Chromatographic purification device

Abstract

The present invention relates to the technical field of biochemical engineering, and provides a chromatography purification apparatus, which comprises: an intersection main body, which comprises a main channel and an interface assembly communicated with the main channel, and the interface assembly at least comprises a first interface to a sixth interface; 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] The invention relates to the technical field of biochemical engineering, and in particular to a chromatography purification device. Background Art

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

[0003] Chromatography is a common separation and purification method that uses the principle that samples are distributed differently in the mobile phase and the stationary phase. Due to the different physical and chemical properties of samples, when the sample solution flows through the stationary phase, different samples will bind to the stationary phase with forces of different strengths, thereby achieving the separation of different sample objects.

[0004] Taking protein as an example, in order to extract protein, the solution containing the target protein needs to be purified to remove impurities. The purification process mainly includes balancing the chromatography column, the sample flow through the chromatography purification column, the gradient elution and collection of impurities and target proteins, etc. In the above purification process, a circulation path will be formed between the purification column and multiple devices.

[0005] Existing chromatography purification equipment improves work efficiency and reduces confusion or cross-contamination between samples by installing driving parts such as constant flow pumps and cooperating with multi-channel valves to switch the liquid paths upstream and downstream of the chromatography column, or cooperating with multiple parallel chromatography pathways.

[0006] However, the parallel chromatography pathways are usually shared by only a few structures such as the collection structure, which has low structural utilization efficiency and high cost. In the chromatography purification equipment of the multi-channel valve body type, one part uses a rotary valve to switch the multiple pathways on the upstream side of the chromatography column. Its valve core structure is complex and difficult to maintain, and the method of rotating to switch the liquid path still has the risk of material and pipeline contamination. The other part uses different solenoid valves to switch the multiple pathways on the upstream and downstream sides of the chromatography column respectively. Its operation, installation and maintenance are relatively complicated, and it is difficult to set up the chromatography circulation loop due to the high difficulty of regulation between different valve bodies. For example, patent document CN111574584A discloses a fully automatic protein purification system device and its use. This chromatography purification device is connected to the chromatography device through multiple valves and multiple containers. Not only is the operation cumbersome, but the peristaltic pump cannot form a selective circulation path between different containers. There are many pipelines that are unpowered pipelines. Whether it can be automated is questionable. Summary of the invention

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

[0008] The present invention provides a chromatography purification device, comprising: a junction body, comprising a main channel and an interface component communicating with the main channel, wherein the interface component comprises at least a first interface, a second interface, a third interface, a fourth interface, a fifth interface and a sixth interface;

[0009] A first functional component includes a collecting unit, a liquid inlet unit, a waste liquid unit and a liquid supply unit, wherein the collecting unit is connected to the intersection body through the first interface, the liquid inlet unit is connected to the intersection body through the second interface, the waste liquid unit is connected to the intersection body through the third interface, and the liquid supply unit is connected to the intersection body through the fourth interface;

[0010] The second functional component includes a chromatography unit and a power unit, wherein the chromatography unit includes a chromatography passage and a chromatography body disposed on the chromatography passage, wherein two ends of the chromatography passage are respectively connected to the fifth interface and the sixth interface, and the power unit is connected to the intersection body, and the fluid is suitable for directional movement in the chromatography passage under the action of the power unit;

[0011] The on-off valve group at least includes 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 arranged in the range from the first interface to the collecting unit, and is suitable for adjusting the on-off between the collecting unit and the first interface; the second on-off valve is arranged in the range from the second interface to the liquid inlet unit, and is suitable for adjusting the on-off between the liquid inlet unit and the second interface; the third on-off valve is arranged in the range from the third interface to the waste liquid unit, and is suitable for adjusting the on-off between the waste liquid unit and the third interface; the fourth on-off valve is arranged in the range from the fourth interface to the liquid supply unit, and is suitable for adjusting the on-off between the liquid supply unit and the fourth interface; the fifth on-off valve is arranged in the range from the fifth interface to the chromatography body, and is suitable for adjusting the on-off between the chromatography body and the fifth interface; the sixth on-off valve is arranged in the range from the sixth interface to the chromatography body, and is suitable for adjusting the on-off between the chromatography body and the sixth interface.

[0012] In an 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 comprises: a power path and a driving body;

[0014] The two ends of the power passage are respectively connected with the seventh interface and the eighth interface. The seventh on-off valve is arranged in the range from the seventh interface to the driving body, and is suitable for adjusting the on-off between the seventh interface and the driving body. The eighth on-off valve is arranged in the range from the eighth interface to the driving body, and is suitable for adjusting the on-off between the eighth interface and the driving body. The driving body is arranged on the power passage.

[0015] In an optional embodiment, the driving body is respectively provided with a first one-way valve and a second one-way valve along the upstream and downstream of the power passage, the eighth interface is arranged on the upstream side of the seventh interface, and the driving body has a driving state of providing positive pressure to drive the fluid between the two one-way valves to flow out from the second one-way valve, and has a suction state of providing negative pressure to drive the fluid on the upstream side of the first one-way valve to flow between the two one-way valves.

[0016] In an optional embodiment, the eighth on-off valve is configured as a single-pole double-throw valve, and the eighth on-off valve includes 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 driving body, and the second regulating valve port is connected to the seventh interface; the eighth on-off valve is suitable for adjusting the eighth interface to be connected to the driving body, and the driving body to be disconnected from the seventh interface, or the eighth interface to be disconnected from the driving body, and the driving body to be connected to the seventh interface; the eighth interface is arranged on the upstream side of the seventh interface.

[0017] In an optional embodiment, the driving body has a built-in storage space and an adjusting component, the storage space is suitable for storing fluid, and the adjusting component is suitable for compressing or expanding the size of the storage space under the action of external force and providing positive and negative pressures to the power pathway accordingly.

[0018] In an 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 an optional embodiment, when a second one-way valve is provided on the power passage, the second one-way valve is correspondingly provided within the range from the chromatography body to the eighth interface.

[0020] In an optional embodiment, the chromatography purification device further comprises: a first liquid detection unit, adapted to detect the chromatography purification object in the fluid of the chromatography passage between the chromatography body and the fifth interface.

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

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

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

[0024] In an optional embodiment, the second interface includes at least one liquid inlet branch interface, and the second on-off valve includes at least one liquid inlet branch valve; the liquid inlet unit includes: at least one liquid inlet passage, whose end is connected to the liquid inlet branch interface and the liquid inlet branch valve is correspondingly arranged; at least one liquid inlet body, with a built-in accommodating cavity, the accommodating cavity is provided with an opening, and its bottom is connected to the other end of the corresponding liquid inlet passage, and the fluid in the liquid inlet body is suitable for flowing at least under the action of the power unit.

