Chromatographic purification device

Abstract

The utility model relates to the technical field of biochemical engineering, and provides a chromatographic purification device, which comprises an intersection main body, a chromatographic column, a chromatographic column and a purification device, the first functional assembly comprises a collecting unit, a liquid inlet unit, a waste liquid unit and a liquid supply unit which are respectively communicated with the first to fourth interfaces; the second functional assembly comprises a chromatography unit and a power unit, the chromatography unit comprises a chromatography passage and a chromatography main body arranged on the chromatography passage, the two ends of the chromatography passage are correspondingly communicated with the fifth connector and the sixth connector respectively, and the power unit is communicated with the intersection main body; and the on-off valve group at least comprises a first on-off valve to a sixth on-off valve and is arranged in a range from the interfaces with the same serial number to the corresponding units. The arrangement structure is high in utilization efficiency, convenient to overhaul and maintain, simple in structure and low in cost, the possibility of pipeline and material pollution is reduced, and meanwhile the regulation and control difficulty is effectively reduced.

Description

Technical Field

[0001] This utility model relates to the field of biochemical engineering technology, specifically to a chromatography purification device. Background Technology

[0002] Proteins and nucleic acids are important research objects in the research field, as well as important materials and products in our social life. Their separation and purification are very important operations in scientific research and industrial production.

[0003] Chromatography, a common method for separation and purification, utilizes the principle that samples are distributed differently in the mobile phase and the stationary phase. Due to the different physicochemical properties of the samples, when the sample solution flows through the stationary phase, different samples will bind to the stationary phase with different intensities of force, thereby achieving the separation of different sample objects.

[0004] Taking proteins as an example, in order to extract proteins, the solution containing the target protein needs to be purified to remove impurities. The purification process mainly involves multiple steps such as equilibrating the chromatography column, passing the sample through the chromatography purification column, gradient elution of impurities and target proteins, and collection. In the above purification process, a circulation pathway is formed between the purification column and multiple devices.

[0005] Existing chromatography purification equipment improves efficiency and reduces sample confusion or cross-contamination by incorporating driving components such as constant flow pumps and multi-channel valves to switch the liquid path upstream and downstream of the chromatography column, or by using multiple parallel chromatography pathways.

[0006] However, parallel chromatography pathways typically share only a few structures, such as the collection structure, resulting in low structural utilization efficiency and high costs. Multi-channel valve-type chromatography purification equipment uses rotary valves to switch multiple pathways upstream of the chromatography column, but these valves have complex core structures, are difficult to maintain, and the rotary switching method still carries the risk of material and pipeline contamination. Another part uses different solenoid valves to switch multiple pathways upstream and downstream of the chromatography column, making operation, installation, and maintenance relatively complex. Furthermore, the difficulty in controlling different valves makes it difficult to set up chromatography circulation loops. For example, patent document CN111574584A discloses a fully automated protein purification system and its application. This chromatography purification device connects to the chromatography apparatus via multiple valves and containers, which is not only cumbersome to operate, but the peristaltic pump cannot form selectable circulation pathways between different containers, and many pipelines are non-powered, raising doubts about its automation capabilities. Utility Model Content

[0007] In view of this, the present invention provides a chromatography purification device to solve the problems of low structural utilization efficiency, high cost, complex valve core structure, difficult maintenance and risk of contamination, or complex installation and maintenance making it difficult to set up chromatography circulation loops in the prior art.

[0008] This utility model provides a chromatography purification device, comprising: a confluence body, including a main channel and an interface component communicating with the main channel, wherein the interface component includes at least a first interface, a second interface, a third interface, a fourth interface, a fifth interface and a sixth interface;

[0009] The first functional component includes a collection unit, a liquid inlet unit, a waste liquid unit, and a liquid supply unit. The collection unit is connected to the confluence body through the first interface, the liquid inlet unit is connected to the confluence body through the second interface, the waste liquid unit is connected to the confluence body through the third interface, and the liquid supply unit is connected to the confluence body through the fourth interface.

[0010] The second functional component includes a chromatography unit and a power unit. The chromatography unit includes a chromatography path and a chromatography body disposed on the chromatography path. The two ends of the chromatography path are respectively connected to the fifth interface and the sixth interface. The power unit is connected to the confluence body. The fluid is adapted to make directional movement in the chromatography path under the action of the power unit.

[0011] An on / off valve assembly includes at least a first on / off valve, a second on / off valve, a third on / off valve, a fourth on / off valve, a fifth on / off valve, and a sixth on / off valve; the first on / off valve is disposed within the range from the first interface to the collection unit, and is adapted to regulate the on / off connection between the collection unit and the first interface; the second on / off valve is disposed within the range from the second interface to the liquid inlet unit, and is adapted to regulate the on / off connection between the liquid inlet unit and the second interface; the third on / off valve is disposed within the range from the third interface to the waste liquid unit, and is adapted to regulate the on / off connection between the waste liquid unit and the third interface; the fourth on / off valve is disposed within the range from the fourth interface to the liquid supply unit, and is adapted to regulate the on / off connection between the liquid supply unit and the fourth interface; the fifth on / off valve is disposed within the range from the fifth interface to the chromatography body, and is adapted to regulate the on / off connection between the chromatography body and the fifth interface; the sixth on / off valve is disposed within the range from the sixth interface to the chromatography body, and is adapted to regulate the on / off connection between the chromatography body and the sixth interface.

[0012] In one optional implementation, the interface assembly further includes a seventh interface and an eighth interface, and the on / off valve group further includes a seventh on / off valve and an eighth on / off valve.

[0013] The power unit includes: a power path and a drive body;

[0014] The power passage is connected to the seventh interface and the eighth interface at both ends, respectively. The seventh on / off valve is located within the range from the seventh interface to the drive body and is suitable for adjusting the on / off connection between the seventh interface and the drive body. The eighth on / off valve is located within the range from the eighth interface to the drive body and is suitable for adjusting the on / off connection between the eighth interface and the drive body. The drive body is located on the power passage.

[0015] In one optional embodiment, the drive body is provided with a first check valve and a second check valve upstream and downstream of the power passage, respectively, and the eighth interface is located upstream of the seventh interface. The drive body has a driving state that provides positive pressure to drive the fluid between the two check valves to flow out of the second check valve, and a suction state that provides negative pressure to drive the fluid upstream of the first check valve to flow between the two check valves.

[0016] In one optional embodiment, the eighth on-off valve is configured as a single-pole double-throw valve, comprising a common end, a first regulating valve port, and a second regulating valve port. The first regulating valve port is connected to the eighth interface, the common end is connected to the drive body, and the second regulating valve port is connected to the seventh interface. The eighth on-off valve is adapted to adjust the connection between the eighth interface and the drive body, and the disconnection between the drive body and the seventh interface, or the disconnection between the eighth interface and the drive body, and the connection between the drive body and the seventh interface. The eighth interface is located upstream of the seventh interface.

[0017] In one alternative embodiment, the drive body has a built-in storage space and an adjustment element. The storage space is adapted to store fluid, and the adjustment element is adapted to compress or expand the size of the storage space under the action of external force, and correspondingly provide positive and negative pressure to the power passage.

[0018] In one optional implementation, the fifth interface and the seventh interface are the same interface, and the sixth interface and the eighth interface are the same interface.

[0019] In one optional embodiment, when a second check valve is provided on the power passage, the second check valve is correspondingly located within the range from the chromatography body to the eighth interface.

[0020] In one alternative embodiment, the chromatography purification apparatus further includes: a first liquid detection unit adapted to detect the chromatographic purification object in the fluid of the chromatography pathway between the chromatography body and the fifth interface.

[0021] In one optional embodiment, the first liquid detection unit is a protein detection unit, which is disposed on the chromatography path downstream of the chromatography body, or disposed outside the chromatography path and aligned with the chromatography path portion downstream of the chromatography body, suitable for detecting proteins in the fluid of the chromatography path.

