Tangential flow filtering device for cells or secreted products thereof

Abstract

The invention relates to a tangential flow filtering device for cells or secreted products thereof. The tangential flow filtering device comprises a pipeline for conveying feed liquid and other different liquids, a central controller is arranged in the shell, a peristaltic pump, a pipeline clamping unit, a tangential flow filter, a pressure control unit and a first liquid switching mechanism are installed on the outer wall of the shell, and a flow meter is installed on the pipeline clamping unit; the shell is electrically connected with a pressure sensor; 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 so as to achieve overall control. According to the invention, integration and overall control of each unit can be realized, the occupied space is reduced, and monitored data can be more timely and accurate.

Description

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

[0002] The present invention relates to the technical field of tangential flow filtration, and in particular to a device for tangential flow filtration of cells or their secretory products, which can be used in the manufacture of biological drugs, such as antibodies or recombinant protein genetic engineering drugs and vaccines. Background Art

[0003] Tangential flow filtration is a crucial process in biopharmaceuticals and other processes, and cells or their secreted products (such as proteins and exosomes) are crucial materials in this field. However, culture vessels often contain a large amount of cell debris and impurities. Therefore, tangential flow filtration is necessary to filter and purify cells or their secreted products, thereby obtaining a purer fraction of the desired cells or their secreted products.

[0004] Currently, in the process of filtering and purifying cells or their secretory products, it is necessary to manually physically stack and integrate the units for filtering and purifying various cells or their secretory products, which takes up a large amount of space, and each unit needs to be operated separately, making the process extremely cumbersome. In addition, in the process of filtering and purifying cells or their secretory products, the data in the process flow cannot be monitored in real time. The process flow requires manual operation and human judgment, which will result in untimely data collection and inaccurate data.

[0005] Therefore, how to integrate the various units to reduce the floor space, control the units as a whole, and make the monitored data more timely and accurate has become an urgent problem that needs to be solved. Summary of the Invention

[0006] The object of the present invention is to provide a device for tangential flow filtration of cells or their secretory products to solve at least some of the technical problems existing in the above-mentioned prior art.

[0007] To achieve the above object, the present invention provides the following solutions: The present invention provides a device for tangential flow filtration of cells or their secretory products, comprising: Pipelines, the pipelines are used to transport feed liquid and other different liquids; A housing is provided with 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 installed on the outer wall of the housing, wherein: The peristaltic pump is used to provide pumping force for the feed liquid or other different liquids in the pipeline, so that the feed 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 into the device; The pipeline clamping unit is used to clamp the pipeline, and a flow meter is installed on the pipeline clamping unit, and the flow meter is used to monitor the flow rate of the feed liquid in the pipeline; The housing is electrically connected to a pressure sensor, which 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 the feed liquid and other different liquids, so as to transport the 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, so as to realize overall control.

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

[0009] According to one embodiment of the present invention, the first pipeline directional clamp, the second pipeline directional clamp, and the third pipeline directional clamp are all detachable two-lobed structures and have pipeline mounting holes formed along the length direction of the two-lobed structures, and the pipelines are clamped in the pipeline mounting holes; The first pipeline directional clamp, the second pipeline directional clamp and the third pipeline directional clamp are all equipped with opening and closing control buttons, and each of the opening and closing control buttons is configured to control the opening and closing of the two-petal structure of the first pipeline directional clamp, the second pipeline directional clamp and the third pipeline directional clamp 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 feed 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 being filtered by the tangential flow filter; The third pressure sensor is used to monitor the delivery pressure of the feed liquid in the pipeline at the filtering 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 correspondingly provided with the second pressure sensor so as to adjust the delivery pressure of the liquid in the pipeline after being filtered by the tangential flow filter according to the pressure monitored by the second pressure sensor; The second pressure regulating valve is provided corresponding to the third pressure sensor so as to adjust the delivery pressure of the feed liquid in the pipeline at the filtering end of the tangential flow filter according to 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, the end of the connecting rod is rotatably connected to a filter bracket, the filter bracket is installed with a bidirectional clamp, 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 rack is installed at the top of the telescopic locking mechanism. A U-shaped groove adapted to the pipeline is opened on the U-shaped outer wall of the U-shaped pipe rack, and the pipeline is detachably installed in the U-shaped groove; the telescopic locking mechanism is configured to adjust the height of the U-shaped pipe rack and lock the height of the U-shaped pipe rack.

[0014] According to one embodiment of the present invention, a hinge is installed on the shell, and a pH value-conductivity sensor is installed in the hinge. The pH value-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 hinged to each other, and the fixing plate is connected to the outer wall of the housing; A liquid switching mechanism locking portion is mounted on the fixed plate, and the liquid switching mechanism locking portion is used to lock the cover plate and the fixed plate; The fixing plate is provided with a main pipeline installation groove and a plurality of branch pipeline installation grooves that are interconnected, and the main pipeline installation groove and the plurality of branch pipeline installation grooves are both used to install the pipelines; A liquid switching extrusion portion is also installed on the fixed plate. The liquid switching extrusion portion is electrically connected to the central controller and 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, and the PLC data display screen is configured to display the monitored real-time data and enable manual control of the central controller by means of a touch screen; An operating status indicator light is installed on the housing, and the operating status indicator light is configured to indicate the operating status; An emergency stop button is installed on the shell, and the emergency stop button is configured to be able to perform an emergency stop process on the device.

