Tangential flow filtering device with cleaning device and perfusion culture system

Abstract

The utility model discloses a tangential flow filtering device with a cleaning device and a perfusion culture system.The tangential flow filtering device comprises a hollow fiber column assembly, a pressure detection meter, a first diaphragm pump and a second diaphragm pump, the hollow fiber column assembly comprises a hollow fiber column and a sleeve, the sleeve is arranged outside the hollow fiber column in a sleeving mode, and the pressure detection meter is arranged on the hollow fiber column; a waste liquid cavity is formed between the inner wall of the sleeve and the hollow fiber column; a first butt-joint port and a second butt-joint port are formed in the upper end and the lower end of the hollow fiber column assembly respectively, and a first liquid outlet and a second liquid outlet are formed in the upper end side wall and the lower end side wall of the hollow fiber column assembly respectively; the first diaphragm pump is in butt joint with the second butt joint opening, the second diaphragm pump is in butt joint with the second liquid outlet, and the pressure detection meter is connected with the waste liquid cavity through the second liquid outlet. According to the utility model, the pressure change of the liquid outlet is monitored through the pressure detection meter to judge the blockage condition of the hollow fiber column, and the liquid is driven by the second diaphragm pump to reversely wash the hollow fiber column, so that the smoothness of the hollow fiber column is ensured.

Description

Technical Field

[0001] The utility model relates to the field of biopharmaceuticals, in particular to a tangential flow filtration device with a cleaning device and a perfusion culture system. Background Art

[0002] In recent years, the biopharmaceutical industry has frequently used hollow fibers for perfusion culture to achieve high-density cell culture results. The perfusion culture process allows for the production of high-density, highly active cells while also enabling the continuous harvesting of cell products. A key component of the perfusion culture process is the hollow fiber. Hollow fiber columns are composed of numerous tiny hollow fibers whose sidewalls have uniform pore sizes and surface bioaffinity groups. The pore size of the fiber column sidewalls can be adjusted as needed to accommodate different separation and purification requirements. The exterior of the fiber column has a fixed shell that secures the fibers and maintains structural stability.

[0003] Existing perfusion devices cannot monitor hollow fiber clogging online. Blockage can only be inferred by comparing the concentration of the target product in the reactor with that in the effluent using offline sampling. This limitation necessitates termination of the test or production batch, significantly reducing production efficiency. Utility Model Content

[0004] The purpose of the utility model is to provide a tangential flow filtration device with a cleaning device and a perfusion culture system to achieve online monitoring of hollow fiber blockage and reverse flushing of the hollow fiber to ensure smooth flow of the hollow fiber.

[0005] In order to solve the above technical problems, the utility model provides a tangential flow filtration device with a cleaning device, comprising: a hollow fiber column assembly, a pressure detection gauge, a first diaphragm pump and a second diaphragm pump;

[0006] The hollow fiber column assembly includes a plurality of hollow fiber columns and a sleeve, wherein the sleeve is sleeved on the outside of the plurality of hollow fiber columns, and a waste liquid cavity is formed between the inner wall of the sleeve and the plurality of hollow fiber columns;

[0007] The upper and lower ends of the hollow fiber column assembly are respectively provided with a first pairing interface and a second pairing interface, and the first pairing interface and the second pairing interface are both interconnected with a plurality of fluid channels of the hollow fiber columns, and the upper end side wall and the lower end side wall of the hollow fiber column assembly are respectively provided with a first drain port and a second drain port, and the first drain port and the second drain port are both interconnected with the waste liquid chamber;

[0008] The first diaphragm pump is sealed and docked with the second docking port, the second diaphragm pump is sealed and docked with the second liquid discharge port, the pressure detection gauge is connected to the waste liquid chamber of the hollow fiber column assembly through the second liquid discharge port, and the pressure detection gauge is used to detect the change of the liquid pressure in the waste liquid chamber in real time;

[0009] When the liquid pressure change value in the waste liquid chamber is higher than the set value, the first diaphragm pump operates normally and the hollow fiber column assembly performs filtering normally;

[0010] When the liquid pressure change value in the waste liquid chamber is lower than a set value, the second diaphragm pump starts to work, driving the liquid in the waste liquid chamber to reversely flush the hollow fiber column.

