A fully integrated cell or secreted product filtration device

Abstract

This invention relates to a fully integrated cell or its secreted product filtration device, comprising tubing for conveying the feed solution, a housing, and a central controller disposed therein; a main peristaltic pump, a tubing clamping unit suitable for pilot-scale operation, and a tangential flow filter, all mounted on the outer wall of the housing; the main peristaltic pump enables the feed solution in the tubing to be conveyed to the tangential flow filter for filtration and purification; the tubing clamping unit is used to clamp the tubing; a pressure sensor is electrically connected to the housing; the central controller is electrically connected to the main peristaltic pump, the tubing clamping unit, and the pressure sensor. This invention enables the integration and overall control of all units, reduces the footprint, and allows for more timely and accurate monitoring data.

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 cell or its secreted products filtration and purification technology, and in particular to a fully integrated cell or its secreted products filtration device. It is especially useful in the manufacture of biopharmaceuticals, such as antibody or recombinant protein genetically engineered drugs and vaccines. Background Technology

[0003] Cells or their secreted products (such as proteins, exosomes, etc.) are important materials in the biomedical field. However, culture flasks often contain a large amount of cell debris or impurities. Therefore, it is necessary to filter and purify the 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 fully integrated cell or its secreted product filtration device 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:

[0008] This invention provides a fully integrated cell or its secreted product filtration device, comprising:

[0009] Pipeline, the pipeline being used to transport liquid material;

[0010] A housing, within which a central controller is housed;

[0011] It also includes a main peristaltic pump, a pipeline clamping unit suitable for pilot-scale operation, and a tangential flow filter, all mounted on the outer wall of the housing, wherein:

[0012] The main peristaltic pump is 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 main peristaltic pump;

[0013] The pipe clamping unit includes at least a first 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, and the third pipe orientation clamp is used to clamp the pipe at the filtration end of the tangential flow filter.

[0014] 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;

[0015] The central controller is electrically connected to the main peristaltic pump, the pipeline clamping unit, and the pressure sensor to achieve overall control.

[0016] According to one embodiment of the present invention, the pipe clamping unit further includes a second pipe orientation clamp, a fourth pipe orientation clamp, a fifth pipe orientation clamp, and a sixth pipe orientation clamp;

[0017] The second pipe orientation clamp is used to clamp the pipe before filtration by the tangential flow filter;

[0018] The fourth and fifth pipe orientation clamps are used to clamp the pipes after filtration by the tangential flow filter;

[0019] The sixth pipe orientation clamp is used to clamp the pipe at the filter end of the tangential flow filter;

[0020] Both the second and fourth pipe orientation clamps are equipped with flow meters. The flow meter on the second pipe orientation clamp is used to monitor the flow rate of the liquid in the pipe before filtration by the tangential flow filter, and the flow meter on the fourth pipe orientation clamp is used to monitor the flow rate of the liquid in the pipe after filtration by the tangential flow filter. The flow meters are electrically connected to the central controller.

[0021] According to one embodiment of the present invention, the first pipe orientation clamp, the second pipe orientation clamp, the third pipe orientation clamp, the fourth pipe orientation clamp, the fifth pipe orientation clamp, and the sixth pipe orientation clamp are all separable two-part structures and have pipe mounting through holes opened along the length direction of the two-part structure, and the pipe is clamped in the pipe mounting through holes;

[0022] Each of the first, second, third, fourth, fifth, and sixth pipe orientation clamps is equipped with an opening / closing control button. Each opening / closing control button is configured to control the opening and closing of the two-part structure of the first, second, third, fourth, fifth, and sixth pipe orientation clamps, respectively.

[0023] 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.

[0024] 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;

[0025] The first pressure sensor is used to monitor the delivery pressure of the liquid in the pipeline before filtration by the tangential flow filter;

[0026] The second pressure sensor is used to monitor the delivery pressure of the liquid in the pipeline after filtration by the tangential flow filter;

[0027] 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.

[0028] According to one embodiment of the present invention, the device further includes a pressure control unit configured to adjust the delivery pressure of the liquid in the pipeline according to the pressure monitored by the pressure sensor, the pressure control unit being electrically connected to the central controller;

[0029] The pressure control unit includes a first pressure regulating valve and a second pressure regulating valve.

[0030] 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;

[0031] 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.