[0017] The present invention has at least the following technical effects: First, certain embodiments of the present invention can integrate the peristaltic pump, the pipe clamping unit, the tangential flow filter, the pressure control unit and the first liquid switching mechanism into the housing, thereby realizing the integration of the various units and reducing the occupied space.

[0018] Secondly, certain embodiments of the present invention can achieve overall control of each unit by electrically connecting the central controller to the peristaltic pump, pipeline clamping unit, pressure control unit, pressure control unit, pressure sensor and first liquid switching mechanism.

[0019] Finally, certain embodiments of the present invention can make the monitored data more timely and accurate by integrating a flow meter, a pressure sensor, and a pH-conductivity sensor into the device. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0021] Figure 1 It is a schematic diagram of the overall structure of the present invention; Figure 2 for Figure 1 Schematic diagram of the overall structure from another angle; Figure 3 for Figure 2 Schematic diagram of the overall structure from another angle; Figure 4 Schematic diagram of the overall structure of the peristaltic pump in the present invention; Figure 5 This is a schematic diagram of the overall structure of the second pipeline directional clamp in the present invention; Figure 6 for Figure 5 Schematic diagram of the overall structure containing the flow meter; Figure 7 Schematic diagram of the overall structure of the first pressure regulating valve or the second pressure regulating valve in the present invention; Figure 8 for Figure 7 Schematic diagram of the overall structure of the internal pressing block; Figure 9 Schematic diagram of the overall structure of the first liquid switching mechanism in the present invention; Figure 10 for Figure 9 Schematic diagram of the overall structure from another angle; Figure 11 for Figure 10 A partial enlarged view of point A in the middle; Figure 12 for Figure 9 Schematic diagram of the overall internal structure; Figure 13 for Figure 12 A partial enlarged view of point B in the middle; Figure 14 Schematic diagram of the overall structure of the hinge clip and pH-conductivity sensor in the present invention; Figure 15 for Figure 14 Schematic diagram of the overall structure from another angle; Figure 16 for Figure 15 A partial enlarged view of point C in the middle; Description of reference numerals: 1. Housing; 2. Bidirectional clamp; 3. First pipeline directional clamp; 4. Bidirectional clamp locking knob; 5. Second pipeline directional clamp; 6. Third pipeline directional 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 bracket; 15. Operation status indicator light; 16. Emergency stop button; 17. U-shaped pipeline rack; 18. Filter bracket; 19. Connecting rod; 20. Flow meter; 21. Press block; 22. pH value-conductivity sensor; 23. Opening and closing control button; 24. Main pipeline installation slot; 25. Branch pipeline installation slot; 26. Extrusion 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 DESCRIPTION

[0022] The features and exemplary embodiments of various aspects of the present invention will be described in detail below. In order to make the purposes, technical solutions and advantages of the present invention more clear, the present invention will be further described in detail below in conjunction with 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 are used to illustrate 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 areas in the drawings may be enlarged for other structural components or areas to facilitate understanding of the embodiments of the present invention.

[0023] The directional words appearing in the following description refer to the directions shown in the drawings and do not 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 specified, the terms "installed", "connected", and "connected" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral connection; it can be directly connected or indirectly connected through an intermediate medium. For those skilled in the art, the specific meanings of the above terms in the present invention can be understood according to the specific circumstances.

[0024] In addition, the terms "include", "comprising", "having" or any other variations thereof are intended to cover non-exclusive inclusion, so that a structure or component comprising a series of elements includes not only those elements, but also other mechanical elements not explicitly listed or inherent in the structure or component. In the absence of more limitations, the elements defined by the sentence "comprising..." do not exclude the presence of other identical elements in the article or device comprising the elements.

[0025] Spatially relative terms such as "below," "beneath," "under," "low," "above," "on," "high," and the like are used to facilitate description to explain the positioning of one element relative to a second element, indicating that these terms are intended to encompass different orientations of the device in addition to those shown in the figures. Additionally, for example, "one element is above / below another element" may indicate that the two elements are in direct contact, or may indicate that there are other elements between the two elements. Furthermore, terms such as "first," "second," and the like are also used to describe various elements, regions, portions, and the like, and do not specifically refer to an order or sequence, and should not be considered limiting. Similar terms are used throughout the description to indicate similar elements.

[0026] For those skilled in the art, the present invention can be implemented without some of these specific details. The following description of the embodiments is only intended to provide a better understanding of the present invention by showing examples of the present 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 device for tangential flow filtration of cells or their secretory 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 purpose of more conveniently describing the implementation of the present invention. It is only an exemplary general concept and does not specifically limit a specific person.

[0029] Example 1 Reference Figure 1-16 The present invention provides a device for tangential flow filtration of cells or their secretory products, the device comprising at least: The pipeline (only a portion is shown in the figure) is used to transport the cell or secretory product liquid. The pipeline can also be used to transport various other liquids. For example, before performing tangential flow filtration of cells or their secretory products, water, alkaline solution, and buffer can be passed through the pipeline to clean and soak the pipeline and the tangential flow filter in the device.

[0030] In this embodiment, the liquid transported in the pipeline is cells or their secretory product liquid.

[0031] In this embodiment, for the convenience of description, the cell or derivative liquid in the pipeline is referred to as the liquid.

