body 2, which can be used for connection between two adjacent reactor bodies 2. The connecting component consists of two connection ports 211, which are respectively connected to the upper and lower ends of the reactor body 2, and the two connection ports 211 are inclined and symmetrical.
[0039] It is worth noting that the connection port 211 at the bottom of the upper reactor body 2 and the connection port 211 at the top of the lower reactor body 2 are interconnected, and several reactor bodies 2 can rotate clockwise or counterclockwise along the central axis of the reactor body 2.
[0040] In this embodiment, by setting symmetrically inclined connection ports 211 on each reactor body 2, it can be used to connect two adjacent reactor bodies 2. When the scale is small, each reactor body 2 can become a separate module for culture medium. When the scale is increased, the connection ports 211 on multiple reactor bodies 2 can be opened to realize the connection between multiple reactor bodies 2, so that the overall volume of the reactor can be increased, thereby ensuring the consistency of the culture medium environment and avoiding the parameter changes that occur when the volume of a traditional reactor is increased. The reactor body 2 can be inclined at an angle of 0 to 90° with the horizontal plane and can rotate clockwise or counterclockwise along the central axis, thereby realizing the mixing of the culture medium and gas-liquid exchange, reducing the damage caused by shear stress from mechanical stirring.
[0041] In practical use, the two connection ports 231 of each disposable reaction bag 23 are connected to the two connection ports 211 of each reactor body 2, so that each disposable reaction bag 23 is placed in the hollow part inside each reactor body 2. Then, the bottom plate 22 and the side plate 21 of each reactor body 2 are connected, thus completing the installation of a single reactor body 2. Then, each reactor body 2 is connected to the support on one of the vertical tracks 11. Then, the single reactor body 2 is moved vertically so that the single reactor body 2 slides to the limiting block 12 of the vertical track 11. The limiting block 12 can fix the single reactor body 2 to the outer support 1 of the reactor. Then, the above sliding reactor body 2 action is repeated so that multiple reactor bodies 2 are spliced together to form a cylindrical geometry and fixed on the outer support 1 of the reactor, which facilitates the flow of cell fluid. During culture, the cultured cell fluid is directly injected from the connection port 211 on the uppermost reactor body 2. Finally, the cell fluid will flow into each reactor body 2 for culture in sequence.
[0042] However, when the scale is small, the connection port 211 on each reactor body 2 can be closed, so that each reactor body 2 becomes an individual module for culture medium. In this case, the culture medium can be injected into the disposable reaction bag 23 through the connection port 211 on the top of the reactor body 2. Then, the reactor body 2 is rotated clockwise or counterclockwise along the central axis to mix the culture medium and exchange gas and liquid. Then, the pressure relief valve clamp 2 is opened to allow the culture medium in the disposable reaction bag 23 to enter the sampling tube 232. Finally, the pressure relief valve clamp 2 is closed, and the sampling section containing the culture medium is removed by heating or squeezing the sealed part.
[0043] Secondly, when the scale is increased, the connection ports 211 on multiple reactor bodies 2 can be opened and the multiple reactor bodies 2 can be connected to each other, so that the overall volume of the reactor can be increased. This allows the process described above on a smaller scale to be repeated, and the culture medium can be injected into the stacked reactor bodies 2 for cultivation. This ensures that the environment of the culture medium is consistent and there will be no change in parameters after the traditional reactor volume is increased, which would affect the data results.
[0044] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely preferred examples and are not intended to limit the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of the present invention is defined by the appended claims and their equivalents.
Claims
1. A modular bioreactor for cell culture, comprising a reactor support (1), wherein a plurality of reactor bodies (2) are disposed on the reactor support (1), the plurality of reactor bodies (2) are spliced together to form a cylindrical geometry, each reactor body (2) is hollow inside, and each reactor body (2) contains a disposable reaction bag (23), characterized in that, Also includes: A track component is provided along the surface of the reactor outer support (1) and connected to several reactor bodies (2). By moving each reactor body (2), each reactor body (2) can be detached from the reactor outer support (1). A connecting component is provided on each of the reactor bodies (2) and is capable of being used for connection between two adjacent reactor bodies (2); Each of the reactor bodies (2) consists of a side plate (21) and a bottom plate (22). The top two ends of the side plate (21) are flat, and the middle is inclined. A vent pipe (212) is fixedly connected to one side of the side plate (21). A pressure relief valve and a water-stopping clamp are connected to the vent pipe (212). The vent pipe (212) is a telescopic structure. The structure of the base plate (22) and the bottom of the side plate (21) are adapted to each other, and the middle part of the base plate (22) is a temperature control plate; The connecting component consists of two connection ports (211), which are respectively connected to the upper and lower ends of the reactor body (2), and the two connection ports (211) are inclined and symmetrical. The structure of the disposable reaction bag (23) is the same as that of the reactor body (2), and the upper and lower ends of the disposable reaction bag (23) are respectively fixedly connected to the second connection port (231). The two second connection ports (231) are also inclined and symmetrical, and the two second connection ports (231) are respectively connected to the two first connection ports (211) of the reactor body (2).
2. The modular bioreactor for cell culture as described in claim 1, characterized in that: The reactor external support (1) consists of two or more vertical rods.
3. The modular bioreactor for cell culture as described in claim 1, characterized in that: The track component includes: Two rows of vertical rails (11) are set on vertical rods. Each row of vertical rails (11) is provided with a corresponding limiting block (12). A transverse rail (13) is connected between the two rows of vertical rails (11). The transverse rail (13) is set below the limiting block (12). A bracket is slidably connected to each row of vertical rails (11). The other end of the bracket is connected to the side wall of the reactor body (2).
4. The modular bioreactor for cell culture as described in claim 1, characterized in that: A sampling tube (232) is fixedly connected to one side of the disposable reaction bag (23), and a pressure relief valve and a water stop clamp are fixedly connected to the sampling tube (232).