Cell perfusion culture and continuous harvest apparatus for the products thereof

Abstract

The utility model relates to a kind of cell perfusion culture and its product continuous harvesting device, including bottom mounting platform, the top of bottom mounting platform is equipped with shell, main magnetic levitation centrifugal pump and pipeline directional clamp, main magnetic levitation centrifugal pump is correspondingly set with pipeline directional clamp, flowmeter is installed in pipeline directional clamp;Installation rod, first pressure regulating mechanism, first peristaltic pump, second peristaltic pump, second pressure regulating mechanism and third peristaltic pump are installed on the outside wall of shell, and installation rod is used to install hollow fiber filter body;The device further includes first pressure sensor and second pressure sensor, and central controller is installed in the inside of shell, and central controller is all with main magnetic levitation centrifugal pump, flowmeter, first pressure regulating mechanism, first peristaltic pump, second peristaltic pump, second pressure regulating mechanism, third peristaltic pump, first pressure sensor, second pressure sensor communication connection.The utility model can simplify operation, reduce artificial cost, and also can improve work efficiency.

Description

Technical Field

[0001] This utility model relates to the field of perfusion culture technology, and in particular to a device for continuous harvesting of cell perfusion culture and its products. Background Technology

[0002] In recent years, cell perfusion culture technology has become an increasingly important key process in the biopharmaceutical industry due to its ability to maintain cells in an optimal production state of high density and high activity for extended periods, and to significantly improve the production efficiency and total yield of cell products. Among these technologies, tangential flow filtration perfusion based on hollow fiber filters has become one of the preferred techniques for mammalian cell perfusion processes because it can efficiently achieve cell retention and continuous product harvesting.

[0003] However, existing tangential flow filtration irrigation methods based on hollow fiber filters have significant drawbacks. For example, during tangential flow filtration irrigation, operators typically need to temporarily assemble, set up, and debug multiple functionally independent components (such as peristaltic pumps, hollow fiber filters, and multiple sensors) on-site in the laboratory. This approach presents at least the following problems: First, the process of assembling, building, and debugging multiple components is cumbersome, time-consuming, and labor-intensive. This not only greatly increases labor costs but also significantly reduces work efficiency due to the long preparation period.

[0004] Secondly, this method is highly dependent on the experience and proficiency of the operators, which can easily lead to differences in various key physical parameters between different batches of experiments. This can result in poor process repeatability and poor comparability of process data between different batches of experiments, seriously affecting the reliability of subsequent process development data.

[0005] Therefore, there is an urgent need for a highly integrated cell perfusion culture and continuous product harvesting device that does not require temporary assembly and construction. This would simplify operation, reduce labor costs, improve work efficiency, and avoid problems such as poor process repeatability and poor comparability of process data between different batches of experiments, thereby ensuring the reliability of subsequent process development data. Utility Model Content

[0006] The purpose of this invention is to provide a cell perfusion culture and continuous product harvesting device to solve the problems existing in the prior art.

[0007] To achieve the above objectives, this utility model provides the following solution: This utility model provides a cell perfusion culture and continuous product harvesting device, which includes at least a bottom mounting platform. The top of the bottom mounting platform is equipped with a shell, a main magnetic levitation centrifugal pump and a pipeline orientation clamp. The main magnetic levitation centrifugal pump is located on one side of the shell and is correspondingly arranged with the pipeline orientation clamp. A flow meter is installed inside the pipeline orientation clamp. At least an installation rod, a first pressure regulating mechanism, a first peristaltic pump, a second peristaltic pump, a second pressure regulating mechanism, and a third peristaltic pump are installed on the outer side wall of the housing. The installation rod is used to install the hollow fiber filter body. The device further includes a first pressure sensor and a second pressure sensor, wherein the first pressure sensor is configured corresponding to the first pressure regulating mechanism, and the second pressure sensor is configured corresponding to the second pressure regulating mechanism. The housing contains a central controller, which is communicatively connected to the main magnetic levitation centrifugal pump, the flow meter, the first pressure regulating mechanism, the first peristaltic pump, the second peristaltic pump, the second pressure regulating mechanism, the third peristaltic pump, the first pressure sensor, and the second pressure sensor.

[0008] According to one embodiment of the present invention, a first mounting clip is installed on the outer side wall of the housing, and the mounting rod is installed on the outer side wall of the housing through the first mounting clip; A second mounting clip is mounted on the mounting rod, and a third mounting clip is mounted on the second mounting clip. The hollow fiber filter body can be mounted on the third mounting clip and then mounted on the mounting rod via the third mounting clip.

[0009] According to one embodiment of the present invention, the housing is a cuboid structure, and the first mounting clip and the first pressure regulating mechanism are both installed on the outer side wall of the housing near the end of the main magnetic levitation centrifugal pump, and the first mounting clip is located on one side of the first pressure regulating mechanism. Both the first peristaltic pump and the second peristaltic pump are mounted on the outer side wall of the housing adjacent to the first pressure regulating mechanism, and the first peristaltic pump is located above the second peristaltic pump; The second pressure regulating mechanism and the third peristaltic pump are both mounted on the outer side wall of the housing opposite to the first pressure regulating mechanism, and the second pressure regulating mechanism is located on one side of the third peristaltic pump.

[0010] According to one embodiment of the present invention, the pipeline orientation clamp includes a first pipeline orientation clamping block and a second pipeline orientation clamping block, wherein the second pipeline orientation clamping block is located above the first pipeline orientation clamping block, one end of the first pipeline orientation clamping block is hinged to the second pipeline orientation clamping block, and the other end of the first pipeline orientation clamping block is detachably connected to the second pipeline orientation clamping block; The bottom end of the second pipeline directional clamping block and the top end of the first pipeline directional clamping block are both provided with pipeline directional installation grooves. The two pipeline directional installation grooves can form a pipeline directional installation hole, and the flow meter is installed in the pipeline directional installation hole.

