Rotary filter and bioreactor with same
By setting up multi-layer filter fins on the outside of the rotating filter of the bioreactor, the problem of insufficient mixing and stirring force in the prior art is solved, uniform mixing of liquids in the bioreactor is achieved, and the controllability of cell growth is improved.
Patent Information
- Application Number
- CN202421607094.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-07-08
- Publication Date
- 2025-05-02
- Estimated Expiration
- 2034-07-08
AI Technical Summary
In the prior art, the rotary filter cannot provide effective mixing and stirring force, resulting in a large gradient of temperature, flow-added substances, pH, etc. in the bioreactor, and the cell culture medium is unevenly mixed, affecting cell growth.
A rotary filter is designed to be arranged in a bioreactor, including a filter mesh, a connecting plate, a frame and a wing leaf. The wing leaves are arranged on the frame, away from the side of the filter, forming multi-layer filter fins to enhance the mixing performance of the liquid.
By installing multi-layer filter fins on the outside of the rotating filter, the mixing performance of liquids in the bioreactor is improved, ensuring the consistency of physical and chemical environments at each point in the reactor, thereby improving the controllability of cell growth.
Smart Images
Figure CN222821579U_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the field of biomedicine technology, and in particular to a rotary filter and a bioreactor having the rotary filter. Background Art
[0002] Adherent cell culture is a common cell culture technique in which cells need to attach to the walls of microcarriers in order to grow and proliferate.
[0003] In the existing technology, perfusion culture is generally used for adherent cell culture, which can bring many advantages, such as increasing cell density, maintaining cell activity, and increasing product yield.
[0004] During perfusion culture, the use of a perfusion bioreactor with a rotary filter can effectively retain cells while allowing the passage of culture medium and metabolites, thereby achieving continuous perfusion of cells. This ensures a continuous supply of nutrients required by cells and timely removal of harmful metabolic products, providing a stable and excellent growth environment for cells. Furthermore, the rotary filter can be used for online sampling and culture medium replacement, which is particularly important in continuous culture processes because it allows monitoring of cell growth and metabolite production without interrupting the culture process.
[0005] In the prior art, a common rotary filter 100, such as Figure 1 As shown, it has a metal filter 110. The rotary filter 100 is connected to the stirring shaft 120 in the bioreactor and can rotate with the stirring shaft 120. Although the metal filter 110 can rotate with the stirring shaft 120, the stirring force generated is small and cannot provide effective mixing kinetic energy. Therefore, it cannot provide effective mixing. This will cause large gradients in the temperature, feed material, pH, etc. of the cell culture medium in the bioreactor, resulting in uneven mixing of the cell culture medium, which is extremely unfavorable for cell growth control. In the prior art, such as Figure 2 As shown, a stirring paddle 220 is added to the bottom of the stirring shaft 210 to improve the mixing effect. However, flow field analysis shows that there is still a large difference between the liquid at the bottom and the top of the reactor, and the effect is not ideal. Utility Model Content
[0006] In view of this, the present invention aims to solve the technical problems in the prior art that, during the perfusion culture process of adherent cells, the rotary filter cannot provide effective mixing and stirring force, resulting in large gradients in temperature, feed material, pH, etc. in the bioreactor, and uneven mixing of the cell culture fluid.
[0007] An embodiment of the present application provides a rotary filter, which is arranged in a bioreactor, and includes: a filter screen; a connecting plate, which is arranged on the filter screen and connected to the stirring shaft of the bioreactor; a frame, which is sleeved outside the filter screen and connected to the connecting plate; and wings, which are arranged on the side of the frame away from the filter screen.
[0008] Furthermore, the filter screen is a cylindrical filter screen formed by surrounding the filter screen surface.
[0009] Furthermore, the filter screen is sleeved on the stirring shaft and is coaxially arranged with the stirring shaft.
[0010] Furthermore, the filter screen has a plurality of filter holes, and the pore size thereof is 50-200 microns.
[0011] Furthermore, the frame has a plurality of supporting ribs arranged parallel to the axis of the stirring shaft.
[0012] Furthermore, the wing blades are arranged on the supporting ribs.
[0013] Furthermore, there are more than two wing blades, which are evenly distributed on the supporting ribs.