[0025] In an optional embodiment, the liquid inlet unit further includes: a second liquid detection unit, which is arranged on the liquid inlet passage and is suitable for detecting cavitation and / or liquid flow passing therethrough.

[0026] In an optional embodiment, the fourth interface includes a first liquid supply sub-interface and a second liquid supply sub-interface, and the fourth on-off valve includes a first liquid supply sub-valve and a second liquid supply sub-valve; the liquid supply unit includes: a liquid supply part, including a first container and a first liquid supply passage, one end of the first liquid supply passage is connected to the first liquid supply sub-interface, and the first liquid supply sub-valve is correspondingly arranged, and the other end is connected to the first container, and the first container is suitable for accommodating a buffer solution; a liquid supply part two, including a second container and a second liquid supply passage, one end of the second liquid supply passage is connected to the second liquid supply sub-interface, and the second liquid supply sub-valve is correspondingly arranged, and the other end is connected to the second container, and the second container is suitable for accommodating an eluent; the fluid in the first container and the second container is suitable for flowing to the main channel at least under the action of the power unit.

[0027] In an optional embodiment, the fourth on-off valve is arranged as a multi-way valve, the fourth on-off valve is connected to the fourth interface, the fourth on-off valve is also provided with at least a first liquid supply valve port and a second liquid supply valve port, the fourth on-off valve is suitable for regulating the on-off of the fourth interface and the first liquid supply valve port, and the fourth interface and the second liquid supply valve port; the liquid supply unit comprises: a liquid supply part, comprising a first container and a first liquid supply passage, one end of the first liquid supply passage is connected to the first liquid supply valve port, and the other end thereof is connected to the first container, and the first container is suitable for accommodating a buffer solution; a liquid supply part two, comprising a second container and a second liquid supply passage, one end of the second liquid supply passage is connected to the second liquid supply valve port, and the other end thereof is connected to the second container, and the second container is suitable for accommodating an eluent; the fluid in the first container and the second container is suitable for flowing to the main channel at least under the action of the power unit.

[0028] In an optional embodiment, the first liquid supply sub-valve and the second liquid supply sub-valve are communicatively connected.

[0029] In an 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, and the other end of the waste liquid passage is connected to the third container, and the third container is suitable for collecting waste liquid at least under the action of the power unit.

[0030] In an 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; a collection body, including at least one collection container, suitable for receiving the fluid flowing out of the outlet.

[0031] In an optional embodiment, the collecting unit further comprises an adjusting unit, which is disposed at the other end of the collecting passage and is suitable for driving the outlet to move so as to align with the collecting container.

[0032] In an optional embodiment, the adjustment unit is provided as a slide or a robotic arm.

[0033] In an optional implementation, the on-off valve group is a solenoid valve, and / or the intersection body is an eight-way valve.

[0034] In an optional embodiment, the chromatography purification device further comprises: 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 intersection body has a main passage connecting various interfaces. The collection unit, liquid inlet unit, waste liquid unit, liquid supply unit and chromatography unit are connected to the intersection body through the first interface to the sixth interface respectively, so as to realize the interconnection between various units. At the same time, an adjustable on-off valve is arranged between each unit and the intersection body. Then, the user can freely control the connection and disconnection between different units through each on-off valve. The chromatography passage connects the fifth interface and the sixth interface, and cooperates with the power unit to connect with the intersection body, so that the power unit can drive the directional flow of the fluid in the chromatography passage to meet the structure, direction and power requirements of the fluid circulation, and cooperate with various units.

[0037] In addition, each unit is interconnected along the main channel, the structural utilization efficiency is high, the on-off valve is placed outside the intersection body, which is more convenient for inspection and maintenance, and the structure is simple and the cost is low. At the same time, the independent setting of the main passage and the on-off valve in the intersection body makes the main passage where the fluid converges and the on-off valve that controls the on-off of the fluid in different units separate to a certain extent, reducing the possibility of pipeline and material contamination. At the same time, a single intersection body cooperates with each on-off valve to be connected to the two ends of the chromatography passage respectively, and cooperates with the power unit to set a chromatography circulation loop on a single intersection body, effectively reducing the difficulty of regulation and control, and facilitating automation. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0039] Figure 1 It is a schematic structural diagram of a chromatography purification device according to an embodiment of the present invention;

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

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

[0042] Figure 4 for Figure 1 A partial structural enlarged schematic diagram of a power unit of a chromatography purification device;

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

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

[0045] Description of reference numerals:

[0046] 1. Intersection body; 11. Main channel; 12. First interface; 13. Second interface; 131. First liquid inlet sub-interface; 132. Second liquid inlet sub-interface; 14. Third interface; 15. Fourth interface; 151. First liquid supply sub-interface; 152. Second liquid supply sub-interface; 16. Fifth interface; 17. Sixth interface; 18. Seventh interface; 19. Eighth interface; 2. Collection unit; 21. Collection passage; 22. Collection body; 23. Outlet; 3. Liquid inlet unit; 31. Liquid inlet passage; 311. First liquid inlet branch; 312. Second liquid inlet branch; 32. Liquid inlet body; 321. First liquid inlet body; 322. Second liquid inlet body; 33. Second liquid detection unit; 4. Waste liquid unit; 41. Waste liquid passage; 42. Third container; 5. Liquid supply part; 51. First liquid supply passage; 52. The first container; 6, the second liquid supply part; 61, the second liquid supply passage; 62, the second container; 7, the chromatography unit; 71, the chromatography passage; 72, the chromatography body; 73, the first liquid detection unit; 8, the power unit; 81, the power passage; 82, the driving body; 821, the storage space; 822, the regulating member; 823, the extension passage; 83, the first non-return valve; 84, the second non-return valve; 91, the first on-off valve; 92, the second on-off valve; 921, the first liquid inlet valve; 922, the second liquid inlet valve; 93, the third on-off valve; 94, the fourth on-off valve; 941, the first liquid supply valve; 942, the second liquid supply valve; 95, the fifth on-off valve; 96, the sixth on-off valve; 97, the seventh on-off valve; 98, the eighth on-off valve; 981, the common end; 982, the first regulating valve port; 983, the second regulating valve port. DETAILED DESCRIPTION

[0047] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative work are within the scope of protection of the present invention.

[0048] like Figure 1-Figure 6 As shown, the present invention provides a chromatography purification device, comprising: a junction body 1, a first functional component, a second functional component and an on-off valve group.

