Alternating tangential flow filtering structure and perfusion culture system
By designing an alternating tangential flow filtration structure and combining the expansion and contraction of the balloon, the problems of adherent cells and microcarrier sedimentation and gas accumulation in existing technologies have been solved. This achieves effective retention of microcarriers and renewal of culture medium, ensuring the normal operation of the perfusion system.
Patent Information
- Application Number
- CN202520040139.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-08
- Publication Date
- 2025-12-16
- Estimated Expiration
- 2035-01-08
AI Technical Summary
Existing alternating tangential perfusion systems are mainly used for suspended cells, and there is a lack of effective solutions for adherent cells and microcarrier sedimentation and gas accumulation.
An alternating tangential flow filtration structure was designed, including a fixed shell, an air inlet flange, a balloon, an outer shell, a screen, and an elbow. The alternating flow of fluid is achieved by the expansion and contraction of the balloon. Combined with the sedimentation characteristics of the microcarrier, the microcarrier is effectively retained and the influence of air bubbles is avoided, thereby realizing the separation and renewal of the microcarrier and the culture medium.
It achieves effective retention and separation of microcarriers, solves the problem of bubble accumulation affecting the perfusion process, and ensures the normal operation of the microcarrier perfusion system and the renewal of the culture medium.
Smart Images
Figure CN223668764U_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The utility model relates to alternate tangential flow filter structure and perfusion culture system. BACKGROUND
[0002] The alternate tangential perfusion system is a filtering system for cell separation and culture, mainly used in biopharmaceutical and cell culture processes. The system uses alternating tangential flow filtration (ATF) technology to periodically change the flow direction to reduce cell accumulation and contamination, thereby improving filtration efficiency and cell activity.
[0003] The alternate tangential perfusion system is widely used in the biopharmaceutical industry, especially in the production of monoclonal antibodies, virus particles, and biological drug harvesting. Compared with traditional tangential flow filtration (TFF), the ATF system has better performance in cell activity and product retention, which can prolong the process duration and reduce cell accumulation and product retention.
[0004] The existing alternate tangential perfusion system mainly applies to suspended cells, and there is currently a lack of a simple and effective practical structure for adherent cell perfusion and microcarrier perfusion. There is also a lack of reliable solutions for microcarrier sedimentation and gas aggregation.
[0005] Therefore, the alternate tangential flow filter structure and perfusion culture system is proposed to solve the above problems. SUMMARY
[0006] The purpose of the utility model is to overcome the defects of the existing alternate tangential flow filter structure and perfusion culture system, which is simple in structure and easy to install. It can effectively combine the alternate tangential flow perfusion process with adherent cell culture.
[0007] The technical solution to achieve the above-mentioned purpose is: an alternate tangential flow filter structure, comprising: a fixed shell, an air inlet flange, a balloon, an outer shell, a screen and an elbow.
[0008] The upper end of the outer shell is provided with a first interface, and the lower end is provided with a second interface. The upper end of the side wall of the outer shell is provided with a third interface, and the lower end of the side wall is provided with a fourth interface.
[0009] The fixed shell is connected to the third interface by a first chuck, and the other end of the fixed shell is connected to the air inlet flange. The balloon is arranged inside the fixed shell and is sleeved on the third interface through its own opening. The screen is arranged inside the outer shell, and one end of the elbow is connected to the second interface.
[0010] When the balloon expands under the action of pressure difference, fluid flows from the elbow to the outer shell and flows into the balloon through the screen.
[0011] When the balloon shrinks under the pressure difference, fluid flows from the balloon to the shell and back to the elbow through the screen.
[0012] Preferably, the fixed shell connects the air inlet flange through a second chuck, one end of the air inlet flange is a chuck interface for matching the second chuck, and the other end is an internally threaded port for connecting an air pipe joint.
[0013] Preferably, a support is further included, the support is arranged in the balloon, a threaded hole is arranged on the third interface, one end of the support is connected with the threaded hole, and the other end is a flange edge for fixing the position of the balloon.
[0014] Preferably, a fine hole is arranged on the third interface for connecting the balloon, and the fine hole surrounds the threaded hole.
[0015] Preferably, the balloon is a spherical silica gel material membrane, and the screen is a stainless steel screen.
[0016] Preferably, both ends of the elbow, the first interface and the second interface are chuck interfaces.
[0017] Preferably, the screen has a tubular structure with one open end and the other closed end, and the open end of the screen faces the elbow.
[0018] Preferably, a stepped surface is arranged on the open end of the screen and the second interface, and the stepped surface of the screen matches the stepped surface of the second interface.
[0019] Preferably, the closed end of the screen is higher than the third interface, and the mesh size of the screen is smaller than the size of the microcarrier.