[0032] In this embodiment, the tubing can be made of any material known in the art suitable for transporting liquid cells or their derivatives, such as silicone hoses with diameters of 13#, 14#, 25#, 16#, 17#, and 18#, without particular limitation. Because the device is compatible with silicone hoses with diameters of 13#, 14#, 25#, 16#, 17#, and 18#, it can accommodate different liquid transport flow requirements and achieve process volumes ranging from 0.15L to 10L.

[0033] The housing 1 houses a central controller (not shown).

[0034] In this embodiment, referring to Figure 1-3 The housing 1 may be a hollow cubic structure with a length (base) of 495 mm, a width (base) of 405 mm, a height (right-angled side) of 460 mm, and a right-angled trapezoidal cross-section. The housing 1 may be made of stainless steel, a material known in the art, and is not particularly limited herein.

[0035] Preferably, the central controller is installed in the hollow structure of the shell 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 integrated (overall) control of all components on the device, which is not particularly limited here.

[0036] Further, refer to Figure 1-3 , support feet are installed at the four corners of the bottom end of the shell 1 to achieve a more stable placement of the device.

[0037] According to one embodiment of the present invention, referring to Figure 1-3 The device further 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 of which are mounted on the outer wall of the housing 1, wherein: The pipeline can be 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 material liquid in the pipeline, so that the material liquid in the pipeline can be transported to the tangential flow filter for filtration and purification through 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, alkaline solution 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 herein. The peristaltic pump 7 in this embodiment can be any peristaltic pump known in the art that is suitable for use with the device and capable of providing a flow rate of 0.36 mL / min to 2300 mL / min for the liquid in the pipeline connected thereto.

[0040] In this embodiment, referring to Figure 1 , a lever is provided on the peristaltic pump 7, and the lever can be rotated on the peristaltic pump 7. Specifically, when the lever is Figure 1 When the right end of the lever is rotated to the left end, the peristaltic pump 7 will open, and the staff can install the pipeline into the peristaltic pump 7; after the installation is completed, move the lever 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 conventional technology known in the art and is capable of filtering and purifying a liquid feed of cells or their derivatives. A detailed description thereof will not be given here. For example, in this embodiment, the peristaltic pump 7 is used to introduce a liquid feed of cells or their derivatives to be filtered into the liquid inlet of the tangential flow filter. The cells in the liquid feed are filtered by the tangential flow filter and flow out of the liquid outlet of the tangential flow filter, while the derivatives (e.g., proteins) in the liquid feed flow out of the filtration end of the tangential flow filter. This constitutes the filtration and purification of a liquid feed of cells or their derivatives, as well as the separation and extraction of the liquid feed of cells or their derivatives.

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

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

[0044] In this embodiment, the pipeline clamping unit is provided to clamp and store the pipeline, thereby preventing the pipeline from shaking.

[0045] In this embodiment, the flowmeter 20 is a conventional device known in the art and will not be described in detail herein. Since the peristaltic pump 7 can provide a flow rate of 0.36 mL / min to 2300 mL / min for the liquid in the connected pipeline, the flowmeter 20 can be any flowmeter known in the art that is suitable for use with 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) 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 herein. The pressure sensor may be any pressure sensor known in the art that is suitable for the present device and capable of measuring a pressure value of 0 PSI-60 PSI.

[0048] In this embodiment, since the pressure control unit can control the delivery pressure of the slurry in the pipeline, the pressure control unit can control the flow rate of the slurry in the pipeline, and then can control the transmembrane pressure and shear force of the slurry in the pipeline according to actual conditions.

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

[0050] In this embodiment, referring to Figure 1 The number of the first liquid switching mechanism 8 can be two, and they are installed in sequence 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 fixed plate hinged to each other at the top, and the fixed plate is connected to the outer wall of the housing 1, that is, the fixed plate is installed Figure 1 On the left side wall of the middle shell 1, the first liquid switching mechanism 8 is installed on the left side wall of the shell 1. The shape and size of the cover plate and the fixing plate can be the same, and both are rectangular parallelepiped structures.

[0052] Reference Figure 12 The fixing plate is provided with a main pipeline installation groove 24 and a plurality of branch pipeline installation grooves 25 that are interconnected. The main pipeline installation groove 24 and the plurality of branch pipeline installation grooves 25 are both used for installing the pipelines.

[0053] Preferably, a main pipe installation groove 24 and a plurality of branch pipe installation grooves 25 (not shown in the figure) that are interconnected are also provided on the surface where the cover plate and the fixed plate are in contact, and the main pipe installation groove 24 and the plurality of branch pipe installation grooves 25 on the cover plate can respectively form a hollow cylindrical structure with the main pipe installation groove 24 and the plurality of branch pipe installation grooves 25 on the fixed plate, thereby making it possible to better install the cylindrical pipe in the main pipe installation groove 24 and the plurality of branch pipe installation grooves 25.

[0054] In this embodiment, the number of the main line installation groove 24 and the number of the branch line installation grooves 25 can be one and four respectively, so that the pipes installed in the four branch line installation grooves 25 can be respectively connected to water, alkaline solution, buffer solution and feed liquid, and then the water, alkaline solution, buffer solution and feed liquid can be respectively transported to the device through the pipes in the main line installation groove 24 by the pump force of the peristaltic pump 7.

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

[0056] Specifically, refer to Figure 10 and Figure 11 The liquid switching mechanism locking portion 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. Furthermore, a liquid switching mechanism locking groove for receiving the liquid switching mechanism locking rod 27 is formed at the bottom ends of the cover plate and the fixed plate. To lock the cover plate and the fixed plate, the liquid switching mechanism locking rod 27 is rotated into the liquid switching mechanism locking groove, and then the liquid switching mechanism locking knob 28 is rotated until it contacts the outer wall of the cover plate.