[0022] In one optional implementation, the protein detection unit is an ultraviolet detection device.

[0023] In one optional embodiment, the first liquid detection unit is an acid-base detector or a nucleic acid detector, suitable for detecting the pH value or nucleic acid of the downstream fluid of the chromatography body.

[0024] In one optional embodiment, the second interface includes at least one liquid inlet port, and the second on / off valve includes at least one liquid inlet valve; the liquid inlet unit includes: at least one liquid inlet passage, the end of which is connected to the liquid inlet port and is correspondingly provided with the liquid inlet valve; at least one liquid inlet body, which has a built-in receiving cavity, the receiving cavity having an opening, the bottom of which is connected to the other end of the corresponding liquid inlet passage, and the fluid in the liquid inlet body is adapted to flow at least under the action of the power unit.

[0025] In one optional embodiment, the liquid inlet unit further includes a second liquid detection unit disposed on the liquid inlet passage, adapted to detect cavitation and / or the flow rate of the passing liquid.

[0026] In one optional embodiment, the fourth interface includes a first liquid supply sub-port and a second liquid supply sub-port, and the fourth on / off valve includes a first liquid supply valve and a second liquid supply valve; the liquid supply unit includes: a first liquid supply part, including a first container and a first liquid supply passage, one end of the first liquid supply passage being connected to the first liquid supply sub-port and correspondingly provided with the first liquid supply valve, and the other end being connected to the first container, the first container being adapted to contain buffer solution; a second liquid supply part, including a second container and a second liquid supply passage, one end of the second liquid supply passage being connected to the second liquid supply sub-port and correspondingly provided with the second liquid supply valve, and the other end being connected to the second container, the second container being adapted to contain elution solution; the fluid in the first container and the second container is adapted to flow towards the main channel under the action of at least the power unit.

[0027] In one optional embodiment, the fourth on / off valve is configured as a multi-way valve, the fourth on / off valve is connected to the fourth interface, and the fourth on / off valve is further provided with at least a first liquid supply valve port and a second liquid supply valve port. The fourth on / off valve is adapted to adjust the on / off connection between the fourth interface and the first liquid supply valve port, and between the fourth interface and the second liquid supply valve port. The liquid supply unit includes: a first liquid supply part, including a first container and a first liquid supply passage, one end of the first liquid supply passage being connected to the first liquid supply valve port, and the other end being connected to the first container, the first container being adapted to contain buffer solution; and a second liquid supply part, including a second container and a second liquid supply passage, one end of the second liquid supply passage being connected to the second liquid supply valve port, and the other end being connected to the second container, the second container being adapted to contain eluent. The fluid in the first container and the second container is adapted to flow towards the main channel under the action of at least the power unit.

[0028] In one optional implementation, the first liquid supply valve and the second liquid supply valve are communicatively connected.

[0029] In one optional embodiment, the waste liquid unit includes a third container and a waste liquid passage. One end of the waste liquid passage is connected to the third interface and is correspondingly provided with the third on / off valve. The other end of the passage is connected to the third container. The third container is adapted to collect waste liquid at least under the action of the power unit.

[0030] In one optional embodiment, the collection unit includes: a collection passage, one end of which is connected to the first interface and correspondingly provided with the first on / off valve, and the other end of which is provided with an outlet; and a collection body, including at least one collection container, adapted to receive fluid flowing out from the outlet.

[0031] In an alternative embodiment, the collection unit further includes an adjustment unit disposed at the other end of the collection passage, adapted to drive the outlet to move in order to align with the collection container.

[0032] In one alternative implementation, the adjustment unit is provided as a slide or a robotic arm.

[0033] In one alternative embodiment, the on / off valve assembly is a solenoid valve, and / or the junction body is an eight-way valve.

[0034] In one optional embodiment, the chromatography purification apparatus further includes a controller, which is communicatively connected to the on / off valve group, the second liquid detection unit, and the first liquid detection unit, respectively.

[0035] Beneficial effects:

[0036] The main body of the confluence has a main passage connecting all interfaces. The collection unit, liquid inlet unit, waste liquid unit, liquid supply unit, and chromatography unit are connected to the confluence through the first to sixth interfaces, respectively, realizing the interconnection between the various units. At the same time, each unit is equipped with an adjustable on / off valve between itself and the confluence, so that the user can freely control the connection and disconnection between different units through the on / off valves. The chromatography passage is connected to the fifth and sixth interfaces, and is connected to the confluence with the power unit, so that the power unit can drive the fluid in the chromatography passage to flow in a directional manner, meeting the structural, directional, and power requirements of fluid circulation, and cooperating with the various units.

[0037] Furthermore, all units are interconnected along the main channel, resulting in high structural utilization efficiency. The on / off valves are externally located in the main body of the junction, making maintenance easier. The structure is simple and the cost is low. At the same time, the independent setting of the main channel and the on / off valves in the main body of the junction allows for a certain degree of separation between the main channel for fluid collection and the on / off valves controlling fluid flow in other units, reducing the possibility of pipeline and material contamination. In addition, each junction, together with each on / off valve, is connected to both ends of the chromatography channel. With the help of the power unit, a chromatography circulation loop can be set on a single junction, effectively reducing the difficulty of control and facilitating automation. Attached Figure Description

[0038] To more clearly illustrate the specific embodiments of this utility model or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this utility model. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0039] Figure 1 This is a schematic diagram of the structure of a chromatography purification apparatus according to an embodiment of the present invention;

[0040] Figure 2 for Figure 1 A schematic diagram of the main body and on / off valve group of the chromatography purification device;

[0041] Figure 3 for Figure 1 A schematic diagram of the structure of the confluence body, on / off valve group and liquid inlet unit in the chromatography purification device;

[0042] Figure 4 for Figure 1 A partially enlarged schematic diagram of the power unit of the chromatography purification apparatus;

[0043] Figure 5 for Figure 1 A partial structural schematic diagram of another embodiment of a chromatography purification apparatus.

[0044] Figure 6 for Figure 1 A schematic diagram of another embodiment of a chromatography purification apparatus.

[0045] Explanation of reference numerals in the attached figures:

[0046] 1. Converging Body; 11. Main Channel; 12. First Interface; 13. Second Interface; 131. First Liquid Inlet Branch Interface; 132. Second Liquid Inlet Branch Interface; 14. Third Interface; 15. Fourth Interface; 151. First Liquid Supply Branch Interface; 152. Second Liquid Supply Branch Interface; 16. Fifth Interface; 17. Sixth Interface; 18. Seventh Interface; 19. Eighth Interface; 2. Collection Unit; 21. Collection Path; 22. Collection Body; 23. Outlet; 3. Liquid Inlet Unit; 31. Liquid Inlet Path; 311. First Liquid Inlet Branch; 312. Second Liquid Inlet Branch; 32. Liquid Inlet Body; 321. First Liquid Inlet Separator; 322. Second Liquid Inlet Separator; 33. Second Liquid Detection Unit; 4. Waste Liquid Unit; 41. Waste Liquid Path; 42. Third Container; 5. Liquid Supply Unit 1; 51. First Liquid Supply Path; 52. 6. First container; 7. Liquid supply section 2; 8. Second liquid supply passage; 9. Second container; 10. Chromatography unit; 11. Chromatography passage; 12. Chromatography body; 13. First liquid detection unit; 14. Power unit; 15. Power passage; 16. Drive body; 17. Storage space; 18. Adjustment component; 19. Extension passage; 10. First check valve; 11. Second check valve; 12. Second on / off valve; 13. First liquid inlet branch valve; 14. Second liquid inlet branch valve; 15. Third on / off valve; 16. Fourth on / off valve; 17. First liquid supply branch valve; 18. Second liquid supply branch valve; 19. Fifth on / off valve; 10. Sixth on / off valve; 19. Seventh on / off valve; 10. Eighth on / off valve; 11. Common end; 12. First regulating valve port; 13. Second regulating valve port. Detailed Implementation

[0047] To make the objectives, technical solutions, and advantages of the embodiments of this utility model clearer, the technical solutions of the embodiments of this utility model will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this utility model, not all embodiments. Based on the embodiments of this utility model, all other embodiments obtained by those skilled in the art without creative effort are within the protection scope of this utility model.