[0032] 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, and the tangential flow filter is mounted on the filter bracket.

[0033] 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.

[0034] According to one embodiment of the present invention, a conductivity sensor is installed inside the sixth pipeline directional clamp, and the conductivity sensor is used to monitor the conductivity of the liquid in the pipeline at the filtration end of the tangential flow filter.

[0035] 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.

[0036] The housing is equipped with a running status indicator light, which is configured to indicate the running status.

[0037] An emergency stop button is installed on the housing, and the emergency stop button is configured to perform an emergency stop on the device.

[0038] An auxiliary peristaltic pump is installed on the outer wall of the housing. The auxiliary peristaltic pump is used to replenish the biological buffer solution of the feed liquid before it enters the device.

[0039] This invention has at least the following technical effects:

[0040] Some embodiments of the present invention integrate the main peristaltic pump, the tubing clamping unit, the tangential flow filter and the pressure control unit into a housing, thereby reducing the footprint of the various units.

[0041] In some embodiments of the present invention, the central controller is electrically connected to the main peristaltic pump, the pipeline clamping unit, the pressure control unit, the pressure control unit, and the pressure sensor, thereby enabling overall control of each unit.

[0042] Some embodiments of the present invention, by integrating a flow meter and a pressure sensor into the device, enable more timely and accurate monitoring of the data. Attached Figure Description

[0043] 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.

[0044] Figure 1 This is a schematic diagram of the overall structure of the present invention;

[0045] Figure 2 for Figure 1 A schematic diagram of the overall structure from another angle;

[0046] Figure 3 for Figure 2 A schematic diagram of the overall structure from another angle;

[0047] Figure 4 This is a schematic diagram of the overall structure of the main peristaltic pump or the auxiliary peristaltic pump in this invention;

[0048] Figure 5 This is a schematic diagram of the overall structure of the fourth pipeline orientation clamp in this invention;

[0049] Figure 6 for Figure 5 A schematic diagram of the overall structure containing the flow meter;

[0050] Figure 7 This is a schematic diagram of the overall structure of the first or second pressure regulating valve in this invention.

[0051] Figure 8 for Figure 7 Internal overall structure diagram;

[0052] Figure 9 This is a schematic diagram of the overall structure of the sixth pipeline directional clamp in this invention;

[0053] Figure 10 for Figure 9 A schematic diagram of the overall structure containing an internal conductivity sensor;

[0054] The components include: 1. Housing; 2. First pipeline orientation clamp; 3. Second pipeline orientation clamp; 4. Third pipeline orientation clamp; 5. Fourth pipeline orientation clamp; 6. Fifth pipeline orientation clamp; 7. Main peristaltic pump; 8. Auxiliary peristaltic pump; 9. First pressure regulating valve; 10. Second pressure regulating valve; 11. Sixth pipeline orientation 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. Conductivity sensor; 23. Opening / closing control button. Detailed Implementation

[0055] 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.

[0056] 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.

[0057] 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.

[0058] 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.

[0059] 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.

[0060] In this embodiment, there may be descriptions such as "this device". Those skilled in the art should understand that "this device" refers to a fully integrated cell or secretion product filtration device provided by the present invention.

[0061] 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.

[0062] In this embodiment, for ease of description, the cells or their secretory products in the pipeline are referred to simply as the liquid.

[0063] Reference Figure 1-10 The present invention provides a fully integrated cell or its secreted products filtration device, the device comprising at least:

[0064] Piping (not shown in the figure) is used to transport liquid.

[0065] In this embodiment, the tubing can be made of any material known in the art suitable for conveying cells or their secreted products, such as silicone tubing in diameters of 26#, 73#, and 82#, etc., without any particular limitation. Since this device is compatible with silicone tubing in diameters of 26#, 73#, and 82#, it can meet different liquid flow rate requirements and achieve process volumes ranging from 0.5L to 200L.

[0066] Housing 1, with a central controller (not shown in the figure) installed inside housing 1.

[0067] In this embodiment, refer to Figure 1-3 The shell 1 can be a hollow cube structure with a length (base side) of 670mm, a width (base side) of 465mm, a height (right-angled side) of 560mm, 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.

[0068] 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.

[0069] 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.