[0011] According to one embodiment of the present invention, the first pressure adjusting mechanism includes a first pressure adjusting block, a first telescopic motor, and a first pressing block, wherein: The first pressure regulating block is installed on the first telescopic motor, and the first pressing block is installed on the telescopic end of the first telescopic motor; The first pressure regulating block has a first pressure regulating pipe mounting groove and a first pressure regulating through hole that are interconnected, and the first pressure regulating pipe mounting groove and the first pressure regulating through hole are arranged perpendicular to each other. The first pressing block is located in the first pressure regulating through hole. The first pressure regulating block is installed on the outer wall of the housing, and the first telescopic motor is located inside the housing.

[0012] According to one embodiment of the present invention, the second pressure adjusting mechanism includes a second pressure adjusting block, a second telescopic motor, and a second pressing block, wherein: The second pressure regulating block is installed on the second telescopic motor, and the second pressing block is installed on the telescopic end of the second telescopic motor; The second pressure regulating block has a second pressure regulating pipe mounting groove and a second pressure regulating through hole that are interconnected, and the second pressure regulating pipe mounting groove and the second pressure regulating through hole are arranged perpendicular to each other. The second pressing block is located in the second pressure regulating through hole. The second pressure regulating block is installed on the outer wall of the housing, and the second telescopic motor is located inside the housing.

[0013] According to one embodiment of the present invention, an emergency stop button and a running status indicator are also installed on the outer side wall of the housing. The emergency stop button is electrically connected to the central controller, and the running status indicator is communicatively connected to the central controller.

[0014] According to one embodiment of the present invention, the emergency stop button and the running status indicator are both installed on the same outer side wall of the housing as the first peristaltic pump and the second peristaltic pump. The emergency stop button and the running status indicator are both located on one side of the first peristaltic pump, and the emergency stop button is located above the running status indicator.

[0015] According to one embodiment of the present invention, a U-shaped pipe rack is installed at the top of the mounting rod, and a U-shaped pipe mounting groove is provided at the top of the U-shaped pipe rack.

[0016] According to one embodiment of the present invention, both clamping blocks of the third mounting clip are equipped with anti-slip buffer layers, and the hollow fiber filter body can be installed between the two anti-slip buffer layers.

[0017] Beneficial effects This utility model has at least the following technical effects: This invention, through the configuration of a hollow fiber filter body, a main magnetic levitation centrifugal pump, a flow meter, a housing, a central processing unit inside the housing, and a first pressure regulating mechanism, a first peristaltic pump, a second peristaltic pump, a second pressure regulating mechanism, and a third peristaltic pump respectively installed on the outer wall of the housing and all communicatively connected to the central processing unit, eliminates the need for temporary assembly and setup during cell perfusion culture and continuous product harvesting, thereby simplifying operation, reducing labor costs, and improving work efficiency. It also avoids poor process repeatability and data comparability between different batches of experiments, ensuring the reliability of subsequent process development data. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in the embodiments of this utility model 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 this utility model. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0019] Figure 1 This is a schematic diagram of the overall structure of this utility model; Figure 2 for Figure 1 A magnified view of a section at point A in the middle; Figure 3 for Figure 1 A magnified view of a section at point B in the middle; Figure 4 for Figure 1 A schematic diagram of the overall structure from another angle; Figure 5 for Figure 4A schematic diagram of the overall structure from another angle; Figure 6 for Figure 5 A magnified view of a section at point C; Figure 7 This is a schematic diagram of the overall structure of the pipeline directional clamp in this utility model; Figure 8 for Figure 7 A schematic diagram of the overall structure from another angle; Figure 9 This is a schematic diagram of the overall structure of the first pressure regulating mechanism and the second pressure regulating mechanism in this utility model; Figure 10 This is a cross-sectional view of the first pressure regulating block and the second pressure regulating block in this utility model. Figure 11 This is a schematic diagram of the overall structure of the first pressing block and the second pressing block in this utility model; Figure 12 This is a schematic diagram of the overall structure of the hollow fiber filter body in this utility model.

[0020] Explanation of reference numerals in the attached figures: 1. Housing; 2. Bottom mounting platform; 3. Main magnetic levitation centrifugal pump; 4. Pipeline orientation clamp; 401. First pipeline orientation clamping block; 402. Second pipeline orientation clamping block; 5. Pipeline orientation mounting hole; 6. First pressure regulating mechanism; 601. First pressure regulating block; 701. First telescopic motor; 702. Second telescopic motor; 801. First pressing block; 802. Second pressing block; 9. First peristaltic pump; 10. Second peristaltic pump; 11. Second pressure... Force adjustment mechanism; 1101, second pressure regulating block; 12, third peristaltic pump; 13, first mounting clip; 14, mounting rod; 15, second mounting clip; 16, third mounting clip; 17, U-shaped pipe rack; 18, emergency stop button; 19, hollow fiber filter body; 1901, liquid inlet interface; 1902, return interface; 1903, lower permeable interface; 1904, upper permeable interface; 20, running status indicator light; 21, anti-slip buffer layer. Detailed Implementation

[0021] The features and exemplary embodiments of various aspects of this utility model will be described in detail below. To make the objectives, technical solutions, and advantages of this utility model clearer, the following detailed description is provided in conjunction with the accompanying drawings and specific embodiments. It should be understood that the specific embodiments described herein are only configured to explain this utility model and to exemplarily illustrate the principles of this utility model, and are not configured to limit this utility model. 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 this utility model.