[0011] Furthermore, the first diaphragm pump and the second diaphragm pump each include a rigid spherical shell and an elastic balloon, wherein the elastic balloon is disposed within the rigid spherical shell, and an air pressure regulating chamber is formed between an outer wall of the elastic balloon and an inner wall of the rigid spherical shell, wherein the elastic balloon contracts or expands according to changes in air pressure in the air pressure regulating chamber;

[0012] The inner cavity of the elastic balloon of the first diaphragm pump is communicated with the fluid channels of the plurality of hollow fiber columns, and the inner cavity of the elastic balloon of the second diaphragm pump is communicated with the waste liquid cavity.

[0013] Furthermore, a base is provided at the bottom of the rigid spherical shell, and a vent hole is opened on the base, and the external air pump component is connected to the air pressure regulating chamber through the vent hole.

[0014] Furthermore, the first diaphragm pump and the second diaphragm pump each include a transfer tube, which is arranged at the end of the rigid spherical shell away from the base, and the lower ends of the two transfer tubes are respectively sealed and docked with the open ends of the two elastic balloons, the upper end of the transfer tube of the first diaphragm pump is sealed and docked with the second docking interface of the hollow fiber column assembly, and the upper end of the transfer tube of the second diaphragm pump is sealed and docked with the second drainage port of the hollow fiber column assembly, and an infiltration hole is opened on the side wall of the transfer tube, and the infiltration hole is used to connect the wetting tube.

[0015] Furthermore, it also includes a T-shaped equal-diameter tee, the first end of the T-shaped equal-diameter tee is sealed and connected to the transfer tube of the second diaphragm pump through an L-shaped elbow, the second end of the T-shaped equal-diameter tee is sealed and connected to the second discharge port, and the third end of the T-shaped equal-diameter tee is connected to the pressure detection gauge.

[0016] Furthermore, the elastic balloon is provided with an inner support column, and the inner support column is used to fix the upper and lower ends of the elastic balloon.

[0017] Furthermore, the first pair of interfaces is connected to a main pipeline, and the main pipeline is used to connect to a bioreactor; the first drainage port is connected to a drainage pipe, and the drainage pipe is used to discharge waste liquid in the waste liquid chamber.

[0018] In a second aspect, the utility model discloses a perfusion culture system, comprising: a first air pump assembly, a second air pump assembly, a bioreactor, a control unit, and the above-mentioned tangential flow filtration device with a cleaning device;

[0019] The bioreactor is connected to the first port of the hollow fiber column assembly via a main pipeline;

[0020] The first diaphragm pump of the tangential flow filtration device and the first air pump assembly form an axial drive unit, and the second diaphragm pump of the tangential flow filtration device and the second air pump assembly form a radial drive unit;

[0021] The first air pump assembly, the second air pump assembly, and the pressure detection gauge of the tangential flow filtration device are all connected to the control unit, and the control unit controls the working state of the axial drive unit and the radial drive unit according to the pressure change in the waste liquid chamber detected by the pressure detection gauge;

[0022] When the pressure detection gauge detects that the liquid pressure change value in the waste liquid chamber is higher than the set value, the axial drive unit works normally to drive the liquid in the hollow fiber column assembly to flow back and forth, thereby achieving tangential filtration;

[0023] When the pressure detection gauge detects that the liquid pressure change value in the waste liquid chamber is lower than the set value, the radial drive unit starts to work to drive the liquid in the waste liquid chamber to reversely flush the hollow fiber column of the hollow fiber column assembly.

