Bioreactor

Abstract

The utility model belongs to the technical field of cell culture devices, and relates to a bioreactor. The bioreactor comprises a tank body which is provided with an accommodating cavity; the first mounting assembly is arranged on the inner wall of the tank body; the periphery of the first microporous membrane is installed on the first installation assembly, the first microporous membrane is used for dividing the containing cavity into a mixing area and a first stirring area in the height direction of the tank body, and through holes of the first microporous membrane communicate with the first stirring area and the mixing area; the diameter of a through hole of the first microporous membrane is set to be permeable to a culture solution and smaller than the diameter of a cultured cell; and the first stirring assembly comprises a first rotating piece arranged in the first stirring area. The first microporous membrane is installed in the tank body, and the containing cavity is divided into the first stirring area and the mixing area. The diameter of the through holes of the first microporous membrane is smaller than that of the cells, the cells are prevented from entering the stirring area, only the culture solution is allowed to flow, the cells are prevented from being exposed to a shear force environment, and cell damage is reduced.

Description

Technical Field

[0001] The utility model belongs to the technical field of cell culture devices and relates to a bioreactor. Background Art

[0002] During the cell culture process, stirring allows the nutrients in the culture medium to be evenly distributed so that they can be absorbed by the cells. Stirring also helps maintain a constant concentration of oxygen and carbon dioxide in the culture medium, which is essential for cell growth and metabolic activity. At the same time, proper stirring can also prevent cells from settling at the bottom of the container and promote the overall growth and reproduction of cells.

[0003] Bioreactors are specially designed for cell culture, tissue culture or microbial culture. They are usually composed of a tank and a stirring assembly. The tank provides a closed or semi-closed growth environment for cells, while the stirring assembly is responsible for maintaining the uniformity of the environment in the tank, such as uniform distribution of temperature, pH and dissolved oxygen.

[0004] The stirring components of existing bioreactors are usually immersed directly in the culture medium and stir the culture medium by rotating themselves. In this way, although the culture medium can be stirred effectively to ensure material exchange, the shear force generated by the blades of the stirring component during rotation will directly cause physical damage to the cells, thereby affecting the growth of cells and the quality of the product. Utility Model Content

[0005] The utility model aims to provide a bioreactor capable of reducing cell damage.

[0006] In order to achieve the above-mentioned object, the utility model provides the following technical solution: a bioreactor, comprising:

[0007] A tank body is formed with a containing cavity;

[0008] A first mounting assembly is arranged on the inner wall of the tank body;

[0009] A first microporous membrane, the periphery of which is mounted on the first mounting assembly, the first microporous membrane is used to divide the accommodating cavity into a mixing zone and a first stirring zone in the height direction of the tank body, the through holes of the first microporous membrane communicate with the first stirring zone and the mixing zone, and the through hole diameter of the first microporous membrane is set to be able to pass through the culture fluid and smaller than the diameter of the cultured cells; and

[0010] The first stirring assembly includes a first rotating member disposed in the first stirring zone.

[0011] Furthermore, in the height direction, the first stirring zone is located below the mixing zone, and the tank body is provided with a feed inlet and a discharge port connected to the mixing zone, and a liquid discharge port connected to the first stirring zone.

[0012] Furthermore, the first mounting assembly includes an upper mounting block and a lower mounting block disposed in the tank body, and the periphery of the first microporous membrane is defined by the upper mounting block and the lower mounting block.

[0013] Furthermore, in the height direction, the first stirring zone is located above the mixing zone, the tank body is provided with a feed inlet connected to the first stirring zone and a discharge port connected to the mixing zone, and the first microporous membrane is detachably mounted on the first mounting assembly.

[0014] Furthermore, the tank body includes a main body and a cover body, the cover body is detachably connected to the main body, and the first stirring assembly is fixed on the cover body.

[0015] Furthermore, the first installation component includes:

[0016] A projection, disposed in the tank body;

[0017] A clamping member clamps the periphery of the first microporous membrane, the clamping member has a cross-sectional size equal to that of the accommodating cavity, and can slide up and down relative to the tank body, and the clamping member overlaps the protrusion.

