A device for tangential flow filtration of cells or their secreted products

Abstract

The application relates to a device for tangential flow filtration of cells or secreted products thereof, comprising pipelines for feeding liquid and other different liquids; a shell, a central controller arranged in the shell, and a peristaltic pump, a pipeline clamping unit, a tangential flow filter, a pressure control unit and a first liquid switching mechanism mounted on the outer wall of the shell, a flow meter mounted on the pipeline clamping unit; a pressure sensor electrically connected to the shell; the central controller is electrically connected with the peristaltic pump, the pipeline clamping unit, the pressure control unit, the flow meter, the pressure sensor and the first liquid switching mechanism for overall control. The application can realize integration and overall control of each unit, reduce the floor space, and make the monitored data more timely and accurate.

Description

[0001] This application claims priority to application number CN202411286130.6, filed on September 13, 2024, entitled "An Automated Harvesting and Purification System", and to application number CN202411557039.3, filed on November 4, 2024, entitled "An Automated Harvesting and Purification System for Research and Development", the contents of which are incorporated herein by reference in their entirety. Technical Field

[0002] This invention relates to the field of tangential flow filtration technology, and in particular to a device for tangential flow filtration of cells or their secreted products, especially for use in the manufacture of biopharmaceuticals, such as antibody or recombinant protein genetically engineered drugs and vaccines. Background Technology

[0003] Tangential flow filtration is an important process in biopharmaceutical manufacturing, and cells or their secreted products (such as proteins and exosomes) are important materials in the biomedical field. However, culture tanks often contain a large amount of cell debris or impurities. Therefore, tangential flow filtration is necessary to filter and purify cells or their secreted products to obtain purer cells or cell secretions.

[0004] Currently, the process of filtering and purifying cells or their secreted products requires the physical stacking and integration of various cell or secreted product filtering and purification units, which takes up a lot of space and requires separate operation of each unit, making the process extremely cumbersome. Furthermore, during the process of filtering and purifying cells or their secreted products, it is not possible to monitor the data in the process flow in real time. The process flow requires manual operation and human judgment, which can lead to untimely data collection and inaccurate data.

[0005] Therefore, how to integrate the various units, thereby reducing the footprint, while still enabling overall control of each unit and making the monitored data more timely and accurate, has become an urgent problem to be solved. Summary of the Invention

[0006] The purpose of this invention is to provide a device for tangential flow filtration of cells or their secreted products, so as to solve at least some of the technical problems existing in the prior art.

[0007] To achieve the above objectives, the present invention provides the following solution: This invention provides a device for tangential flow filtration of cells or their secreted products, comprising: Piping, the piping being used to transport liquid materials and other different liquids; The housing contains a central controller, and a peristaltic pump, a pipeline clamping unit, a tangential flow filter, a pressure control unit, and a first liquid switching mechanism are mounted on the outer wall of the housing, wherein: The peristaltic pump is used to provide pumping force for the transport of liquid or other different liquids in the pipeline, so that the liquid in the pipeline can be transported to the tangential flow filter for filtration and purification by the pumping force of the peristaltic pump. The peristaltic pump can also transport other different liquids in the pipeline to the device. The pipe clamping unit is used to clamp the pipe, and a flow meter is installed on the pipe clamping unit to monitor the flow rate of the liquid in the pipe; A pressure sensor is electrically connected to the housing, and the pressure sensor is used to monitor the delivery pressure of the liquid in the pipeline; the pressure control unit is used to adjust the delivery pressure of the liquid in the pipeline according to the pressure monitored by the pressure sensor. The first liquid switching mechanism is used to switch between feed liquid and other different liquids, so as to deliver feed liquid and other different liquids into the device through the pipeline and the peristaltic pump; The central controller is electrically connected to the peristaltic pump, the pipeline clamping unit, the pressure control unit, the flow meter, the pressure sensor, and the first liquid switching mechanism, respectively, to achieve overall control.

[0008] According to one embodiment of the present invention, the pipe clamping unit includes a first pipe orientation clamp, a second pipe orientation clamp, and a third pipe orientation clamp; The first pipe orientation clamp is used to clamp the pipe before filtration by the tangential flow filter; The second and third pipe orientation clamps are used to clamp the pipes after filtration by the tangential flow filter; The flow meter is installed on the first pipeline orientation clamp and the second pipeline orientation clamp to monitor the flow rate of the liquid in the pipeline before filtration by the tangential flow filter and the flow rate of the liquid in the pipeline after filtration by the tangential flow filter, respectively.

[0009] According to one embodiment of the present invention, the first pipe orientation clamp, the second pipe orientation clamp, and the third pipe orientation clamp are all separable two-lobed structures and have pipe mounting through holes along the length direction of their two-lobed structures, and the pipe is clamped in the pipe mounting through holes; Each of the first, second, and third pipe orientation clamps is equipped with an opening and closing control button. Each of the opening and closing control buttons is configured to control the opening and closing of the two-part structure of the first, second, and third pipe orientation clamps, respectively.

[0010] According to one embodiment of the present invention, a plurality of pressure sensor interfaces are installed on the housing, the pressure sensors are electrically connected to the pressure sensor interfaces, and the pressure sensor interfaces are electrically connected to the central controller; The pressure sensor includes at least a first pressure sensor, a second pressure sensor, and a third pressure sensor; The first pressure sensor is used to monitor the delivery pressure of the liquid in the pipeline before filtration by the tangential flow filter; The second pressure sensor is used to monitor the delivery pressure of the liquid in the pipeline after filtration by the tangential flow filter; The third pressure sensor is used to monitor the delivery pressure of the liquid in the pipeline at the filtration end of the tangential flow filter.

[0011] According to one embodiment of the present invention, the pressure control unit includes a first pressure regulating valve and a second pressure regulating valve; The first pressure regulating valve is configured in correspondence with the second pressure sensor to regulate the delivery pressure of the liquid material in the pipeline after filtration by the tangential flow filter through the pressure monitored by the second pressure sensor; The second pressure regulating valve is configured in correspondence with the third pressure sensor to regulate the delivery pressure of the liquid in the pipeline at the filtration end of the tangential flow filter by the pressure monitored by the third pressure sensor.

[0012] According to one embodiment of the present invention, a connecting rod is rotatably connected to the housing, and a filter bracket is rotatably connected to the end of the connecting rod. A bidirectional clamp is installed on the filter bracket, and the tangential flow filter is installed on the filter bracket through the bidirectional clamp.

[0013] According to one embodiment of the present invention, a telescopic locking mechanism is installed at the top of the filter bracket, and a U-shaped pipe bracket is installed at the top of the telescopic locking mechanism. A U-shaped groove adapted to the pipe is formed on the U-shaped outer wall of the U-shaped pipe bracket, and the pipe is detachably installed in the U-shaped groove. The telescopic locking mechanism is configured to adjust the height of the U-shaped pipe bracket and lock the height of the U-shaped pipe bracket.

[0014] According to one embodiment of the present invention, a hinge clip is installed on the housing, and a pH-conductivity sensor is installed inside the hinge clip. The pH-conductivity sensor is used to monitor the conductivity and pH value of the liquid in the pipeline at the filtration end of the tangential flow filter.

[0015] According to one embodiment of the present invention, the first liquid switching mechanism includes a cover plate and a fixing plate that are hinged to each other, the fixing plate being connected to the outer wall of the housing; A liquid switching mechanism locking part is installed on the fixed plate, which is used to lock the cover plate and the fixed plate; The fixing plate has interconnected main pipeline installation slots and several branch pipeline installation slots, and both the main pipeline installation slots and the several branch pipeline installation slots are used to install the pipelines. The fixed plate is also equipped with a liquid switching extrusion unit, which is electrically connected to the central controller. The liquid switching extrusion unit is used to extrude the pipeline to switch between the feed liquid and other different liquids.