[0049] The intersection body 1 includes a main channel 11 and an interface component, and 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. Each interface included in the interface component is in communication with the main channel 11. In this embodiment, the main channel 11 is a single straight channel, and each interface included in the interface component has a branch channel extending into the interior of the intersection body 1, which is respectively connected to the lateral arrangement of the main channel 11. Preferably, the number of interfaces included in the interface component is set according to the number of passages of each unit in the first functional component and the second functional component. In addition, among the first interface 12 to the sixth interface 17, each interface can be set as a branch interface connected to the main channel 11 as needed, or can be set as a single interface with other interfaces. In this embodiment, the intersection body 1 is a multi-channel valve body, and can also be a sealed container connected to multiple channels.

[0050] As a convertible embodiment, the main channel 11 can also be arranged in the form of a cavity, multiple channels or a curved channel.

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

[0052] Among them, the collection unit 2 and the waste liquid unit 4 are suitable for unidirectionally exporting different fluids from the intersection body 1, respectively, the liquid supply unit is suitable for unidirectionally introducing fluids into the intersection body 1, and the liquid inlet unit 3 is suitable for unidirectionally introducing fluids at least from the intersection body 1. Specifically, the collection unit 2 is used to collect the fluid after the chromatography purification, the liquid inlet unit 3 is used to provide the raw liquid to be purified, the waste liquid unit 4 is used to discharge and collect and store the waste liquid, the liquid supply unit is used to provide the sample to be combined on the stationary phase, elute impurities or elute the desired sample object, it can be understood that the liquid inlet unit 3 can also store the remaining filtrate after the raw liquid to be purified is purified by chromatography, and the waste liquid unit 4 can also only discharge the 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 passage 71 and a chromatography body 72. Two ends of the chromatography passage 71 are connected to the fifth interface 16 and the sixth interface 17 respectively, and the chromatography body 72 is arranged on the chromatography passage 71.

[0055] It should be noted that: structures such as units, main bodies or on-off valves are arranged on the passage, which means that during the actual connection process, one implementation method is to divide the passage into two or more segments of indefinite length according to the connection needs, and each segment is arranged along the extension direction of the passage. The tail end and the head end of the two adjacent segments correspond to the connection unit, main body or on-off valve. In addition, the head end of the frontmost segment and the tail end of the rearmost segment can also correspond to the connection unit, main body or on-off valve as needed. Another implementation method is to set the passage as a whole section without division as needed, and the unit, main body or on-off valve is corresponding to the end of the whole section 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 can be connected to an on-off valve arranged on the end of the passage to achieve indirect connection with the end of the passage.

[0057] In this embodiment, if Figure 1 As shown, the chromatography pathway 71 is divided into five sections. Along the counterclockwise direction, the head and tail ends of each section are connected in sequence: the head end of the first section is connected to the sixth interface 17 and the sixth on-off valve 96, and the tail end is connected to the first one-way valve 83; the head end of the second section is connected to the first one-way valve 83, and the tail end is connected to the second one-way valve 84; the head end of the third section is connected to the second one-way valve 84, and the tail end is connected to the chromatography body 72; the head end of the fourth section is connected to the chromatography body 72, and the tail end is connected to the first liquid detection unit 73; the head end of the fifth section is connected to the first liquid detection unit 73, and the tail end is connected to the fifth on-off valve 95 and the fifth interface 16.

[0058] As a sample required for the fixed combination, such as protein, nucleic acid, etc., in this embodiment, it is a protein pure column. The power unit 8 is connected to the intersection body 1, and the fluid is suitable for directional movement in the chromatographic passage 71 under the action of the power unit 8;

[0059] The on-off valve group includes at least a first on-off valve 91 to a sixth on-off valve 96 .

[0060] The first on-off valve 91 to the sixth on-off valve 96 are arranged within the range from the same serial number interface to the corresponding unit, and can be specifically arranged 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] Further, the first on-off valve 91 is connected and arranged in the range from the first interface 12 to the collection unit 2, and can be specifically arranged on the first interface 12, or, arranged on the passage from the first interface 12 to the collection unit 2, or arranged on the collection unit 2. The first on-off valve 91 is suitable for adjusting the on-off between the first interface 12 and the collection unit 2.

[0062] The second on-off valve 92 is disposed in the range from the second interface 13 to the liquid inlet unit 3, and can be disposed on the second interface 13, or disposed on the passage from the second interface 13 to the liquid inlet unit 3, or disposed on the liquid inlet unit 3. The second on-off valve 92 is suitable for regulating the on-off between the liquid inlet unit 3 and the second interface 13;

[0063] The third on-off valve 93 is disposed in the range from the third interface 14 to the waste liquid unit 4, and can be disposed on the third interface 14, or disposed on the passage from the third interface 14 to the waste liquid unit 4, or disposed on the waste liquid unit 4. The third on-off valve 93 is suitable for regulating the on-off between the waste liquid unit 4 and the third interface 14;

[0064] The fourth on-off valve 94 is disposed in the range from the fourth interface 15 to the liquid supply unit, and can be disposed on the fourth interface 15, or disposed on the passage from the fourth interface 15 to the liquid supply unit, or disposed on the liquid supply unit. The fourth on-off valve 94 is suitable for regulating the on-off between the liquid supply unit and the fourth interface 15;

[0065] The fifth on-off valve 95 is disposed in the range from the fifth interface 16 to the chromatography body 72, and can be disposed on the fifth interface 16, or on the passage from the fifth interface 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 between the chromatography body 72 and the fifth interface 16;

[0066] The sixth on-off valve 96 is disposed in a range from the sixth interface 17 to the chromatography body 72, and can be disposed on the sixth interface 17, or on a passage from the sixth interface 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 between the chromatography body 72 and the sixth interface 17.

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

[0068] The intersection body 1 has a main passage connecting various interfaces. The collection unit 2, the liquid inlet unit 3, the waste liquid unit 4, the liquid supply unit and the chromatography unit 7 are connected to the intersection body 1 through the first interface 12 to the sixth interface 17 respectively, so as to realize the interconnection between various units. At the same time, an adjustable on-off valve is arranged between each unit and the intersection body 1, so that the user can freely control the connection and disconnection between different units through each on-off valve. The chromatography passage 71 connects the fifth interface 16 and the sixth interface 17, and is connected with the intersection body 1 in coordination with the power unit 8, so that the power unit 8 can drive the directional flow of the fluid in the chromatography passage 71 to meet the structural, directional and power requirements of the fluid circulation, and cooperate with various units.

[0069] In addition, each unit is interconnected along the main channel 11, and the structural utilization efficiency is high. The on-off valve is externally arranged on the intersection body 1, which is more convenient for inspection and maintenance, and has a simple structure and low cost. At the same time, the independent setting of the main passage and the on-off valve in the intersection body 1 makes the main passage where the fluid converges and the on-off valve that controls the on-off of the fluid in different units separate to a certain extent, reducing the possibility of pipeline and material contamination. At the same time, a single intersection body 1 cooperates with each on-off valve to be connected to the two ends of the chromatography passage 71 respectively, and cooperates with the power unit 8 to set a chromatography circulation loop on the single intersection body 1, which effectively reduces the difficulty of regulation and control and facilitates automation.