[0070] According to one embodiment of the present invention, referring to Figure 1-3The device also includes a main peristaltic pump 7, a pipeline clamping unit suitable for pilot-scale operation, a tangential flow filter, and a pressure control unit, all mounted on the outer wall of the housing 1, wherein:

[0071] The pipeline is detachably installed on the main peristaltic pump 7, which can 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 main peristaltic pump 7.

[0072] In this embodiment, the peristaltic pump is a prior art known in the art, and will not be described in detail here. Specifically, the main 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 0.12 L / min to 13 L / min for the liquid in the connected pipeline.

[0073] In this embodiment, refer to Figure 1 The main peristaltic pump 7 is equipped with a lever, which can rotate on the main peristaltic pump 7. Specifically, when the lever moves from... Figure 1 When the right end is rotated to the left end, the main 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 main peristaltic pump 7 can be closed again, thereby achieving a detachable connection between the pipeline and the main peristaltic pump 7.

[0074] 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 secretory product solutions, which will not be elaborated upon here. For example, in this embodiment, the pumping force of the main peristaltic pump 7 allows the cell or secretory product solution to be filtered to be introduced into the inlet end of the tangential flow filter. The cells in the solution will pass through the tangential flow filter and flow out from the outlet end of the tangential flow filter, while the secretory products (i.e., derivatives) in the solution will flow out from the filtration end of the tangential flow filter. The above describes the filtration and purification of the cell or secretory product solution.

[0075] 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.

[0076] 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 is used to monitor the flow rate of liquid in the pipeline.

[0077] In this embodiment, the pipeline clamping unit can clamp and store the pipeline, thereby preventing pipeline vibration.

[0078] In this embodiment, the flow meter 20 is a prior art known in the art, and will not be described in detail here. Since the main peristaltic pump 7 can provide a flow rate of 0.12 L / min to 13 L / min to 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 0.12 L / min to 13 L / min.

[0079] 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.

[0080] 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.

[0081] 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.

[0082] According to one embodiment of the present invention, the central controller is electrically connected to the main peristaltic pump 7, the pipeline clamping unit, the pressure control unit, the flow meter 20 and the pressure sensor, so as to realize the integrated (overall) control of all components in the device by the central controller.

[0083] This invention, through the aforementioned configuration, integrates the various units, thereby reducing the footprint of each unit during the filtration and purification of cells or their secreted products. Simultaneously, it enables overall control of each unit, allowing for "one person, one machine" or "one person, multiple machines," 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 intermediates or finished products, resulting in more stable quality of manufactured products (e.g., pharmaceuticals).

[0084] 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.

[0085] According to one embodiment of the present invention, referring to Figure 1-3The pipe clamping unit includes a first pipe orientation clamp 2, a second pipe orientation clamp 3, a third pipe orientation clamp 4, and a fourth pipe orientation clamp 5 (see reference). Figure 5 and Figure 6 The fifth pipeline directional clamp 6 and the sixth pipeline directional clamp 11. Among them:

[0086] In this embodiment, the first pipe orientation clamp 2 and the second pipe orientation clamp 3 can be used to clamp the pipe before the tangential flow filter, that is, to clamp the pipe connected to the liquid inlet end of the tangential flow filter to prevent the pipe connected to the liquid inlet end of the tangential flow filter from shaking.

[0087] In this embodiment, the fourth pipe orientation clamp 5 and the fifth pipe orientation clamp 6 can be used to clamp the pipe after filtration by the tangential flow filter, that is, to clamp the pipe connected to the liquid outlet end of the tangential flow filter to prevent the pipe connected to the liquid outlet end of the tangential flow filter from shaking.

[0088] In this embodiment, the third pipe orientation clamp 4 and the sixth pipe orientation clamp 11 can be used to clamp the pipes at the filter end of the tangential flow filter, that is, to clamp the pipes connected to the filter end of the tangential flow filter to prevent the pipes connected to the filter end of the tangential flow filter from shaking.

[0089] In this embodiment, refer to Figure 1 and Figure 2 The first pipeline directional clamp 2, the second pipeline directional clamp 3, the fourth pipeline directional clamp 5, the fifth pipeline directional clamp 6, and the main peristaltic pump 7 can all be installed on the vertical surface of the housing 1. For example, Figure 1 As shown, the main peristaltic pump 7 can be installed in the middle of the vertical surface of the housing 1 (the motor of the main peristaltic pump 7 is located inside the housing 1, see reference). Figure 4 The first pipe orientation clamp 2, the second pipe orientation clamp 3, the fourth pipe orientation clamp 5, and the fifth pipe orientation clamp 6 can be installed at the lower left, lower right, upper right, and upper left corners of the vertical surface of the housing 1, respectively.