[0048] like Figures 1-6 As shown, this utility model provides a chromatography purification device, including: a confluence body 1, a first functional component, a second functional component, and an on / off valve group.

[0049] The confluence body 1 includes a main channel 11 and interface components. The interface components include at least a first interface 12, a second interface 13, a third interface 14, a fourth interface 15, a fifth interface 16, and a sixth interface 17. Each interface in the interface components communicates with the main channel 11. In this embodiment, the main channel 11 is a single, straight channel. Each interface in the interface components extends into the confluence body 1 as a branch channel, connecting laterally to the main channel 11. Preferably, the number of interfaces in the interface components is set according to the number of pathways in each unit of the first and second functional components. Furthermore, each of the first to sixth interfaces 17 can be configured as a sub-interface connected to the main channel 11, or integrated with other interfaces as a single interface, as needed. In this embodiment, the confluence body 1 is a multi-channel valve body, or it can be a sealed container connected to multiple channels.

[0050] As a possible implementation, the main channel 11 can also be configured as a cavity, multiple channels, or a curved channel.

[0051] The first functional component includes a collection unit 2, a liquid inlet unit 3, a waste liquid unit 4, and a liquid supply unit, which are connected to the main body 1 in sequence through a first interface 12 to a fourth interface 15. Specifically, the collection unit 2 is connected to the first interface 12, the liquid inlet unit 3 is connected to the second interface 13, the waste liquid unit 4 is connected to the third interface 14, and the liquid supply unit is connected to the fourth interface 15.

[0052] The collection unit 2 and waste liquid unit 4 are adapted to unidirectionally discharge different fluids from the confluence body 1, respectively. The supply unit is adapted to unidirectionally introduce fluid into the confluence body 1, and the inlet unit 3 is adapted to unidirectionally introduce fluid from at least the confluence body 1. Specifically, the collection unit 2 is used to collect the fluid after chromatography purification, the inlet unit 3 is used to provide the original solution to be purified, the waste liquid unit 4 is used to discharge and collect and store waste liquid, and the supply unit is used to provide the sample bound to the stationary phase to elute impurities or the desired sample. Understandably, the inlet unit 3 can also store the remaining filtrate after the original solution to be purified by chromatography, and the waste liquid unit 4 can also only discharge waste liquid.

[0053] The second functional component includes a chromatography unit 7 and a power unit 8.

[0054] The chromatography unit 7 includes a chromatography path 71 and a chromatography body 72. The two ends of the chromatography path 71 are connected to the fifth interface 16 and the sixth interface 17, respectively, and the chromatography body 72 is disposed on the chromatography path 71.

[0055] It should be noted that: when structures such as units, main bodies, or on / off valves are set on the passage, it means that in the actual connection process, one implementation is to divide the passage into two or more segments of varying lengths according to the connection needs. Each segment is arranged along the extension direction of the passage, and the end and beginning of two adjacent segments are connected to the unit, main body, or on / off valve. In addition, the beginning of the foremost segment and the end of the last segment can also be connected to the unit, main body, or on / off valve as needed. Another implementation is to set the passage as an undivided whole segment as needed, and the unit, main body, or on / off valve is set at the end of the whole segment structure.

[0056] Furthermore, the interface is connected to the end of the passage, which means that the interface can be directly connected to the end of the passage, or it can be connected to the on / off valve set at the end of the passage to achieve indirect connection with the end of the passage.

[0057] In this embodiment, as Figure 1 As shown, the chromatography pathway 71 is divided into five segments. In a counterclockwise direction, the beginning and end of each segment are connected as follows: the beginning of the first segment is connected to the sixth interface 17 and the sixth on / off valve 96, and its end is connected to the first one-way valve 83; the beginning of the second segment is connected to the first one-way valve 83, and its end is connected to the second one-way valve 84; the beginning of the third segment is connected to the second one-way valve 84, and its end is connected to the chromatography body 72; the beginning of the fourth segment is connected to the chromatography body 72, and its end is connected to the first liquid detection unit 73; the beginning of the fifth segment is connected to the first liquid detection unit 73, and its end is connected to the fifth on / off valve 95 and the fifth interface 16.

[0058] The sample required for immobilization, such as protein or nucleic acid, is a pure protein column in this embodiment. The power unit 8 is connected to the confluence body 1, and the fluid is adapted to move directionally within the chromatography pathway 71 under the action of the power unit 8.

[0059] The on / off valve assembly includes at least the first on / off valve 91 to the sixth on / off valve 96.

[0060] The first on / off valve 91 to the sixth on / off valve 96 are set within the range from the same serial number interface to the corresponding unit. Specifically, they can be set on the same serial number interface, or on the passage from the same serial number interface to the corresponding unit, or on the corresponding unit, and are suitable for adjusting the on / off between the same serial number interface and the corresponding unit.

[0061] Furthermore, the first on / off valve 91 is connected within the range from the first interface 12 to the collection unit 2. Specifically, it can be installed on the first interface 12, or in the passage from the first interface 12 to the collection unit 2, or on the collection unit 2. The first on / off valve 91 is adapted to regulate the on / off connection between the first interface 12 and the collection unit 2.

[0062] The second on / off valve 92 is connected within the range from the second interface 13 to the liquid inlet unit 3. Specifically, it can be installed on the second interface 13, or on the passage from the second interface 13 to the liquid inlet unit 3, or on the liquid inlet unit 3. The second on / off valve 92 is suitable for regulating the on / off connection between the liquid inlet unit 3 and the second interface 13.

[0063] The third on / off valve 93 is connected within the range from the third port 14 to the waste liquid unit 4. Specifically, it can be installed on the third port 14, or on the passage from the third port 14 to the waste liquid unit 4, or on the waste liquid unit 4. The third on / off valve 93 is suitable for regulating the on / off connection between the waste liquid unit 4 and the third port 14.

[0064] The fourth on / off valve 94 is connected within the range from the fourth port 15 to the liquid supply unit. Specifically, it can be installed on the fourth port 15, or in the passage from the fourth port 15 to the liquid supply unit, or on the liquid supply unit. The fourth on / off valve 94 is suitable for regulating the on / off connection between the liquid supply unit and the fourth port 15.

[0065] The fifth on / off valve 95 is connected within the range from the fifth port 16 to the chromatography body 72. Specifically, it can be installed on the fifth port 16, or on the passage from the fifth port 16 to the chromatography body 72, or on the chromatography body 72. The fifth on / off valve 95 is suitable for regulating the on / off connection between the chromatography body 72 and the fifth port 16.

[0066] The sixth on / off valve 96 is connected within the range from the sixth port 17 to the chromatography body 72. Specifically, it can be installed on the sixth port 17, or on the passage from the sixth port 17 to the chromatography body 72, or on the chromatography body 72. The sixth on / off valve 96 is suitable for regulating the on / off connection between the chromatography body 72 and the sixth port 17.

[0067] Furthermore, the number of on / off valves in the on / off valve assembly and the number of interfaces in the interface components can be adjusted according to the number of units and connection requirements. The on / off valves can be two-way valves, three-way valves, multi-way valves, or single-pole double-throw valves, etc.

[0068] The main body 1 has a main passage connecting all interfaces. The collection unit 2, liquid inlet unit 3, waste liquid unit 4, liquid supply unit and chromatography unit 7 are connected to the main body 1 through the first interface 12 to the sixth interface 17, respectively, to realize the interconnection between the various units. At the same time, each unit is provided with an adjustable on / off valve between itself and the main body 1. Thus, the user can freely control the connection and disconnection between different units through the on / off valves. The chromatography passage 71 is connected to the fifth interface 16 and the sixth interface 17. It is connected to the main body 1 in conjunction with the power unit 8, so that the power unit 8 can drive the fluid in the chromatography passage 71 to flow in a directional manner, which meets the structural, directional and power requirements of fluid circulation and works in conjunction with the various units.