[0022] 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 this utility model. In the description of this utility model, 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 this utility model according to the specific circumstances.

[0023] 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.

[0024] 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.

[0025] For those skilled in the art, this invention can be implemented without some of these specific details. The following description of the embodiments is merely intended to provide a better understanding of the invention by illustrating examples.

[0026] In the following embodiments, there may be descriptions such as "this device". Those skilled in the art should understand that "this device" refers to a cell perfusion culture and continuous harvesting device for its products provided by this utility model.

[0027] like Figures 1-12 As shown, this utility model provides a cell perfusion culture and a device for continuous harvesting of its products.

[0028] In this embodiment, the device is particularly suitable for developing large-scale cell perfusion culture and continuous harvesting of its products.

[0029] like Figure 1 , Figure 4 and Figure 5 As shown, this device includes at least a bottom mounting platform 2. At least a housing 1, a main magnetic levitation centrifugal pump 3, and a pipeline orientation clamp 4 are mounted on the top of the bottom mounting platform 2. The main magnetic levitation centrifugal pump 3 is located on one side of the housing 1 (i.e., located at...). Figure 1 The middle shell 1 is located on the left side and is correspondingly arranged with the pipeline orientation clamp 4. A flow meter (not shown in the figure) is installed inside the pipeline orientation clamp 4.

[0030] In this embodiment, as Figure 4 As shown, the bottom mounting platform 2 can be a flat cuboid structure or a roughly flat cuboid structure, without any particular limitation.

[0031] In this embodiment, as Figure 1 As shown, the shell 1 can be a cuboid structure or approximately a cuboid structure, and no particular limitation is made here.

[0032] In this embodiment, the main magnetic levitation centrifugal pump 3 and the pipeline orientation clamp 4 can be located on the same side of the housing 1 at the same time, that is, the main magnetic levitation centrifugal pump 3 and the pipeline orientation clamp 4 are arranged correspondingly to each other.

[0033] In this embodiment, the main magnetic levitation centrifugal pump 3 and the flow meter are both existing technologies known in the art, and will not be described in detail here.

[0034] In this embodiment, the bottom mounting platform 2 on the side where the main magnetic levitation centrifugal pump 3 and the pipeline orientation clamp 4 are installed can be integrally formed with the bottom mounting platform 2 on the side where the housing 1 is installed, or it can be a detachable structure, thus adapting to a variety of different working conditions.

[0035] like Figure 1 , Figure 4 and Figure 5As shown, at least a mounting rod 14, a first pressure regulating mechanism 6, a first peristaltic pump 9, a second peristaltic pump 10, a second pressure regulating mechanism 11, and a third peristaltic pump 12 are mounted on the outer side wall of the housing 1. The mounting rod 14 is used to mount the hollow fiber filter body 19 (an exemplary overall structure of the hollow fiber filter body 19 can be found in [reference needed]). Figure 12 ).

[0036] It should be understood that the hollow fiber filter body 19 is prior art known in the art (i.e., hollow fiber filters known in the art), for example, it can be the commercially available "Whaleintelli hollow fiber filter assembly," which will not be elaborated upon here. Among them, such as... Figure 12 As shown, the hollow fiber filter body 19 can be generally cylindrical in shape, and includes at least a hollow fiber filter housing, an inlet port 1901, a return port 1902, a lower permeable port 1903, an upper permeable port 1904, and a hollow fiber filter element (not shown in the figure but known in the art) located inside the hollow fiber filter housing. The inlet port 1901 can be used to receive a liquid containing cells and their products. The hollow fiber filter element can perform tangential flow filtration of the liquid containing cells and their products, allowing cell products in the liquid to flow out through the lower permeable port 1903 and the upper permeable port 1904, while simultaneously allowing cells in the liquid to flow out through the return port 1902. The above descriptions are all prior art known in the art and will not be elaborated further.

[0037] Furthermore, in order to improve the thermal insulation of the hollow fiber filter body 19, a layer of thermal insulation sleeve (not shown in the figure) known in the art is wrapped around the outside of the hollow fiber filter body 19.

[0038] In this embodiment, the mounting rod 14 can be a cylindrical structure or a roughly cylindrical structure, and there is no particular limitation.

[0039] In this embodiment, the first peristaltic pump 9, the second peristaltic pump 10, and the third peristaltic pump 12 are all prior art known in the art (i.e., peristaltic pumps known in the art), and will not be described in detail here.

[0040] Specifically, such as Figure 1 and Figure 2 As shown, a first mounting clip 13 is installed on the outer side wall of the housing, that is, the mounting rod 14 will be installed on the outer side wall of the housing 1 through the first mounting clip 13.

[0041] In this embodiment, as Figure 1 As shown, the first mounting clip 13 can be T-shaped or roughly T-shaped. For example, Figure 2As shown, the two clamping blocks of the first mounting clamp 13 can be detachably connected to each other by the first hand-tightened bolt to securely clamp the mounting rod 14, which is not particularly limited here.

[0042] like Figure 3 and Figure 6 As shown, a second mounting clip 15 is mounted on the mounting rod 14 (which can also be considered as being on the side wall of the mounting rod 14), and a third mounting clip 16 is mounted on the second mounting clip 15. The hollow fiber filter body 19 can be mounted on the third mounting clip 16 (i.e., mounted between the two clips of the third mounting clip 16), and is mounted on the mounting rod 14 via the third mounting clip 16. In other words, the hollow fiber filter body 19 is mounted on the mounting rod 14 via the third mounting clip 16.

[0043] In this embodiment, as Figure 3 and Figure 6 As shown, the second mounting clip 15 and the third mounting clip 16 can be integrally formed, and no special limitation is made here.