[0014] Furthermore, the wing blades are paddle blades that generate axial thrust along the stirring shaft.
[0015] The present application also provides a bioreactor, comprising: a tank body; a stirring shaft arranged in the tank body; a driving device connected to the stirring shaft; a stirring paddle connected to the stirring shaft, and further comprising: a rotary filter as described above.
[0016] Furthermore, the bioreactor also includes: a liquid extraction pipe, whose liquid extraction end is inserted into the rotary filter and whose liquid discharge end is exposed outside the tank body; an air inlet pipe, whose air outlet end is inserted into the rotary filter and whose air inlet end is exposed outside the tank body.
[0017] The rotary filter provided in the present application is provided with multiple layers of filter fins on the outer side of the filter screen, which greatly improves the mixing performance of the liquid in the reactor tank. In particular, these fins can form a rapid up and down circulation of the liquid, making the physical and chemical environment of each point in the reactor tank as consistent as possible, thereby improving the controllability of cell growth.
[0018] This application provides an effective solution for the perfusion culture of adherent cells, achieving separation of cells from culture medium, continuous nutrient supply, timely removal of metabolites, improving the cell growth environment, and facilitating process scale-up. This is of great significance for improving the production efficiency and product quality of adherent cells. BRIEF DESCRIPTION OF THE DRAWINGS
[0019] The following is a brief introduction to the drawings used in describing the embodiments of this application:
[0020] Figure 1 It is a structural diagram of a rotary filter in the prior art;
[0021] Figure 2 It is a schematic structural diagram of a bioreactor with a rotary filter in the prior art;
[0022] Figure 3 A schematic structural diagram of a rotary filter provided in one embodiment of the present application;
[0023] Figure 4 A schematic structural diagram of a bioreactor with a rotary filter provided in another embodiment of the present application. DETAILED DESCRIPTION
[0024] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the specific implementation methods of the present application will be described below with reference to the accompanying drawings. The drawings described below are only some embodiments of the present application. For those of ordinary skill in the art, other drawings and other implementation methods can be obtained based on these drawings without any creative work. Adjustments and improvements made without departing from the concept of the present application are all within the scope of protection of the present application.
[0025] To simplify the drawings, the drawings in the embodiments of this application schematically illustrate only the portions relevant to the present application and do not represent the actual structure of the product. Furthermore, to simplify the drawings and facilitate understanding, in some drawings, only a portion of components with the same structure or function are schematically depicted; in practice, more or fewer components with the same structure or function may exist.
[0026] In this application, unless otherwise expressly specified and limited, ordinal numbers such as "first", "second", etc. are only used to distinguish and describe related objects, and cannot be understood as indicating or implying the relative importance or order between related objects; in addition, they do not represent the number of related objects. "And / or" is used to describe the relationship between related objects, which includes any relationship between related objects. For example, "a and / or b" includes: "a alone", "b alone", or "a and b". The terms "installation" and "connection" should be understood in a broad sense. For example, "installation" can be direct installation or installation through other components; "connection" can be direct connection or connection through other components. The term "relative arrangement" includes parallel relative or relative at a certain angle. The angle is not limited and is determined according to the number of relatively arranged objects.
[0027] In the embodiments shown in the drawings, directional indications (such as up, down, left, right, front, and back, etc.) are not absolute but relative when describing the structure and movement of each component, and are not used to limit the direction of the product in actual use.
[0028] In view of the fact that in the prior art, during the perfusion culture process of adherent cells, the rotary filter is connected to the stirring shaft in the bioreactor, and although the filter can rotate with the stirring shaft, the contact surface of the filter with the flow of cell culture fluid is small during rotation, and the stirring force is small, and effective mixing stirring force cannot be provided. Therefore, effective mixing cannot be provided, resulting in large gradients in temperature, flow material, pH, etc. in the bioreactor, uneven mixing of the cell culture fluid, and other technical problems.
[0029] An embodiment of the present application provides a rotary filter to solve the above-mentioned problems of the prior art.