[0069] Furthermore, all units are interconnected along the main channel 11, resulting in high structural utilization efficiency. The on / off valves are externally located in the junction body 1, making inspection and maintenance easier. The structure is simple and the cost is low. At the same time, the independent setting of the main channel and the on / off valves in the junction body 1 separates the main channel for fluid collection from the on / off valves that control the fluid flow in different units, reducing the possibility of pipeline and material contamination. In addition, each junction body 1, together with each on / off valve, is connected to both ends of the chromatography channel 71. With the help of the power unit 8, a chromatography circulation loop can be set on a single junction body 1, effectively reducing the difficulty of control and facilitating automation.

[0070] In this embodiment, the interface component further includes a seventh interface 18 and an eighth interface 19, and the on / off valve group further includes a seventh on / off valve 97 and an eighth on / off valve 98.

[0071] The power unit 8 includes a power passage 81 and a drive body 82.

[0072] The two ends of the power path 81 are connected to the seventh interface 18 and the eighth interface 19, respectively.

[0073] The seventh on / off valve 97 is located within the range of the seventh interface 18 and the drive body 82. Specifically, it can be located on the seventh interface 18, or on the passage between the seventh interface 18 and the drive body 82, or on the drive body 82. The seventh on / off valve 97 is suitable for adjusting the on / off state between the seventh interface 18 and the drive body 82.

[0074] The eighth on / off valve 98 is located within the range of the eighth port 19 and the drive body 82. Specifically, it can be located on the eighth port 19, or on the passage between the eighth port 19 and the drive body 82, or on the drive body 82. The eighth on / off valve 98 is suitable for regulating the on / off connection between the seventh port 18 and the drive body 82.

[0075] The drive unit 82 is mounted on the power passage 81.

[0076] In this embodiment, the drive body 82 is provided with a first check valve 83 and a second check valve 84 disposed upstream and downstream of the power passage 81. The eighth interface 19 is located upstream of the seventh interface 18. The drive body 82 has a drive state and a suction state. In the drive state, the drive body 82 provides positive pressure to drive the fluid between the first check valve 83 and the second check valve 84 to flow out of the second check valve 84. In the suction state, the drive body 82 provides negative pressure to drive the fluid upstream of the first check valve 83 to flow between the two check valves.

[0077] like Figure 6As shown, in a variable implementation, the eighth on-off valve 98 is configured as a single-pole double-throw valve. A single-pole double-throw valve typically includes a common end 981, a first regulating valve port 982, and a second regulating valve port 983. The common end 981 can be connected to both the first regulating valve port 982 and the second regulating valve port 983. When the common end 981 is connected to the first regulating valve port 982, it is disconnected from the second regulating valve port 983. Conversely, when the common end 981 is connected to the second regulating valve port 983, it is disconnected from the first regulating valve port 982. These two connection methods cannot coexist. Specifically, the single-pole double-throw valve can be a solenoid valve, etc., and can achieve on-off control under the control of electromagnetic force, spring elastic force, or other forces.

[0078] like Figure 6 As shown, in the variable embodiment where the eighth on-off valve 98 is configured as a single-pole double-throw valve, the common end 981 is connected to the drive body 82, the first regulating valve port 982 is connected to the eighth interface 19, and the second regulating valve port 983 is connected to the seventh interface 18. The eighth on-off valve 98 is suitable for adjusting two connection modes: one is that the eighth interface 19 is connected to the drive body 82 and the drive body 82 is disconnected from the seventh interface 18; the other is that the eighth interface 19 is disconnected from the drive body 82 and the drive body 82 is connected to the seventh interface 18. One of these modes can be selected during adjustment. Furthermore, the eighth interface 19 is located upstream of the seventh interface 18.

[0079] like Figure 6As shown, the aforementioned eighth on / off valve 98 is configured as a single-pole double-throw valve. Compared to the configuration of two check valves, it can reduce the number of valves required. Furthermore, its cost may increase compared to the configuration of two check valves, depending on the valve body type and model of the single-pole double-throw valve. However, the advantage of setting a single-pole double-throw valve is that it does not restrict the backflow of the power unit 8 towards the main channel 11 through the eighth port 19. Thus, the user can choose to close the passage to the seventh port 18 side, so that the liquid, driven by the power unit 8, cannot flow towards the seventh port 18, but flows towards the eighth port 19. When chromatography unit 7 is connected to the seventh interface 18 or is in the same side passage (the fifth interface 16 and the seventh interface 18 are the same interface, and the power passage 81 and the part of chromatography passage 71 where chromatography unit 7 is located overlap), the eighth shut-off valve 98 and the sixth shut-off valve 96 have the same structure. The liquid can flow directly toward the eighth interface 19 without passing through chromatography unit 7. Under the action of the main channel 11 and other shut-off valves, the flow direction is distributed to achieve more flexible liquid control. For example, when it is not desired that liquid enters chromatography unit 7 when cleaning the pipeline, or when it is not desired that liquid enters chromatography unit 7 when draining the pipeline, the single-pole double-throw valve can be controlled to connect power unit 8 and main channel 11 only through the eighth interface 19. In this way, after closing the fifth shut-off valve 95, chromatography unit 7 can be isolated from liquid interaction with other parts when power unit 8 is running, thus protecting the packing.

[0080] It should be noted that the upstream side refers to the upstream side of each passage in the direction of fluid flow, and the downstream side refers to the downstream side of each passage in the direction of fluid flow.

[0081] In this embodiment, the power unit 8 drives fluid movement through positive and negative pressure. This arrangement, combined with the main channel 11 and interface components in the confluence body 1, allows the pressure provided by the power unit 8 to be transmitted to each unit, providing power to each functional component. This expands the range of driving force provided by the power unit 8 and facilitates the automation of the chromatography purification device.

[0082] Preferably, the drive body 82 is a syringe or injection pump, with a built-in storage space 821 and an adjusting member 822. The storage space 821 is suitable for storing fluid, and the adjusting member 822 is suitable for compressing or expanding the size of the storage space 821 under external force, and correspondingly providing positive and negative pressure to the power passage 81. The adjusting member 822 can be driven manually or by a structure such as a motor, electric actuator, cylinder, or electric cylinder. Preferably, an extension passage 823 is correspondingly provided on the end of the drive body 82, and the drive body 82 is connected to the power passage 81 through the extension passage 823. Understandably, the end of the drive body 82 can be directly connected to the power passage 81.

[0083] Preferably, such as Figure 2As shown, the fifth interface 16 and the seventh interface 18 are the same interface, and the sixth interface 17 and the eighth interface 19 are the same interface. More preferably, at this time, the power passage 81 and the chromatography passage 71 are the same passage, the eighth shut-off valve 98 and the sixth shut-off valve 96 have the same structure, and the fifth shut-off valve 95 and the seventh shut-off valve 97 have the same structure.

[0084] This design shortens the total length of the chromatography pathway, saves costs, reduces the power loss transmitted to position 71 of the chromatography pathway, improves the power support for chromatography, and thus improves the efficiency of chromatography.

[0085] As a variable implementation method, such as Figure 5 As shown, only the fifth interface 16 and the seventh interface 18 can be set as the same interface, while the sixth interface 17 and the eighth interface 19 are independent interfaces, with the power path 81 and the chromatography path 71 partially overlapping.

[0086] Furthermore, when the power passage 81 and the chromatography passage 71 are the same passage, and a second one-way valve 84 is provided on the power passage 81, the second one-way valve 84 is correspondingly located within the range of the chromatography body 72 and the eighth interface 19.

[0087] The chromatography purification apparatus also includes a first liquid detection unit 73, which is adapted to detect the chromatographic purification target in the fluid of the chromatography pathway 71 between the chromatography body 72 and the fifth interface 16, or the seventh interface 18. The chromatographic purification target refers to the purification target separated from the original solution to be purified and bound and fixed by the chromatography body 72.