[0044] In this embodiment, as Figure 1 As shown, the second mounting clip 15 and the third mounting clip 16 are both located above the first mounting clip 13.

[0045] In this embodiment, as Figure 3 and Figure 6 As shown, the two clamping blocks of the second mounting clip 15 can be detachably connected to each other via the second hand-tightened bolt to securely clamp the outer wall of the mounting rod 14, which is not particularly limited here. Similarly, the two clamping blocks of the third mounting clip 16 can be detachably connected to each other via the third hand-tightened bolt to securely clamp the hollow fiber filter body 19, which is not particularly limited here.

[0046] More specifically, such as Figure 1 , Figure 4 and Figure 5 As shown, the first mounting clip 13 and the first pressure regulating mechanism 6 can both be mounted on the outer wall of the housing 1 near the end of the main magnetic levitation centrifugal pump 3 (i.e., Figure 1 (on the left side wall of the middle housing 1), and the first mounting clip 13 will be located on one side of the first pressure regulating mechanism 6.

[0047] In this embodiment, as Figure 1 As shown, the first mounting clip 13 can also be located between the main magnetic levitation centrifugal pump 3 and the pipeline orientation clip 4.

[0048] In this embodiment, as Figure 1 , Figure 4 and Figure 5As shown, the first peristaltic pump 9 and the second peristaltic pump 10 can both be installed on the outer side wall of the housing 1 adjacent to the first pressure regulating mechanism 6 (that is, the first peristaltic pump 9 and the second peristaltic pump 10 can both be installed on the outer side wall of the housing 1 adjacent to the first mounting clip 13), and the first peristaltic pump 9 can be located directly above the second peristaltic pump 10.

[0049] In this embodiment, as Figure 4 and Figure 5 As shown, the second pressure regulating mechanism 11 and the third peristaltic pump 12 can both be installed on the outer side wall of the housing 1 opposite to the first pressure regulating mechanism 6 (that is, the second pressure regulating mechanism 11 and the third peristaltic pump 12 can both be installed on the outer side wall of the housing 1 opposite to the first mounting clip 13), and the second pressure regulating mechanism 11 can be located on one side of the third peristaltic pump 12.

[0050] It should be understood that since the second pressure regulating mechanism 11 and the third peristaltic pump 12 can both be installed on the outer side wall of the housing 1 opposite to the first pressure regulating mechanism 6, that is, the second pressure regulating mechanism 11 and the third peristaltic pump 12 can both be installed on the outer side wall of the housing 1 adjacent to the first peristaltic pump 9 (or the second peristaltic pump 10).

[0051] According to one embodiment of the present invention, the device further includes a first pressure sensor and a second pressure sensor (both not shown in the figure). The first pressure sensor is correspondingly disposed with the first pressure regulating mechanism 6, and the second pressure sensor is correspondingly disposed with the second pressure regulating mechanism 11.

[0052] In this embodiment, the first pressure sensor and the second pressure sensor are capable of real-time monitoring of the pressure of cells and their product liquid in the pipeline (not shown in the figure) that transports cells and / or their product liquid.

[0053] In this embodiment, both the first pressure sensor and the second pressure sensor are existing technologies known in the art (i.e., pressure sensors known in the art), and will not be described in detail here.

[0054] According to one embodiment of this utility model, at least a central controller (not shown in the figure) is installed inside the housing 1. The central controller is communicatively connected to the main magnetic levitation centrifugal pump 3, the flow meter, the first pressure regulating mechanism 6, the first peristaltic pump 9, the second peristaltic pump 10, the second pressure regulating mechanism 11, the third peristaltic pump 12, the first pressure sensor, and the second pressure sensor, thereby enabling the overall adjustment and control of the above-mentioned components.

[0055] In this embodiment, the central controller is a prior art known in the art; for example, it can be a Raspberry Pi PLC central controller, which is known in the art, and is not particularly limited here. Furthermore, how the central controller communicates with the aforementioned components is also a prior art known in the art, and will not be elaborated upon here.

[0056] According to one embodiment of the present invention, such as Figure 5 As shown, at least a power connection port and a device start switch, which are known in the art, are also provided on the outer side wall of the housing 1, so as to realize the power supply and start-up control of the device. These will not be described in detail here.

[0057] According to one embodiment of the present invention, such as Figure 7 and Figure 8 As shown, specifically, the pipe orientation clamp 4 includes at least a first pipe orientation clamping block 401 and a second pipe orientation clamping block 402, with the second pipe orientation clamping block 402 located above the first pipe orientation clamping block 401. One end of the first pipe orientation clamping block 401 is hinged to one end of the second pipe orientation clamping block 402 (the hinge can be used to connect them), and the other end of the first pipe orientation clamping block 401 is detachably connected to the other end of the second pipe orientation clamping block 402, meaning the second pipe orientation clamping block 402 can cover the top of the first pipe orientation clamping block 401.

[0058] In this embodiment, as Figure 7 and Figure 8 As shown, the first pipeline orientation clamping block 401 and the second pipeline orientation clamping block 402 can both be cuboid structures with the same cross-sectional shape and area, and no special limitation is made here.

[0059] In this embodiment, as Figure 7 and Figure 8 As shown, both the bottom end of the second pipe orientation clamping block 402 and the top end of the first pipe orientation clamping block 401 are provided with pipe orientation mounting grooves. When the first pipe orientation clamping block 401 and the second pipe orientation clamping block 402 are detachably connected (i.e., when the second pipe orientation clamping block 402 covers the top end of the first pipe orientation clamping block 401), the two pipe orientation mounting grooves can form a pipe orientation mounting hole 5. The flow meter can be installed in the pipe orientation mounting hole 5, that is, the flow meter can be installed in any one of the pipe orientation mounting grooves, without any particular limitation.