[0024] Compared with the prior art, the present invention has at least the following beneficial effects:

[0025] The utility model monitors the pressure change at the discharge port of the waste liquid chamber through a pressure detection gauge, thereby judging the blockage condition of the hollow fiber column, and drives the liquid to pass through the hollow fiber column in the reverse direction through the second diaphragm pump online, and reversely dredges and cleans the micropores on the hollow fiber column, thereby ensuring the unobstructed flow of the hollow fiber column, thereby improving the working efficiency of perfusion culture. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is a schematic diagram of the overall structure of the tangential flow filtration device with a cleaning device of the utility model;

[0027] Figure 2 This is a schematic cross-sectional view of the tangential flow filtration device with a cleaning device according to the present invention;

[0028] Figure 3 This is a schematic diagram of the structure of the fiber column assembly of the tangential flow filtration device with a cleaning device of the utility model;

[0029] Figure 4 This is a schematic diagram of the infiltration state structure of the perfusion culture system of the utility model;

[0030] Figure 5 This is a schematic diagram of the production state structure of the perfusion culture system of the utility model;

[0031] Figure 6 This is a schematic diagram of the cleaning state structure of the perfusion culture system of the utility model. DETAILED DESCRIPTION

[0032] The following schematic diagrams provide a more detailed description of the tangential flow filtration device with a cleaning device and the perfusion culture system of the present invention. These schematic diagrams illustrate preferred embodiments of the present invention. It should be understood that those skilled in the art may modify the present invention described herein while still achieving the beneficial effects of the present invention. Therefore, the following description should be understood as a general guide for those skilled in the art and not as a limitation of the present invention.

[0033] The following paragraphs describe the present invention in more detail by way of example with reference to the accompanying drawings. The advantages and features of the present invention will become more apparent from the following description. It should be noted that the drawings are greatly simplified and not to exact scale, and are intended solely to facilitate and clearly illustrate the embodiments of the present invention.

[0034] Example 1

[0035] like Figures 1 to 3 As shown, the embodiment of the present invention proposes a tangential flow filtration device with a cleaning device, including: a hollow fiber column 3 component, a pressure detection meter 1, a first diaphragm pump and a second diaphragm pump.

[0036] Specifically, the hollow fiber column 3 assembly includes several hollow fiber columns 3 and a sleeve 4, the sleeve 4 is sleeved on the outside of the several hollow fiber columns 3, and a waste liquid cavity 5 is formed between the inner wall of the sleeve 4 and the several hollow fiber columns 3.

[0037] The upper and lower ends of the hollow fiber column 3 assembly are respectively provided with a first and a second docking port, each of which is interconnected with a plurality of fluid channels of the hollow fiber column 3. The upper and lower side walls of the hollow fiber column 3 assembly are respectively provided with a first and a second drain port, each of which is interconnected with the waste liquid chamber 5. The first docking port is connected to the main line 6, which is used to connect to the bioreactor; the first drain port is connected to the drain pipe 14, which is used to discharge the waste liquid in the waste liquid chamber 5.

[0038] The first diaphragm pump is sealed and docked with the second docking port, the second diaphragm pump is sealed and docked with the second drainage port, and the pressure detection meter 1 is connected to the waste liquid chamber 5 of the hollow fiber column 3 component through the second drainage port. The pressure detection meter 1 is used to detect the liquid pressure changes of the second drainage port in real time, and then obtain the change value of the liquid pressure in the waste liquid chamber 5.

[0039] During operation, the first diaphragm pump and the second diaphragm pump adjust their operating states according to the real-time detection values ​​of the pressure detection meter 1, as shown in the following:

[0040] When the liquid pressure change value in the waste liquid chamber 5 is higher than the set value, the first diaphragm pump operates normally and the hollow fiber column 3 assembly performs filtering normally.

[0041] When the change value of the liquid pressure in the waste liquid chamber 5 is lower than the set value, the second diaphragm pump starts to work, driving the liquid in the waste liquid chamber 5 to reversely flush the hollow fiber column 3.