[0016] According to one embodiment of the present invention, a PLC data display screen is installed on the outer wall of the housing. The PLC data display screen is configured to display real-time monitored data and to allow manual control of the central controller via touch screen. The housing is equipped with a running status indicator light, which is configured to indicate the running status. An emergency stop button is installed on the housing, and the emergency stop button is configured to perform an emergency stop on the device.

[0017] This invention has at least the following technical effects: First, some embodiments of the present invention integrate the peristaltic pump, the pipeline clamping unit, the tangential flow filter, the pressure control unit and the first liquid switching mechanism into a housing, thereby enabling the integration of the various units and reducing the footprint.

[0018] Secondly, in some embodiments of the present invention, the central controller is electrically connected to the peristaltic pump, the pipeline clamping unit, the pressure control unit, the pressure sensor, and the first liquid switching mechanism, respectively, which enables the overall control of each unit.

[0019] Finally, some embodiments of the present invention, by integrating a flow meter, a pressure sensor, and a pH-conductivity sensor into the device, enable more timely and accurate monitoring of the data. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 This is a schematic diagram of the overall structure of the present invention; Figure 2 for Figure 1 A schematic diagram of the overall structure from another angle; Figure 3 for Figure 2 A schematic diagram of the overall structure from another angle; Figure 4 This is a schematic diagram of the overall structure of the peristaltic pump in this invention; Figure 5 This is a schematic diagram of the overall structure of the second pipeline orientation clamp in this invention; Figure 6 for Figure 5 A schematic diagram of the overall structure containing the flow meter; Figure 7 This is a schematic diagram of the overall structure of the first or second pressure regulating valve in this invention. Figure 8 for Figure 7 A schematic diagram of the overall structure of the internal pressing block; Figure 9 This is a schematic diagram of the overall structure of the first liquid switching mechanism in this invention; Figure 10 for Figure 9 A schematic diagram of the overall structure from another angle; Figure 11 for Figure 10 A magnified view of a section at point A in the middle; Figure 12 for Figure 9 Internal overall structure diagram; Figure 13 for Figure 12 A magnified view of a section at point B in the middle; Figure 14 This is a schematic diagram of the overall structure of the hinge clip and pH-conductivity sensor in this invention; Figure 15 for Figure 14 A schematic diagram of the overall structure from another angle; Figure 16 for Figure 15 A magnified view of a section at point C; Explanation of reference numerals in the attached figures: 1. Housing; 2. Two-way clamp; 3. First pipeline orientation clamp; 4. Two-way clamp locking knob; 5. Second pipeline orientation clamp; 6. Third pipeline orientation clamp; 7. Peristaltic pump; 8. First liquid switching mechanism; 9. First pressure regulating valve; 10. Second pressure regulating valve; 11. Hinge clamp; 12. Pressure sensor interface; 13. PLC data display screen; 14. Adjustment frame; 15. Running status indicator light; 16. Emergency stop button; 17. U-shaped pipeline bracket; 18. Filter bracket; 19. Connecting rod; 20. Flow meter; 21. Pressing block; 22. pH-conductivity sensor; 23. Opening and closing control button; 24. Main pipeline mounting slot; 25. Branch pipeline mounting slot; 26. Squeezing block; 27. Liquid switching mechanism locking rod; 28. Liquid switching mechanism locking knob; 29. ​​Second liquid switching mechanism; 30. Hinge clamp locking rod; 31. Hinge clamp locking knob. Detailed Implementation

[0022] The features and exemplary embodiments of various aspects of the present invention will now be described in detail. To make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments. It should be understood that the specific embodiments described herein are only configured to explain the present invention and to exemplify the principles of the present invention, and are not configured to limit the present invention. In addition, the structural components in the drawings are not necessarily drawn to scale. For example, the dimensions of some structural components or regions in the drawings may be enlarged for other structural components or regions to aid in the understanding of the embodiments of the present invention.

[0023] The directional terms used in the following description refer to the directions shown in the figures and are not intended to limit the specific structure of the embodiments of the present invention. In the description of the present invention, it should be noted that, unless otherwise stated, the terms "installation," "connection," and "joining" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a direct connection or an indirect connection through an intermediate medium. Those skilled in the art can understand the specific meaning of the above terms in the present invention according to the specific circumstances.

[0024] Furthermore, the terms "comprising," "including," "having," or any other variations thereof are intended to cover non-exclusive inclusion, such that a structure or component that includes a list of elements includes not only those elements but also other structural elements that are not expressly listed or inherent to the structure or component. Without further limitations, an element defined by the phrase "comprising..." does not exclude the presence of other identical elements in the article or apparatus that includes the element.

[0025] Spatial relation terms such as "below," "under," "under," "low," "above," "on," and "high" are used for descriptive convenience to explain the positioning of one element relative to a second element, indicating that these terms are intended to cover different orientations of the device, in addition to those different from those shown in the figure. Furthermore, phrases such as "one element on / below another element" can indicate that two elements are in direct contact, or that there are other elements between the two elements. In addition, terms such as "first" and "second" are also used to describe individual elements, areas, parts, etc., without specifically indicating order or sequence, and should not be considered restrictive. Similar terms are used throughout the description to represent similar elements.

[0026] It will be apparent to those skilled in the art that the present invention can be practiced without requiring some of these specific details. The following description of embodiments is merely intended to provide a better understanding of the invention by illustrating examples of the invention.

[0027] In this embodiment, there may be descriptions such as "this device". Those skilled in the art should understand that "this device" refers to a tangential flow filtration device for cells or their secreted products provided by the present invention.

[0028] In this embodiment, there may be descriptions such as "staff". Those skilled in the art should understand that the description of "staff" is only for the convenience of describing the implementation of the present invention. It is just an exemplary general concept and is not specifically limited to a particular person.

[0029] Example 1 Reference Figure 1-16 The present invention provides an apparatus for tangential flow filtration of cells or their secreted products, the apparatus comprising at least: The tubing (only a portion is shown in the diagram) is used to transport cells or their secreted products in liquid form. The tubing can also be used to transport other liquids; for example, water, alkali, and buffer solutions can be passed through the tubing before tangential flow filtration of cells or their secreted products to clean and wet the tubing and the tangential flow filter within the device.

[0030] In this embodiment, the liquid transported in the pipeline is the liquid containing cells or their secreted products.

[0031] In this embodiment, for ease of description, the liquid containing cells or their derivatives in the pipeline is simply referred to as the liquid.

[0032] In this embodiment, the tubing can be made of any material known in the art suitable for conveying cell or its derivative liquids, such as silicone tubing with diameters of 13#, 14#, 25#, 16#, 17#, and 18#, etc., without particular limitation. Since this device is compatible with silicone tubing of diameters of 13#, 14#, 25#, 16#, 17#, and 18#, it can meet different liquid flow rate requirements and achieve process volumes ranging from 0.15L to 10L.

[0033] Housing 1, with a central controller (not shown in the figure) installed inside housing 1.

[0034] In this embodiment, refer to Figure 1-3 The shell 1 can be a hollow cube structure with a length (base side) of 495mm, a width (base side) of 405mm, a height (right-angled side) of 460mm, and a cross-section of a right trapezoid. The material of the shell 1 can be stainless steel, which is known in the art, and is not particularly limited here.

[0035] Preferably, the central controller is installed inside the hollow structure of the housing 1, and the central controller can be a PLC controller with central control function such as "Raspberry Pi" known in the art, so as to realize the integrated (overall) control of all components on the device, without any particular limitation.

[0036] Furthermore, referring to Figure 1-3 Support feet are installed at the four corners of the bottom of the housing 1 to make the device more stable.

[0037] According to one embodiment of the present invention, referring to Figure 1-3 The device also includes a peristaltic pump 7, a pipeline clamping unit, a tangential flow filter, a pressure control unit, and a first liquid switching mechanism 8, all mounted on the outer wall of the housing 1, wherein: The pipeline is detachably installed on the peristaltic pump 7, the pipeline clamping unit and the first liquid switching mechanism 8. The peristaltic pump 7 can be used to provide pumping force for the delivery of liquid in the pipeline, so that the liquid in the pipeline can be delivered to the tangential flow filter for filtration and purification by the pumping force of the peristaltic pump 7.