[0060] In this embodiment, the pipeline orientation mounting hole 5 can be used to install pipelines for transporting cells and / or their product liquids (not shown in the figure). At the same time, the flow meter in the pipeline orientation mounting hole 5 (that is, in any pipeline orientation mounting groove) can monitor the flow rate of cells and their product liquids in the pipelines for transporting cells and / or their product liquids (not shown in the figure) in real time.

[0061] In this embodiment, as Figure 7 and Figure 8 As shown, the pipe directional installation groove can be a square groove structure, so the pipe directional installation hole 5 formed by it will be a cuboid structure.

[0062] In this embodiment, as Figure 7 As shown, the first pipeline orientation clamping block 401 can be detachably connected to the second pipeline orientation clamping block 402 via the fourth hand-tightened bolt, which is not particularly limited here.

[0063] According to one embodiment of the present invention, such as Figure 9 , Figure 10 and Figure 11 As shown, specifically, the first pressure adjusting mechanism 6 includes at least a first pressure adjusting block 601, a first telescopic motor 701, and a first pressing block 801, wherein: The first pressure adjusting block 601 is mounted on the first telescopic motor 701 (that is, the first pressure adjusting block 601 can be mounted on the first telescopic motor 701 by bolt connection methods known in the art). Figure 9 (on the left side), while the first pressing block 801 is installed on the telescopic end of the first telescopic motor 701.

[0064] In this embodiment, the first telescopic motor 701 is prior art known in the art (i.e., telescopic motors known in the art), and is not particularly limited herein.

[0065] like Figure 9 and Figure 10 As shown, the first pressure regulating block 601 has a first pressure regulating pipe mounting groove and a first pressure regulating through hole that are interconnected, and the first pressure regulating pipe mounting groove and the first pressure regulating through hole are arranged perpendicularly to each other. When the telescopic end of the first telescopic motor 701 is not extended, the first pressing block 801 will be entirely located inside the first pressure regulating through hole.

[0066] In this embodiment, as Figure 9 and Figure 10As shown, the end of the first pressing block 801 away from the first telescopic motor 701 can have an angled structure. When the telescopic end of the first telescopic motor 701 extends, the first pressing block 801 can enter the interior of the first pressure regulating pipeline mounting groove, thereby regulating the pressure of the pipeline transporting cells and / or their product liquid.

[0067] In this embodiment, as Figure 1 As shown, the first pressure adjusting block 601 can be installed on the outer wall of the housing 1 by bolt connection as known in the art, that is, the first pressure adjusting block 601 will be located entirely outside the housing 1, while the first telescopic motor 701 will be located entirely inside the housing 1.

[0068] According to one embodiment of the present invention, such as Figure 9 , Figure 10 and Figure 11 As shown, similarly, the second pressure regulating mechanism 11 includes at least a second pressure regulating block 1101, a second telescopic motor 702, and a second pressing block 802, wherein: The second pressure adjusting block 1101 is mounted on the second telescopic motor 702 (that is, the second pressure adjusting block 1101 can be mounted on the second telescopic motor 702 by bolt connection methods known in the art). Figure 9 (one end on the left), while the second pressing block 802 is installed on the telescopic end of the second telescopic motor 702.

[0069] In this embodiment, the second telescopic motor 702 is prior art known in the art (i.e., telescopic motors known in the art), and is not particularly limited herein.

[0070] like Figure 9 and Figure 10 As shown, the second pressure regulating block 1101 has a second pressure regulating pipe mounting groove and a second pressure regulating through hole that are interconnected, and the second pressure regulating pipe mounting groove and the second pressure regulating through hole are arranged perpendicularly to each other. When the telescopic end of the second telescopic motor 702 is not extended, the second pressing block 802 will be entirely located within the second pressure regulating through hole.

[0071] In this embodiment, as Figure 9 and Figure 10 As shown, the end of the second pressing block 802 away from the second telescopic motor 702 can have an angled structure. When the telescopic end of the second telescopic motor 702 extends, the second pressing block 802 can enter the interior of the second pressure regulating pipe mounting groove.

[0072] In this embodiment, as Figure 4 and Figure 5As shown, the second pressure regulating block 1101 can be installed on the outer wall of the housing 1 by bolt connection as known in the art, that is, the second pressure regulating block 1101 will be located entirely outside the housing 1, while the second telescopic motor 702 will be located entirely inside the housing 1.

[0073] It should be understood that, since the first pressure regulating mechanism 6 and the second pressure regulating mechanism 11 have the same overall structure, therefore... Figure 9 , Figure 10 and Figure 11 This allows one to understand the overall structure of both the first pressure regulating mechanism 6 and the second pressure regulating mechanism 11.

[0074] Furthermore, such as Figure 1 and Figure 4 As shown, an emergency stop button 18 and a running status indicator light 20 are also installed on the outer wall of the housing 1. The emergency stop button 18 is electrically connected to the central controller, and the running status indicator light 20 is communicatively connected to the central controller.

[0075] In this embodiment, the emergency stop button 18 and the running status indicator 20 are both existing technologies known in the art. How the emergency stop button 18 is electrically connected to the central controller and how the running status indicator 20 is communicatively connected to the central controller are also existing technologies known in the art, and will not be described in detail here.

[0076] The emergency stop button 18 allows the device to stop immediately in case of abnormal operation. The operating status indicator light 20 displays the device's operating status. For example, the indicator light 20 will illuminate green when the device is operating normally, and red when the device is operating abnormally.