[0042] Furthermore, the first diaphragm pump and the second diaphragm pump both include a rigid spherical shell 7 and an elastic balloon 2. The elastic balloon 2 is arranged in the rigid spherical shell 7, and the inner cavity of the elastic balloon 2 is interconnected with several fluid channels of the hollow fiber columns 3 or the waste liquid chamber 5. An air pressure regulating chamber (not shown) is formed between the outer wall of the elastic balloon 2 and the inner wall of the rigid spherical shell 7. The elastic balloon 2 contracts or expands according to the air pressure changes in the air pressure regulating chamber.

[0043] Specifically, a base 8 is provided at the bottom of the rigid spherical shell 7 , and a vent hole 9 is opened on the base 8 , and the external air pump component is connected to the air pressure regulating chamber through the vent hole 9 .

[0044] In this embodiment, the air pump assembly is connected to the air pressure regulating chamber through the vent 9, and switches the elastic balloon 2 between the contraction state and the expansion state by changing the air pressure in the air pressure regulating chamber. Specifically:

[0045] When the air pump assembly inflates the air into the air pressure regulating chamber through the vent 9, the air pressure inside the air pressure regulating chamber increases. When the air pressure inside the air pressure regulating chamber is greater than the pressure inside the elastic balloon 2, the elastic balloon 2 contracts under the pressure of the external pressure.

[0046] When the air pump assembly draws air to the outside of the air pressure regulating chamber through the vent 9, the air pressure inside the air pressure regulating chamber decreases, and the air pressure inside the air pressure regulating chamber is lower than the pressure inside the elastic airbag, and the elastic balloon 2 expands under the pressure of the internal pressure.

[0047] In order to prevent the elastic balloon 22 from blocking the outlet when it contracts, an inner-balloon support 10 is provided on the elastic balloon 2 , and the inner-balloon support 10 is used to fix the upper and lower ends of the elastic balloon 2 .

[0048] In a specific embodiment, the first diaphragm pump and the second diaphragm pump each further include a transfer tube 11, which is arranged at the end of the rigid spherical shell 7 away from the base 8, and the lower ends of the two transfer tubes 11 are respectively sealed and docked with the open ends of the two elastic balloons 2, the upper end of the transfer tube 11 of the first diaphragm pump is sealed and docked with the second docking interface of the hollow fiber column 3 assembly, and the upper end of the transfer tube 11 of the second diaphragm pump is sealed and docked with the second discharge port of the hollow fiber column 3 assembly, and an infiltration hole is opened on the side wall of the transfer tube 11, and the infiltration hole is used to connect the wetting tube 12.

[0049] When connecting and installing the transfer tube 11, the waste liquid chamber 5, and the pressure detection gauge 1, a T-shaped equal-diameter tee 13 is used for installation. The first end of the T-shaped equal-diameter tee 13 is sealed and docked with the transfer tube 11 of the second diaphragm pump through an L-shaped elbow, the second end of the T-shaped equal-diameter tee 13 is sealed and docked with the second liquid discharge port, and the third end of the T-shaped equal-diameter tee 13 is connected to the pressure detection gauge 1.

[0050] Example 2

[0051] As shown in the figure, the utility model discloses a perfusion culture system, comprising: a first air pump assembly, a second air pump assembly, a bioreactor, a control unit and the above-mentioned tangential flow filtration device with a cleaning device.

[0052] Specifically, the bioreactor is connected to the first docking port of the hollow fiber column 3 assembly via the main line 6 .

[0053] The first diaphragm pump of the tangential flow filtration device and the first air pump assembly form an axial drive unit, and the second diaphragm pump of the tangential flow filtration device and the second air pump assembly form a radial drive unit.

[0054] The first air pump assembly, the second air pump assembly, and the pressure detection meter 1 of the tangential flow filtration device are all connected to the control unit. The control unit controls the working state of the axial drive unit and the radial drive unit according to the pressure change in the waste liquid chamber 5 detected by the pressure detection meter 1, specifically:

[0055] When the pressure detection meter 1 detects that the liquid pressure change value in the waste liquid chamber 5 is higher than the set value, the axial drive unit works normally to drive the liquid in the hollow fiber column 3 assembly to flow back and forth, thereby achieving tangential filtration.