[0070] In this embodiment, the interface assembly further includes a seventh interface 18 and an eighth interface 19, and the on-off valve assembly 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 driving body 82 .

[0072] Both ends of the power passage 81 are communicated with the seventh port 18 and the eighth port 19 respectively.

[0073] The seventh on-off valve 97 is arranged within the range of the seventh interface 18 and the driving body 82, and can be specifically arranged on the seventh interface 18, or arranged on the passage between the seventh interface 18 and the driving body 82, or arranged on the driving body 82. The seventh on-off valve 97 is suitable for adjusting the on-off between the seventh interface 18 and the driving body 82;

[0074] The eighth on-off valve 98 is arranged within the range of the eighth interface 19 and the driving body 82, and can be specifically arranged on the eighth interface 19, or on the passage between the eighth interface 19 and the driving body 82, or on the driving body 82. The eighth on-off valve 98 is suitable for adjusting the on-off between the seventh interface 18 and the driving body 82.

[0075] The driving body 82 is disposed on the power passage 81 .

[0076] In this embodiment, the driving body 82 is provided with a first one-way valve 83 and a second one-way valve 84 along the upstream and downstream of the power passage 81, the eighth interface 19 is provided on the upstream side of the seventh interface 18, and the driving body 82 has a driving state and a suction state. In the driving state, the driving body 82 provides positive pressure to drive the fluid between the first one-way valve 83 and the second one-way valve 84 to flow out from the second one-way valve 84, and in the suction state, the driving body 82 provides negative pressure to drive the fluid on the upstream side of the first one-way valve 83 to flow between the two one-way valves.

[0077] like Figure 6As shown, as a convertible implementation, the eighth on-off valve 98 is configured as a single-pole double-throw valve, which generally includes a common end 981, a first regulating valve port 982, and a second regulating valve port 983, wherein the common end 981 can be connected to the first regulating valve port 982 and the second regulating valve port 983, respectively. When the common end 981 is connected to the first regulating valve port 982, the common end 981 is disconnected from the second regulating valve port 983. At the same time, when the common end 981 is connected to the second regulating valve port 983, the common end 981 is disconnected from the first regulating valve port 982, and the two types of connection cannot coexist. The single-pole double-throw valve can specifically be a solenoid valve, etc., which can realize conduction control under the control of electromagnetic force, spring elastic force, and other forces.

[0078] like Figure 6 As shown, in the above-mentioned convertible embodiment in which the eighth on-off valve 98 is a single-pole double-throw valve, the common end 981 is connected to the driving 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 of which is that the eighth interface 19 is connected to the driving body 82, and the driving body 82 is disconnected from the seventh interface 18, and the second is that the eighth interface 19 is disconnected from the driving body 82, and the driving body 82 is connected to the seventh interface 18. One of the two is selected during adjustment. In addition, the eighth interface 19 is arranged on the upstream side of the seventh interface 18.

[0079] like Figure 6As shown, the eighth on-off valve 98 is a single-pole double-throw valve, which can reduce the number of valves compared with the arrangement of two one-way valves. Furthermore, its cost may increase relative to the arrangement of two one-way valves depending on the type and model of the valve body of the single-pole double-throw valve. However, the advantage of setting a single-pole double-throw valve is that it does not limit the backflow of the power unit 8 toward the main channel 11 through the eighth interface 19, and the user can choose to close the passage to the seventh interface 18, so that the liquid cannot flow toward the seventh interface 18 under the drive of the power unit 8, but flows toward the eighth interface 19. When the chromatography unit 7 is connected with 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 overlaps with the part of the chromatography passage 71 provided with the chromatography unit 7), at this time, the eighth on-off valve 98 and the sixth on-off valve 96 have the same structure, and the liquid can flow directly toward the eighth interface 19 without passing through the chromatography unit 7, and the flow direction is distributed under the action of the main channel 11 and other on-off valves to achieve more flexible liquid control. For example, when liquid does not want to enter the chromatography unit 7 when the pipeline is not cleaned, or when liquid does not want to enter the chromatography unit 7 when the pipeline is emptied, the single-pole double-throw valve can be controlled to connect the power unit 8 and the main channel 11 only through the eighth interface 19. In this way, after closing the fifth on-off valve 95, the chromatography unit 7 can be isolated from the liquid interaction with other parts when the power unit 8 is running, thereby protecting the filler.

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

[0081] In this embodiment, the power unit 8 drives the fluid movement through positive and negative pressure. This setting cooperates with the setting of the main channel 11 and the interface component in the intersection body 1, and can transmit the pressure provided by it to each unit to provide power for each functional component, thereby expanding the scope of driving force provided by the power unit 8 and facilitating the automation of the chromatography purification device.

[0082] Preferably, the driving body 82 is a syringe or a syringe pump, with a storage space 821 and an adjusting member 822 built in, 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 the action of an external force, and correspondingly providing positive and negative pressures to the power passage 81. The adjusting member 822 can be driven manually, or by a motor, an electric push rod, a cylinder or an electric cylinder. Preferably, an extension passage 823 is correspondingly provided on the end of the driving body 82, and the driving body 82 is connected to the power passage 81 through the extension passage 823. It can be understood that the end of the driving body 82 can be directly connected to the power passage 81.

[0083] Preferably, if 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. Further preferably, at this time, the power path 81 and the chromatography path 71 are the same path, the eighth on-off valve 98 and the sixth on-off valve 96 are the same structure, and the fifth on-off valve 95 and the seventh on-off valve 97 are the same structure.

[0084] This arrangement shortens the total length of the passage, saves costs, and reduces the power loss transmitted to the position of the chromatography passage 71, thereby improving the power support for chromatography and thus improving the efficiency of chromatography.

[0085] As a convertible implementation method, Figure 5 As shown, only the fifth interface 16 and the seventh interface 18 may be set as the same interface, and the sixth interface 17 and the eighth interface 19 may be independent interfaces, wherein the power pathway 81 and the chromatography pathway 71 partially overlap.

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

[0087] The chromatography purification device further includes a first liquid detection unit 73, which is suitable for detecting the chromatography purification object in the fluid of the chromatography passage 71 between the chromatography body 72 and the fifth interface 16, or the seventh interface 18. The chromatography purification object refers to the purification object separated from the raw liquid to be purified and bound and fixed by the chromatography body 72.