[0088] The fluid in the chromatographic pathway 71 between the chromatography body 72 and the fifth interface 16 is the filtrate after the original solution to be purified has passed through the chromatography body 72. When the first liquid detection unit 73 detects that the chromatographic purification target is still present in the filtrate, it can be confirmed that the chromatography body 72 has not completely separated from the original solution to be purified and bound all the chromatographic purification targets. This prompts the operator to repeat the chromatography step of passing the filtrate through the chromatography body 72 to further purify the filtrate, ensure the effectiveness of the chromatography, and avoid sample waste.

[0089] In this embodiment, the first liquid detection unit 73 is a protein detection unit, which detects the chromatographic purification object as protein. Specifically, the protein detection unit is located downstream of the chromatographic body 72 along the chromatographic pathway 71.

[0090] As an alternative implementation, the protein detection unit can be positioned outside the chromatography pathway 71 and aligned with the portion of the chromatography pathway 71 downstream of the chromatography body 72.

[0091] Preferably, the protein detection unit is an ultraviolet detection device. Since proteins have obvious absorption peaks in the UV280 ultraviolet band, the ultraviolet detection device can detect the presence of proteins in the fluid downstream of the chromatography body 72 by detecting this absorption peak. Once the presence of proteins is confirmed, the operator can repeat the chromatography step to further purify the filtrate, ensuring the effectiveness of the chromatography and avoiding sample waste.

[0092] As another alternative implementation, the protein detection unit can also be replaced with other protein detection devices, such as a nitrogen analyzer.

[0093] As another alternative implementation, when the chromatographic purification target to be detected in the fluid downstream of the chromatography body 72 is a non-protein, such as nucleic acid, or when it is necessary to indirectly confirm the presence of the chromatographic purification target in the fluid downstream of the chromatography body 72 through indicators such as pH value, the first detection unit can be set as a nucleic acid detector or an acid-base detector respectively.

[0094] In addition, the second interface 13 includes at least one liquid inlet port, and the second on / off valve 92 includes at least one liquid inlet valve.

[0095] The liquid inlet unit 3 includes a liquid inlet passage 31 and a liquid inlet body 32, and at least one of the liquid inlet passage 31 and the liquid inlet body 32 is provided.

[0096] Each liquid inlet passage 31 has its two ends connected to a liquid inlet connector and a liquid inlet body 32, respectively. A liquid inlet valve is provided within the range from the liquid inlet connector to the liquid inlet body 32. Specifically, the liquid inlet valve can be located on the liquid inlet connector, on the liquid inlet passage 31 between the liquid inlet connector and the liquid inlet body 32, or on the liquid inlet body 32, and is suitable for adjusting the flow between the liquid inlet connector and the liquid inlet body 32. In this embodiment, the liquid inlet valve is located at the end of the liquid inlet passage 31 facing the liquid inlet connector and is connected to the liquid inlet connector.

[0097] In this embodiment, specifically, the second interface 13 includes two liquid inlet sub-interfaces, specifically named the first liquid inlet sub-interface 131 and the second liquid inlet sub-interface 132. The second on / off valve 92 includes two liquid inlet valves, specifically named the first liquid inlet valve 921 and the second liquid inlet valve 922. The liquid inlet unit 3 includes two liquid inlet passages 31 and two liquid inlet bodies 32. The two liquid inlet passages 31 are specifically named the first liquid inlet branch 311 and the second liquid inlet branch 312, respectively. The two liquid inlet bodies 32 are specifically named the first liquid inlet detachment 321 and the second liquid inlet detachment 322, respectively.

[0098] The first inlet separator 321, the first inlet branch 311, the first inlet valve 921, and the first inlet port 131 are interconnected, and this single-path structure is used to provide the raw liquid to be purified. The second inlet separator 322, the second inlet branch 312, the second inlet valve 922, and the second inlet port 132 are interconnected, and this single-path structure is used to collect the remaining filtrate after the raw liquid to be purified has passed through the chromatography body 72, thus achieving filtrate recovery. Understandably, when it is necessary to repeat the step of passing the filtrate through the chromatography body 72, the single-path structure with interconnected first inlet separator 321, first inlet branch 311, first inlet valve 921, and first inlet port 131 can also be used to store the remaining filtrate after passing through the chromatography body 72 again for purification.

[0099] This setup allows for the separation of the raw liquid to be purified and the filtrate after chromatography. The raw liquid to be purified can be separated into the filtrate in a single step, or the purity of the filtrate can be improved by circulating the column between the two structures. Circulating the column means that the filtrate obtained after passing the liquid in one single-path structure through the column is collected into another single-path structure, and then passed through the column from the other single-path structure back to the first single-path structure, and so on.

[0100] As an alternative implementation, only one of the liquid inlet interface, liquid inlet valve, liquid inlet passage 31, and liquid inlet body 32 may be provided, and the four may be interconnected. The filtered liquid may be discharged to the waste liquid unit 4 or into the collection unit 2. As another alternative implementation, three or more of the liquid inlet interface, liquid inlet valve, liquid inlet passage 31, and liquid inlet body 32 may be provided.

[0101] The liquid inlet body 32 has a built-in receiving cavity, which is a through structure with an opening on top, preferably located at the top for easy liquid addition. Its bottom is connected to the other end of the corresponding liquid inlet passage 31. The fluid in the liquid inlet body 32 is suitable for flowing under the drive of the power unit 8, or it can flow under the combined action of gravity and the power unit 8.

[0102] Preferably, the liquid inlet unit 3 further includes a second liquid detection unit 33, which is disposed on the liquid inlet passage 31. In this embodiment, the second liquid detection unit 33 is a sensor that can detect bubbles in the liquid or the cavity in the passage after the liquid has been transported, thereby indirectly knowing whether the original sample liquid in the liquid inlet body 32 has been used up, thus realizing liquid detection. Specifically, it can be a photoelectric bubble sensor, an ultrasonic bubble sensor, or a capacitive bubble sensor, etc.

[0103] As an alternative implementation, the second liquid detection unit 33 can also be a flow sensor to detect the total flow rate of the liquid passing through, or it can be set as a liquid level sensor to indirectly determine the amount of sample stock solution used in the liquid inlet body 32 by detecting the liquid level.

[0104] The second liquid detection unit 33 can provide users with data on the amount of sample stock solution used, indirectly indicating whether the sample stock solution in the liquid inlet body 32 has been used up, effectively determining whether it needs to proceed to the next process. In addition, it can also prevent air from entering the chromatography body 72 and causing the purification packing material to fail.

[0105] The fourth interface 15 includes a first liquid supply sub-interface 151 and a second liquid supply sub-interface 152, and the fourth on / off valve 94 includes a first liquid supply sub-valve 941 and a second liquid supply sub-valve 942.

[0106] The liquid supply unit includes a first liquid supply unit 5 and a second liquid supply unit 6. Each unit provides buffer and elution buffer, respectively. The separate configuration allows users to adjust the buffer-to-elution buffer ratio as needed, preparing mixed elution buffers with different concentration gradients. For protein chromatography purification, a low-concentration elution buffer is used to wash away loosely bound proteins, while a high-concentration elution buffer is used to elute the proteins to be collected. As an alternative implementation, the type of liquid provided by the first liquid supply unit 5 and the second liquid supply unit 6 can be adjusted according to the chromatographic purification target, and can be an alkaline solution or a low-concentration alcohol solution, etc.

[0107] In this embodiment, the liquid supply unit 5 includes a first container 52 and a first liquid supply passage 51. One end of the first liquid supply passage 51 is connected to a first liquid supply port 151. A first liquid supply valve 941 can be specifically disposed on the first liquid supply port 151, or on the first liquid supply passage 51 between the first liquid supply port 151 and the first container 52, or on the first container 52, suitable for adjusting the flow between the first liquid supply port 151 and the first container 52. In this embodiment, the first liquid supply valve 941 is disposed on the end of the first liquid supply passage 51 facing the first liquid supply port 151 and connected to the first liquid supply port 151. The other end of the first liquid supply passage 51 is connected to the first container 52, which is suitable for containing buffer solution.