[0038] In this embodiment, the peristaltic pump 7 can also provide pumping force for the delivery of other different liquids (such as the water, alkali and buffer solution mentioned above), so the pumping force provided by the peristaltic pump 7 can also deliver other different liquids in the pipeline into this device.

[0039] In this embodiment, the peristaltic pump is a prior art known in the art, and will not be described in detail here. Specifically, the peristaltic pump 7 in this embodiment can be any peristaltic pump known in the art that is suitable for this device and capable of providing a flow rate of 0.36 mL / min to 2300 mL / min for the liquid in the connected pipeline.

[0040] In this embodiment, refer to Figure 1 The peristaltic pump 7 is equipped with a lever, and the lever can rotate on the peristaltic pump 7. Specifically, when the lever moves from... Figure 1 When the right end is rotated to the left end, the peristaltic pump 7 will open, allowing the operator to install the tubing into it; after installation, the lever will be moved from... Figure 1 By rotating the left end to the right end, the peristaltic pump 7 can be closed again, thereby achieving a detachable connection between the pipeline and the peristaltic pump 7.

[0041] In one embodiment of the present invention, a tangential flow filter is a prior art known in the art, capable of filtering and purifying cell or derivative liquids, which will not be elaborated upon here. For example, in this embodiment, the cell or derivative liquid to be filtered is introduced into the inlet end of the tangential flow filter by the pumping force of the peristaltic pump 7. The cells in the liquid will pass through the tangential flow filter and flow out from the outlet end of the tangential flow filter, while the derivatives (e.g., proteins) in the liquid will flow out from the filtration end of the tangential flow filter. The above describes the filtration and purification of the cell or derivative liquid, as well as the separation and extraction of the cell or derivative liquid.

[0042] In this embodiment, although the inlet, outlet, and filtration ends of the tangential flow filter need to be connected to a separate pipeline, those skilled in the art should understand that, for ease of description, the pipelines connected to the inlet, outlet, and filtration ends of the tangential flow filter are all the pipelines described in this embodiment.

[0043] According to one embodiment of the present invention, a pipe clamping unit is used to clamp a pipe, and a flow meter 20 is mounted on the pipe clamping unit (see reference). Figure 6 ), flow meter 20 can be used to monitor the flow rate of liquid in pipeline.

[0044] In this embodiment, the pipeline clamping unit can clamp and store the pipeline, thereby preventing pipeline vibration.

[0045] In this embodiment, the flow meter 20 is prior art known in the art, and will not be described in detail here. Since the peristaltic pump 7 can provide a flow rate of 0.36 mL / min to 2300 mL / min for the liquid in the pipeline connected to it, the flow meter 20 can be any flow meter known in the art that is suitable for this device and capable of measuring a flow rate of 0.36 mL / min to 2300 mL / min.

[0046] According to one embodiment of the present invention, a pressure sensor (not shown in the figure) is electrically connected to the housing 1. The pressure sensor can be used to monitor the delivery pressure of the liquid in the pipeline. The pressure control unit can adjust the delivery pressure of the liquid in the pipeline based on the delivery pressure monitored by the pressure sensor.

[0047] In this embodiment, the pressure sensor is a prior art known in the art, and will not be described in detail here. The pressure sensor can be any pressure sensor known in the art that is suitable for this device and capable of measuring pressure values ​​from 0 PSI to 60 PSI.

[0048] In this embodiment, since the pressure control unit can control the delivery pressure of the liquid in the pipeline, it can control the flow rate of the liquid in the pipeline, and thus control the transmembrane pressure and shear force of the liquid in the pipeline according to the actual situation.

[0049] According to one embodiment of the present invention, the first liquid switching mechanism 8 can be used to switch between feed liquid and other different liquids (such as the water, alkali and buffer solution mentioned above) so as to deliver the feed liquid and other different liquids into the device through pipelines and the pumping force of the peristaltic pump 7.

[0050] In this embodiment, refer to Figure 1 The number of first liquid switching mechanisms 8 can be two, and they are installed sequentially. Figure 1 On the left side wall of the middle shell 1.

[0051] Specifically, refer to Figures 9-13 The first liquid switching mechanism 8 includes a cover plate and a fixing plate hinged together at the top. The fixing plate is connected to the outer wall of the housing 1, that is, the fixing plate is installed on... Figure 1 The first liquid switching mechanism 8 is mounted on the left side wall of the housing 1. The cover plate and the fixing plate can be the same in shape and size, and both are cuboid structures.

[0052] Reference Figure 12 The fixing plate has interconnected main pipeline installation slots 24 and several branch pipeline installation slots 25, which are used to install the pipelines.

[0053] Preferably, a main pipeline mounting groove 24 and several branch pipeline mounting grooves 25 (not shown in the figure) are also provided on the side of the cover plate that is in contact with the fixing plate. The main pipeline mounting groove 24 and several branch pipeline mounting grooves 25 on the cover plate can form a hollow cylindrical structure with the main pipeline mounting groove 24 and several branch pipeline mounting grooves 25 on the fixing plate, so that the cylindrical pipeline can be better installed in the main pipeline mounting groove 24 and several branch pipeline mounting grooves 25.

[0054] In this embodiment, the number of main pipeline installation slot 24 and several branch pipeline installation slots 25 can be one and four respectively. This allows the pipelines installed in the four branch pipeline installation slots 25 to be connected to water, alkali solution, buffer solution and material solution respectively. Then, water, alkali solution, buffer solution and material solution can be transported to the device by the peristaltic pump 7 through the pipeline in the main pipeline installation slot 24.

[0055] In this embodiment, a liquid switching mechanism locking part is installed on the fixing plate, which is used to lock the cover plate and the fixing plate.

[0056] Specifically, refer to Figure 10 and Figure 11 The liquid switching mechanism locking part includes a liquid switching mechanism locking rod 27 rotatably connected to the bottom end of the fixed plate and a liquid switching mechanism locking knob 28 threadedly connected to the end of the liquid switching mechanism locking rod 27 away from the fixed plate; at the bottom ends of the cover plate and the fixed plate, liquid switching mechanism locking grooves are provided for inserting the liquid switching mechanism locking rod 27. When it is necessary to lock the cover plate and the fixed plate, rotate the liquid switching mechanism locking rod 27 into the liquid switching mechanism locking groove, and then rotate the liquid switching mechanism locking knob 28 until it abuts against the outer wall of the cover plate to complete the locking.

[0057] In this embodiment, a liquid switching extrusion unit is also installed on the fixed plate. The liquid switching extrusion unit is electrically connected to the central controller. The liquid switching extrusion unit is used to extrude the pipeline to switch the feed liquid and other different liquids (such as water, alkali, and buffer solution).

[0058] Specifically, refer to Figure 10 , Figure 12 and Figure 13The liquid switching compression unit includes five liquid switching telescopic motors mounted on a fixed plate. One liquid switching telescopic motor corresponds to the main pipeline mounting slot 24, and the other four liquid switching telescopic motors correspond to the four branch pipeline mounting slots 25. Compression blocks 26 are installed on the telescopic ends (i.e., output ends) of the liquid switching telescopic motors. One compression block 26 can extend into the main pipeline mounting slot 24, and the other four compression blocks 26 can extend into the four branch pipeline mounting slots 25 respectively. When it is necessary to switch between water, alkali solution, buffer solution, and feed solution, the four liquid switching telescopic motors can be activated respectively, causing the four compression blocks 26 to compress the pipelines in the four branch pipeline mounting slots 25, thereby achieving the switching of water, alkali solution, buffer solution, and feed solution. The compression block 26 corresponding to the main pipeline mounting slot 24 can compress the pipelines in the main pipeline mounting slot 24, thus achieving the overall liquid flow control.

[0059] According to one embodiment of the present invention, the central controller is electrically connected to the peristaltic pump 7, the pipeline clamping unit, the pressure control unit, the flow meter 20 and the pressure sensor respectively (i.e., the connection that can transmit signals and information), so as to realize the integrated (whole) control of all components in the device by the central controller.