[0090] In this embodiment, refer to Figure 2 and Figure 3 The third pipe orientation clamp 4 and the sixth pipe orientation clamp 11 can be installed on the vertical surface of the housing 1. Figure 2 On the right-side side wall of the housing 1. The sixth pipe directional clamp 11 can be installed on the vertical surface of the housing 1. Figure 2 The middle part of the right side wall, while the third pipe orientation clamp 4 is installed below the sixth pipe orientation clamp 11.

[0091] In this embodiment, refer to Figure 1 and Figure 2The cross-sections of the first pipe orientation clamp 2 and the second pipe orientation clamp 3 can both be pentagonal structures with right angles, the cross-sections of the third pipe orientation clamp 4 and the fourth pipe orientation clamp 5 can both be L-shaped structures, and the cross-sections of the fifth pipe orientation clamp 6 and the sixth pipe orientation clamp 11 can both be cuboid structures.

[0092] 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 fourth pipe directional clamp 5. However, in this embodiment, flow meters 20 are installed on both the second pipe directional clamp 3 and the fourth pipe directional clamp 5, so as to monitor the flow rate of the liquid in the pipe before and after tangential flow filtration. Therefore, although the attached diagram shows... Figure 6 The diagram only shows a schematic of the flow meter 20 installed on the fourth pipe directional clamp 5, but those skilled in the art should understand that the flow meter 20 is installed on the second pipe directional clamp 3 in the same manner as in the attached diagram. Figure 6 The medium flow meter 20 is installed on the fourth 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 second pipeline directional clamp 3.

[0093] According to one embodiment of the present invention, the first pipe orientation clamp 2, the second pipe orientation clamp 3, the third pipe orientation clamp 4, and the fourth pipe orientation clamp 5 (see reference) Figure 5 ), fifth pipe directional clamp 6 and sixth pipe directional clamp 11 (refer to Figure 9 All of them are separable two-part structures with pipe installation through holes opened along the length of the two-part structure, and the pipes can be clamped in the pipe installation through holes.

[0094] In this embodiment, with Figure 5 For example, the fourth pipe directional 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, 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 gripping section have the same volume. For ease of description, the gripping section closer to the power unit is named the fixed gripping block (because it is connected to the fixed end of the telescopic motor), and the gripping section farther from the power unit is named the movable gripping block (because it is connected to the telescopic end of the telescopic motor).

[0095] In this embodiment, refer to Figure 6 The telescopic end of the telescopic motor can be connected by two connecting rods (i.e. Figure 6Two 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 the 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.

[0096] In addition, although Figure 5 Only the specific structure of the fourth pipe orientation clamp 5 is shown, but those skilled in the art should understand that the specific structures of the first pipe orientation clamp 2, the second pipe orientation clamp 3, the third pipe orientation clamp 4, the fifth pipe orientation clamp 6, and the sixth pipe orientation clamp 11 are the same as the specific structure of the fourth 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 fourth pipe orientation clamp 5 based on the attached diagram. Figure 5 and attached Figure 6 Understand the specific structure of the first pipe orientation clamp 2, the second pipe orientation clamp 3, the third pipe orientation clamp 4, the fifth pipe orientation clamp 6, and the sixth pipe orientation clamp 11.

[0097] According to one embodiment of the present invention, referring to Figure 1-6 and Figure 9 Each of the first pipe orientation clamp 2, the second pipe orientation clamp 3, the third pipe orientation clamp 4, the fourth pipe orientation clamp 5, the fifth pipe orientation clamp 6, and the sixth pipe orientation clamp 11 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 of the first pipe orientation clamp 2, the second pipe orientation clamp 3, the third pipe orientation clamp 4, the fourth pipe orientation clamp 5, the fifth pipe orientation clamp 6, and the sixth pipe orientation clamp 11, respectively.