[0057] In this embodiment, a liquid switching extrusion part is also installed on the fixed plate, which is electrically connected to the central controller. The liquid switching extrusion part is used to squeeze the pipeline to switch the feed liquid and other different liquids (the above-mentioned water, alkali solution, buffer solution).

[0058] Specifically, refer to Figure 10 、 Figure 12 and Figure 13The liquid switching and squeezing part includes five liquid switching telescopic motors mounted on a fixed plate, one of which is arranged corresponding to the main line mounting slot 24, and the other four liquid switching telescopic motors are arranged corresponding to the four branch line mounting slots 25, respectively. An squeezing block 26 is installed on the telescopic end (i.e., the output end) of the liquid switching telescopic motor, one of which can be inserted into the main line mounting slot 24, and the other four squeezing blocks 26 can be inserted into the four branch line mounting slots 25, respectively. When it is necessary to switch between water, alkali solution, buffer solution, and feed liquid, the four liquid switching telescopic motors can be started separately, and the four squeezing blocks 26 can be used to squeeze the pipes in the four branch line mounting slots 25, respectively, thereby realizing the switching between water, alkali solution, buffer solution, and feed liquid. Among them, the squeezing block 26 arranged corresponding to the main line mounting slot 24 can squeeze the pipes in the main line mounting slot 24, that is, realize the overall liquid switching.

[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., a connection that can transmit signals and information), so that the central controller can achieve integrated (overall) control of all components in the device.

[0060] Through the above-mentioned configuration, the present invention integrates various units, thereby reducing the footprint of each separation and extraction unit. Furthermore, it enables integrated control of each unit, enabling "one person, one machine" or "one person, multiple machines," further reducing the labor cost of biopharmaceutical production and alleviating the financial burden on patients. It also makes monitored data more timely and accurate, helping to reduce variability between batches of intermediates and finished products and ensuring more stable quality of raw products (e.g., pharmaceuticals).

[0061] In addition, the present invention can also realize intelligent operation through the above-mentioned settings, which helps to achieve standardization of bioprocess control, 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 pipeline clamping unit includes a first pipeline orientation clamp 3 and a second pipeline orientation clamp 5 (refer to Figure 5 and Figure 6 ) and the third pipeline directional clamp 6. Among them: 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 liquid inlet end of the tangential flow filter to prevent the pipeline connected to the liquid inlet end of the tangential flow filter from shaking.

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

[0064] In this embodiment, referring to Figure 1 and Figure 2 The first pipeline directional clamp 3, the second pipeline directional clamp 5, the third pipeline directional clamp 6 and the peristaltic pump 7 can all be arranged on the vertical surface of the housing 1. 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 ), and the first pipeline orientation clamp 3, the second pipeline orientation clamp 5 and the third pipeline orientation clamp 6 can be installed at the lower right corner, upper right corner and upper left corner of the vertical surface of the shell 1 respectively. Figure 1 and Figure 2 The cross section of the first pipeline orientation clamp 3 may be a pentagonal structure with a right angle, the cross section of the second pipeline orientation clamp 5 may be an L-shaped structure, and the cross section of the third pipeline orientation clamp 6 may be a rectangular parallelepiped structure.

[0065] In this embodiment, refer to Figure 6 , Figure 6 FIG2 is a schematic diagram of a flow meter 20 mounted on the second pipeline directional clamp 5. However, in this embodiment, flow meters 20 are mounted on both the first pipeline directional clamp 3 and the second pipeline directional clamp 5, so as to be able to monitor the flow rates of the feed liquid before and after filtration of the tangential flow filter. Figure 6 Only a schematic diagram of the flow meter 20 being installed on the second pipeline orientation clamp 5 is shown in FIG. 1 , but those skilled in the art should understand that the flow meter 20 is installed on the first pipeline orientation clamp 3 in the same manner as the attached FIG. Figure 6 The flow meter 20 is installed on the second pipeline directional clamp 5 in the same manner, that is, those skilled in the art can Figure 6 Understand how the flow meter 20 is installed on the first pipeline orientation clamp 3.

[0066] According to one embodiment of the present invention, the first pipeline orientation clamp 3 and the second pipeline orientation clamp 5 (see Figure 5 ) and the third pipeline directional clamp 6 are both detachable two-lobed structures and have pipeline installation holes along the length direction of the two-lobed structures, and the pipeline can be clamped in the pipeline installation holes.

[0067] In this embodiment, Figure 5For example, the second pipeline directional clamp 5 includes a clamping part and a power part, wherein the clamping part is a detachable two-petal structure. The power part can be a telescopic motor known in the art (for the convenience of description, it is named as a pipeline directional clamp telescopic motor), which can control the clamping part of the two-petal structure to clamp, thereby clamping the pipeline. Preferably, referring to Figure 5 The two-lobed structure of the clamping part has the same volume. For ease of description, the clamping part close to the power unit is named the fixed clamping block (because it is connected to the fixed end of the pipeline directional clamp's telescopic motor), and the clamping part away from the power unit is named the movable clamping block (because it is connected to the telescopic end of the pipeline directional clamp's telescopic motor).