[0060] This invention, through the aforementioned configuration, enables the integration of various units, thereby reducing the floor space required for each separation and extraction unit. Simultaneously, it allows for overall control of each unit, enabling "one person, one machine" or "one person, multiple machines," further reducing the cost of biopharmaceutical production from a labor perspective and alleviating the economic burden on patients. It also ensures more timely and accurate monitoring data, helping to reduce batch-to-batch variations in intermediate or finished products and resulting in more stable quality of manufactured products (e.g., pharmaceuticals).

[0061] Furthermore, through the above-described design, this invention enables intelligent operation, which helps to standardize the control of bioprocesses, reduce process failures caused by human error, and improve the efficiency of biomanufacturing.

[0062] According to one embodiment of the present invention, referring to Figure 1-3 The pipe clamping unit includes a first pipe orientation clamp 3 and a second pipe orientation clamp 5 (see reference). Figure 5 and Figure 6 ) and the third pipeline directional clamp 6. Wherein: In this embodiment, the first pipeline orientation clamp 3 can be used to clamp the pipeline before filtration, that is, to clamp the pipeline connected to the inlet end of the tangential flow filter, so as to prevent the pipeline connected to the inlet end of the tangential flow filter from shaking.

[0063] In this embodiment, the second pipe orientation clamp 5 and the third pipe orientation clamp 6 can be used to clamp the filtered pipe, that is, to clamp the pipe connected to the outlet end of the tangential flow filter, so as to prevent the pipe connected to the outlet end of the tangential flow filter from shaking.

[0064] In this embodiment, refer to Figure 1 and Figure 2 The first pipeline orientation clamp 3, the second pipeline orientation clamp 5, the third pipeline orientation clamp 6, and the peristaltic pump 7 can all be installed on the vertical surface of the housing 1. For example, Figure 1 As shown, the peristaltic pump 7 can be installed in the middle of the vertical surface of the housing 1 (the motor of the peristaltic pump 7 is located inside the housing 1, and the motor of the peristaltic pump 7 can be referred to...). Figure 4 The first pipe orientation clamp 3, the second pipe orientation clamp 5, and the third pipe orientation clamp 6 can be installed at the lower right corner, upper right corner, and upper left corner of the vertical surface of the housing 1, respectively. In this embodiment, refer to... Figure 1 and Figure 2 The first pipe orientation clamp 3 can have a pentagonal structure with right angles, the second pipe orientation clamp 5 can have an L-shaped structure, and the third pipe orientation clamp 6 can have a cuboid structure.

[0065] In this embodiment, it can be referred to Figure 6 , Figure 6 This is a schematic diagram of a flow meter 20 installed on the second pipe directional clamp 5. However, in this embodiment, a flow meter 20 is installed on both the first pipe directional clamp 3 and the second pipe directional clamp 5, so that the flow rates of the liquid before and after tangential flow filtration can be monitored separately. Therefore, although the attached diagram shows... Figure 6 The diagram only shows a schematic of the flow meter 20 installed on the second pipeline directional clamp 5, but those skilled in the art should understand that the flow meter 20 is installed on the first pipeline directional clamp 3 in the same manner as in the attached diagram. Figure 6 The medium flow meter 20 is installed on the second pipeline directional clamp 5 in the same way, that is, those skilled in the art can refer to the attached... Figure 6 Understand how the flow meter 20 is installed on the first pipeline directional clamp 3.

[0066] According to one embodiment of the present invention, the first pipe orientation clamp 3 and the second pipe orientation clamp 5 (see reference) Figure 5 Both the first and the third pipe orientation clamp 6 are separable two-part structures with pipe installation through holes along the length of the two-part structure, allowing the pipe to be clamped in the pipe installation through holes.

[0067] In this embodiment, with Figure 5For example, the second pipe orientation clamp 5 includes a clamping part and a power part, wherein the clamping part is a separable two-part structure. The power part can be a telescopic motor known in the art (for ease of description, it is named a pipe orientation clamp telescopic motor), which can control the clamping part of the two-part structure to clamp, thereby realizing the clamping of the pipe. Preferably, referring to... Figure 5 The two halves of the clamping section have the same volume. For ease of description, the clamping section closer to the power unit is named the fixed clamping block (because it is connected to the fixed end of the pipe directional clamp telescopic motor), and the clamping section farther from the power unit is named the movable clamping block (because it is connected to the telescopic end of the pipe directional clamp telescopic motor).

[0068] In this embodiment, refer to Figure 6 The telescopic end of the pipe directional clamp telescopic motor can be connected by two connecting rods (i.e. Figure 6 Two cylindrical rods located on either side of the opening / closing control button 23 are connected to the movable clamping block, thereby enabling the movement of the movable clamping block and clamping of the pipeline. Pipeline mounting through holes can be respectively formed on the fixed clamping block and the movable clamping block. Preferably, half of the pipeline mounting through hole is located on the fixed clamping block, and the other half is also located on the fixed clamping block. That is, when the fixed clamping block and the movable clamping block are joined, they form a pipeline mounting through hole; when the fixed clamping block and the movable clamping block are separated, the pipeline mounting through hole is a long groove formed on each of the fixed clamping block and the movable clamping block, allowing the pipeline to be installed within the pipeline mounting through hole. In this embodiment, refer to... Figure 5 The cross-section of the through hole for pipe installation (in) Figure 5 The vertical section (in the middle) can be a hexagonal structure.

[0069] In addition, although Figure 5 Only the specific structure of the second pipe orientation clamp 5 is shown, but those skilled in the art should understand that the specific structures of the first pipe orientation clamp 3 and the third pipe orientation clamp 6 are the same as those of the second pipe orientation clamp 5 (except for slight differences in the shape of the clamping part of each pipe orientation clamp), that is, those skilled in the art can understand the structure of the second pipe orientation clamp 5 based on the attached diagram. Figure 5 and attached Figure 6 Understand the specific structure of the first pipeline orientation clamp 3 and the third pipeline orientation clamp 6.

[0070] According to one embodiment of the present invention, referring to Figure 1-6 and Figure 9 Each of the first pipe orientation clamp 3, the second pipe orientation clamp 5, and the third pipe orientation clamp 6 is equipped with an opening and closing control button 23. Each opening and closing control button 23 is configured to control the opening and closing of the two-part structure (i.e., the fixed clamping block and the movable clamping block) of the first pipe orientation clamp 3, the second pipe orientation clamp 5, and the third pipe orientation clamp 6 respectively.

[0071] In this embodiment, the opening / closing control button 23 is a push-button switch known in the art, which is electrically connected to the pipe directional clamp telescopic motor to control the start of the pipe directional clamp telescopic motor, and will not be described in detail here. Among them, with Figure 5 For example, when the opening and closing control button 23 is pressed, the movable clamping block of the second pipe orientation clamp 5 will separate from the fixed clamping block, so that the pipe can be installed in the second pipe orientation clamp 5 (the operation mode of the first pipe orientation clamp 3 and the third pipe orientation clamp 6 is the same as that of the second pipe orientation clamp 5).

[0072] In this embodiment, with Figure 5 For example, when the second pipe orientation clamp 5 is installed on the housing 1, its power unit (i.e., the pipe orientation clamp telescopic motor) will be located inside the housing 1, and its clamping part will be located outside the housing 1 (see reference). Figure 1 and Figure 2 ).

[0073] In this embodiment, since the pipe diameter can be 13#, 14#, 25#, 16#, 17# and 18# (i.e., the pipe diameter can be less than or equal to 25#), the diameter of the through hole for pipe installation is also less than or equal to 25# (i.e., suitable for R&D scale) to better match the pipe diameter.

[0074] According to one embodiment of the present invention, referring to Figure 2 The housing 1 is equipped with several pressure sensor interfaces 12. The pressure sensors are electrically connected to the pressure sensor interfaces 12. The pressure sensor interfaces 12 can be electrically connected to the central controller (i.e., the connection mentioned above that can transmit signals and information).