[0098] In this embodiment, the opening / closing control button 23 is a push-button switch known in the art, which is electrically connected to the telescopic motor to control its start-up; details will not be elaborated further here. Among other things, [the following text is missing from the original extract]. Figure 5 For example, when the opening and closing control button 23 is pressed, the movable clamping block of the fourth pipe orientation clamp 5 will separate from the fixed clamping block, so that the pipe can be installed in the fourth pipe orientation clamp 5 (the first pipe orientation clamp 2, the second pipe orientation clamp 3, the third pipe orientation clamp 4, the fifth pipe orientation clamp 6 and the sixth pipe orientation clamp 11 all operate in the same way as the fourth pipe orientation clamp 5).

[0099] In this embodiment, with Figure 5For example, when the fourth pipe directional clamp 5 is installed on the housing 1, its power unit (i.e., the 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 ).

[0100] In this embodiment, since the pipe diameter can be 26#, 73#, or 82# (i.e., the pipe diameter can be less than or equal to 82#), the diameter of the through hole for pipe installation is also less than or equal to 82# (i.e., suitable for pilot-scale operation) to better match the pipe diameter.

[0101] 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, and the pressure sensor interfaces 12 can be electrically connected to the central controller.

[0102] In this embodiment, refer to Figure 2 There are three pressure sensor interfaces 12, and all of them are located on the same surface as the sixth pipeline orientation clamp 11 mounted on the housing 1.

[0103] 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. Wherein:

[0104] The first pressure sensor, the second pressure sensor, and the third pressure sensor are respectively plugged into the three pressure sensor interfaces 12;

[0105] The first pressure sensor is used to monitor the delivery pressure of the liquid in the pipeline before filtration by the tangential flow filter, that is, it can monitor the delivery pressure of the liquid in the pipeline connected to the inlet end of the tangential flow filter.

[0106] The second pressure sensor is used to monitor the delivery pressure of the liquid in the pipeline after tangential flow filter filtration, that is, it can monitor the delivery pressure of the liquid in the pipeline connected to the outlet end of the tangential flow filter.

[0107] 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, that is, it can monitor the delivery pressure of the liquid in the pipeline connected to the filtration end of the tangential flow filter.

[0108] 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.

[0109] According to one embodiment of the present invention, referring to Figure 1 and Figure 2 , Figure 7 and Figure 8The pressure control unit includes a first pressure regulating valve 9 and a second pressure regulating valve 10 (liquid switch).

[0110] 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 and purified by the tangential flow filter, it immediately passes through the inside of the first pressure regulating valve 9. The delivery pressure of the liquid in the pipeline after tangential flow filter is adjusted by the delivery pressure monitored by the second pressure sensor.

[0111] 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 of the tangential flow filter is regulated by the delivery pressure monitored by the third pressure sensor.

[0112] 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, 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 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 motor's telescopic end, based on the delivery pressure monitored by the second pressure sensor, thereby squeezing the pipeline and regulating the delivery pressure of the filtered liquid in the pipeline.

[0113] In this embodiment, refer to Figure 1 and Figure 2 The first pressure regulating valve 9 can be installed on the vertical surface of the housing 1 and located between the fourth pipeline directional clamp 5 and the fifth pipeline directional clamp 6.

[0114] 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 sixth pipeline directional clamp 11 installed on the housing 1, and is located directly above the sixth pipeline directional clamp 11.

[0115] In this embodiment, when the first pressure regulating valve 9 and the second pressure regulating valve 10 are installed on the housing 1, their telescopic 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.

[0116] In addition, when the first pressure regulating valve 9 and the second pressure regulating valve 10 are fully closed, they can also completely close (completely block) the pipeline.

[0117] 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 tangential flow filter is installed on the filter bracket 18.

[0118] 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.

[0119] In this embodiment, the connection method between the filter support 18 and the tangential flow filter is not particularly limited. They can be connected using any parts known in the art and suitable for their connection. For example, several bidirectional clamps (known in the art) can be installed on the filter support 18 along its axial direction, and the other end of the bidirectional clamps can be used to clamp the tangential flow filter, thereby achieving the connection between the filter support 18 and the tangential flow filter.

[0120] 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.

[0121] 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.

[0122] 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.

[0123] 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.

[0124] 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.

[0125] According to one embodiment of the present invention, referring to Figure 10 A conductivity sensor 22 is installed inside the sixth pipeline directional clamp 11. The conductivity sensor 22 is used to monitor the conductivity of the liquid in the pipeline at the filtration end of the tangential flow filter.