[0018] Furthermore, the bioreactor further comprises:

[0019] A second mounting assembly is arranged on the inner wall of the tank body;

[0020] a second microporous filter membrane, the periphery of which is mounted on the second mounting assembly, the second microporous membrane is used to divide the mixing zone into a second stirring zone and a liquid storage zone located between the first stirring zone and the second stirring zone in the height direction of the tank body, the through holes of the second microporous membrane communicate with the second stirring zone and the liquid storage zone, and the through hole diameter of the second microporous membrane is set to be able to pass through the culture solution and smaller than the diameter of the cultured cells;

[0021] A second stirring assembly includes a second rotating member disposed in the second stirring zone;

[0022] Wherein, if the first microporous filter membrane is located above the second microporous filter membrane, the first microporous filter membrane can be detachably installed on the first mounting assembly; if the second microporous filter membrane is located above the first microporous filter membrane, the second microporous filter membrane can be detachably installed on the second mounting assembly.

[0023] Furthermore, the diameter of the through hole is any value between 1 micrometer and 10 micrometers.

[0024] Furthermore, the first stirring assembly further includes a driving member disposed on the inner wall of the tank body, and the driving member is used to drive the rotating member to rotate in the stirring zone.

[0025] The beneficial effect of the utility model is that the application divides the accommodating chamber into a first stirring zone and a mixing zone by installing the first microporous membrane on the first mounting assembly of the tank body. The through-hole diameter of the first microporous membrane is smaller than the diameter of the cells, so as to prevent the cells from entering the first stirring zone from the mixing zone, and only allow the culture fluid to flow back and forth, thereby preventing the cells from being directly exposed to the stirring environment that may generate large shear forces. The first stirring assembly is only arranged in the first stirring zone, and the culture fluid is stirred by the rotation of the first rotating member to ensure the uniformity of the culture fluid and the appropriate physical environment without directly causing physical damage to the cells. In this way, not only the physical damage to the cells is reduced, but also the ideal state of the culture environment can be maintained, thereby improving the efficiency and quality of cell culture.

[0026] The above description is only an overview of the technical solution of the utility model. In order to more clearly understand the technical means of the utility model and implement it according to the contents of the specification, the following is a detailed description of the preferred embodiments of the utility model in conjunction with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is a schematic diagram of the structure of a bioreactor shown in one embodiment of the utility model;

[0028] Figure 2 This is a schematic structural diagram of a bioreactor shown in another embodiment of the utility model;

[0029] Figure 3 This is a schematic structural diagram of a bioreactor according to another embodiment of the present invention;

[0030] Figure 4 This is a schematic structural diagram of a bioreactor shown in yet another embodiment of the present utility model. DETAILED DESCRIPTION

[0031] The technical solution of the utility model will be described clearly and completely below in conjunction with the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the utility model, not all of the embodiments. Based on the embodiments of the utility model, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the utility model.

[0032] In the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc., indicating the orientation or positional relationship, are based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limiting the present invention. In addition, the terms "first", "second", and "third" are used for descriptive purposes only, and cannot be understood as indicating or implying relative importance.

[0033] In the description of the present invention, it should be noted that, unless otherwise clearly specified and limited, the terms "installation", "connection" and "connection" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0034] In addition, the technical features involved in the different embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0035] Example 1

[0036] See also Figure 1 and Figure 2 The bioreactor 100 shown in a preferred embodiment of the present application includes a tank body 1, a first mounting component 2, a first microporous membrane 3 and a first stirring component 4.

[0037] The tank body 1 is formed with a containing cavity 11 for containing culture fluid and cultured cells. An inlet 12 and an outlet 13 communicating with the containing cavity 11 are provided on the tank body 1 to facilitate the input of culture fluid and nutrients and the output of culture fluid and waste.

[0038] The first mounting assembly 2 is arranged on the inner wall of the tank body 1, and the periphery of the first microporous membrane 3 is mounted on the first mounting assembly 2. In this embodiment, the first mounting assembly 2 includes an upper mounting block 21 and a lower mounting block 22 arranged in the tank body 1, and the periphery of the first microporous membrane 3 is defined by the upper mounting block 21 and the lower mounting block 22. The upper mounting block 21 and the lower mounting block 22 not only provide support, but also ensure the close fit of the first microporous membrane 3, thereby preventing the displacement of the first microporous membrane 3, and further ensuring the sealing of the culture environment.