[0030] The following is a description with reference to the accompanying drawings:
[0031] Please refer to Figure 3 , which is a structural diagram of a rotary filter provided in one embodiment of the present application. As shown in the figure, the embodiment of the present application provides a rotary filter 300, which is arranged in a bioreactor 400, and includes: a filter screen 310; a connecting disk 320, which is arranged on the filter screen 310 and connected to the stirring shaft 410 of the bioreactor; a frame 330, which is sleeved outside the filter screen 310 and connected to the connecting disk 320; and a wing 340, which is arranged on the side of the frame 330 away from the filter screen 310. Since multiple layers of filter fins are arranged on the outside of the frame of the rotary filter, when the rotary filter rotates with the drive shaft, its fins are fully in contact with the liquid in the reactor and stirred, so that the mixing performance of the liquid in the reactor is greatly improved.
[0032] In one embodiment of the present application, the filter screen is a cylindrical filter screen formed by a filter surface, wherein the filter screen is sleeved on the stirring shaft of the bioreactor and is coaxially arranged with the stirring shaft.
[0033] For example, the cell culture fluid is fed to a rotary filter, and the retentate is returned to the bioreactor again. The substance to be extracted is then removed and discharged from the rotary filter as a filtrate or permeate. The filter screen defining the filtrate space rotates in an axial direction, for example, at a speed within the range of 100 revolutions per minute, and the filtrate is discharged from the space. The greatest advantage of these rotary filters is that the filter screen is less likely to coagulate (caking), for example, by coagulation of solids contained in the fluid. Due to the rotation of the filter screen, centrifugal force is generated, which causes the sediment in or on the filter screen to fall off.
[0034] In the embodiments of the present application, the design of the filter screen needs to consider multiple factors, including the material, pore size, and structural form of the filter screen, to ensure efficient filtration while avoiding clogging. The filter screen is generally made of corrosion-resistant and non-deformable materials, such as stainless steel. In the embodiments of the present application, the filter screen has a variety of physical forms and material compositions, such as a filter screen woven from stainless steel filaments, a filter screen formed by sintering stainless steel or ceramic materials, and a polymer fiber membrane.
[0035] The pore size of the filter must be suitable for the passage of the culture medium, but can effectively block cell clusters. In an embodiment of the present application, the filter has multiple filter holes with a pore size of 50-200 microns. This can block the microspheres (polymerized polymer particles with a diameter of approximately 50-200 microns) in the liquid in the reactor. Since many cells (adherent cells) grow on the microspheres to form cell clusters, they cannot enter the filter, preventing the microspheres from entering the rotary filter, preventing the cells on the microspheres from contacting the bubbles inside the rotary filter, and avoiding cell damage and death.
[0036] In an embodiment of the present application, the frame has a plurality of support ribs arranged parallel to the axis of the agitator shaft. This creates a hollow structure on the frame, preventing obstruction of the filter screen and ensuring the filter's filtration effectiveness. In an embodiment of the present application, the wings are mounted on the support ribs.
[0037] In the embodiment of the present application, there are more than two wing blades, which are evenly distributed on the supporting ribs.
[0038] Because these fins can quickly circulate the liquid in the reactor up and down, the physical and chemical environment at each point in the reactor is as uniform as possible, thereby improving the controllability of cell growth.
[0039] The design morphology of the wing blades is a key factor in ensuring the efficiency of cell culture and product quality in the bioreactor. The wing blade design needs to consider the generation of a suitable mixing flow field to achieve rapid transfer of nutrients and serve as a power source to drive cell growth. The shear force generated by the wing blades during the stirring process may cause damage to the cells, so it is necessary to find a suitable reactor type and structural parameters during design to reduce damage to the cells. In an embodiment of the present application, the wing blades are in the shape of blades that are conducive to generating axial thrust. The wing blades can be designed in different forms, such as a pitched blade agitator low shear propeller, which helps to adapt to different stirring and filtration requirements while reducing the formation of bubbles. The design of the rotary filter and blades should be compatible with the size, shape and other components of the bioreactor to achieve the best culture effect.
[0040] In addition, in this embodiment, the number, position and shape of the fins can be adjusted, so as to conveniently achieve the best mixing effect.
[0041] See Figure 4 , which is a schematic structural diagram of a bioreactor with a rotary filter provided in another embodiment of the present application.
[0042] The bioreactor 400 includes: a tank body 420; a stirring shaft 410 disposed in the tank body; a driving device 430 connected to the stirring shaft 410; and a stirring paddle 440 connected to the stirring shaft 410. It also includes: a rotary filter 300 as described in any of the above embodiments.