[0075] In this embodiment, refer to Figure 2 There are three pressure sensor interfaces 12, all of which are located on the vertical surface of the housing 1. Figure 2 On the right side wall.

[0076] According to one embodiment of the present invention, the pressure sensor includes at least a first pressure sensor, a second pressure sensor, and a third pressure sensor, preferably only including a first pressure sensor, a second pressure sensor, and a third pressure sensor. Wherein: The first pressure sensor, the second pressure sensor, and the third pressure sensor are respectively plugged into the three pressure sensor interfaces 12; The first pressure sensor is used to monitor the delivery pressure of the liquid in the pipeline before filtration, that is, it can monitor the delivery pressure of the liquid in the pipeline connected to the inlet end of the tangential flow filter.

[0077] The second pressure sensor is used to monitor the delivery pressure of the liquid in the filtered pipeline, that is, it can monitor the delivery pressure of the liquid in the pipeline connected to the outlet end of the tangential flow filter.

[0078] The third pressure sensor is used to monitor the delivery pressure of the liquid in the pipeline at the filter end, that is, it can monitor the delivery pressure of the liquid in the pipeline connected to the filter end of the tangential flow filter.

[0079] In this embodiment, the monitoring range of the first pressure sensor, the second pressure sensor, and the third pressure sensor can all be 0PSI-60PSI.

[0080] According to one embodiment of the present invention, referring to Figure 1 and Figure 2 , Figure 7 and Figure 8 The pressure control unit includes a first pressure regulating valve 9 and a second pressure regulating valve 10 (liquid switch).

[0081] The first pressure regulating valve 9 is set in correspondence with the second pressure sensor. That is, after the liquid in the pipeline is filtered by the tangential flow filter, it immediately passes through the inside of the first pressure regulating valve 9. The delivery pressure of the filtered liquid in the pipeline is adjusted by the delivery pressure monitored by the second pressure sensor. The second pressure regulating valve 10 is set in correspondence with the third pressure sensor. That is, when the liquid in the pipeline passes through the filter end of the tangential flow filter, it immediately passes through the inside of the first pressure regulating valve 9. In this way, the delivery pressure of the liquid in the pipeline at the filter end is regulated by the delivery pressure monitored by the third pressure sensor.

[0082] In this embodiment, Figure 7 The schematic diagrams of the first pressure regulating valve 9 and the second pressure regulating valve 10 are exemplary. The first pressure regulating valve 9 and the second pressure regulating valve 10 can be equally divided into a pressure regulating power unit and a pressure clamping unit with a U-shaped cross-section. Referring to... Figure 8 The pressure regulating power unit can be a telescopic motor (for ease of description, it is named the pressure regulating valve telescopic motor), and its telescopic end is connected to a pressing block 21 with an angled head. Taking the first pressure regulating valve 9 as an example, when it is necessary to regulate the delivery pressure of the pipeline, the pressing block 21 can extend into the pressure clamping part of the U-shaped structure under the power of the telescopic end of the pressure regulating valve telescopic motor according to the delivery pressure monitored by the second pressure sensor, thereby squeezing the pipeline and adjusting the delivery pressure of the filtered liquid in the pipeline.

[0083] In this embodiment, refer to Figure 1 and Figure 2The first pressure regulating valve 9 can be installed on the vertical surface of the housing 1 and located between the second pipeline directional clamp 5 and the third pipeline directional clamp 6.

[0084] In this embodiment, refer to Figure 1 and Figure 2 The second pressure regulating valve 10 can be installed on the same side wall as the pressure sensor interface 12 installed on the housing 1.

[0085] In this embodiment, when the first pressure regulating valve 9 and the second pressure regulating valve 10 are installed on the housing 1, their pressure regulating valve extension motors (i.e., the pressure regulating power units mentioned above) are located inside the housing 1, while their pressure clamping parts are located outside the housing 1.

[0086] In addition, when the first pressure regulating valve 9 and the second pressure regulating valve 10 are fully closed, they can also completely close the pipeline.

[0087] According to one embodiment of the present invention, referring to Figure 2 A connecting rod 19 is rotatably connected to the housing 1, and a filter bracket 18 is rotatably connected to the end of the connecting rod 19. A bidirectional clamp 2 is installed on the filter bracket 18, and the tangential flow filter is installed on the filter bracket 18 through the bidirectional clamp 2 (not shown in the figure).

[0088] In this embodiment, the filter support 18 can be a long cylindrical structure, which can be configured to freely install tangential flow filters with a diameter of less than 80mm.

[0089] Specifically, refer to Figure 1-3 One end of the bidirectional clamp 2 clamps the filter support 18, and the other end of the bidirectional clamp 2 clamps the tangential flow filter (not shown in the figure), thereby realizing the connection between the filter support 18 and the tangential flow filter.

[0090] Furthermore, referring to Figure 1-3 Two bidirectional clamps 2 have two clamping plates through which bidirectional clamp locking knobs 4 are threaded and connected. The two bidirectional clamp locking knobs 4 can lock the two clamping plates of bidirectional clamp 2 at the ends that are far apart from each other, thereby making the bidirectional clamp 2 clamp the filter bracket 18 and the tangential flow filter more firmly, and thus improving the connection between the filter bracket 18 and the tangential flow filter.

[0091] In this embodiment, refer to Figure 2 A connecting rod mounting block can be installed on the bottom side wall of the housing 1. The connecting rod 19 is rotatably connected to the end of the connecting rod mounting block, thereby increasing the degree of freedom of the connecting rod 19 on the housing 1.

[0092] According to one embodiment of the present invention, a telescopic locking mechanism is installed at the top of the filter bracket 18, and a U-shaped pipe bracket 17 is installed at the top of the telescopic locking mechanism. A U-shaped groove adapted to the pipe is formed on the U-shaped outer wall of the U-shaped pipe bracket 17, and the pipe is detachably installed in the U-shaped groove. The telescopic locking mechanism is configured to adjust the height of the U-shaped pipe bracket 17 and lock the height of the U-shaped pipe bracket 17.

[0093] In this embodiment, refer to Figure 2 The bottom of the U-shaped pipe rack 17 can be an M-shaped structure, with the middle part connected to the top of the filter bracket 18.

[0094] In this embodiment, the pipe connected to the tangential flow filter at the filtration end can be installed in the U-shaped groove of the U-shaped pipe rack 17, or the pipe connected to the liquid outlet end of the tangential flow filter can be installed in the U-shaped groove of the U-shaped pipe rack 17. No particular limitation is made here, and both can achieve the technical effect of better fixing of the pipe.

[0095] In this embodiment, the filter bracket 18 can be a nut-adjustable telescopic rod structure, and the telescopic locking mechanism is a rotating nut located at the top of the filter bracket 18. The rotating nut can fix the height of the filter bracket 18. When the required height of the filter bracket 18 is needed, the rotating nut can be loosened to adjust the height of the filter bracket 18 (i.e., to telescopically adjust the filter bracket 18), and conversely, the rotating nut can be tightened to fix the height of the filter bracket 18.

[0096] According to one embodiment of the present invention, referring to Figure 2 , Figures 14-16 A hinge clip 11 is installed on the housing 1, and a pH-conductivity sensor 22 is installed inside the hinge clip 11. The pH-conductivity sensor 22 is used to monitor the conductivity and pH value of the liquid in the pipeline at the filtration end of the tangential flow filter.

[0097] In this embodiment, the pH-conductivity sensor 22 is a prior art technology known in the art. It can monitor the conductivity and pH of the feed liquid at the filtration end, so as to determine the concentration of dissociable ions and pH value in the feed liquid at the filtration end according to actual needs. The pH monitoring range of the pH-conductivity sensor 22 can be 0.1-14, and the conductivity monitoring range can be 0.1 mS / cm-100 mS / cm.

[0098] In this embodiment, refer to Figure 2 and Figure 3 The hinge clip 11 can be installed on the vertical surface of the housing 1. Figure 2On the right side wall of the housing 1 (i.e., on the same side wall as the second pressure regulating valve 10). The hinge clip 11 can be installed on the vertical surface of the housing 1. Figure 2 The middle part of the right side wall.