[0039] The first microporous membrane 3 is used to divide the accommodating chamber 11 into a mixing zone 112 and a first stirring zone 111 in the height direction of the tank body 1. The through hole (not shown) of the first microporous membrane 3 connects the first stirring zone 111 and the mixing zone 112, and the through hole diameter of the first microporous membrane 3 is set to be able to pass through the culture medium and is smaller than the diameter of the cultured cells, thereby preventing the cells from entering the first stirring zone 111 and protecting the cells from shear force damage generated during the stirring process. At the same time, the culture medium is allowed to flow freely between the two areas, ensuring uniform distribution of the culture medium and a good growth environment for the cells.

[0040] Generally, the diameter of the through hole is any value between 1 micron and 10 microns. The first microporous membrane 3 with a suitable through hole size is selected according to the cell type to be cultured. For larger cells such as stem cells, a microporous membrane with a through hole diameter of 10 microns is selected to ensure that they are not blocked from entering the first stirring zone 111. For smaller cells such as T cells, a microporous membrane with a through hole diameter of 5 microns can be selected to effectively block them from entering the first stirring zone 111 to maintain the stability of the culture environment. In this way, customized selection of through holes of different sizes can maximize the optimization of the adaptability of the culture environment to specific cell types and growth conditions.

[0041] In this embodiment, in the height direction, the first stirring zone 111 is located below the mixing zone 112, and the tank body 1 is provided with a feed port 12 and a discharge port 13 connected to the mixing zone 112, and a drain port 14 connected to the first stirring zone 111. The culture fluid in the mixing zone 112 is exchanged with the external environment through the feed port 12 and the discharge port 13. However, due to the presence of the first microporous membrane 3, the mixing zone 112 and the first stirring zone 111 are separated, so it is necessary to additionally open a drain port in the tank body 1 connected to the first stirring zone 111, so as to discharge the culture fluid that does not contain cultured cells.

[0042] In this embodiment, the first stirring component 4 includes a first rotating member 42 arranged in the first stirring zone 111 and a first driving member 41 arranged on the inner wall of the tank body 1. The first driving member 41 is used to drive the first rotating member 42 to rotate in the first stirring zone 111 to achieve stirring of the culture solution.

[0043] In this embodiment, the first rotating member 42 can be a paddle or a stirring rod, and its specific structure is not limited, as long as it can stir the culture solution. The first driving member 41 is a magnetic driving device, which drives the first rotating member 42 to rotate by magnetic force, thereby providing a contactless power transmission method, avoiding lubricant contamination or wear problems that may occur in mechanical transmission, and also reducing maintenance costs.

[0044] Specifically, the first driving member 41 includes an outer shell 411, a driving motor 412, a driving magnet 413 and a stirring magnet 414. Among them, the outer shell 411 is arranged on the inner wall of the tank body 1, and the driving motor 412 is arranged on the inner wall of the outer shell 411. The driving magnet 413 is arranged on the inner wall of the outer shell 411 and is connected to the output shaft of the driving motor 412. The driving motor 412 drives the driving magnet 413 to rotate along the output shaft of the driving motor 412. The stirring magnet 414 is arranged on the axis of the outer shell 411, is magnetically coupled with the driving magnet 413, and is connected to the first rotating member 42. When the driving magnet 413 rotates, it drives the stirring magnet 414 and the rotating member 414 to rotate. This structure is relatively common in the prior art and will not be described in detail here.

[0045] Optionally, the first driving member 41 may also be driven by a conventional motor, wherein the first driving member 41 only includes an isolation shell 415 and a motor 416. The isolation shell 415 is disposed on the inner wall of the tank body 1 and is located in the first stirring zone 111. The motor 416 is disposed in the isolation shell 415, and the output shaft of the motor 416 protrudes from the isolation shell 415. The first rotating member 42 is disposed on the output shaft of the motor 416, and the motor 416 directly drives the first rotating member 42 to rotate to stir the culture solution.

[0046] Example 2

[0047] See also Figure 3 The bioreactor 100 shown in this embodiment 2 has substantially the same structure as the bioreactor 100 of embodiment 1, except that the first stirring zone 111 is located above the mixing zone 112 in the height direction.