[0068] In this embodiment, referring to Figure 6 The telescopic end of the pipeline directional clamp telescopic motor can be connected by two connecting rods (i.e. Figure 6 The two cylindrical rods located on both sides of the opening and closing control button 23 are connected to the movable clamping block, thereby realizing the movement of the movable clamping block and realizing the clamping of the pipeline. The pipeline mounting through-holes can be respectively opened 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 of the pipeline mounting through-hole is located on the fixed clamping block, that is, when the fixed clamping block and the movable clamping block are merged, they form the pipeline mounting through-hole, and when the fixed clamping block and the movable clamping block are separated, the pipeline mounting through-holes are long grooves each opened on the fixed clamping block and the movable clamping block, so that the pipeline can be installed in the pipeline mounting through-hole. In this embodiment, referring to Figure 5 , the cross section of the pipe installation hole (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 pipeline orientation clamp 5 is shown, but those skilled in the art should understand that the specific structures of the first pipeline orientation clamp 3 and the third pipeline orientation clamp 6 are the same as the specific structure of the second pipeline orientation clamp 5 (except that the shapes of the clamping parts of each pipeline orientation clamp are slightly different). That is, those skilled in the art can understand the specific structures of the first pipeline orientation clamp 3 and the third pipeline orientation clamp 6 according to the attached drawings. Figure 5 and attached Figure 6 Understand the specific structures of the first pipeline directional clamp 3 and the third pipeline directional clamp 6.

[0070] According to one embodiment of the present invention, referring to Figure 1-6 and Figure 9 The first pipeline directional clamp 3, the second pipeline directional clamp 5 and the third pipeline directional clamp 6 are all 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-petal structure (i.e., the fixed clamping block and the movable clamping block) of the first pipeline directional clamp 3, the second pipeline directional clamp 5 and the third pipeline directional clamp 6 respectively.

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

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

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

[0074] According to one embodiment of the present invention, referring to Figure 2 Several pressure sensor interfaces 12 are installed on the housing 1. 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 (ie, the connection that can transmit signals and information).

[0075] In this embodiment, referring to Figure 2 There are three pressure sensor interfaces 12, and they are all arranged 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, and preferably includes only the first pressure sensor, the second pressure sensor, and the third pressure sensor. 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 liquid inlet end of the tangential flow filter.

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

[0078] The third pressure sensor is used to monitor the delivery pressure of the feed liquid in the pipeline at the filtration end, that is, it can monitor the delivery pressure of the feed liquid in the pipeline connected to the filtration 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 may 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 provided correspondingly to the second pressure sensor, that is, after the liquid in the pipeline is filtered by the tangential flow filter, it immediately passes through the interior of the first pressure regulating valve 9, and 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 arranged correspondingly to the third pressure sensor, that is, when the liquid in the pipeline passes through the filtering end of the tangential flow filter, it immediately passes through the inside of the first pressure regulating valve 9, thereby adjusting the delivery pressure of the liquid in the pipeline at the filtering end according to the delivery pressure monitored by the third pressure sensor.

[0082] In this embodiment, Figure 7 The first pressure regulating valve 9 and the second pressure regulating valve 10 are schematic diagrams of the specific structures. The first pressure regulating valve 9 and the second pressure regulating valve 10 can be divided into a pressure regulating power part and a pressure clamping part with a concave cross-section. Figure 8 The pressure regulating power unit can be a telescopic motor (for ease of description, it will be named the pressure regulating valve telescopic motor), whose telescopic end is connected to a pressing block 21 with an angled head. Taking the first pressure regulating valve 9 as an example, when the pipeline delivery pressure needs to be adjusted, the pressing block 21 can be driven by the telescopic end of the pressure regulating valve telescopic motor to extend into the pressure clamping portion of the concave structure based on 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, referring 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, referring to Figure 1 and Figure 2 The second pressure regulating valve 10 can be installed on the same side wall of the housing 1 as the pressure sensor interface 12 .

[0085] In this embodiment, when the first pressure regulating valve 9 and the second pressure regulating valve 10 are installed on the shell 1, the pressure regulating valve telescopic motors (i.e., the above-mentioned pressure regulating power parts) of the two will be located inside the shell 1, and the pressure clamping parts of the two will be located outside the shell 1.

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

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

[0088] In this embodiment, the filter holder 18 may be a long cylindrical structure, which may be configured to be able to freely mount a tangential flow filter with a diameter of less than 80 mm.

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

[0090] Further, refer to Figure 1-3 The two clips of the two-way clamp 2 are penetrated and threadedly connected with a two-way clamp locking knob 4. The two two-way clamp locking knobs 4 can respectively lock the two clips of the two-way clamp 2 at one end away from each other, thereby enabling the two-way clamp 2 to clamp the filter bracket 18 and the tangential flow filter more firmly, thereby improving the connection firmness between the filter bracket 18 and the tangential flow filter.

[0091] In this embodiment, referring to Figure 2 A connecting rod mounting block can be installed on the bottom side wall of the shell 1, and 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 shell 1.

[0092] According to one embodiment of the present invention, a telescopic locking mechanism is mounted on the top of filter holder 18. A U-shaped pipe holder 17 is mounted on the top of the telescopic locking mechanism. The U-shaped outer wall of U-shaped pipe holder 17 is provided with a U-shaped groove adapted to accommodate the pipe, and the pipe is removably mounted within the groove. The telescopic locking mechanism is configured to adjust and lock the height of U-shaped pipe holder 17.