[0088] The fluid in the chromatography passage 71 between the chromatography body 72 and the fifth interface 16 is the filtrate after the raw liquid to be purified passes through the chromatography body 72. When the first liquid detection unit 73 detects that the chromatography purification object is still present in the filtrate, it can be confirmed that the chromatography body 72 has not completely separated from the raw liquid to be purified and combined with and fixed all the chromatography purification objects, thereby prompting the operator to repeat the chromatography step of passing the filtrate through the chromatography body 72 to further purify the filtrate, thereby ensuring the effectiveness of the chromatography and avoiding sample waste.

[0089] In this embodiment, the first liquid detection unit 73 is a protein detection unit, and the chromatography purification object detected by the first liquid detection unit 73 is protein. Specifically, the protein detection unit is disposed on the downstream side of the chromatography body 72 along the chromatography passage 71 .

[0090] As an alternative embodiment, the protein detection unit may be disposed outside the chromatography passage 71 and aligned with the portion of the chromatography passage 71 on the downstream side of the chromatography body 72 .

[0091] Preferably, the protein detection unit is an ultraviolet detection device. Since protein has an obvious absorption peak in the UV280 ultraviolet band, the ultraviolet detection device confirms whether there is protein in the fluid downstream of the chromatography body 72 by detecting the absorption peak. When the presence of protein is confirmed, the operator can repeat the chromatography step to further purify the filtrate to ensure the effectiveness of the chromatography and avoid sample waste.

[0092] As another convertible implementation, the protein detection unit may also be replaced by other detection components for protein, such as a nitrogen analyzer.

[0093] As another convertible embodiment, when the chromatographic purification object to be detected in the fluid on the downstream side of the chromatography body 72 is non-protein, such as nucleic acid, or when it is necessary to indirectly confirm whether the chromatographic purification object exists in the fluid on the downstream side of the chromatography body 72 through indicators such as pH value, the first detection unit can be set to be a nucleic acid detector or a acid-base detector respectively.

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

[0095] The liquid inlet unit 3 comprises: 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] The two ends of each liquid inlet passage 31 are respectively connected to the liquid inlet tap and the liquid inlet body 32, and a liquid inlet tap valve is provided in the range from the liquid inlet tap to the liquid inlet body 32. The liquid inlet tap valve can be provided on the liquid inlet tap, or on the liquid inlet passage 31 between the liquid inlet tap and the liquid inlet body 32, or on the liquid inlet body 32, and is suitable for regulating the connection and disconnection between the liquid inlet tap and the liquid inlet body 32. In this embodiment, the liquid inlet tap valve is provided at the end of the liquid inlet passage 31 facing the liquid inlet tap, and is connected to the liquid inlet tap.

[0097] In this embodiment, specifically, the second interface 13 includes two liquid inlet sub-interfaces, specifically named as the first liquid inlet sub-interface 131 and the second liquid inlet sub-interface 132, and the second on-off valve 92 includes two liquid inlet sub-valves, specifically named as the first liquid inlet sub-valve 921 and the second liquid inlet sub-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 as: the first liquid inlet branch 311 and the second liquid inlet branch 312, and the two liquid inlet bodies 32 are specifically named as the first liquid inlet split body 321 and the second liquid inlet split body 322.

[0098] The first liquid inlet split body 321, the first liquid inlet branch 311, the first liquid inlet valve 921 and the first liquid inlet tapping interface 131 are interconnected, and the single-channel structure is used to provide the stock solution to be purified. The second liquid inlet split body 322, the second liquid inlet branch 312, the second liquid inlet valve 922 and the second liquid inlet tapping interface 132 are interconnected, and the single-channel structure is used to collect the filtrate remaining after the stock solution to be purified passes through the chromatography body 72 to achieve filtrate recovery. It can be understood that when it is necessary to repeat the step of passing the filtrate through the chromatography body 72, the single-channel structure in which the first liquid inlet split body 321, the first liquid inlet branch 311, the first liquid inlet valve 921 and the first liquid inlet tapping interface 131 are interconnected can also be used to store the remaining filtrate after passing through the chromatography body 72 again.

[0099] This arrangement allows 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 time, or the purity of the filtrate can be improved by circulating through the column between the two structures. The circulating column means that the filtrate obtained by separating the liquid in a single-channel structure after passing through the column is collected in another single-channel structure, and then passed through the column from the other single-channel structure back to the first single-channel structure, and the cycle is repeated.

[0100] As a convertible embodiment, the liquid inlet sub-interface, the liquid inlet sub-valve, the liquid inlet passage 31 and the liquid inlet body 32 can be provided with only one, and the four are interconnected, and the filtrate can be discharged to the waste liquid unit 4, or discharged into the collection unit 2. As another convertible embodiment, the liquid inlet sub-interface, the liquid inlet sub-valve, the liquid inlet passage 31 and the liquid inlet body 32 can be provided with three or more.

[0101] The liquid inlet body 32 has a built-in accommodating chamber, which is a through structure with an opening, preferably located at the top for easy liquid addition, 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 suitable for flowing under the drive of the power unit 8, and can also flow under the combined action of gravity and the power unit 8.

[0102] Preferably, the liquid inlet unit 3 also includes a second liquid detection unit 33, and the second liquid detection unit 33 is arranged on the liquid inlet passage 31. In the present embodiment, the second liquid detection unit 33 is a sensor, which can detect bubbles in the liquid or the passage cavity after the liquid is delivered, and indirectly know whether the sample original liquid in the liquid inlet body 32 is used up, thereby realizing liquid detection. Specifically, it can be a photoelectric bubble sensor, an ultrasonic bubble sensor, a capacitive bubble sensor, etc.

[0103] As a convertible implementation, the second liquid detection unit 33 can also be a flow sensor to detect the total flow of liquid passing through, or it can be set as a liquid level sensor to indirectly know the amount of sample original liquid in the liquid inlet body 32 by detecting the liquid level.

[0104] The second liquid detection unit 33 can provide the user with the usage data of the sample stock solution, and indirectly know whether the sample stock solution in the liquid inlet body 32 is used up, and effectively judge whether it is necessary to enter the next process. In addition, it can also prevent air from entering the chromatography body 72 and causing the purification filler 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 liquid supply part 1 5 and a liquid supply part 2 6. The two parts provide a buffer and an eluent respectively, and the two parts are set separately, so that the user can adjust the ratio of the buffer and the eluent according to the needs, and prepare mixed eluents with different concentration gradients. For protein as the chromatography purification object, the low-concentration eluent is used to wash away the impurities that are not tightly bound to the filler, and the high-concentration eluent is used to elute the protein to be collected. As a convertible embodiment, the type of liquid provided by the liquid supply part 1 5 and the liquid supply part 2 6 can be adjusted according to the chromatography purification object, and can be an alkaline solution or a low-concentration alcohol solution, etc.