[0077] In this embodiment, specifically, as Figure 1 and Figure 4 As shown, the emergency stop button 18 and the running status indicator light 20 can both be installed on the same outer wall of the housing 1 as the first peristaltic pump 9 and the second peristaltic pump 10 (that is, on the outer wall of the housing 1 adjacent to the first pressure regulating mechanism 6). The emergency stop button 18 and the running status indicator light 20 can both be located on one side of the first peristaltic pump 9, and the emergency stop button 18 can be located directly above the running status indicator light 20.

[0078] In this embodiment, as Figure 1 As shown, the emergency stop button 18 can be roughly circular in shape, while the running status indicator light 20 can be elongated in shape.

[0079] According to one embodiment of the present invention, such as Figure 1As shown, a U-shaped pipe rack 17 is installed at the top of the mounting rod 14, and a U-shaped pipe mounting groove is provided at the top of the U-shaped pipe rack 17. The U-shaped pipe mounting groove can be used to install pipes for transporting cells and / or their product liquids (not shown in the figure), so as to improve the stability of the pipes for transporting cells and / or their product liquids during operation.

[0080] According to one embodiment of the present invention, such as Figure 3 and Figure 6 As shown, anti-slip buffer layers 21 are installed on both clamps of the third mounting clip 16, and the hollow fiber filter body 19 can be installed between the two anti-slip buffer layers 21.

[0081] The anti-slip buffer layer 21 improves the stability of the third mounting clip 16 in holding the hollow fiber filter body 19, and also prevents the hollow fiber filter body 19 from being damaged due to excessive clamping force of the third mounting clip 16. The anti-slip buffer layer 21 is a prior art known in the art; for example, it can be made of soft silicone material known in the art, and is not specifically limited here.

[0082] The most preferred operating process of this device will be briefly described below with reference to the above embodiments: First, before performing cell perfusion culture and continuous harvesting of its products, the tubing for transporting cells and / or their product solution needs to be connected to this device. The most preferred connection method is as follows: like Figure 12 As shown, since the hollow fiber filter body 19 has an inlet port 1901, a return port 1902, a lower permeation port 1903, and an upper permeation port 1904, the pipeline for transporting cells and / or their product liquid can be regarded as four independent pipelines. For ease of description, these four independent pipelines are named the inlet pipeline, the return pipeline, the lower permeation pipeline, and the upper permeation pipeline, respectively (none of which are shown in the figure).

[0083] The inlet pipe is installed on the main magnetic levitation centrifugal pump 3 to enable the main magnetic levitation centrifugal pump 3 to provide pumping force to the cells and / or their product liquid in the inlet pipe. Simultaneously, the inlet pipe is installed within the pipe orientation mounting hole 5 in the pipe orientation clamp 4, and a flow meter within the pipe orientation mounting hole 5 is installed on the inlet pipe to monitor the flow rate and velocity of the cells and / or their product liquid in the inlet pipe (in this embodiment, the pipe orientation clamp 4 is located upstream of the main magnetic levitation centrifugal pump 3). One end of the inlet pipe is connected to the inlet port 1901 of the hollow fiber filter body 19, while the other end is connected to a bioreactor known in the art (not shown in the figure).

[0084] The return end pipeline can be regarded as having a structure with one main return end pipeline and two branch return end pipelines. The main return end pipeline and the two branch return end pipelines can be connected and interconnected with each other through a tee pipe (not shown in the figure) known in the art (for easy distinction, this tee pipe is named the first tee pipe). The main reflux pipe is connected to the reflux port 1902 of the hollow fiber filter body 19 at the end furthest from the first tee pipe. One branch reflux pipe is installed in the first pressure regulating mechanism 6, and a first pressure sensor is installed on the branch reflux pipe to monitor and regulate the pressure of the cells and / or their product liquid in the branch reflux pipe. The end of the branch reflux pipe furthest from the first tee pipe is connected to the bioreactor. The other branch reflux pipe is installed on the first peristaltic pump 9 to enable the first peristaltic pump 9 to provide pumping force to the cells and / or their product liquid in the branch reflux pipe. The end of the branch reflux pipe furthest from the first tee pipe is connected to a cell discharge collection container (not shown in the figure) known in the art.

[0085] One end of the lower permeable end pipe is connected to and connected to the lower permeable end interface 1903 of the hollow fiber filter body 19, and one end of the upper permeable end pipe is connected to and connected to the upper permeable end interface 1904 of the hollow fiber filter body 19. The other end of the lower permeable end pipe can be connected to and connected to the upper permeable end pipe through a tee pipe (not shown in the figure) known in the art (for ease of distinction, this tee pipe is named the second tee pipe).

[0086] The upper permeation end pipe is installed on the third peristaltic pump 12 and the second pressure regulating mechanism 11 (in this embodiment, the third peristaltic pump 12 is located upstream of the second pressure regulating mechanism 11) to monitor and regulate the pressure of the cells and / or their product liquid in the upper permeation end pipe, and also to provide pumping force to the cells and / or their product liquid in the upper permeation end pipe. The other end of the upper permeation end pipe (i.e., the end of the upper permeation end pipe away from the second tee pipe) is connected and communicated with a sampling container known in the art (not shown in the figure). A permeation end branch pipe can be connected and communicated on the upper permeation end pipe between the third peristaltic pump 12 and the second pressure regulating mechanism 11 via a tee pipe known in the art (not shown in the figure) (for ease of distinction, this tee pipe is named the third tee pipe). The end of this permeation end branch pipe away from the third tee pipe is connected and communicated with a harvesting container known in the art (not shown in the figure).