[0099] In this embodiment, refer to Figure 15 The two clips of the hinge clip 11 can both be hexagonal structures of the same size, and a hinge clip locking part is installed on the hinge clip 11. The hinge clip locking part can lock the two clips of the hinge clip 11 to install the pH value-conductivity sensor 22 inside the hinge clip 11.

[0100] Specifically, refer to Figure 16 The hinge clip locking part includes a hinge clip locking rod 30 rotatably mounted on the clip of any one of the hinge clips 11. The other end of the hinge clip locking rod 30 is threadedly connected to a hinge clip locking knob 31, and each of the two clips of the hinge clip 11 has a hinge clip locking groove into which the hinge clip locking rod 30 can be inserted. When it is necessary to lock the two clips of the hinge clip 11, the operator can rotate the hinge clip locking rod 30 into the hinge clip locking groove, and then turn the hinge clip locking knob 31 until the hinge clip locking knob 31 abuts against the side wall of the other clip of the hinge clip 11, thereby locking the two clips of the hinge clip 11.

[0101] According to one embodiment of the present invention, referring to Figure 2 A second liquid switching mechanism 29 is installed on the side wall of the housing 1, and the second liquid switching mechanism 29 is installed on the same side wall as the hinge clip 11.

[0102] In this embodiment, the second liquid switching mechanism 29 has a structure that is roughly the same as that of the first liquid switching mechanism 8. The difference is that the second liquid switching mechanism 29 only has two branch pipe mounting slots 25 (it can also be regarded as the second liquid switching mechanism 29 being exactly half of the first liquid switching mechanism 8). Therefore, those skilled in the art can understand the specific structure of the second liquid switching mechanism 29 through the structure of the first liquid switching mechanism 8.

[0103] In this embodiment, the second liquid switching mechanism 29 can direct the feed liquid and different liquids (water, alkali, and buffer solution mentioned above) flowing from the tangential flow filter end into different objects according to actual working needs. For example, the pipes in the two branch pipe mounting slots 25 of the second liquid switching mechanism 29 can be respectively connected to the waste liquid collection tank and the process waste liquid collection tank. Then, when water, alkali, and buffer solution are introduced into the device, one of the squeezing blocks 26 in the second liquid switching mechanism 29 can squeeze and close the pipe leading to the process waste liquid collection tank, thereby allowing water, alkali, and buffer solution to flow from the tangential flow filter end into the waste liquid collection tank; conversely, when feed liquid is introduced into the device, the other squeezing block 26 can squeeze and close the pipe leading to the waste liquid collection tank, thereby allowing feed liquid to flow from the tangential flow filter end into the process waste liquid collection tank.

[0104] According to one embodiment of the present invention, referring to Figure 1-3 A PLC data display screen 13 is installed on the outer wall of the housing 1. The PLC data display screen 13 is configured to display the monitored real-time data and to manually control the central controller (i.e., the Raspberry Pi in this embodiment) via touch screen, so as to integrate (overall) control of various components on this device.

[0105] In this embodiment, the PLC data display screen 13 is prior art known in the art, and will not be described in detail here. The PLC data display screen 13 can be a 13-inch LCD display screen with / with LED backlighting.

[0106] In this embodiment, an adjustment bracket 14 can be hinged to the back of the PLC data display screen 13. The end of the adjustment bracket 14 is hinged to the top of the housing 1, thereby allowing the position of the PLC data display screen 13 to be adjusted according to the height and usage habits of the operator. In other words, the height and tilt angle of the PLC data display screen 13 can be adjusted, improving the comfort of using the device.

[0107] In this embodiment, the PLC data display screen 13 integrates the operating software MR(C), which is known in the art and has auxiliary programming functions. Therefore, operators can call up process programs through the PLC data display screen 13 to control the tangential flow filtration process of cells or their secreted products.

[0108] According to one embodiment of the present invention, referring to Figure 1 The housing 1 is equipped with a running status indicator light 15, which is configured to indicate the running status.

[0109] In this embodiment, the operating status indicator light 15 can be installed on the top of the first pressure regulating valve 9, and it can be elongated. When the device is operating normally, the operating status indicator light 15 can light up green, and when the device is operating abnormally, the operating status indicator light 15 can light up red.

[0110] According to one embodiment of the present invention, referring to Figure 1 An emergency stop button 16 is installed on the housing 1. The emergency stop button 16 is configured to perform emergency stop processing on the device.

[0111] In this embodiment, the emergency stop button 16 can be located above the third pipeline directional clamp 6. When the operating status indicator light 15 turns red, the operator can press the emergency stop button 16 to stop the device from operating immediately.

[0112] According to one embodiment of the present invention, an auxiliary peristaltic pump (not shown in the figure) may also be installed on the outer wall of the housing 1. The auxiliary peristaltic pump can be used to replenish the biological buffer solution of the feed liquid before it enters the device.

[0113] In this embodiment, the auxiliary peristaltic pump can be any peristaltic pump known in the art that is suitable for this device and capable of providing a flow rate of 0.3 mL / min to 324 mL / min for the liquid in the pipeline connected to it.

[0114] In one embodiment of the present invention, by providing an auxiliary peristaltic pump, a biological buffer solution required for the biological purification process can be pumped into the inlet end of the pipeline (i.e., the feed liquid before entering the device) as needed, so that the composition of the feed liquid sample filtered by the tangential flow filter meets the requirements of the purification process. The auxiliary peristaltic pump can be any peristaltic pump known in the art that is compatible with tubing diameters of 14#, 25#, and 16#.

[0115] In addition, this device is equipped with a power supply (known in the art) for energizing the components on the device. The power supply may have a power rating of 400W and a maximum operating current of 1.4A.

[0116] Meanwhile, a balance, as known in the art, can be installed at the outlet and filtration ends of the tangential flow filter to facilitate real-time measurement of the weight of the filtered liquid at both ends as needed. Preferably, a balance connection port (known in the art) is provided on the housing, and the balance connection port is electrically connected to the central processing unit. An external balance can be electrically connected to the central processing unit through the balance connection port, thereby enabling real-time synchronization of the balance measurement data to the PLC data display screen 13, and thus realizing automatic management and automatic control of the balance.

[0117] The most preferred operating process of this device in this embodiment will be briefly described below with reference to the accompanying drawings and the above embodiments: For ease of description, in the following text, the pipeline connected to the inlet end of the tangential flow filter will be described as the inlet pipeline, the pipeline connected to the outlet end of the tangential flow filter will be described as the outlet pipeline, the pipeline connected to the filtration end of the tangential flow filter will be described as the filtration end pipeline, and the pipeline installed on the auxiliary peristaltic pump will be named the auxiliary pipeline.

[0118] First, the tangential flow filter is installed on the filter bracket 18 using the bidirectional clamp 2 and locked using the bidirectional clamp locking knob 4. Then, the three pressure sensors (i.e., the first pressure sensor, the second pressure sensor, and the third pressure sensor) are respectively plugged into the three pressure sensor interfaces 12.

[0119] Then, the installation of the piping can be divided into the following steps: Step 1: Install the inlet pipe into the first liquid switching mechanism 8, and connect the four branches of the inlet pipe to water, alkali solution, buffer solution and feed solution respectively.

[0120] Step 2: Install the inlet pipe at the outlet of the first liquid switching mechanism 8 in sequence on the inlet of the peristaltic pump 7, the first pipe orientation clamp 3, and the tangential flow filter, and install the first pressure sensor on the inlet pipe between the first pipe orientation clamp 3 and the inlet of the tangential flow filter.

[0121] Step 3: Install the outlet pipe in sequence on the outlet end of the tangential flow filter, the second pipe directional clamp 5, the first pressure regulating valve 9, and the third pipe directional clamp 6, and install the second pressure sensor on the outlet pipe between the second pipe directional clamp 5 and the first pressure regulating valve 9.