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

[0094] In this embodiment, the pipeline connected to the filtering end of the tangential flow filter can be installed in the U-shaped groove of the U-shaped pipeline rack 17, or the pipeline connected to the liquid outlet end of the tangential flow filter can be installed in the U-shaped groove of the U-shaped pipeline rack 17. There is no special limitation here. Both can achieve the technical effect of better fixing the pipeline.

[0095] In this embodiment, the filter holder 18 may be a nut-adjustable telescopic rod structure, and the telescopic locking mechanism is a rotating nut disposed at the top of the filter holder 18. Turning the nut can fix the height of the filter holder 18. When the height of the filter holder 18 is desired, the nut is loosened to adjust the height of the filter holder 18 (i.e., to adjust the telescopic length of the filter holder 18). Conversely, the nut is tightened to fix the height of the filter holder 18.

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

[0097] In this embodiment, the pH-conductivity sensor 22 is a conventional technology known in the art and is capable of monitoring the conductivity and pH of the filtrate at the filtration end, thereby determining the concentration of dissociable ions and the pH of the filtrate at the filtration end as needed. The pH-conductivity sensor 22 can monitor pH values ​​in the range of 0.1-14, and the conductivity can be monitored in the range of 0.1 mS / cm-100 mS / cm.

[0098] In this embodiment, referring to Figure 2 and Figure 3 The hinge clip 11 can be installed on the vertical surface of the housing 1. Figure 2On the side wall on the right side of the housing (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 of the right side wall.

[0099] In this embodiment, referring 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, which can lock the two clips of the hinge clip 11 to install the pH value-conductivity sensor 22 in the hinge clip 11.

[0100] Specifically, refer to Figure 16 The hinge locking portion includes a hinge locking rod 30 rotatably mounted on a clip of any one of the hinges 11. The other end of the hinge locking rod 30 is threadedly connected to a hinge locking knob 31. Both clips of the hinge 11 are provided with hinge locking grooves capable of receiving the hinge locking rod 30. When the two clips of the hinge 11 need to be locked, the staff can rotate the hinge locking rod 30 into the hinge locking groove and then turn the hinge locking knob 31 until the hinge locking knob 31 abuts against the side wall of the other clip of the hinge 11, thereby locking the two clips of the hinge 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 structure of the second liquid switching mechanism 29 is roughly the same as that of the first liquid switching mechanism 8, the difference being that the second liquid switching mechanism 29 only has two branch pipe mounting grooves 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 (the aforementioned water, alkali solution, and buffer solution) flowing out of the filtration end of the tangential flow filter into different locations, depending on actual operational needs. For example, the pipes within the two branch pipe mounting slots 25 of the second liquid switching mechanism 29 can be connected to a waste liquid collection tank and a process waste liquid collection tank, respectively. Then, when water, alkali solution, and buffer solution are introduced into the device, one of the squeeze blocks 26 within the second liquid switching mechanism 29 squeezes and closes the pipe leading to the process waste liquid collection tank, thereby allowing the water, alkali solution, and buffer solution to flow from the filtration end of the tangential flow filter into the waste liquid collection tank. Conversely, when feed liquid is introduced into the device, the other squeeze block 26 squeezes and closes the pipe leading to the waste liquid collection tank, thereby allowing the feed liquid to flow from the filtration end of the tangential flow filter 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 shell 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) through a touch screen to integrate (overall) control of various components on the device.

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

[0106] In this embodiment, the back of the PLC data display screen 13 can be hinged with an adjustment frame 14, and the end of the adjustment frame 14 is hinged to the top of the shell 1, so that the position of the PLC data display screen 13 can be adjusted according to the height and usage habits of the staff, that is, the height and elevation angle of the PLC data display screen 13 can be adjusted, thereby improving the comfort of using the device.

[0107] In this embodiment, the PLC data display screen 13 integrates the operating software MR(C) known in the art. The MR(C) software has a programming-assisted function. Therefore, the operator can call the process program through the PLC data display screen 13 to achieve control of the tangential flow filtration process of cells or their secreted products.

[0108] According to one embodiment of the present invention, referring to Figure 1 An operating status indicator light 15 is installed on the housing 1, and the operating status indicator light 15 is configured to indicate the operating status.

[0109] In this embodiment, the operating status indicator light 15 can be installed at the top of the first pressure regulating valve 9 and can be in the shape of a long strip. 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, and the emergency stop button 16 is configured to be able to perform an emergency stop process on the device.

[0111] In this embodiment, the emergency stop button 16 can be arranged above the third pipeline directional clamp 6. When the operating status indicator light 15 is red, the staff can press the emergency stop button 16 to stop the device from working urgently.

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

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

[0114] In one embodiment of the present invention, an auxiliary peristaltic pump can be provided to pump the biological buffer solution required for the biological purification process into the inlet of the pipeline (i.e., before the feed liquid enters the device), as needed. This ensures that the composition of the feed sample after filtration 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 sizes of 14#, 25#, and 16#.

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

[0116] At the same time, scales known in the art can be installed at the liquid outlet and filtration end of the tangential flow filter to facilitate real-time measurement of the weight of the filtered and filtered liquid, as needed. Preferably, a scale connection port (known in the art) is provided on the housing and electrically connected to the central processing unit. A scale external to the device can be electrically connected to the central processing unit via the balance connection port, thereby synchronizing the data measured by the scale to the PLC data display screen 13 in real time, thereby enabling automatic management and control of the scale.