[0108] The liquid supply section 6 includes a second container 62 and a second liquid supply passage 61. One end of the second liquid supply passage 61 is connected to a second liquid supply port 152. A second liquid supply valve 942 can be specifically disposed on the second liquid supply port 152, or on the second liquid supply passage 61 between the second liquid supply port 152 and the second container 62, or on the second container 62, suitable for adjusting the flow between the second liquid supply port 152 and the second container 62. In this embodiment, the second liquid supply valve 942 is disposed on the end of the second liquid supply passage 61 facing the second liquid supply port 152 and connected to the second liquid supply port 152. The other end of the second liquid supply passage 61 is connected to the second container 62, which is suitable for containing the eluent. The fluids in the first container 52 and the second container 62 are suitable for flowing towards the main channel 11 under the driving action of the power unit 8. Understandably, the fluids in both containers can also flow towards the main channel 11 under the combined driving action of the power unit 8, or gravity and the power unit 8.

[0109] As an alternative implementation, the fourth shut-off valve 94 is configured as a multi-way valve, specifically a three-way valve, or it can be configured as a four-way valve or a valve with more or more ports as needed. In this implementation, the fourth shut-off valve 94 is connected to the fourth interface 15. The fourth shut-off valve 94 is also provided with at least a first liquid supply valve port and a second liquid supply valve port. The fourth shut-off valve 94 is suitable for adjusting the connection and disconnection between the fourth interface 15 and the first liquid supply valve port, and between the fourth interface 15 and the second liquid supply valve port. The liquid supply unit includes: a first liquid supply unit 5 and a second liquid supply unit 6. The first liquid supply unit 5 includes a first container 52 and a first liquid supply passage 51. One end of the first liquid supply passage 51 is connected to a first liquid supply valve port, and the other end is connected to the first container 52. The first container 52 is adapted to contain buffer solution. The second liquid supply unit 6 includes a second container 62 and a second liquid supply passage 61. One end of the second liquid supply passage 61 is connected to a second liquid supply valve port, and the other end is connected to the second container 62. The second container 62 is adapted to contain elution solution. The fluid in the first container 52 and the second container 62 is adapted to flow to the main channel 11 at least under the action of the power unit 8.

[0110] In the above-described alternative embodiments, the fourth shut-off valve 94 configured in this way can reduce the number of valves required. Furthermore, the fourth interface 15 is configured as a single interface and connected to the main channel 11 through a single passage. The next level connected to the fourth interface 15 is a fourth shut-off valve 94 that is a three-way valve, a four-way valve, or a multi-way valve. More channels can be selected, so that two, three, or more types of liquids can be connected as needed. Liquids of different concentrations can be mixed before entering the main channel 11, avoiding local liquid concentration fluctuations in the main channel 11 due to incomplete mixing. However, this configuration will relatively increase the number of connected pipelines and liquid-containing devices, increasing the equipment size and cost. Users need to select according to their needs.

[0111] Preferably, the first liquid supply valve 941 and the second liquid supply valve 942 are connected by communication, specifically by electrical connection or wireless signal connection. This arrangement facilitates on / off control via electrical signals and precise adjustment of the liquid ratio. The connection between the first liquid supply valve 941 and the second liquid supply valve 942 can be an indirect communication connection via a controller, or a direct communication connection.

[0112] Waste liquid unit 4 includes a third container 42 and a waste liquid passage 41.

[0113] One end of the waste liquid passage 41 is connected to the third interface 14. The third on-off valve 93 can be specifically installed on the third interface 14, or on the waste liquid passage 41 between the third interface 14 and the third container 42, or on the third container 42, suitable for adjusting the on-off state between the third interface 14 and the third container 42. In this embodiment, the third on-off valve 93 is located at the end of the waste liquid passage 41 facing the third interface 14 and is connected to the third interface 14.

[0114] The other end of the waste liquid passage 41 is connected to the third container 42, which is adapted to collect waste liquid under the combined driving force of gravity and the power unit 8. Understandably, the third container 42 can collect waste liquid solely under the action of the power unit 8. As an alternative implementation, the waste liquid unit 4 can also be configured as a single pipe or drain outlet connected to an external purification device. As another alternative implementation, provided that the containers in the collection unit 2 or the inlet unit 3 can be replaced or reused without affecting the detection and collection of the chromatographic purification target, the waste liquid unit 4 can also be integrated with the collection unit 2 or the inlet unit 3.

[0115] The collection unit 2 includes a collection path 21 and a collection body 22.

[0116] In this embodiment, one end of the collection passage 21 is connected to the first interface 12. The first on-off valve 91 can be specifically disposed on the first interface 12, or on the collection passage 21 between the first interface 12 and the collection body 22, or on the collection body 22, and is suitable for adjusting the on-off state between the first interface 12 and the collection body 22. In this embodiment, the first on-off valve 91 is disposed on the end of the collection passage 21 facing the first interface 12 and is connected to the first interface 12. The other end of the collection passage 21 is provided with an outlet 23.

[0117] The collection body 22 includes at least one collection container. The specific structure of the collection container is not limited, as long as it can hold the fluid that flows out from the outlet 23 and has been purified by chromatography. In this embodiment, it is specifically a test tube on the frame.

[0118] Furthermore, the collection unit 2 also includes an adjustment unit. Specifically, the adjustment unit is located at the other end of the collection passage 21. The adjustment unit can drive the outlet 23 to move to align with the collection container. Preferably, the alignment process can be performed by aligning the target collection container from two or more collection containers as needed to achieve coarse calibration, or by further aligning the opening of the target collection container to achieve fine calibration.

[0119] Preferably, the adjustment unit is provided as a slide or a robotic arm. As an alternative implementation, the adjustment unit may be omitted, and the user can manually pick up and place the collection body 22 for receiving.

[0120] In this embodiment, each on / off valve and the junction body 1 are combined to form an eight-way valve, and the eight-way valve is preferably a solenoid valve, whose various ports can be controlled by circuitry for on / off switching. It is understood that the eight-way valve can also be configured as a manually operated eight-way valve. As a variable implementation, the eight-way valve can also be modified to have a valve body corresponding to the number of ports, depending on the change in the number of ports corresponding to each unit in the first and second functional components.

[0121] As another alternative implementation, the on / off valve group and the junction body 1 are set as two independent separate structures. The two can be connected to each other through pipes, flanges, threaded parts and other connecting parts. The junction body 1 is a sealed container with a built-in main channel 11 and branch channels or interfaces connected to multiple main channels 11. The on / off valve group includes solenoid valves, or some of them are solenoid valves and the other part are manual valves, or all of them are manual valves.

[0122] As another alternative implementation, the on / off valve group, the main channel 11, and the multiple branch channels connected to the main channel 11 with corresponding interfaces are all independent structures, and are interconnected by pipes, flanges, threaded parts and other connecting parts.

[0123] Furthermore, the chromatography purification apparatus also includes a controller, which can be a microcontroller, PC, PLC, etc., and is communicatively connected to the on / off valve group, the second liquid detection unit 33, and the first liquid detection unit 73, respectively, specifically through electrical or wireless connections. It is understood that it may also be communicatively connected only to one or more of the on / off valves in the on / off valve group, the second liquid detection unit 33, and the first liquid detection unit 73.

[0124] Working process (taking proteins as an example):

[0125] 1. Add the stock solution to be purified:

[0126] There are two liquid inlet bodies 32, which are respectively positioned as the first liquid inlet section 321 and the second liquid inlet section 322. The order of the two can be interchanged. This is only for illustrative purposes. The first liquid inlet section 321 is the supply structure for the raw liquid to be purified, and the second liquid inlet section 322 is the collection structure for the filtrate flowing through the chromatography body 72. The raw liquid to be purified becomes filtrate after flowing through the chromatography body 72.