[0087] Then, after the above steps, the process of connecting the tubing for transporting cells and / or their product solutions to this device is completed, thereby enabling cell perfusion culture and continuous harvesting of its products, as detailed below: The main magnetic levitation centrifugal pump 3 pumps the cells and their product liquid from the bioreactor into the inlet port 1901 of the hollow fiber filter body 19 through the inlet pipe. This allows the cells and their product liquid to be pumped into the hollow fiber filter element of the hollow fiber filter body 19 for tangential flow filtration. After tangential flow filtration, the cell products in the cell and product liquid flow out from the lower permeation port 1903 and the upper permeation port 1904, and are then introduced into the harvesting container through the lower and upper permeation pipes to complete the harvesting of the cell product liquid. The third peristaltic pump 12 provides pumping force for the cell product liquid in the upper permeation pipe. Simultaneously, the second pressure regulating mechanism 11 controls the opening and closing of the upper permeation pipe downstream of the third peristaltic pump 12, allowing the cell product liquid to be introduced into the sampling container as needed to complete the sampling of the cell product liquid.

[0088] After tangential flow filtration, the cells and their product solution flow out from the reflux port 1902. The cell solution flowing out from the reflux port 1902 is then returned to the bioreactor through one of the branch reflux pipes, thus completing the cell reflux. Simultaneously, a portion of the cell solution flowing out from the reflux port 1902 is also pumped into the cell discharge collection container through another branch reflux pipe and the pumping force of the first peristaltic pump 9, thereby maintaining a constant cell density within the bioreactor.

[0089] In the above scheme, both the bottom of the bioreactor and the bottom of the harvesting container can be equipped with weighing scales known in the art, thereby enabling real-time monitoring of the real-time weight of the bioreactor and the real-time weight of the harvesting container.

[0090] In the above scheme, an auxiliary pump (not shown in the figure), known in the art, can also be installed on the lower permeation end pipeline to provide additional pumping force to the cell product liquid in the lower permeation end pipeline. The auxiliary pump can be a magnetic levitation centrifugal pump or a peristaltic pump, both known in the art, but preferably a magnetic levitation centrifugal pump. For ease of description, this auxiliary pump is named an auxiliary magnetic levitation centrifugal pump. The auxiliary magnetic levitation centrifugal pump can be installed on one side of the housing 1 or on the top of the housing 1; no particular limitation is made here.

[0091] It should be understood that both the main magnetic levitation centrifugal pump 3 and the auxiliary magnetic levitation centrifugal pump are magnetic levitation centrifugal pumps, and therefore both have the characteristic of low shear force, which can reduce damage to cells.

[0092] Furthermore, since the lower permeable end pipe and the upper permeable end pipe can be connected and interconnected through the second three-way pipe, the auxiliary magnetic levitation centrifugal pump can also pump the cell product liquid in the upper permeable end interface 1904 into the lower permeable end interface 1903, thereby forming a circulation of the cell product liquid from the upper permeable end interface 1904 to the lower permeable end interface 1903, which can balance the pressure drop generated on the hollow fiber filter element in the hollow fiber filter body 19.

[0093] Meanwhile, when the cell product liquid circulates from the upper permeation port 1904 to the lower permeation port 1903, the auxiliary magnetic levitation centrifugal pump can also make the internal pressure of the cell product liquid in the direction from the upper permeation port 1904 to the lower permeation port 1903 decrease linearly, so that the internal pressure of the cell product liquid at the middle position of the lower permeation port is the highest while the internal pressure of the cell product liquid at both ends is low. This can prevent the cell product liquid from flowing back and ensure the normal operation of tangential flow filtration.

[0094] In the above scheme, although some of the cell feed liquid flowing out from the reflux end interface 1902 can be discharged into the cell discharge collection container, thereby maintaining a constant cell density in the bioreactor, this scheme is only applicable to preventing the cell density in the bioreactor from exceeding the constant density. To prevent the cell density in the bioreactor from falling below the constant density, in this embodiment, a cell replenishment pipeline (not shown in the figure) can be installed on the second peristaltic pump 10. One end of this cell replenishment pipeline is connected to a fresh cell culture medium container (not shown in the figure), which is known in the art, while the other end is connected to the aforementioned bioreactor. When the cell density in the bioreactor is lower than the constant density, the pumping force of the second peristaltic pump 10 can be used to introduce fresh cells from the fresh cell culture medium container into the bioreactor through this cell replenishment pipeline, thereby replenishing the cells in the bioreactor and maintaining a constant cell density in the bioreactor.

[0095] In the above scheme, because the internal pressure of the hollow fiber filter element within the hollow fiber filter body 19 is higher than the external pressure, contaminants such as cell debris will gradually accumulate on the hollow fiber filter element, thus affecting the normal operation of tangential flow filtration. Therefore, after a period of cell perfusion culture and continuous harvesting of its products, the third peristaltic pump 12 can be reversed for a short period of time. This creates a backlash force on the hollow fiber filter element, flushing out contaminants such as cell debris. This prevents the accumulation of contaminants such as cell debris on the hollow fiber filter element, ensuring the normal operation of tangential flow filtration.

[0096] It should be understood that the above-described embodiments or examples of this utility model can be combined with each other and have corresponding technical effects.

[0097] The above are merely preferred embodiments of the present utility model and are not intended to limit the present utility model. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present utility model shall be included within the protection scope of the present utility model.