[0056] When the pressure detection meter 1 detects that the liquid pressure change value in the waste liquid chamber 5 is lower than the set value, the radial drive unit starts to work to drive the liquid in the waste liquid chamber 5 to reversely flush the hollow fiber column 3 of the hollow fiber column 3 assembly.

[0057] Example 3

[0058] The utility model discloses a perfusion culture method, which adopts the perfusion culture system in Example 2 and includes the following steps:

[0059] The axial drive unit drives the liquid in the hollow fiber column 3 to flow back and forth along the axial direction. During this process, new liquid is added to the bioreactor while the waste liquid in the hollow fiber column 3 assembly is discharged, thereby achieving continuous tangential filtration of the liquid inside the bioreactor;

[0060] When the pressure detection meter 1 detects that the liquid pressure change value in the waste liquid chamber 5 is lower than the set value, the fiber column 3 of the hollow fiber column 3 assembly is reversely flushed through the radial driving unit;

[0061] The working process of the axial drive unit includes:

[0062] Step S11: Inflate the rigid spherical shell 7 by the first air pump assembly to squeeze the elastic balloon 2 of the first diaphragm pump, causing the elastic balloon 2 of the first diaphragm pump to shrink, and the liquid in the elastic balloon 2 flows into the hollow fiber column 3 of the hollow fiber column 3 assembly through the second docking port;

[0063] Step S12, using the first air pump assembly to evacuate the rigid spherical shell 7, so that the elastic balloon 2 of the first diaphragm pump expands, and the liquid in the hollow fiber column 3 flows into the elastic balloon 2 through the second docking port;

[0064] Step S13, continuously looping steps S11 to S12 until the change in the liquid pressure in the waste liquid chamber 5 is lower than the set value.

[0065] The working process of the radial drive unit includes:

[0066] In step S21, the rigid spherical shell 7 is inflated by the second air pump assembly to squeeze the elastic balloon 2 of the second diaphragm pump, causing the elastic balloon 2 of the second diaphragm pump to shrink. The liquid in the elastic balloon 2 flows into the waste liquid chamber 5 through the second drain port, and drives the liquid in the waste liquid chamber 5 to reversely flush the hollow fiber column 3.

[0067] In step S22, the rigid spherical shell 7 is evacuated by the second air pump assembly to expand the elastic balloon 2 of the second diaphragm pump, so that the liquid in the hollow fiber column 3 assembly flows tangentially into the elastic balloon 2 of the second diaphragm pump again through the second liquid discharge port.

[0068] Step S23, continuously looping steps S21 to S22 until the liquid pressure change value in the waste liquid chamber 5 is higher than the set value.

[0069] In the process of biopharmaceutical manufacturing, the specific workflow and steps are as follows:

[0070] (1) Use sterile connection method to pre-connect the pipeline and related supporting devices.

[0071] (2) Figure 4 As shown, the liquid inlet end of the wetting tube 12 is connected to the infiltration bottle using a sterile pipette, and the liquid outlet end of the discharge tube 14 is connected to the liquid collection bag. The culture medium in the infiltration bottle is pumped into the hollow fiber column 3 using a peristaltic pump until the hollow fiber column 3 is filled with liquid. Excess wetting liquid flows through the discharge tube 14 into the liquid collection bottle, ensuring that the entire device is filled with liquid. The ends of the wetting tube 12 are then welded shut, the Robert clamp between the two elastic balloons 2 is closed, and the wetting liquid bag is removed.