[0107] In this embodiment, the liquid supply part 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 tapping port 151, and the first liquid supply sub-valve 941 can be specifically arranged on the first liquid supply tapping port 151, or arranged on the first liquid supply passage 51 between the first liquid supply tapping port 151 and the first container 52, or arranged on the first container 52, and is suitable for regulating the connection and disconnection between the first liquid supply tapping port 151 and the first container 52. In this embodiment, the first liquid supply sub-valve 941 is arranged on the end of the first liquid supply passage 51 facing the first liquid supply tapping port 151, and is connected to the first liquid supply tapping port 151, and the other end of the first liquid supply passage 51 is connected to the first container 52, and the first container 52 is suitable for containing the buffer solution.

[0108] The second liquid supply part 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 tap 152. The second liquid supply valve 942 can be specifically arranged on the second liquid supply tap 152, or arranged on the second liquid supply passage 61 between the second liquid supply tap 152 and the second container 62, or arranged on the second container 62, and is suitable for regulating the connection and disconnection between the second liquid supply tap 152 and the second container 62. In this embodiment, the second liquid supply valve 942 is arranged on the end of the second liquid supply passage 61 facing the second liquid supply tap 152, and is connected to the second liquid supply tap 152. The other end of the second liquid supply passage 61 is connected to the second container 62, and the second container 62 is suitable for containing the eluent; the fluid in the first container 52 and the second container 62 is suitable for flowing to the main channel 11 under the driving action of the power unit 8. It can be understood that the fluid in the two containers can also flow to the main channel 11 under the driving action of the power unit 8, or the combined driving action of gravity and the power unit 8.

[0109] As a convertible embodiment, the fourth on-off valve 94 is arranged as a multi-way valve, specifically a three-way valve, and can also be arranged as a four-way valve or more as needed. In this embodiment, the fourth on-off valve 94 is connected to the fourth interface 15, and 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 suitable for adjusting the on-off of the fourth interface 15 and the first liquid supply valve port, and the fourth interface 15 and the second liquid supply valve port; the liquid supply unit includes: a liquid supply part 1 5 and a liquid supply part 2 6. The first liquid supply part 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 thereof is connected to the first container 52. The first container 52 is suitable for accommodating a buffer solution. The second liquid supply part 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 thereof is connected to the second container 62. The second container 62 is suitable for accommodating an eluent. The fluids in the first container 52 and the second container 62 are suitable for flowing toward the main channel 11 at least under the action of the power unit 8.

[0110] In the above-mentioned convertible embodiment, the fourth on-off valve 94 arranged in this way can reduce the number of valve arrangements. Further, the fourth interface 15 is arranged only as a single interface and is connected to the main channel 11 through a single passage. The next level connected to the fourth interface 15 is a fourth on-off valve 94 in the form of a three-way valve, a four-way valve or more. More channels can be selected, so that two, three or more types of liquids can be connected as needed, and liquids of different concentrations can be mixed before entering the main channel 11, avoiding local liquid concentration fluctuations in the main channel 11 when the mixing is not completely uniform. However, such an arrangement will relatively increase the number of connected pipelines and liquid-containing equipment, increase the equipment volume and cost, and require users to select according to their needs.

[0111] Preferably, the first liquid supply valve 941 and the second liquid supply valve 942 are connected in communication, specifically electrically or wirelessly, so that the connection can be controlled by electrical signals to accurately adjust 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 between the two via a controller, or a direct communication connection between the two.

[0112] The 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, and the third on-off valve 93 can be specifically arranged 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 regulating the on-off between the third interface 14 and the third container 42. In this embodiment, the third on-off valve 93 is on 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, and the third container 42 is suitable for receiving waste liquid under the joint driving action of gravity and the power unit 8. It can be understood that the third container 42 can receive waste liquid only under the action of the power unit 8. As a convertible embodiment, the waste liquid unit 4 can also be set as only a single pipeline or drain port, connected to an external purification device. As another convertible embodiment, the waste liquid unit 4 can also be set as an integral part with the collection unit 2 or the liquid inlet unit 3, under the premise that the container in the collection unit 2 or the liquid inlet unit 3 can be replaced or reused without affecting the detection and collection of the chromatographic purification object.

[0115] The collecting unit 2 includes a collecting passage 21 and a collecting body 22 .

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

[0117] The collecting body 22 includes at least one collecting container. The specific structure of the collecting container is not limited, and it only needs to be able to hold the fluid flowing out of the outlet 23 and purified by chromatography. In this embodiment, it is specifically a test tube on a rack.

[0118] Furthermore, the collecting unit 2 further includes an adjusting unit, specifically, the adjusting unit is arranged at the other end of the collecting passage 21, and the adjusting unit can drive the flow outlet 23 to move to align with the collecting container. Preferably, the alignment process can align the target collecting container from two or more collecting containers to achieve rough calibration as needed, and can also further align with the opening of the target collecting container to achieve fine calibration.

[0119] Preferably, the adjustment unit is provided in the form of a slide or a mechanical arm. As a modified implementation, the adjustment unit may not be provided, and the user manually takes and places the collection body 22 to receive it.

[0120] In this embodiment, each on-off valve and the intersection body 1 are combined into an eight-way valve, and the eight-way valve is preferably a solenoid valve, and each interface thereof can be controlled on and off by a circuit. It can be understood that the eight-way valve can also be set as an eight-way valve that is manually opened and closed. As a convertible embodiment, the eight-way valve can also be changed to a valve body with a corresponding number of passes according to the change in the number of interfaces corresponding to each unit in the first functional component and the second functional component.

[0121] As another convertible embodiment, the on-off valve group and the intersection body 1 are arranged as two independent separate structures, which can be interconnected by connecting parts such as pipes, flanges, and threaded parts, wherein the intersection body 1 is a sealed container with a built-in main channel 11 and a plurality of branch channels or branch interfaces connected to the main channel 11, and the on-off valves included in the on-off valve group can all be solenoid valves, or some of them can be solenoid valves and the other part can be manual valves, or all of them can be manual valves.

[0122] As another convertible implementation, the on-off valve group, the main channel 11, and a plurality of branch channels connected to the main channel 11 and having corresponding interfaces are all independent separate structures and are interconnected through connectors such as pipes, flanges, and threaded parts.

[0123] Further, the chromatography purification device also includes a controller, which can be a single chip microcomputer, a PC PLC, etc., which is respectively connected to the on-off valve group, the second liquid detection unit 33 and the first liquid detection unit 73, specifically electrically or wirelessly. It can be understood that it can also be connected to only one or more of the on-off valves of the on-off valve group, the second liquid detection unit 33 and the first liquid detection unit 73.