[0020] The perfusion culture system based on the alternating tangential flow filtration structure comprises an upper filtrate pipe, an air pipe, a lower filtrate pipe, a main pipe, a peristaltic pump, a control electric box and a reactor.
[0021] One end of the upper filtrate pipe is connected with the first interface at the upper end of the shell, and the peristaltic pump is connected with the upper filtrate pipe.
[0022] One end of the air pipe is connected with the air inlet flange, and the other end of the air pipe is connected with the control electric box.
[0023] One end of the lower filtrate pipe is connected with the fourth interface of the sidewall at the lower end of the shell.
[0024] One end of the main pipe is connected with the elbow, and the other end of the main pipe is connected with the reactor, and the reactor is connected with a liquid supplement pipe.
[0025] The utility model discloses a beneficial effect is: this alternate tangential flow filtration structure and perfusion culture system, drive balloon is set at the top of whole perfusion structure, this structure can cooperate microcarrier own sedimentation characteristic (because microcarrier own density is greater than culture medium, so microcarrier will have the sinking phenomenon in culture medium), and microcarrier will concentrate in the main pipe road mouth nearby, when the balloon suction movement will preferentially suction the culture medium of microcarrier in the main pipe road mouth nearby, and the exchange action of microcarrier in perfusion structure interior and reactor interior microcarrier is convenient.
[0026] The system drive balloon is installed in the side direction of the whole perfusion structure, and the upper filtrate pipe is at the top of the whole perfusion structure, which can effectively avoid the problem that bubbles enter the drive balloon and affect the operation of the equipment. When the bubbles are sucked into the perfusion structure, due to the physical property of light density in the bubbles, they will float to the top of the whole structure and be sucked out through the filtrate pipe. If the bubbles are sucked by the drive balloon during the floating process, the bubbles will also be discharged when the drive balloon contracts, so that the bubbles return to the floating process.
[0027] The system can effectively realize the interception of microcarriers, complete the separation of the culture medium and the microcarriers in the reactor and the update of the culture medium, and achieve the purpose of replacing the liquid in the reactor. At the same time, the special structure of the system can effectively solve the problem of bubble accumulation affecting normal perfusion action during perfusion, and ensure the normal operation of the microcarrier perfusion system. BRIEF DESCRIPTION OF DRAWINGS
[0028] Figure 1 It is the schematic diagram of the alternate tangential flow filtration structure of the utility model;
[0029] Figure 2 It is the sectional view of the alternate tangential flow filtration structure of the utility model;
[0030] Figure 3 It is the schematic diagram of the perfusion culture system of the utility model.
[0031] In the drawing: 1, fixed shell;2, air inlet flange;3, support;4, balloon;5, shell;6, screen;7, elbow;8, first interface;9, second interface;10, third interface;11, fourth interface;12, first chuck;13, second chuck;14, threaded hole;15, fine hole;16, upper filtrate pipe;17, air pipe;18, lower filtrate pipe;19, main pipe road;20, peristaltic pump;21, control electric box;22, reactor;23, liquid supplement pipe. DETAILED DESCRIPTION
[0032] The technical solution of this utility model will now be clearly and completely described in conjunction with the accompanying drawings. In the description of this utility model, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicating the orientation or positional relationship, are based on the orientation or positional relationship shown in the accompanying drawings and are only for the convenience of describing this utility model and simplifying the description. They 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, and therefore should not be construed as a limitation of this utility model. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.
[0033] The present invention will be further described below with reference to the accompanying drawings.
[0034] like Figures 1-2 As shown, the alternating tangential flow filter structure includes: a fixed shell 1, an inlet flange 2, a balloon 4, an outer shell 5, a screen 6, and an elbow 7; the upper end of the outer shell 5 is provided with a first interface 8, the lower end with a second interface 9, the upper end of the side wall of the outer shell 5 is provided with a third interface 10, and the lower end of the side wall is provided with a fourth interface 11; the fixed shell 1 is connected to the third interface 10 through a first chuck 12, and the other end of the fixed shell 1 is connected to the inlet flange 2; the balloon 4 is disposed inside the fixed shell 1 and is fitted onto the third interface 10 through its own opening; the screen 6 is disposed inside the outer shell 5, and one end of the elbow 7 is connected to the second interface 9; the internal space of the balloon 4 is connected to the internal space of the outer shell 5 through the third interface 10.
[0035] Specifically, when the balloon 4 expands under the action of pressure difference, the fluid flows from the elbow 7 to the outer shell 5 and through the screen 6 into the balloon 4; the screen 6 is used to intercept microcarriers in the fluid to prevent microcarriers from entering the balloon 4.