[0122] Step 4: Install the filter end pipeline in sequence on the filter end of the tangential flow filter, the U-shaped pipeline bracket 17, the second pressure regulating valve 10 and the hinge clip 11, and install the third pressure sensor on the filter end pipeline between the U-shaped pipeline bracket 17 and the second pressure regulating valve 10.

[0123] Step 5: Connect the inlet end of the liquid inlet pipe to an object for storing the liquid to be filtered (e.g., a culture tank known in the art), connect the outlet end of the liquid outlet pipe to an object for collecting cells (e.g., a cell culture tank known in the art), and connect the outlet end of the filtration end pipe to an object for collecting derivatives or waste liquid (e.g., a waste liquid collection tank and a process waste liquid collection tank known in the art).

[0124] Next, before performing tangential flow filtration, the tangential flow filter needs to be cleaned and soaked, which can be divided into the following steps: Step 1: The operator can input the required work data through the touch screen on the PLC data display screen 13. Then, the first liquid switching mechanism 8 can be used to close the other three branch pipes of the pipeline, allowing only the branch pipe through which water is introduced to flow. Next, the outlet end of the filter end pipeline is connected to the waste liquid collection tank, and the peristaltic pump 7 is used to pump water into the tangential flow filter for preliminary cleaning. The cleaned water will flow from the outlet end of the filter end pipeline into the waste liquid collection tank.

[0125] Step 2: The first liquid switching mechanism 8 allows only the branch pipe through which the alkali solution is allowed to flow, and the peristaltic pump 7 is used to push the alkali solution into the tangential flow filter for further cleaning. The cleaned alkali solution will flow from the outlet end of the filter end pipe into the waste liquid collection tank.

[0126] Step 3: Again, the first liquid switching mechanism 8 is used to allow water to flow through the branch pipe, and the peristaltic pump 7 is used to pump water into the tangential flow filter for rinsing (to clean the alkaline solution). The rinsed water will flow from the outlet end of the filter end pipe into the waste liquid collection tank.

[0127] Step 4: Using the first liquid switching mechanism 8, only the branch tube that allows the buffer solution to flow is used, and the pumping force of the peristaltic pump 7 is used to pass the buffer solution into the tangential flow filter for wetting. After wetting, the buffer solution will flow from the outlet end of the filter end tube into the waste liquid collection tank.

[0128] Finally, tangential flow filtration can be performed. The first liquid switching mechanism 8 allows only the branch pipe through which the feed liquid flows, and the outlet end of the filtration end pipe is connected to the process waste liquid collection tank. Then, the operator can input the required working data via touchscreen on the PLC data display screen 13. At this time, the peristaltic pump 7 will restart, thereby simultaneously providing pumping force to the feed liquid in the inlet, outlet, and filtration end pipes, thus achieving tangential flow filtration of cells or their secreted products.

[0129] In the above steps, the flow meter 20 can monitor the flow rate of the liquid in the inlet and outlet pipes in real time, and the pH-conductivity sensor 22 can monitor the pH and conductivity of the liquid in the filter pipe in real time.

[0130] In the above steps, the second pressure regulating valve 10 can adjust the pressure of the liquid in the filter end pipeline in real time according to the pressure data monitored by the third pressure sensor; the first pressure regulating valve 9 can adjust the pressure of the liquid in the outlet end pipeline in real time according to the pressure data monitored by the second pressure sensor.

[0131] In the above steps, if it is necessary to replenish the biological buffer solution required for biological purification in the container used to store the liquid to be filtered (i.e., the above-mentioned culture tank), an auxiliary pipeline can be installed on an auxiliary peristaltic pump and the outlet end of the auxiliary pipeline can be connected to the container used to store the liquid to be filtered (i.e., the above-mentioned culture tank). At the same time, the inlet end of the auxiliary pipeline can be connected to the container used to store the biological buffer solution. By starting the auxiliary peristaltic pump, the biological buffer solution required for biological purification can be replenished in the container used to store the liquid to be filtered, thereby enabling the composition of the filtered liquid (sample) to meet the requirements of the purification process.

[0132] In the above steps, since two first liquid switching mechanisms 8 are installed on the side wall of the housing 1 in this embodiment, the four branch pipes of the pipelines in the two first liquid switching mechanisms 8 can be connected in sequence, and then the liquids in the four branch pipes can be switched on and off by the two first liquid switching mechanisms 8, thereby improving the liquid switching effect.

[0133] Furthermore, the tangential flow filtration device for cells or their secreted products provided by the present invention can be used for the manufacture of biopharmaceuticals, such as antibodies or recombinant protein genetically engineered drugs and vaccines, because it is capable of separating and purifying, for example, cells or their derivatives (especially proteins).

[0134] Example 2 This device includes a main peristaltic pump (equivalent to peristaltic pump 7), an auxiliary peristaltic pump, a pipeline directional clamp (equivalent to the first pipeline directional clamp 3, the second pipeline directional clamp 5, and the third pipeline directional clamp 6), a flow meter (equivalent to flow meter 20), a pressure regulating valve (equivalent to the first pressure regulating valve 9 and the second pressure regulating valve 10), a pressure sensor (equivalent to pressure sensor interface 12), a filter bracket (equivalent to filter bracket 18), a conductivity sensor (equivalent to pH value-conductivity sensor 22), and a PLC display (equivalent to PLC data display screen 13).

[0135] In this embodiment, the main peristaltic pump is compatible with 13#, 14#, 25#, 16#, 17# and 18# hoses.

[0136] In this embodiment, the auxiliary peristaltic pump is a snap-fit ​​type, compatible with 14#, 25# and 16# hoses.

[0137] In this embodiment, the pipe directional clamp and the inner cavity of the flow meter are provided with grooves to clamp and store hoses with an outer diameter of ≤11.2mm. The directional clamp is fitted with the flow meter for flow measurement. The directional clamp has a built-in motor, which can realize one-button touch control opening and closing.

[0138] In this embodiment, the pressure regulating valve can be adjusted automatically or manually to achieve the goal of hose compression and pressure regulation.

[0139] In this embodiment, the pressure sensor can detect the pressure before, after and in the permeation chamber.

[0140] In this embodiment, the filter holder can freely clamp filters with a diameter of 80mm or less. It is connected via a bottom hinge.

[0141] In this embodiment, the conductivity sensor is integrated on the right side of the system.

[0142] In this embodiment, the PLC display can freely adjust its tilt angle using a drive shaft.

[0143] In this embodiment, all power delivery units, monitoring units, control units, auxiliary support accessories, display and control units required for cell harvesting and purification (i.e., tangential flow filtration of cells or their secretions) are organically integrated into one unit.

[0144] The above embodiments of the present invention can be combined with each other and have corresponding technical effects.