[0043] In the embodiment of the present application, the bioreactor further includes: a liquid extraction tube 450, the liquid extraction end of which is inserted in the rotary filter 300, and the liquid discharge end is exposed outside the tank body 420; an air inlet tube 460, the air outlet end of which is inserted in the rotary filter 300, and the air inlet end is exposed outside the tank body 420.
[0044] A vent pipe is provided in the rotary filter. The gas in the pipe forms dissolved oxygen in the liquid. The liquid rich in dissolved oxygen can penetrate into the liquid in the tank through the surface of the rotary filter, while the bubbles in the rotary filter are restricted by the filter mesh of the rotary filter, thereby isolating them from the cells outside the rotary filter. When the liquid in the reactor is changed, the liquid is extracted from the reactor through the extraction pipe, but the microspheres cannot be extracted together. Therefore, the extraction pipe is set inside the filter mesh to prevent the microspheres from being extracted.
[0045] In short, the function of the spin filter is to isolate the microspheres (microspheres filled with cells) from the bubbles formed by ventilation and to ensure that the microspheres are not removed during liquid extraction. Aeration is to obtain dissolved oxygen in the liquid, providing the oxygen required for cell growth and ensuring a good growth environment for cells.
[0046] The rotary filter and bioreactor having the rotary filter provided in the embodiments of the present application have multiple layers of filter fins arranged on the outer side of the filter, which greatly improves the mixing performance of the liquid in the reactor tank. In particular, these fins can form a rapid upward and downward circulation of the liquid, making the physical and chemical environment of each point in the reactor tank as consistent as possible, thereby improving the controllability of cell growth.
[0047] This application provides an effective solution for the perfusion culture of adherent cells, achieving separation of cells from culture medium, continuous supply of nutrients, timely removal of metabolites, improving the cell growth environment, and facilitating process amplification. It is of great significance to improve the production efficiency and product quality of adherent cells.
[0048] In the above embodiments, the description of each embodiment has its own focus. For parts that are not described or recorded in detail in a certain embodiment, reference can be made to the relevant description of other embodiments.
[0049] It should be noted that the above embodiments can be freely combined as needed. The above are only some of the implementation methods of this application. For those skilled in the art, without departing from the principles of this application, they can make several improvements and modifications, and these improvements and modifications should also be considered as the scope of protection of this application.
Claims
1. A rotary filter, arranged in a bioreactor, characterized in that: include: Filter; A connecting plate, disposed on the filter screen and connected to the stirring shaft of the bioreactor; A frame, which is sleeved outside the filter screen and connected to the connecting plate; The wing blade is arranged on a side of the frame away from the filter screen.
2. The rotary filter according to claim 1, characterized in that The filter screen is a cylindrical filter screen formed by surrounding the filter screen surface.
3. The rotary filter according to claim 2, characterized in that The filter screen is sleeved on the stirring shaft and is coaxially arranged with the stirring shaft.
4. The rotary filter according to claim 1, characterized in that The filter screen has a plurality of filter holes, and the pore diameters thereof are 50-200 microns.
5. The rotary filter according to claim 1, characterized in that The frame has a plurality of supporting ribs arranged parallel to the axial direction of the stirring shaft.
6. The rotary filter according to claim 5, characterized in that The wing blades are arranged on the supporting ribs.
7. The rotary filter according to claim 6, characterized in that There are more than two wing blades, which are evenly distributed on the supporting ribs.
8. The rotary filter according to claim 1, characterized in that The wing blades are blades that generate axial thrust along the stirring shaft.
9. A bioreactor comprising: Tank; A stirring shaft is arranged in the tank body; A driving device is connected to the stirring shaft; The stirring paddle is connected to the stirring shaft, and is characterized in that it also includes: A rotary filter as claimed in any one of claims 1 to 8.
10. The bioreactor according to claim 9, characterized in that Also includes: A liquid extraction tube, the liquid extraction end of which is inserted into the rotary filter and the liquid discharge end is exposed outside the tank body; The air inlet pipe has an air outlet end inserted in the rotary filter and an air inlet end exposed outside the tank body.