[0036] Specifically, when the balloon 4 contracts under the action of pressure difference, the fluid flows from the balloon 4 to the outer shell 5 and then flows back to the elbow 7 through the screen 6.
[0037] Specifically, the fixed housing 1 is connected to the air intake flange 2 via the second chuck 13. One end of the air intake flange 2 is a chuck-type interface for engaging with the second chuck 13, and the other end is an internal thread for connecting the air pipe connector.
[0038] Specifically, it further comprises a support 3 arranged in the balloon 4, a threaded hole 14 is arranged on the third interface 10, one end of the support 3 is connected with the threaded hole 14, and the other end is a flange edge for fixing the position of the balloon 4. A fine hole 15 is arranged on the third interface 10 for communicating the balloon 4, and the fine hole 15 surrounds the threaded hole 14. The balloon 4 is a spherical silica gel material diaphragm, and the screen 6 is a stainless steel screen. The two ends of the elbow 7, the first interface 8 and the second interface 9 are chuck type interfaces. The screen 6 is in a cylindrical structure with one open end and the other closed end, and the open end of the screen 6 faces the elbow 7.
[0039] Specifically, the open end of the screen 6 and the second interface 9 are both provided with a stepped surface, the stepped surface of the screen 6 cooperates with the stepped surface of the second interface 9 for alignment and installation. The closed end of the screen 6 is higher than the third interface 10, and the mesh size of the screen 6 is smaller than the size of the microcarrier. The microcarrier refers to a microbead with a diameter of 60-250 μm and suitable for the growth of adherent cells. It is generally composed of natural dextran or various synthetic polymers.
[0040] As shown in Figure 3 The perfusion culture system based on the alternating tangential flow filtration structure comprises an upper filtrate pipe 16, an air pipe 17, a lower filtrate pipe 18, a main pipe 19, a peristaltic pump 20, a control electric box 21, a reactor 22 and the control electric box 21. One end of the upper filtrate pipe 16 is connected with the first interface 8 at the upper end of the shell 5, and the peristaltic pump 20 is connected with the upper filtrate pipe 16. One end of the air pipe 17 is connected with the air flange 2, and the other end of the air pipe 17 is connected with the control electric box 21. One end of the lower filtrate pipe 18 is connected with the fourth interface 11 at the lower end of the sidewall of the shell 5. One end of the main pipe 19 is connected with the elbow 7, and the other end is connected with the reactor 22. The reactor 22 is connected with a liquid supplement pipe 23.
[0041] The starting device opens the control electric box 21 to generate power to drive the balloon 4 to expand or contract. When the balloon 4 expands, the balloon 4 absorbs the culture medium in the perfusion structure, and at the same time, a negative pressure is generated in the structure, so that the culture medium containing microcarriers in the reactor 22 is sucked into the inside of the screen 6 through the main pipe 19, and the screen 6 retains the microcarriers inside the screen 6. When the balloon 4 contracts, the balloon 4 spits out the culture medium in the inside of the balloon 4, flushes the screen 6, spits out the culture medium containing microcarriers inside the screen 6 into the reactor 22, and completes the exchange of the culture medium in the perfusion structure and the culture medium in the reactor.
[0042] When in use, clamp the peristaltic pump 20 on the upper filtrate pipe 16, draw the medium outside the screen 6 through the peristaltic pump 20, and at the same time, the medium without microcarriers in the perfusion structure is drawn out, the medium with microcarriers in the screen 6 is separated due to the pressure difference between the inside and outside of the screen 6, the microcarriers are left in the inside of the screen 6, the medium permeates through the screen 6 to the inside of the perfusion structure, and is drawn out by the peristaltic pump 20 through the upper filtrate pipe 16, at the same time, the liquid supplement pipe 23 connected to the reactor 22 end supplements the reactor 22, the separation of the medium and the microcarriers in the reactor 22 and the update of the medium are completed, and the liquid in the reactor is replaced.
[0043] For the previous suspension cell perfusion structure, the ballonet 4 of the system is driven above the entire perfusion structure, which can cooperate with the sedimentation characteristics of the microcarriers (since the microcarriers have a density greater than the medium, the microcarriers will sink in the medium), and the microcarriers will be concentrated near the main pipe 19, and when the ballonet 4 is drawn, the medium with microcarriers near the main pipe 19 will be preferentially drawn, facilitating the exchange of microcarriers in the perfusion structure and the reactor.
[0044] For the existing microcarrier perfusion structure on the market, a small amount of bubbles will be sucked into the perfusion structure during the operation of the perfusion structure, resulting in a large number of bubbles at the top of the perfusion structure, which will enter the driving diaphragm pump, thereby affecting the normal pumping action of the perfusion structure.