[0117] The following is a brief description of the most preferred working process of the device in this embodiment in conjunction with the accompanying drawings and the above embodiments: For the convenience of description, in the following content, the pipeline connected to the liquid inlet end of the tangential flow filter is described as the liquid inlet end pipeline, the pipeline connected to the liquid outlet end of the tangential flow filter is described as the liquid outlet end pipeline, the pipeline connected to the filtration end of the tangential flow filter is described as the filtration end pipeline, and the pipeline installed on the auxiliary peristaltic pump is named as the auxiliary pipeline.

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

[0119] Then, install the pipeline, which can be divided into the following steps: Step 1: Install the liquid inlet pipeline in the first liquid switching mechanism 8, and let the four branches of the liquid inlet pipeline flow into water, alkaline solution, buffer solution and feed solution respectively.

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

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

[0122] Step 4: Install the filtration end pipeline on the filtration end of the tangential flow filter, the U-shaped pipeline rack 17, the second pressure regulating valve 10 and the pH value-conductivity sensor 22 on the hinge clamp 11 in sequence, and install the third pressure sensor on the filtration end pipeline between the U-shaped pipeline rack 17 and the second pressure regulating valve 10.

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

[0124] Then, 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 staff can input the required working data on the PLC data display screen 13 by means of the touch screen, thereby using the first liquid switching mechanism 8 to close the other three branches of the pipeline and only allow the branch through which water is introduced to flow; then the outlet end of the filtration end pipeline is passed into the waste liquid collection tank, and the pumping force of the peristaltic pump 7 is used to pass water into the tangential flow filter for preliminary cleaning. The cleaned water will flow into the waste liquid collection tank from the outlet end of the filtration end pipeline.

[0125] Step 2: Use the first liquid switching mechanism 8 to allow only the branch pipe that allows the alkali solution to flow, and use the pumping force of the peristaltic pump 7 to pass the alkali solution into the tangential flow filter for re-cleaning. The cleaned alkali solution will flow into the waste liquid collection tank from the outlet end of the filtration end pipeline.

[0126] Step 3: Use the first liquid switching mechanism 8 again to only allow the branch pipe for water to flow, and use the pumping force of the peristaltic pump 7 to pass water into the tangential flow filter for rinsing (rinsing the alkali solution clean). The rinsed water will flow into the waste liquid collection tank from the outlet end of the filtration end pipeline.

[0127] Step 4: Use the first liquid switching mechanism 8 to allow only the branch pipe that allows the buffer solution to flow, and use the pumping force of the peristaltic pump 7 to pass the buffer solution into the tangential flow filter for infiltration. The infiltrated buffer solution will flow into the waste liquid collection tank from the outlet end of the filtration end pipeline.

[0128] Finally, tangential flow filtration can begin. The first liquid switching mechanism 8 allows only the branch pipe that receives the feed liquid to flow, and directs the outlet of the filtration-end pipeline to the process waste liquid collection tank. The operator can then input the required operating data via the touchscreen on the PLC data display 13, at which point the peristaltic pump 7 will restart, simultaneously providing pumping force to the feed liquid in the inlet, outlet, and filtration-end pipelines, thereby 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 liquid inlet and outlet pipes in real time, and the pH value-conductivity sensor 22 can monitor the pH value and conductivity of the liquid in the filtration pipe in real time.

[0130] In the above steps, the second pressure regulating valve 10 can adjust the pressure of the feed liquid in the filtration 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 feed liquid in the liquid 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 object used to store the feed liquid to be filtered (i.e., the above-mentioned culture tank), the auxiliary pipeline can be installed on the auxiliary peristaltic pump and the outlet end of the auxiliary pipeline can be connected to the object used to store the feed 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 object 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 object used to store the feed liquid to be filtered, thereby ensuring that the components of the filtered feed liquid (sample) 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 shell 1 in this embodiment, the four branches of the pipeline in the two first liquid switching mechanisms 8 can be connected in sequence, and then the two first liquid switching mechanisms 8 can be used to switch on and off the liquid in the branches of the four pipelines, thereby improving the effect of liquid switching.

[0133] In addition, the present invention provides a device for tangential flow filtration of cells or their secretory products. Since it can separate and purify cells or their derivatives (especially proteins), the device can be used in the manufacture of biopharmaceuticals, such as antibodies or recombinant protein genetically engineered drugs and vaccines.

[0134] Example 2 The device includes a main peristaltic pump (equivalent to the 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) and a flow meter (equivalent to the 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 the pressure sensor interface 12), a filter bracket (equivalent to the filter bracket 18), a conductivity sensor (equivalent to the pH value-conductivity sensor 22) and a PLC display (equivalent to the 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 of embedded type and is compatible with 14#, 25# and 16# hoses.

[0137] In this embodiment, the pipe directional clamp and the flow meter cavity are designed with grooves to clamp and accommodate hoses with an outer diameter of ≤11.2mm. The directional clamp is integrated with the flow meter for flow measurement. The directional clamp is equipped with a motor, which enables one-touch opening and closing.

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

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

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

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

[0142] In this embodiment, the elevation angle of the PLC display can be freely adjusted by means of a transmission shaft.