[0048] At this time, it is necessary to first add culture fluid into the tank body 1, and then install the first microporous membrane 3 from top to bottom. Since the cultured cells cannot pass through the first microporous membrane 3, the cultured cells are always blocked under the first microporous membrane 3 during the downward sliding of the first microporous membrane 3. When the first microporous membrane 3 is installed to the designated position, the internal accommodating cavity 11 is divided into a first stirring zone 111 and a mixing zone 112 from top to bottom.

[0049] The tank body 1 is provided with a feed port 12 connected to the first stirring zone 111 and a discharge port 13 connected to the mixing zone 112. In this embodiment, since the mixing zone 112 is located at the bottom, the culture solution can be discharged directly through the discharge port 13, and no additional discharge port 14 is required.

[0050] The tank body 1 includes a main body 15 and a cover body 16, the cover body 16 is detachably connected to the main body 15, and the first stirring assembly 4 is fixed to the cover body 16, so that the first stirring assembly 4 and the cover body 16 can be removed at the same time. As for the connection method between the cover body 16 and the main body 15, it can be a threaded connection, a snap connection, etc. This structure is more common in the prior art and will not be described in detail here.

[0051] In this embodiment, the first mounting assembly 2 includes a protrusion 23 and a clamping member 24. The protrusion 23 is arranged in the tank body 1. The clamping member 24 clamps the periphery of the first microporous membrane 3. The cross-sectional size of the clamping member 24 is equal to that of the accommodating cavity 11, and the clamping member 24 can slide up and down relative to the tank body 1, and the clamping member 24 overlaps the protrusion 23. After the clamping member 24 clamps the periphery of the first microporous mold 3, the clamping member 24 is sent into the accommodating cavity 11 from the top of the body 15. At this time, since the cross-sectional size of the clamping member 24 is equal to that of the accommodating cavity 11, the culture fluid can only flow through the through hole of the first microporous mold 3, and the cultured cells are isolated below the first microporous mold 3. The clamping member 24 continues to move downward until it touches the protrusion 23, and finally overlaps the protrusion 23, thereby realizing that the first microporous membrane 3 can be detachably mounted on the first mounting assembly 2.

[0052] Example 3

[0053] See also Figure 4 The structure of the bioreactor 100 shown in this embodiment 3 is roughly the same as that of the bioreactor 100 in embodiments 1 and 2, except that this embodiment combines the schemes of the bioreactor 100 in embodiments 1 and 2, and stirs at the top and bottom at the same time.

[0054] Specifically, in this embodiment, the bioreactor 100 further includes a second mounting component 5 , a second microporous filter membrane 6 and a second stirring component 7 .

[0055] The second mounting assembly 5 is arranged on the inner wall of the tank body 1. The periphery of the second microporous filter membrane 6 is mounted on the second mounting assembly 5. The second microporous membrane 6 is used to divide the mixing area 112 into a second stirring area 1121 and a liquid storage area 1122 located between the first stirring area 111 and the second stirring area 1121 in the height direction of the tank body 1. The through hole of the second microporous membrane 6 connects the second stirring area 1121 and the liquid storage area 1122, and the through hole diameter of the second microporous membrane 6 is set to be able to pass through the culture fluid and smaller than the diameter of the cultured cells. The second stirring assembly 7 includes a second rotating member 72 arranged in the second stirring area 1121 and a second driving member 71 arranged on the inner wall of the tank body 1. The second driving member 71 drives the second rotating member 72 to rotate in the second stirring area 1121.

[0056] Among them, if the first microporous filter membrane 3 is located above the second microporous filter membrane 6, the first microporous filter membrane 3 can be detachably installed on the first installation component 2; if the second microporous filter membrane 6 is located above the first microporous filter membrane 3, the second microporous filter membrane 6 can be detachably installed on the second installation component 5.

[0057] For the convenience of description, the accommodating chamber 11 is divided into a first stirring zone 111, a liquid storage zone 1122 and a second stirring zone 1121 from top to bottom. The tank body 1 is also provided with a feed port 12 connected to the first stirring zone 111, a discharge port 13 connected to the liquid storage zone 1122, and a discharge port 13 connected to the second stirring zone 1121.

[0058] Since this embodiment combines the solutions of Embodiment 1 and Embodiment 2, the corresponding structures have been described, and thus will not be described again.