[0127] First, the raw liquid to be purified is loaded into the first liquid inlet section 321. The first liquid inlet valve 921, the sixth shut-off valve 96, and the first check valve 83 are opened, while the other valves are closed. The drive body 82 is started to the suction state, and the raw liquid in the first liquid inlet section 321 is driven through the first liquid inlet valve 921, the main channel 11, the sixth shut-off valve 96, and the first check valve 83, and flows into the drive body 82 for storage.

[0128] Subsequently, the first liquid inlet valve 921, the sixth shut-off valve 96, and the first check valve 83 are closed, while the second liquid inlet valve 922, the fifth shut-off valve 95, and the second check valve 84 are opened. The drive body 82 is adjusted to the drive state, and the raw liquid to be purified is driven to flow through the chromatography body to become filtrate. The filtrate flows through the fifth shut-off valve 95, the main channel 11, and the second liquid inlet valve 922 into the second liquid inlet section 322, thereby realizing the recovery of filtrate.

[0129] 2. Elution of extraneous proteins:

[0130] By adjusting the amount of liquid drawn from the first container 52 and the second container 62 by the driving body 82, the buffer solution and the elution solution are mixed in a certain proportion.

[0131] When eluting impurities, a low concentration of eluent is required. At this time, first open the second supply valve 942, the sixth shut-off valve 96, and the first check valve 83, and close the other shut-off valves and the second check valve 84. Adjust the drive body 82 to the suction state so that it can draw a small amount of eluent from the second container 62. Then, control the second supply valve 942 to close and the first supply valve 941 to open. Adjust the drive body 82 to draw a large amount of buffer solution from the first container 52. The buffer solution and the eluent are mixed in the drive body 82 to form a low concentration mixture.

[0132] Next, the first liquid supply valve 941, the sixth shut-off valve 96, and the first check valve 83 are closed, the third shut-off valve 93, the fifth shut-off valve 95, and the second check valve 84 are opened, and the remaining shut-off valves are closed. The drive body 82 is adjusted to the drive state, driving the low-concentration mixed liquid to flow to the chromatography body 72. After passing through the chromatography body 72, the impurities and proteins on the chromatography body 72 are eluted. After elution, the waste liquid flows into the third container 42 through the fifth shut-off valve 95 and the third shut-off valve 93.

[0133] 3. Elution of target protein:

[0134] A high concentration of elution buffer is required when eluting the target protein.

[0135] First, open the second liquid supply valve 942, the sixth on / off valve 96, and the first one-way valve 83, while closing the remaining on / off valves and the second one-way valve 84. Adjust the drive body 82 to the suction state, and the drive body 82 will draw the elution solution from the second container 62. This elution solution is a high-concentration elution solution. Whether to draw the buffer solution at this time depends on the situation. If the elution solution needs to be diluted, refer to the steps for eluting impurities and adjust the amount of liquid drawn by the drive body 82 from the first container 52 and the second container 62 so that the buffer solution and the elution solution are mixed in a certain proportion. At this time, the proportion of elution solution is relatively high. If the elution solution does not need to be diluted, proceed directly to the next step.

[0136] Next, the second liquid supply valve 942, the sixth shut-off valve 96, and the first check valve 83 are closed, while the first shut-off valve 91, the fifth shut-off valve 95, and the second check valve 84 are opened, and the remaining shut-off valves are closed. The driving body 82 pushes the high-concentration eluent through the chromatography body 72, allowing the high-concentration eluent to flow through the chromatography body 72 and separate the target protein from the chromatography body 72. The separated target protein continues to flow into the collection unit 2 under the drive of the driving body 82 through the fifth shut-off valve 95 and the first shut-off valve 91, thus achieving collection.

[0137] 4. Pipeline cleaning:

[0138] The first liquid supply valve 941, the sixth on / off valve 96, and the first check valve 83 are opened, while the remaining on / off valves and the second check valve 84 are closed.

[0139] Adjust the drive body 82 to the suction state. The drive body 82 draws buffer solution from the first container 52. Then, control the first liquid supply valve 941, the sixth on / off valve 96 and the first one-way valve 83 to close. Control the fifth on / off valve 95, the third on / off valve 93 and the second one-way valve 84 to open. The drive body 82 drives the buffer solution to flow through the chromatography body 72 and the main channel 11 and then into the third container 42, realizing the cleaning of the pipeline and the recovery of waste liquid.

[0140] In this embodiment, the above-mentioned processes can be performed sequentially, and it is understood that the order of the processes can be adjusted as needed.

[0141] As a variable implementation method, the connection position of each unit to the main channel 11 can be adjusted as needed. For example, in order to further ensure the integrity of the cleaning of the entire pipeline of the main channel 11, the fifth interface 16 and the third interface 14 corresponding to the fifth shut-off valve 95 and the third shut-off valve 93 can be set at both ends of the main channel 11.

[0142] Although embodiments of the present invention have been described in conjunction with the accompanying drawings, those skilled in the art can make various modifications and variations without departing from the spirit and scope of the present invention, and such modifications and variations all fall within the scope defined by the appended claims.

Claims

1. A chromatographic purification device, characterized in that, include: The converging body (1) includes a main channel (11) and an interface component communicating with the main channel (11). The interface component includes at least a first interface (12), a second interface (13), a third interface (14), a fourth interface (15), a fifth interface (16), and a sixth interface (17). The first functional component includes a collection unit (2), a liquid inlet unit (3), a waste liquid unit (4), and a liquid supply unit. The collection unit (2) is connected to the confluence body (1) through the first interface (12), the liquid inlet unit (3) is connected to the confluence body (1) through the second interface (13), the waste liquid unit (4) is connected to the confluence body (1) through the third interface (14), and the liquid supply unit is connected to the confluence body (1) through the fourth interface (15). The second functional component includes a chromatography unit (7) and a power unit (8). The chromatography unit (7) includes a chromatography path (71) and a chromatography body (72) disposed on the chromatography path (71). The two ends of the chromatography path (71) are respectively connected to the fifth interface (16) and the sixth interface (17). The power unit (8) is connected to the confluence body (1). The fluid is adapted to make directional movement in the chromatography path (71) under the action of the power unit (8). The on / off valve assembly includes at least a first on / off valve (91), a second on / off valve (92), a third on / off valve (93), a fourth on / off valve (94), a fifth on / off valve (95), and a sixth on / off valve (96); The first on / off valve (91) is located within the range from the first interface (12) to the collection unit (2), and is suitable for adjusting the on / off connection between the collection unit (2) and the first interface (12); The second on / off valve (92) is located within the range from the second interface (13) to the liquid inlet unit (3), and is suitable for adjusting the on / off connection between the liquid inlet unit (3) and the second interface (13); The third on / off valve (93) is located within the range from the third interface (14) to the waste liquid unit (4), and is suitable for adjusting the on / off connection between the waste liquid unit (4) and the third interface (14); The fourth on / off valve (94) is located within the range from the fourth port (15) to the liquid supply unit and is suitable for adjusting the on / off connection between the liquid supply unit and the fourth port (15). The fifth on / off valve (95) is located within the range from the fifth interface (16) to the chromatography body (72) and is suitable for adjusting the on / off connection between the chromatography body (72) and the fifth interface (16); The sixth on / off valve (96) is located within the range from the sixth interface (17) to the chromatography body (72) and is suitable for adjusting the on / off connection between the chromatography body (72) and the sixth interface (17).

2. The chromatography purification apparatus according to claim 1, characterized in that, The interface assembly further includes a seventh interface (18) and an eighth interface (19), and the on / off valve group further includes a seventh on / off valve (97) and an eighth on / off valve (98); The power unit (8) includes: a power passage (81) and a drive body (82); The two ends of the power passage (81) are respectively connected to the seventh interface (18) and the eighth interface (19). The seventh on-off valve (97) is located within the range from the seventh interface (18) to the drive body (82) and is suitable for adjusting the on-off state between the seventh interface (18) and the drive body (82). The eighth on-off valve (98) is located within the range from the eighth interface (19) to the drive body (82) and is suitable for adjusting the on-off state between the eighth interface (19) and the drive body (82). The drive body (82) is disposed on the power passage (81).