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

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

[0126] There are two liquid inlet bodies 32, which are positioned as the first liquid inlet split body 321 and the second liquid inlet split body 322 respectively. The order of the two can be exchanged. It is only for the convenience of explanation at this time. Among them, the first liquid inlet split body 321 is a supply structure for the raw liquid to be purified, and the second liquid inlet split body 322 is a collection structure for the filtrate flowing through the chromatography body 72. The raw liquid to be purified flows through the chromatography body 72 and becomes the filtrate.

[0127] First, the raw liquid to be purified is loaded into the first liquid inlet sub-body 321, the first liquid inlet sub-valve 921, the sixth on-off valve 96 and the first one-way valve 83 are controlled to be open, and the other valves are closed, and the driving body 82 is started to the suction state, and the raw liquid in the first liquid inlet sub-body 321 is driven to pass through the first liquid inlet sub-valve 921, the main channel 11, the sixth on-off valve 96 and the first one-way valve 83, and flows into the driving body 82 for storage;

[0128] Afterwards, the first liquid inlet valve 921, the sixth on-off valve 96 and the first one-way valve 83 are controlled to be closed, and the second liquid inlet valve 922, the fifth on-off valve 95 and the second one-way valve 84 are controlled to be opened, the driving body 82 is adjusted to the driving state, and the raw liquid to be purified is driven to flow through the chromatography body to become a filtrate, and the filtrate flows into the second liquid inlet body 322 through the fifth on-off valve 95, the main channel 11 and the second liquid inlet valve 922, thereby realizing the recovery of the filtrate.

[0129] 2. Elution of impurities:

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

[0131] When eluting impurities, a low-concentration eluent is required. At this time, the second liquid supply sub-valve 942, the sixth on-off valve 96 and the first one-way valve 83 are opened first, and the other on-off valves and the second one-way valve 84 are closed. The driving body 82 is adjusted to the suction state to absorb a small amount of eluent from the second container 62, and then the second liquid supply sub-valve 942 is controlled to be closed, and the first liquid supply sub-valve 941 is opened. The driving body 82 is adjusted to absorb a large amount of buffer solution from the first container 52, and the buffer solution and the eluent are mixed in the driving body 82 to form a low-concentration mixed solution;

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

[0133] 3. Elution of target protein:

[0134] When eluting the target protein, a high concentration of elution buffer is required.

[0135] First, control the second liquid supply valve 942, the sixth on-off valve 96 and the first one-way valve 83 to open, and the other on-off valves and the second one-way valve 84 are closed. Adjust the driving body 82 to the suction state, and the driving body 82 absorbs the eluent from the second container 62. The eluent is a high-concentration eluent. Whether to absorb the buffer solution at this time depends on the situation. If the eluent needs to be diluted, refer to the step of eluting impurities, and adjust the amount of liquid absorbed by the driving body 82 from the first container 52 and the second container 62, so that the buffer solution and the eluent are mixed in a certain proportion. At this time, the proportion of the eluent is relatively high. If the eluent does not need to be diluted, go directly to the next step.

[0136] Next, the second liquid supply valve 942, the sixth on-off valve 96 and the first one-way valve 83 are controlled to be closed, the first on-off valve 91, the fifth on-off valve 95 and the second one-way valve 84 are opened, and the other on-off valves are closed. The driving body 82 passes the high-concentration eluent through the chromatography body 72, so that the high-concentration eluent flows through the chromatography body 72, and the target protein on the chromatography body 72 is separated from the chromatography body 72. The separated target protein continues to flow into the collection unit 2 through the fifth on-off valve 95 and the first on-off valve 91 under the drive of the driving body 82 to achieve collection.

[0137] 4. Pipeline cleaning:

[0138] The first liquid supply sub-valve 941 , the sixth on-off valve 96 and the first one-way valve 83 are controlled to be open, and the remaining on-off valves and the second one-way valve 84 are controlled to be closed.

[0139] The driving body 82 is adjusted to the suction state, the driving body 82 absorbs the buffer solution from the first container 52, and then controls the first liquid supply valve 941, the sixth on-off valve 96 and the first one-way valve 83 to be closed, and controls the fifth on-off valve 95, the third on-off valve 93 and the second one-way valve 84 to be opened. The driving body 82 drives the buffer solution to flow through the chromatography body 72 and the main channel 11 and then flows into the third container 42, thereby realizing pipeline cleaning and waste liquid recovery.

[0140] In this embodiment, the above steps can be performed sequentially. It is understandable that the sequence of the steps can also be adjusted as needed.

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

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

Claims

1. A chromatography purification device, characterized in that: include: The junction body (1) comprises a main channel (11) and an interface component communicating with the main channel (11), wherein the interface component comprises 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); A first functional component, comprising a collecting unit (2), a liquid inlet unit (3), a waste liquid unit (4) and a liquid supply unit, wherein the collecting unit (2) is connected to the confluence body (1) via the first interface (12), the liquid inlet unit (3) is connected to the confluence body (1) via the second interface (13), the waste liquid unit (4) is connected to the confluence body (1) via the third interface (14), and the liquid supply unit is connected to the confluence body (1) via the fourth interface (15); The second functional component comprises a chromatography unit (7) and a power unit (8), wherein the chromatography unit (7) comprises a chromatography passage (71) and a chromatography body (72) arranged on the chromatography passage (71), wherein two ends of the chromatography passage (71) are respectively connected to the fifth interface (16) and the sixth interface (17), and the power unit (8) is connected to the intersection body (1), and the fluid is suitable for making a directional movement in the chromatography passage (71) under the action of the power unit (8); An on-off valve group, comprising 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 arranged in the range from the first interface (12) to the collecting unit (2), and is suitable for adjusting the on-off between the collecting unit (2) and the first interface (12); The second on-off valve (92) is arranged in the range from the second interface (13) to the liquid inlet unit (3), and is suitable for regulating the on-off between the liquid inlet unit (3) and the second interface (13); The third on-off valve (93) is arranged in the range from the third interface (14) to the waste liquid unit (4), and is suitable for regulating the on-off between the waste liquid unit (4) and the third interface (14); The fourth on-off valve (94) is arranged in the range from the fourth interface (15) to the liquid supply unit, and is suitable for adjusting the on-off between the liquid supply unit and the fourth interface (15); The fifth on-off valve (95) is arranged in the range from the fifth interface (16) to the chromatography body (72), and is suitable for adjusting the on-off between the chromatography body (72) and the fifth interface (16); The sixth on-off valve (96) is arranged in the range from the sixth interface (17) to the chromatography body (72), and is suitable for regulating the on-off between the chromatography body (72) and the sixth interface (17).