[0072] (3) Biological culture. Figure 5 As shown, the first air pump assembly alternates between pumping and inflating, driving the elastic balloon 2 connected to the hollow fiber column 3 to cyclically expand and contract. When the first air pump assembly pumps air, the elastic balloon 2 expands, drawing the liquid in the bioreactor into the elastic balloon 2. When the first air pump assembly inflates, the elastic balloon 2 contracts, pushing the culture medium into the hollow fiber column 3. The culture medium in the hollow fiber column 3 flows into the bioreactor, while the peristaltic pump simultaneously extracts the liquid filtered by the fiber from the drain pipe 14. The liquid in the infusion bottle is continuously pumped into the bioreactor via the peristaltic pump. This ensures that new liquid always enters the bioreactor, while some liquid is filtered by the hollow fiber column 3 and discharged from the drain pipe 14, thereby replacing the liquid in the bioreactor and maintaining a favorable growth environment for the cultured target. During the culture process, the culture medium flows back and forth along the axial direction of the hollow fiber column 3. Under the action of transmembrane pressure, some liquid and small molecules pass through the micropores to become filtrate and enter the waste liquid chamber 5.

[0073] (4) Cleaning of the device. Figure 6 As shown, during perfusion culture, due to the high cell density, the hollow fiber column 3 is prone to clogging. When clogging is imminent, the liquid flow within the hollow fiber column 3 becomes abnormal, causing the internal pressure to fluctuate differently than in normal operation. The internal pressure of the waste liquid chamber 5 is monitored by a pressure gauge 1. If the pressure change detected by the pressure gauge 1 is lower than the programmed value, the control program will indicate an impending clogging. The waste liquid tube clamp is closed, and the control program simultaneously activates the second air pump assembly, which alternately pumps air and inflates it, driving the elastic balloon 2 connected to the waste liquid chamber 5 in a cycle of contraction and expansion. When the elastic balloon 2 contracts, it pushes culture medium into the waste liquid chamber 5, which then backflushes the hollow fiber column 3. When the elastic balloon 2 expands, it draws culture medium from the waste liquid chamber 5 into the elastic balloon 2, preparing for the next backflushing cycle. This backflushing cycle is repeated until the pressure within the waste liquid chamber 5 returns to normal and the clogging is resolved.

[0074] Compared with the prior art, the present invention has at least the following beneficial effects:

[0075] The utility model monitors the pressure changes at the discharge port of the waste liquid chamber through a pressure detection gauge to determine the blockage condition of the hollow fiber column, and drives the liquid through the hollow fiber column in the reverse direction through the second diaphragm pump online to reversely dredge and clean the micropores on the hollow fiber column, thereby ensuring the smooth flow of the hollow fiber column and improving the production efficiency of the product.

[0076] Obviously, those skilled in the art may make various modifications and variations to the present invention without departing from the spirit and scope of the present invention. Thus, if such modifications and variations fall within the scope of the claims of the present invention and their equivalents, the present invention is intended to include such modifications and variations.

Claims

1. A tangential flow filtration device with a cleaning device, characterized in that: include: Hollow fiber column assembly, pressure detection gauge, first diaphragm pump and second diaphragm pump; The hollow fiber column assembly includes a plurality of hollow fiber columns and a sleeve, wherein the sleeve is sleeved on the outside of the plurality of hollow fiber columns, and a waste liquid cavity is formed between the inner wall of the sleeve and the plurality of hollow fiber columns; The upper and lower ends of the hollow fiber column assembly are respectively provided with a first pairing interface and a second pairing interface, and the first pairing interface and the second pairing interface are both interconnected with a plurality of fluid channels of the hollow fiber columns, and the upper end side wall and the lower end side wall of the hollow fiber column assembly are respectively provided with a first drain port and a second drain port, and the first drain port and the second drain port are both interconnected with the waste liquid chamber; The first diaphragm pump is sealed and docked with the second docking port, the second diaphragm pump is sealed and docked with the second liquid discharge port, the pressure detection gauge is connected to the waste liquid chamber of the hollow fiber column assembly through the second liquid discharge port, and the pressure detection gauge is used to detect the change of the liquid pressure in the waste liquid chamber in real time; When the liquid pressure change value in the waste liquid chamber is higher than the set value, the first diaphragm pump operates normally and the hollow fiber column assembly performs filtering normally; When the liquid pressure change value in the waste liquid chamber is lower than a set value, the second diaphragm pump starts to work, driving the liquid in the waste liquid chamber to reversely flush the hollow fiber column.