Claims

1. A device for continuous harvesting of cell perfusion culture and its products, characterized in that, It includes at least a bottom mounting platform (2), on the top of which a housing (1), a main magnetic levitation centrifugal pump (3) and a pipeline orientation clamp (4) are mounted. The main magnetic levitation centrifugal pump (3) is located on one side of the housing (1) and is correspondingly arranged with the pipeline orientation clamp (4). A flow meter is installed inside the pipeline orientation clamp (4). At least one mounting rod (14), a first pressure regulating mechanism (6), a first peristaltic pump (9), a second peristaltic pump (10), a second pressure regulating mechanism (11) and a third peristaltic pump (12) are installed on the outer side wall of the housing (1). The mounting rod (14) is used to install the hollow fiber filter body (19). The device further includes a first pressure sensor and a second pressure sensor, wherein the first pressure sensor is configured corresponding to the first pressure regulating mechanism (6), and the second pressure sensor is configured corresponding to the second pressure regulating mechanism (11); The housing (1) is equipped with a central controller, which is communicatively connected to the main magnetic levitation centrifugal pump (3), the flow meter, the first pressure regulating mechanism (6), the first peristaltic pump (9), the second peristaltic pump (10), the second pressure regulating mechanism (11), the third peristaltic pump (12), the first pressure sensor, and the second pressure sensor.

2. The cell perfusion culture and continuous product harvesting device according to claim 1, characterized in that, A first mounting clip (13) is installed on the outer side wall of the housing (1), and the mounting rod (14) is installed on the outer side wall of the housing (1) through the first mounting clip (13); A second mounting clip (15) is mounted on the mounting rod (14), and a third mounting clip (16) is mounted on the second mounting clip (15). The hollow fiber filter body (19) can be mounted on the third mounting clip (16) and mounted on the mounting rod (14) through the third mounting clip (16).

3. The cell perfusion culture and continuous product harvesting device according to claim 2, characterized in that, The housing (1) is a cuboid structure. The first mounting clip (13) and the first pressure regulating mechanism (6) are both installed on the outer side wall of the housing (1) near the end of the main magnetic levitation centrifugal pump (3), and the first mounting clip (13) is located on one side of the first pressure regulating mechanism (6). The first peristaltic pump (9) and the second peristaltic pump (10) are both installed on the outer side wall of the housing (1) adjacent to the first pressure regulating mechanism (6), and the first peristaltic pump (9) is located above the second peristaltic pump (10); The second pressure regulating mechanism (11) and the third peristaltic pump (12) are both installed on the outer side wall of the housing (1) opposite to the first pressure regulating mechanism (6), and the second pressure regulating mechanism (11) is located on one side of the third peristaltic pump (12).

4. The cell perfusion culture and continuous product harvesting apparatus according to claim 1, characterized in that, The pipeline orientation clamp (4) includes a first pipeline orientation clamping block (401) and a second pipeline orientation clamping block (402), and the second pipeline orientation clamping block (402) is located above the first pipeline orientation clamping block (401). One end of the first pipeline orientation clamping block (401) is hinged to the second pipeline orientation clamping block (402), and the other end of the first pipeline orientation clamping block (401) is detachably connected to the second pipeline orientation clamping block (402). The bottom end of the second pipeline orientation clamping block (402) and the top end of the first pipeline orientation clamping block (401) are both provided with pipeline orientation installation grooves. The two pipeline orientation installation grooves can form a pipeline orientation installation hole (5), and the flow meter is installed in the pipeline orientation installation hole (5).

5. The cell perfusion culture and continuous product harvesting apparatus according to claim 1, characterized in that, The first pressure regulating mechanism (6) includes a first pressure regulating block (601), a first telescopic motor (701), and a first pressing block (801), wherein: The first pressure regulating block (601) is installed on the first telescopic motor (701), and the first pressing block (801) is installed on the telescopic end of the first telescopic motor (701); The first pressure regulating block (601) has a first pressure regulating pipeline mounting groove and a first pressure regulating through hole that are interconnected, and the first pressure regulating pipeline mounting groove and the first pressure regulating through hole are arranged perpendicular to each other. The first pressing block (801) is located in the first pressure regulating through hole. The first pressure regulating block (601) is installed on the outer wall of the housing (1), and the first telescopic motor (701) is located inside the housing (1).

6. The cell perfusion culture and continuous product harvesting apparatus according to claim 1, characterized in that, The second pressure regulating mechanism (11) includes a second pressure regulating block (1101), a second telescopic motor (702), and a second pressing block (802), wherein: The second pressure regulating block (1101) is installed on the second telescopic motor (702), and the second pressing block (802) is installed on the telescopic end of the second telescopic motor (702); The second pressure regulating block (1101) has a second pressure regulating pipeline mounting groove and a second pressure regulating through hole that are interconnected, and the second pressure regulating pipeline mounting groove and the second pressure regulating through hole are arranged perpendicular to each other. The second pressing block (802) is located in the second pressure regulating through hole. The second pressure regulating block (1101) is installed on the outer wall of the housing (1), and the second telescopic motor (702) is located inside the housing (1).

7. The cell perfusion culture and continuous product harvesting apparatus according to claim 1, characterized in that, An emergency stop button (18) and a running status indicator (20) are also installed on the outer side wall of the housing (1). The emergency stop button (18) is electrically connected to the central controller, and the running status indicator (20) is communicatively connected to the central controller.

8. The cell perfusion culture and continuous product harvesting apparatus according to claim 7, characterized in that, The emergency stop button (18) and the running status indicator (20) are both installed on the same outer side wall of the housing (1) as the first peristaltic pump (9) and the second peristaltic pump (10). The emergency stop button (18) and the running status indicator (20) are both located on one side of the first peristaltic pump (9), and the emergency stop button (18) is located above the running status indicator (20).

9. The cell perfusion culture and continuous product harvesting apparatus according to claim 1, characterized in that, The top of the mounting rod (14) is equipped with a U-shaped pipe rack (17), and the top of the U-shaped pipe rack (17) is provided with a U-shaped pipe mounting groove.

10. The cell perfusion culture and continuous product harvesting apparatus according to claim 2, characterized in that, The third mounting clip (16) has anti-slip buffer layers (21) installed on both clips, and the hollow fiber filter body (19) can be installed between the two anti-slip buffer layers (21).

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