[0045] The driving ballonet of the system is installed on the side of the entire perfusion structure, and the upper filtrate pipe 16 is at the top of the entire perfusion structure, which can effectively avoid the problem of bubbles entering the driving ballonet affecting the operation of the equipment. When the bubbles are sucked into the perfusion structure, due to the physical characteristics of the light density inside the bubbles, they will float to the top of the entire structure and be drawn out through the filtrate pipe. If the bubbles are sucked into the driving ballonet during the floating process, the bubbles will also be discharged when the driving ballonet contracts, so that the bubbles return to the floating process.
[0046] The system can effectively achieve the trapping action of microcarriers, complete the separation of the medium and the microcarriers in the reactor and the update of the medium, and achieve the purpose of replacing the liquid in the reactor. At the same time, the special structure of the system can effectively solve the problem of bubble accumulation affecting the normal perfusion action during perfusion, and ensure the normal operation of the microcarrier perfusion system.
[0047] The above embodiments are only used to illustrate the technical solutions of the present application, and are not limited thereto; although the present application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that the technical solutions recorded in the foregoing embodiments can still be modified, or some or all of the technical features can be replaced equivalently; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present application.
Claims
1. An alternating tangential flow filtration structure, characterized in that, The utility model relates to a kind of microcarrier separation device, including: Fixed shell (1), air inlet flange (2), balloon (4), shell (5), screen (6) and elbow (7); The upper end of the shell (5) is provided with a first interface (8), and the lower end is provided with a second interface (9). The upper end of the side wall of the shell (5) is provided with a third interface (10), and the lower end of the side wall is provided with a fourth interface (11). The fixed shell (1) is connected to the third interface (10) by a first chuck (12). The other end of the fixed shell (1) is connected to the air inlet flange (2). The balloon (4) is arranged inside the fixed shell (1) and is sleeved on the third interface (10) through its own opening. The screen (6) is arranged inside the shell (5). One end of the elbow (7) is connected to the second interface (9). When the balloon (4) expands under the action of pressure difference, fluid flows from the elbow (7) to the shell (5) and flows into the balloon (4) through the screen (6). When the balloon (4) shrinks under the action of pressure difference, fluid flows from the balloon (4) to the shell (5) and flows back into the elbow (7) through the screen (6).
2. The alternating tangential flow filtration structure of claim 1, wherein, The fixed shell (1) is connected to the air inlet flange (2) by a second chuck (13). One end of the air inlet flange (2) is a chuck interface for matching the second chuck (13). The other end is an internally threaded port for connecting a gas pipe joint.
3. The alternating tangential flow filtration structure of claim 1, wherein, It also includes a support (3) arranged in the balloon (4). A threaded hole (14) is formed in the third interface (10). One end of the support (3) is connected to the threaded hole (14). The other end is a flange edge for fixing the position of the balloon (4).
4. The alternating tangential flow filtration structure of claim 3, wherein, A fine hole (15) is formed in the third interface (10) for communicating with the balloon (4). The fine hole (15) surrounds the threaded hole (14).
5. The alternating tangential flow filtration structure of claim 1, wherein, The balloon (4) is a spherical silica gel material membrane. The screen (6) is a stainless steel screen.
6. The alternating tangential flow filtration structure of claim 1, wherein, Both ends of the elbow (7), the first interface (8) and the second interface (9) are chuck interfaces.
7. The alternating tangential flow filtration structure of claim 1, wherein, The screen (6) has a tubular structure with one open end and the other closed end. The open end of the screen (6) faces the elbow (7).
8. The alternating tangential flow filtration structure of claim 7, wherein, Step surfaces are arranged on the open end of the screen (6) and the second interface (9). The step surface of the screen (6) matches the step surface of the second interface (9).
9. The alternating tangential flow filtration structure of claim 7, wherein, The closed end of the screen (6) is higher than the third interface (10). The mesh size of the screen (6) is smaller than the size of the microcarrier.
10. A perfusion culture system based on the alternating tangential flow filtration structure according to any one of claims 1 to 6, characterized in that The utility model relates to a kind of microcarrier separation device, including: Upper filtrate pipe (16), gas pipe (17), lower filtrate pipe (18), main pipeline (19), peristaltic pump (20), control electric box (21) and reactor (22); One end of the upper filtrate pipe (16) is connected to the first interface (8) at the upper end of the shell (5). The peristaltic pump (20) is connected to the upper filtrate pipe (16). One end of the gas pipe (17) is connected to the air inlet flange (2). The other end of the gas pipe (17) is connected to the control electric box (21). One end of the lower filtrate pipe (18) is connected with the fourth interface (11) of the lower end side wall of the shell (5); One end of the main pipe (19) is connected with the elbow (7), and the other end is connected with the reactor (22), and the reactor (22) is connected with a liquid supplement pipe (23).