[0059] The present application divides the accommodating chamber 11 into a first stirring zone 111 and a mixing zone 112 by installing the first microporous membrane 3 on the first mounting assembly 2 of the tank body 1. The through-hole diameter of the first microporous membrane 3 is smaller than the diameter of the cells, so as to prevent the cells from entering the first stirring zone 111 from the mixing zone 112, and only allow the culture fluid to flow back and forth, thereby preventing the cells from being directly exposed to a stirring environment that may generate a large shear force. The first stirring assembly 4 is only arranged in the first stirring zone 111, and the culture fluid is stirred by the rotation of the first rotating member 42 to ensure the uniformity of the culture fluid and a suitable physical environment without directly causing physical damage to the cells. In this way, not only the physical damage to the cells is reduced, but also the ideal state of the culture environment can be maintained, thereby improving the efficiency and quality of cell culture.

[0060] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0061] The above-mentioned embodiments only express several implementation methods of the utility model, and the description is relatively specific and detailed, but it cannot be understood as limiting the scope of the utility model patent. It should be pointed out that for ordinary technicians in this field, several modifications and improvements can be made without departing from the concept of the utility model, which all belong to the protection scope of the utility model. Therefore, the protection scope of the utility model patent shall be based on the attached claims.

Claims

1. A bioreactor, characterized in that: include: A tank body is formed with a containing cavity; A first mounting assembly is arranged on the inner wall of the tank body; A first microporous membrane, the periphery of which is mounted on the first mounting assembly, the first microporous membrane is used to divide the accommodating cavity into a mixing zone and a first stirring zone in the height direction of the tank body, the through holes of the first microporous membrane communicate with the first stirring zone and the mixing zone, and the through hole diameter of the first microporous membrane is set to be able to pass through the culture fluid and smaller than the diameter of the cultured cells; and The first stirring assembly includes a first rotating member disposed in the first stirring zone.

2. The bioreactor according to claim 1, characterized in that In the height direction, the first stirring zone is located below the mixing zone, and the tank body is provided with a feed inlet and a discharge port connected to the mixing zone, and a liquid discharge port connected to the first stirring zone.

3. The bioreactor according to claim 2, characterized in that The first mounting assembly includes an upper mounting block and a lower mounting block disposed in the tank body, and the periphery of the first microporous membrane is defined by the upper mounting block and the lower mounting block.

4. The bioreactor according to claim 1, characterized in that In the height direction, the first stirring zone is located above the mixing zone, the tank body is provided with a feed inlet connected to the first stirring zone and a discharge port connected to the mixing zone, and the first microporous membrane is detachably mounted on the first mounting assembly.

5. The bioreactor according to claim 4, characterized in that The tank body comprises a main body and a cover body, the cover body is detachably connected to the main body, and the first stirring assembly is fixed on the cover body.

6. The bioreactor according to claim 5, characterized in that The first installation component comprises: A projection, disposed in the tank body; A clamping member clamps the periphery of the first microporous membrane, the clamping member has a cross-sectional size equal to that of the accommodating cavity, and can slide up and down relative to the tank body, and the clamping member overlaps the protrusion.

7. The bioreactor according to claim 1, characterized in that The bioreactor also includes: A second mounting assembly is arranged on the inner wall of the tank body; a second microporous membrane, the periphery of which is mounted on the second mounting assembly, the second microporous membrane is used to divide the mixing zone into a second stirring zone and a liquid storage zone located between the first stirring zone and the second stirring zone in the height direction of the tank body, the through holes of the second microporous membrane communicate with the second stirring zone and the liquid storage zone, and the through hole diameter of the second microporous membrane is set to be able to pass through the culture solution and smaller than the diameter of the cultured cells; A second stirring assembly includes a second rotating member disposed in the second stirring zone; Wherein, if the first microporous membrane is located above the second microporous membrane, the first microporous membrane can be detachably mounted on the first mounting assembly; if the second microporous membrane is located above the first microporous membrane, the second microporous membrane can be detachably mounted on the second mounting assembly.

8. The bioreactor according to claim 1, characterized in that The diameter of the through hole is any value between 1 micrometer and 10 micrometers.

9. The bioreactor according to claim 1, characterized in that The first stirring assembly further includes a driving member disposed on the inner wall of the tank body, and the driving member is used to drive the first rotating member to rotate in the first stirring zone.

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