[0126] In this embodiment, the conductivity sensor 22 is a prior art technology known in the art. It can monitor the conductivity of the feed liquid at the filtration end, so as to determine the concentration of dissociable ions in the feed liquid at the filtration end according to actual needs. The monitoring range of the conductivity sensor 22 can be 0.1 mS / cm-100 mS / cm.

[0127] 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.

[0128] 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 15.6-inch LCD / LED backlit display screen.

[0129] 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.

[0130] 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 the process program through the PLC data display screen 13 to achieve automatic control of the cell filtration and purification process.

[0131] According to one embodiment of the present invention, referring to Figure 1The housing 1 is equipped with a running status indicator light 15, which is configured to indicate the running status.

[0132] 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.

[0133] 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.

[0134] In this embodiment, the emergency stop button 16 can be located above the fifth 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.

[0135] According to one embodiment of the present invention, referring to Figure 1 An auxiliary peristaltic pump 8 is installed on the outer wall of the housing 1. The auxiliary peristaltic pump 8 is used to replenish the biological buffer solution of the feed liquid before it enters the device.

[0136] In this embodiment, refer to Figure 1 The auxiliary peristaltic pump 8 can be installed on the vertical surface of the housing 1. Figure 1 On the left side wall.

[0137] In this embodiment, the main peristaltic pump 7 and the auxiliary peristaltic pump 8 can have the same structure. Therefore, those skilled in the art should understand that the specific structures of the main peristaltic pump 7 and the auxiliary peristaltic pump 8 can be referred to. Figure 4 .

[0138] In this embodiment, the auxiliary peristaltic pump 8 can provide a flow rate of 0.36 mL / min to 2300 mL / min for the liquid in the pipeline connected to it.

[0139] In one embodiment of the present invention, by providing an auxiliary peristaltic pump 8, a biological buffer solution required for the filtration and purification process can be pumped into the inlet end of the pipeline (i.e., the liquid before it enters the device) as needed, so that the composition of the liquid sample filtered by the tangential flow filter meets the requirements of the purification process. The auxiliary peristaltic pump 8 can be any peristaltic pump known in the art that is compatible with both 25# and 16# tubing.

[0140] 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 770W and a maximum operating current of 3.3A.

[0141] 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.

[0142] 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:

[0143] 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 8 will be named the auxiliary pipeline.

[0144] First, the tangential flow filter is mounted on the filter bracket 18 using several bidirectional clamps, and 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.

[0145] Then, installing the piping can be divided into at least four steps:

[0146] Step 1: Install the inlet pipes sequentially on the inlet ends of the first pipe directional clamp 2, the main peristaltic pump 7, the second pipe directional clamp 3, and the tangential flow filter, and install the first pressure sensor on the inlet pipe between the second pipe directional clamp 3 and the inlet end of the tangential flow filter.

[0147] Step 2: Install the outlet pipe in sequence on the outlet end of the tangential flow filter, the U-shaped pipe bracket 17, the fourth pipe directional clamp 5, the first pressure regulating valve 9, and the fifth pipe directional clamp 6, and install the second pressure sensor on the outlet pipe between the fourth pipe directional clamp 5 and the first pressure regulating valve 9.

[0148] Step 3: Install the filter end pipeline in sequence on the filter end of the tangential flow filter, the second pressure regulating valve 10, the sixth pipeline directional clamp 11 and the third pipeline directional clamp 4, 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.

[0149] Step four: 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 tank known in the art), and connect the outlet end of the filtration end pipe to an object for collecting secreted products (e.g., cell derivatives) (e.g., a collection tank known in the art).

[0150] Finally, staff can input the required work data via touch screen on the PLC data display screen 13. At this time, the main peristaltic pump 7 will start, thereby providing pumping force to the liquid in the inlet pipe, outlet pipe and filtration pipe at the same time, so as to realize the filtration and purification of cells or their secreted products.

[0151] 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 conductivity sensor 22 can monitor the conductivity of the liquid in the filter pipe in real time.

[0152] 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.

[0153] In the above steps, if it is necessary to replenish the biological buffer solution required for filtration and purification into the container used to store the liquid to be filtered (i.e., the above-mentioned culture tank), an auxiliary pipeline can be installed on the auxiliary peristaltic pump 8 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 8, the biological buffer solution required for biological purification can be replenished into the container used to store the liquid to be filtered, so that the composition of the filtered liquid (sample) meets the requirements of the purification process.