3. The chromatography purification apparatus according to claim 2, characterized in that, The drive body (82) is provided with a first check valve (83) and a second check valve (84) upstream and downstream of the power passage (81), respectively. The eighth interface (19) is located upstream of the seventh interface (18). The drive body (82) has a driving state that provides positive pressure to drive the fluid between the two check valves to flow out from the second check valve (84), and a suction state that provides negative pressure to drive the fluid upstream of the first check valve (83) to flow between the two check valves.

4. The chromatography purification apparatus according to claim 2, characterized in that, The eighth on / off valve (98) is configured as a single-pole double-throw valve. The eighth on / off valve (98) includes a common end (981), a first regulating valve port (982) and a second regulating valve port (983). The first regulating valve port (982) is connected to the eighth interface (19), the common end (981) is connected to the drive body (82), and the second regulating valve port (983) is connected to the seventh interface (18). The eighth on / off valve (98) is adapted to adjust the eighth port (19) to be connected to the driving body (82), and the driving body (82) to be disconnected from the seventh port (18), or the eighth port (19) to be disconnected from the driving body (82), and the driving body (82) to be connected to the seventh port (18); The eighth interface (19) is located upstream of the seventh interface (18).

5. A chromatography purification device according to claim 3 or 4, characterized in that, The drive body (82) has a built-in storage space (821) and an adjustment component (822). The storage space (821) is suitable for storing fluid, and the adjustment component (822) is suitable for compressing or expanding the size of the storage space (821) under the action of external force, and correspondingly providing positive and negative pressure to the power passage (81).

6. The chromatography purification apparatus according to claim 3 or 4, characterized in that, The fifth interface (16) and the seventh interface (18) are the same interface, and the sixth interface (17) and the eighth interface (19) are the same interface.

7. The chromatography purification apparatus according to claim 6, characterized in that, When a second check valve (84) is provided on the power passage (81), the second check valve (84) is provided in the range from the chromatography body (72) to the eighth interface (19).

8. The chromatographic purification device according to any one of claims 1-4, 7, characterized in that, Also includes: The first liquid detection unit (73) is adapted to detect the chromatographically purified object in the fluid of the chromatographic pathway (71) between the chromatographic body (72) and the fifth interface (16).

9. The chromatography purification apparatus according to claim 8, characterized in that, The first liquid detection unit (73) is a protein detection unit. The protein detection unit is disposed on the chromatography path (71) downstream of the chromatography body (72), or disposed outside the chromatography path (71) and aligned with the section of the chromatography path (71) downstream of the chromatography body (72), and is suitable for detecting proteins in the fluid of the chromatography path (71).

10. The chromatography purification device of claim 9, wherein, The protein detection unit is an ultraviolet detection device.

11. The chromatography purification device of claim 8, wherein, The first liquid detection unit (73) is an acid-base detector or a nucleic acid detector, which is suitable for detecting the pH value or nucleic acid of the fluid downstream of the chromatography body (72).

12. The chromatography purification apparatus according to any one of claims 1-4, 7, and 9-11, characterized in that, The second interface (13) includes at least one liquid inlet port, and the second on / off valve (92) includes at least one liquid inlet valve; The liquid inlet unit (3) includes: At least one liquid inlet passage (31) is connected at its end to the liquid inlet branch interface and is provided with the liquid inlet branch valve accordingly; At least one liquid inlet body (32) has a built-in receiving cavity with an opening and its bottom is connected to the other end of the corresponding liquid inlet passage (31). The fluid in the liquid inlet body (32) is adapted to flow under the action of at least the power unit (8).

13. The chromatography purification device of claim 12, wherein, The liquid inlet unit (3) also includes: The second liquid detection unit (33) is disposed on the liquid inlet passage (31) and is suitable for detecting cavitation and / or the flow rate of the liquid passing through.

14. The chromatography purification apparatus according to any one of claims 1-4, 7, 9-11, and 13, characterized in that, The fourth interface (15) includes a first liquid supply sub-interface (151) and a second liquid supply sub-interface (152), and the fourth on / off valve (94) includes a first liquid supply sub-valve (941) and a second liquid supply sub-valve (942). The liquid supply unit includes: The liquid supply unit (5) includes a first container (52) and a first liquid supply passage (51). One end of the first liquid supply passage (51) is connected to the first liquid supply port (151) and is provided with the first liquid supply valve (941). The other end of the first liquid supply passage (51) is connected to the first container (52). The first container (52) is suitable for containing buffer solution. The liquid supply section (6) includes a second container (62) and a second liquid supply passage (61). One end of the second liquid supply passage (61) is connected to the second liquid supply port (152) and is provided with a corresponding second liquid supply valve (942). The other end of the second liquid supply passage (61) is connected to the second container (62). The second container (62) is suitable for containing the eluent. The fluid in the first container (52) and the second container (62) is adapted to flow into the main channel (11) at least under the action of the power unit (8).

15. The chromatography purification apparatus according to any one of claims 1-4, 7, 9-11, and 13, characterized in that, The fourth on / off valve (94) is configured as a multi-port valve. The fourth on / off valve (94) is connected to the fourth interface (15). The fourth on / off valve (94) is also provided with at least a first liquid supply valve port and a second liquid supply valve port. The fourth on / off valve (94) is adapted to adjust the on / off state between the fourth interface (15) and the first liquid supply valve port, and between the fourth interface (15) and the second liquid supply valve port. The liquid supply unit includes: The liquid supply unit (5) includes a first container (52) and a first liquid supply passage (51). One end of the first liquid supply passage (51) is connected to the first liquid supply valve port, and the other end is connected to the first container (52). The first container (52) is adapted to contain the buffer solution. The liquid supply section (6) includes a second container (62) and a second liquid supply passage (61). One end of the second liquid supply passage (61) is connected to the second liquid supply valve port, and the other end is connected to the second container (62). The second container (62) is adapted to contain the eluent. The fluid in the first container (52) and the second container (62) is adapted to flow into the main channel (11) at least under the action of the power unit (8).

16. The chromatography purification device of claim 14, wherein, The first liquid supply valve (941) and the second liquid supply valve (942) are connected in communication.

17. The chromatographic purification device according to any one of claims 1-4, 7, 9-11, 13, 16, wherein, The waste liquid unit (4) includes a third container (42) and a waste liquid passage (41). One end of the waste liquid passage (41) is connected to the third interface (14) and is provided with the third on / off valve (93). The other end of the passage is connected to the third container (42). The third container (42) is adapted to collect waste liquid at least under the action of the power unit (8).

18. The chromatographic purification device of any one of claims 1-4, 7, 9-11, 13, 16, wherein, The collection unit (2) includes: A collection passage (21) is provided, one end of which is connected to the first interface (12) and is provided with the first on / off valve (91), and the other end is provided with an outlet (23); The collection body (22) includes at least one collection container adapted to receive fluid flowing out from the outlet (23).

19. The chromatography purification apparatus according to claim 18, characterized in that, The collection unit (2) also includes an adjustment unit disposed at the other end of the collection passage (21) and adapted to drive the outlet (23) to move in order to align with the collection container.

20. The chromatography purification device of claim 19, wherein, The adjustment unit is configured as a slide or a robotic arm.

21. The chromatographic purification device of any one of claims 1-4, 7, 9-11, 13, 16, 19-20, wherein, The on / off valve assembly is a solenoid valve, and / or the junction body (1) is an eight-way valve.

22. The chromatography purification apparatus according to claim 21, characterized in that, Also includes: The controller is communicatively connected to the on / off valve group, the second liquid detection unit (33), and the first liquid detection unit (73), respectively.

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