[0145] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A tangential flow filtration device specifically designed for filtering and separating protein drugs from cell or its secretory product liquid, characterized in that, include: Piping, the piping being used to transport cells or their secreted products in liquid form and other different liquids; A housing (1) is provided inside which is a central controller, and a peristaltic pump (7), a pipeline clamping unit, a tangential flow filter, a pressure control unit, an electrically connected pressure sensor, and a first liquid switching mechanism (8) are installed on the outer wall of the housing (1), wherein: The peristaltic pump (7) is used to provide pumping force for the transport of liquid or other different liquids in the pipeline, so that the liquid in the pipeline can be transported to the tangential flow filter for filtration and purification by the pumping force of the peristaltic pump (7). The peristaltic pump (7) can also transport other different liquids in the pipeline to the device. The pipe clamping unit is used to clamp the pipe, and a flow meter (20) is installed on the pipe clamping unit. The flow meter (20) is used to monitor the flow rate of the liquid in the pipe. The pressure sensor is used to monitor the delivery pressure of the liquid in the pipeline, and the pressure control unit is used to adjust the delivery pressure of the liquid in the pipeline according to the pressure monitored by the pressure sensor. The first liquid switching mechanism (8) is used to switch between the feed liquid and other different liquids, so as to deliver the feed liquid and other different liquids to the device through the pipeline and the peristaltic pump (7); The central controller is electrically connected to the peristaltic pump (7), the pipeline clamping unit, the pressure control unit, the flow meter (20), the pressure sensor and the first liquid switching mechanism (8) respectively to achieve overall control; The pipeline clamping unit includes a first pipeline orientation clamp (3), a second pipeline orientation clamp (5), and a third pipeline orientation clamp (6). The first pipeline orientation clamp (3) is used to clamp the pipeline before filtration by the tangential flow filter. The second pipeline orientation clamp (5) has an L-shaped cross-section. The third pipeline orientation clamp (6) has a cuboid structure. The second pipeline orientation clamp (5) and the third pipeline orientation clamp (6) are used to clamp the pipeline after filtration by the tangential flow filter. The flow meter (20) is fitted on the first pipeline orientation clamp (3) and the second pipeline orientation clamp (5). The first pipeline orientation clamp (3), the second pipeline orientation clamp (5), and the inner cavity of the flow meter are provided with grooves for clamping and storing hoses with an outer diameter of ≤11.2mm, so as to monitor the flow rate of the liquid in the pipeline before filtration by the tangential flow filter and the flow rate of the liquid in the pipeline after filtration by the tangential flow filter, respectively. The first pipe orientation clamp (3), the second pipe orientation clamp (5) and the third pipe orientation clamp (6) are all separable two-part structures and have pipe installation through holes along the length of their two-part structures. The pipe is clamped in the pipe installation through holes. The first pipe orientation clamp (3), the second pipe orientation clamp (5) and the third pipe orientation clamp (6) are each equipped with an opening and closing control button (23). Each opening and closing control button (23) is configured to control the opening and closing of the two-part structure of the first pipe orientation clamp (3), the second pipe orientation clamp (5) and the third pipe orientation clamp (6) respectively. The first liquid switching mechanism (8) includes a cover plate and a fixing plate that are hinged to each other. The fixing plate is connected to the outer wall of the housing (1). A liquid switching mechanism locking part is installed on the fixing plate. The liquid switching mechanism locking part is used to lock the cover plate and the fixing plate. The liquid switching mechanism locking part includes a liquid switching mechanism locking rod (27) rotatably connected to the bottom end of the fixed plate and a liquid switching mechanism locking knob (28) threadedly connected to the end of the liquid switching mechanism locking rod (27) away from the fixed plate; the bottom ends of the cover plate and the fixed plate are provided with liquid switching mechanism locking grooves that can be used to insert the liquid switching mechanism locking rod (27); The fixing plate is provided with a main pipeline installation slot (24) and four branch pipeline installation slots (25) that are interconnected. The main pipeline installation slot (24) and the four branch pipeline installation slots (25) are all used to install the pipelines. The fixed plate is also equipped with a liquid switching extrusion unit, which is electrically connected to the central controller. The liquid switching extrusion unit is used to extrude the pipeline to switch between the feed liquid and other different liquids. The liquid switching extrusion unit includes at least five liquid switching telescopic motors mounted on the fixed plate. One of the liquid switching telescopic motors is correspondingly arranged with respect to the main pipeline mounting slot (24), and the other four liquid switching telescopic motors are respectively corresponding to the four branch pipeline mounting slots (25). An extrusion block (26) is installed on the telescopic end of the liquid switching telescopic motor. One of the extrusion blocks (26) can extend into the main pipeline mounting slot (24), and the other four extrusion blocks (26) can respectively extend into the four branch pipeline mounting slots (25). The first liquid switching mechanism is configured to perform the following steps: Step 1: Close the other three branch pipes of the pipeline and only allow water to flow through the branch pipe; then connect the outlet end of the filter end pipeline into the waste liquid collection tank, and use the pumping force of the peristaltic pump to push the water into the tangential flow filter for preliminary cleaning. The cleaned water flows into the waste liquid collection tank from the outlet end of the filter end pipeline. Only the branch pipe through which the alkali solution is introduced is allowed to flow, and the alkali solution is pushed into the tangential flow filter by the pumping force of the peristaltic pump for further cleaning. The cleaned alkali solution will flow into the waste liquid collection tank from the outlet end of the filter end pipe. Only the branch pipes through which water is introduced are allowed to circulate, and the water is pushed into the tangential flow filter by the pumping force of the peristaltic pump for rinsing to clean the alkaline solution. The rinsed water will flow from the outlet end of the filter end pipe into the waste liquid collection tank. Only the branch tube into which the buffer solution is introduced is allowed to flow, and the buffer solution is pushed into the tangential flow filter by the pumping force of the peristaltic pump for impregnation. After impregnation, the buffer solution will flow into the waste liquid collection tank from the outlet end of the filter end tube. Finally, tangential flow filtration is performed. The first liquid switching mechanism allows only the branch pipe through which the feed liquid flows, and the outlet end of the filter end pipe is connected to the process waste liquid collection tank. Then, the operator inputs the required working data on the PLC data display screen via touch screen according to actual needs. At this time, the peristaltic pump is restarted, thereby providing pumping force to the feed liquid in the inlet end pipe, outlet end pipe and filter end pipe at the same time, thus realizing the tangential flow filtration of cells or their secreted products.

2. The apparatus according to claim 1, characterized in that, The housing (1) is equipped with several pressure sensor interfaces (12), the pressure sensors are electrically connected to the pressure sensor interfaces (12), and the pressure sensor interfaces (12) are electrically connected to the central controller. The pressure sensor includes at least a first pressure sensor, a second pressure sensor, and a third pressure sensor; The first pressure sensor is used to monitor the delivery pressure of the liquid in the pipeline before filtration by the tangential flow filter; The second pressure sensor is used to monitor the delivery pressure of the liquid in the pipeline after filtration by the tangential flow filter; The third pressure sensor is used to monitor the delivery pressure of the liquid in the pipeline at the filtration end of the tangential flow filter.

3. The apparatus according to claim 2, characterized in that, The pressure control unit includes a first pressure regulating valve (9) and a second pressure regulating valve (10); The first pressure regulating valve (9) is configured to correspond to the second pressure sensor, so as to regulate the conveying pressure of the liquid in the pipeline after filtration by the tangential flow filter by the pressure monitored by the second pressure sensor; The second pressure regulating valve (10) is configured in correspondence with the third pressure sensor to regulate the conveying pressure of the liquid in the pipeline at the filtration end of the tangential flow filter by the pressure monitored by the third pressure sensor.

4. The apparatus according to claim 1, characterized in that, A connecting rod (19) is rotatably connected to the housing (1), and a filter bracket (18) is rotatably connected to the end of the connecting rod (19). A bidirectional clamp (2) is installed on the filter bracket (18), and the tangential flow filter is installed on the filter bracket (18) through the bidirectional clamp (2).

5. The apparatus according to claim 4, characterized in that, The filter bracket (18) is equipped with a telescopic locking mechanism at its top end, and a U-shaped pipe rack (17) is installed at the top end of the telescopic locking mechanism. A U-shaped groove adapted to the pipe is provided on the U-shaped outer wall of the U-shaped pipe rack (17), and the pipe is detachably installed in the U-shaped groove. The telescopic locking mechanism is configured to adjust the height of the U-shaped pipe rack (17) and lock the height of the U-shaped pipe rack (17).

6. The apparatus according to claim 1, characterized in that, A hinge clip (11) is installed on the housing (1), and a pH-conductivity sensor (22) is installed inside the hinge clip (11). The pH-conductivity sensor (22) is used to monitor the conductivity and pH value of the liquid in the pipeline at the filtration end of the tangential flow filter.

7. The apparatus according to claim 1, characterized in that, A PLC data display screen (13) is installed on the outer wall of the housing (1). The PLC data display screen (13) is configured to display the monitored real-time data and to manually control the central controller via touch screen. The housing (1) is equipped with a running status indicator (15), which is configured to indicate the running status. An emergency stop button (16) is installed on the housing (1), and the emergency stop button (16) is configured to perform an emergency stop on the device.

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