2. The tangential flow filtration device with a cleaning device according to claim 1, characterized in that: The first diaphragm pump and the second diaphragm pump each include a rigid spherical shell and an elastic balloon, wherein the elastic balloon is disposed within the rigid spherical shell, and an air pressure regulating chamber is formed between an outer wall of the elastic balloon and an inner wall of the rigid spherical shell, wherein the elastic balloon contracts or expands according to changes in air pressure in the air pressure regulating chamber; The inner cavity of the elastic balloon of the first diaphragm pump is communicated with the fluid channels of the plurality of hollow fiber columns, and the inner cavity of the elastic balloon of the second diaphragm pump is communicated with the waste liquid cavity.

3. The tangential flow filtration device with a cleaning device according to claim 2, characterized in that: A base is provided at the bottom of the rigid spherical shell, and a vent hole is opened on the base. The external air pump component is connected to the air pressure regulating chamber through the vent hole.

4. The tangential flow filtration device with a cleaning device according to claim 3, characterized in that: The first diaphragm pump and the second diaphragm pump each include a transfer tube, which is arranged at the end of the rigid spherical shell away from the base, and the lower ends of the two transfer tubes are respectively sealed and docked with the open ends of the two elastic balloons, the upper end of the transfer tube of the first diaphragm pump is sealed and docked with the second docking port of the hollow fiber column assembly, and the upper end of the transfer tube of the second diaphragm pump is sealed and docked with the second drainage port of the hollow fiber column assembly, and an infiltration hole is opened on the side wall of the transfer tube, and the infiltration hole is used to connect the wetting tube.

5. The tangential flow filtration device with a cleaning device according to claim 4, characterized in that: It also includes a T-shaped equal-diameter tee, the first end of which is sealed and connected to the transfer tube of the second diaphragm pump through an L-shaped elbow, the second end of which is sealed and connected to the second discharge port, and the third end of which is connected to the pressure detection gauge.

6. The tangential flow filtration device with a cleaning device according to claim 2, characterized in that: The elastic balloon is provided with an inner ball support, and the inner ball support is used to fix the upper and lower ends of the elastic balloon.

7. The tangential flow filtration device with a cleaning device according to claim 1, characterized in that: The first pair of interfaces is connected to a main pipeline, and the main pipeline is used to connect to a bioreactor; the first drainage port is connected to a drainage pipe, and the drainage pipe is used to discharge waste liquid in the waste liquid cavity.

8. A perfusion culture system, characterized in that: include: a first air pump assembly, a second air pump assembly, a bioreactor, a control unit, and a tangential flow filtration device with a cleaning device according to any one of claims 1 to 7; The bioreactor is connected to the first port of the hollow fiber column assembly via a main pipeline; The first diaphragm pump of the tangential flow filtration device and the first air pump assembly form an axial drive unit, and the second diaphragm pump of the tangential flow filtration device and the second air pump assembly form a radial drive unit; The first air pump assembly, the second air pump assembly, and the pressure detection gauge of the tangential flow filtration device are all connected to the control unit, and the control unit controls the working state of the axial drive unit and the radial drive unit according to the pressure change in the waste liquid chamber detected by the pressure detection gauge; When the pressure detection gauge detects that the liquid pressure change value in the waste liquid chamber is higher than the set value, the axial drive unit works normally to drive the liquid in the hollow fiber column assembly to flow back and forth, thereby achieving tangential filtration; When the pressure detection gauge detects that the liquid pressure change value in the waste liquid chamber is lower than the set value, the radial drive unit starts to work to drive the liquid in the waste liquid chamber to reversely flush the hollow fiber column of the hollow fiber column assembly.

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