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

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

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

Claims

1. A device for tangential flow filtration of cells or their secretory products, characterized in that: include: Pipelines, the pipelines are used to transport feed liquid and other different liquids; A housing (1) is provided with a central controller, and a peristaltic pump (7), a pipeline clamping unit, a tangential flow filter, a pressure control unit and a first liquid switching mechanism (8) are mounted on the outer wall of the housing (1), wherein: The peristaltic pump (7) is used to provide pumping force for the feed liquid or other different liquids in the pipeline, so that the feed liquid in the pipeline can be transported to the tangential flow filter for filtration and purification through the pumping force of the peristaltic pump (7). The peristaltic pump (7) can also transport other different liquids in the pipeline into the device; The pipeline clamping unit is used to clamp the pipeline, and a flow meter (20) is installed on the pipeline clamping unit, and the flow meter (20) is used to monitor the flow rate of the liquid in the pipeline; The housing (1) is electrically connected to a pressure sensor, which 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 (8) is used to switch between the feed liquid and other different liquids, so as to transport the feed liquid and other different liquids into 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, so as to realize overall control.

2. The device for tangential flow filtration of cells or their secretory products according to claim 1, characterized in that: The pipeline clamping unit comprises 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 filtering by the tangential flow filter; The second pipeline orientation clamp (5) and the third pipeline orientation clamp (6) are used to clamp the pipeline after filtering by the tangential flow filter; The flow meter (20) is mounted on the first pipeline directional clamp (3) and the second pipeline directional clamp (5) to monitor the flow rate of the feed liquid in the pipeline before filtration by the tangential flow filter and the flow rate of the feed liquid in the pipeline after filtration by the tangential flow filter, respectively.

3. The device for tangential flow filtration of cells or their secretory products according to claim 2, characterized in that: The first pipeline orientation clamp (3), the second pipeline orientation clamp (5) and the third pipeline orientation clamp (6) are all detachable two-flap structures and are provided with pipeline installation through holes along the length direction of the two-flap structures, and the pipelines are clamped in the pipeline installation through holes; The first pipeline directional clamp (3), the second pipeline directional clamp (5) and the third pipeline directional clamp (6) are all equipped with an opening and closing control button (23), and each of the opening and closing control buttons (23) is configured to be able to control the opening and closing of the two-petal structure of the first pipeline directional clamp (3), the second pipeline directional clamp (5) and the third pipeline directional clamp (6).

4. The device for tangential flow filtration of cells or their secretory products according to claim 1, characterized in that: A plurality of pressure sensor interfaces (12) are installed on the housing (1), 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 feed 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 being filtered by the tangential flow filter; The third pressure sensor is used to monitor the delivery pressure of the feed liquid in the pipeline at the filtering end of the tangential flow filter.

5. The device for tangential flow filtration of cells or their secretory products according to claim 4, characterized in that: The pressure control unit comprises a first pressure regulating valve (9) and a second pressure regulating valve (10); The first pressure regulating valve (9) is provided corresponding to the second pressure sensor so as to adjust the delivery pressure of the liquid in the pipeline after being filtered by the tangential flow filter by means of the pressure monitored by the second pressure sensor; The second pressure regulating valve (10) is arranged corresponding to the third pressure sensor to regulate the delivery pressure of the liquid in the pipeline at the filtering end of the tangential flow filter through the pressure monitored by the third pressure sensor.

6. The device for tangential flow filtration of cells or their secretory products according to claim 1, characterized in that: A connecting rod (19) is rotatably connected to the housing (1), and the end of the connecting rod (19) is rotatably connected to a filter bracket (18). A bidirectional clamp (2) is installed on the filter bracket (18), and the tangential flow filter is installed on the filter bracket (18) via the bidirectional clamp (2).

7. The device for tangential flow filtration of cells or their secretory products according to claim 6, characterized in that: A telescopic locking mechanism is installed at the top of the filter bracket (18), and a U-shaped pipe rack (17) is installed at the top 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 be able to adjust the height of the U-shaped pipe rack (17) and lock the height of the U-shaped pipe rack (17).

8. The device for tangential flow filtration of cells or their secretory products according to claim 3, characterized in that: A hinge clip (11) is installed on the housing (1), and a pH value-conductivity sensor (22) is installed in the hinge clip (11). The pH value-conductivity sensor (22) is used to monitor the conductivity and pH value of the liquid in the pipeline at the filtering end of the tangential flow filter.

9. The device for tangential flow filtration of cells or their secretory products according to claim 1, characterized in that: The first liquid switching mechanism (8) comprises a cover plate and a fixing plate hinged to each other, and the fixing plate is connected to the outer wall of the housing (1); A liquid switching mechanism locking portion is mounted on the fixed plate, and the liquid switching mechanism locking portion is used to lock the cover plate and the fixed plate; The fixing plate is provided with a main pipeline installation groove (24) and a plurality of branch pipeline installation grooves (25) that are interconnected, and the main pipeline installation groove (24) and the plurality of branch pipeline installation grooves (25) are both used for installing the pipelines; A liquid switching extrusion portion is also installed on the fixed plate. The liquid switching extrusion portion is electrically connected to the central controller and is used to extrude the pipeline to switch between the feed liquid and other different liquids.

10. The device for tangential flow filtration of cells or their secretory products according to claim 1, characterized in that: A PLC data display screen (13) is installed on the outer wall of the housing (1), and the PLC data display screen (13) is configured to display monitored real-time data and to enable manual control of the central controller by means of a touch screen; An operating status indicator light (15) is mounted on the housing (1), and the operating status indicator light (15) is configured to indicate the operating status; An emergency stop button (16) is installed on the housing (1), and the emergency stop button (16) is configured to be able to perform an emergency stop process on the device.

Images