[0154] Furthermore, the fully integrated cell or secreted product filtration device provided by the present invention can be used for the manufacture of biopharmaceuticals, such as antibody or recombinant protein genetically engineered drugs and vaccines, because it is capable of filtering, separating and purifying, for example, cells or their secreted products.

[0155] The above embodiments of the present invention can be combined with each other and have corresponding technical effects.

[0156] 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 fully integrated device for filtering and separating protein drugs from cells or their secretory product liquids, characterized in that, include: Pipeline, the pipeline being used to deliver cells or their secretory product liquid; Housing (1), wherein a central controller is provided inside the housing (1); It also includes a main peristaltic pump (7) mounted on the outer wall of the housing (1), a pipeline clamping unit suitable for pilot-scale operation, and a tangential flow filter, wherein: The main peristaltic pump (7) is used to provide pumping force for the transport of liquid 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 main peristaltic pump (7); The pipe clamping unit includes at least a first pipe orientation clamp (2) and a third pipe orientation clamp (4). The first pipe orientation clamp (2) is used to clamp the pipe before filtration by the tangential flow filter, and the third pipe orientation clamp (4) is used to clamp the pipe at the filtration end of the tangential flow filter. A pressure sensor is electrically connected to the housing (1), and the pressure sensor is used to monitor the conveying pressure of the liquid in the pipeline; The central controller is electrically connected to the main peristaltic pump (7), the pipeline clamping unit, and the pressure sensor to achieve overall control. The pipe clamping unit also includes a second pipe orientation clamp (3), a fourth pipe orientation clamp (5), a fifth pipe orientation clamp (6), and a sixth pipe orientation clamp (11). The second pipe orientation clamp (3) is used to clamp the pipe before filtration by the tangential flow filter; The fourth pipe orientation clamp (5) and the fifth pipe orientation clamp (6) are used to clamp the pipe after filtration by the tangential flow filter. The cross-section of the fourth pipe orientation clamp (5) is L-shaped, and the fifth pipe orientation clamp (6) is a cuboid structure. The sixth pipe orientation clamp (11) is used to clamp the pipe at the filter end of the tangential flow filter; Both the second pipe orientation clamp (3) and the fourth pipe orientation clamp (5) are equipped with flow meters (20). The flow meter (20) on the second pipe orientation clamp (3) is used to monitor the flow rate of the liquid in the pipe before filtration by the tangential flow filter, and the flow meter (20) on the fourth pipe orientation clamp (5) is used to monitor the flow rate of the liquid in the pipe after filtration by the tangential flow filter. The flow meter (20) is electrically connected to the central controller. The first pipe orientation clamp (2), the second pipe orientation clamp (3), the third pipe orientation clamp (4), the fourth pipe orientation clamp (5), the fifth pipe orientation clamp (6) and the sixth pipe orientation clamp (11) are all separable two-part structures and have pipe installation through holes along the length direction of the two-part structure. The pipe is clamped in the pipe installation through holes. The first pipe orientation clamp (2), the second pipe orientation clamp (3), the third pipe orientation clamp (4), the fourth pipe orientation clamp (5), the fifth pipe orientation clamp (6), and the sixth pipe orientation clamp (11) are all equipped with opening and closing control buttons (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 (2), the second pipe orientation clamp (3), the third pipe orientation clamp (4), the fourth pipe orientation clamp (5), the fifth pipe orientation clamp (6), and the sixth pipe orientation clamp (11).

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.

3. The apparatus according to claim 2, characterized in that, 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.

4. The apparatus according to claim 3, characterized in that, The device further includes a pressure control unit configured to adjust the delivery pressure of the liquid in the pipeline according to the pressure monitored by the pressure sensor, and the pressure control unit is electrically connected to the central controller. 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.

5. 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). The tangential flow filter is installed on the filter bracket (18).

6. The apparatus according to claim 5, 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).

7. The apparatus according to claim 1, characterized in that, A conductivity sensor (22) is installed inside the sixth pipeline directional clamp (11). The conductivity sensor (22) is used to monitor the conductivity of the liquid in the pipeline at the filtration end of the tangential flow filter.

8. 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; An auxiliary peristaltic pump (8) is installed on the outer wall of the housing (1). The auxiliary peristaltic pump (8) is used to replenish the biological buffer solution of the feed liquid before it enters the device.

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