2. The chromatography purification device according to claim 1, characterized in that: The interface assembly further comprises a seventh interface (18) and an eighth interface (19), and the on-off valve assembly further comprises a seventh on-off valve (97) and an eighth on-off valve (98); The power unit (8) comprises: a power passage (81) and a driving 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 arranged in the range from the seventh interface (18) to the driving body (82), and is suitable for adjusting the on-off between the seventh interface (18) and the driving body (82); the eighth on-off valve (98) is arranged in the range from the eighth interface (19) to the driving body (82), and is suitable for adjusting the on-off between the eighth interface (19) and the driving body (82); The driving body (82) is arranged on the power passage (81).

3. The chromatography purification device according to claim 2, characterized in that: The driving body (82) is provided with a first one-way valve (83) and a second one-way valve (84) respectively along the upstream and downstream of the power passage (81); the eighth interface (19) is provided on the upstream side of the seventh interface (18); the driving body (82) has a driving state of providing positive pressure to drive the fluid between the two one-way valves to flow out from the second one-way valve (84), and has a suction state of providing negative pressure to drive the fluid on the upstream side of the first one-way valve (83) to flow between the two one-way valves.

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

5. The chromatography purification device according to claim 3 or 4, characterized in that: The driving body (82) has a storage space (821) and an adjusting member (822) built therein, 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 the action of an external force, and correspondingly providing positive and negative pressures to the power passage (81).

6. The chromatography purification device 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 device according to claim 6, characterized in that: When a second one-way valve (84) is provided on the power passage (81), the second one-way valve (84) is correspondingly arranged within the range from the chromatography body (72) to the eighth interface (19).

8. The chromatography purification device according to any one of claims 1 to 4 and 7, characterized in that: Also includes: The first liquid detection unit (73) is suitable for detecting the chromatography purification object in the fluid of the chromatography passage (71) between the chromatography body (72) and the fifth interface (16).

9. The chromatography purification device according to claim 8, characterized in that: The first liquid detection unit (73) is a protein detection unit, which is arranged on the chromatography passage (71) on the downstream side of the chromatography body (72), or is arranged outside the chromatography passage (71) and aligned with the portion of the chromatography passage (71) on the downstream side of the chromatography body (72), and is suitable for correspondingly detecting proteins in the fluid of the chromatography passage (71).

10. The chromatography purification device according to claim 9, characterized in that: The protein detection unit is an ultraviolet detection device.

11. The chromatography purification device according to claim 8, characterized in that: The first liquid detection unit (73) is an acid-base detector or a nucleic acid detector, suitable for detecting the pH value or nucleic acid of the fluid on the downstream side of the chromatography body (72).

12. The chromatography purification device according to any one of claims 1-4, 7, 9-11, characterized in that: The second interface (13) includes at least one liquid inlet branch interface, and the second on-off valve (92) includes at least one liquid inlet branch valve; The liquid inlet unit (3) comprises: At least one liquid inlet passage (31), an end of which is in communication with the liquid inlet branch interface and is correspondingly provided with the liquid inlet branch valve; At least one liquid inlet body (32) has a built-in accommodating cavity, the accommodating cavity is provided with an opening, and the bottom of the accommodating cavity is connected to the other end of the corresponding liquid inlet passage (31), and the fluid in the liquid inlet body (32) is suitable for flowing at least under the action of the power unit (8).

13. The chromatography purification device according to claim 12, characterized in that: The liquid inlet unit (3) further comprises: The second liquid detection unit (33) is arranged on the liquid inlet passage (31) and is suitable for detecting cavitation and / or the flow of liquid passing therethrough.

14. The chromatography purification device according to any one of claims 1-4, 7, 9-11, and 13, characterized in that: The fourth interface (15) comprises a first liquid supply sub-interface (151) and a second liquid supply sub-interface (152), and the fourth on-off valve (94) comprises a first liquid supply sub-valve (941) and a second liquid supply sub-valve (942); The liquid supply unit comprises: A liquid supply part (5), comprising a first container (52) and a first liquid supply passage (51), wherein one end of the first liquid supply passage (51) is communicated with the first liquid supply outlet (151) and is correspondingly provided with the first liquid supply valve (941), and the other end thereof is communicated with the first container (52), and the first container (52) is suitable for containing a buffer solution; The second liquid supply part (6) comprises 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 outlet (152) and is correspondingly provided with the second liquid supply valve (942), and the other end thereof is connected to the second container (62), and the second container (62) is suitable for containing the eluent; The fluid in the first container (52) and the second container (62) is suitable for flowing toward the main channel (11) at least under the action of the power unit (8).

15. The chromatography purification device according to any one of claims 1-4, 7, 9-11, and 13, characterized in that: The fourth on-off valve (94) is arranged as a multi-way valve, the fourth on-off valve (94) is in communication with 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 suitable for regulating the on-off of the fourth interface (15) and the first liquid supply valve port, and the fourth interface (15) and the second liquid supply valve port; The liquid supply unit comprises: A liquid supply part (5), comprising a first container (52) and a first liquid supply passage (51), wherein one end of the first liquid supply passage (51) is connected to the first liquid supply valve port, and the other end thereof is connected to the first container (52), and the first container (52) is suitable for containing a buffer solution; The second liquid supply part (6) comprises a second container (62) and a second liquid supply passage (61), wherein one end of the second liquid supply passage (61) is connected to the second liquid supply valve port, and the other end thereof is connected to the second container (62), and the second container (62) is suitable for containing an eluent; The fluid in the first container (52) and the second container (62) is suitable for flowing toward the main channel (11) at least under the action of the power unit (8).

16. The chromatography purification device according to claim 14, characterized in that: The first liquid supply sub-valve (941) and the second liquid supply sub-valve (942) are in communication connection.

17. The chromatography purification device according to any one of claims 1-4, 7, 9-11, 13, and 16, characterized in that: The waste liquid unit (4) comprises a third container (42) and a waste liquid passage (41); one end of the waste liquid passage (41) is in communication with the third interface (14) and is correspondingly provided with the third on-off valve (93); the other end of the waste liquid passage (41) is in communication with the third container (42); the third container (42) is suitable for receiving waste liquid at least under the action of the power unit (8).

18. The chromatography purification device according to any one of claims 1-4, 7, 9-11, 13, and 16, characterized in that: The collecting unit (2) comprises: A collecting passage (21), one end of which is in communication with the first interface (12) and is correspondingly provided with the first on-off valve (91), and the other end of which is provided with an outlet (23); The collecting body (22) comprises at least one collecting container, which is suitable for receiving the fluid flowing out from the outlet (23).

19. The chromatography purification device according to claim 18, characterized in that: The collecting unit (2) further comprises an adjusting unit, which is arranged at the other end of the collecting passage (21) and is suitable for driving the outlet (23) to move so as to align with the collecting container.

20. The chromatography purification device according to claim 19, characterized in that: The adjustment unit is provided in the form of a slide table or a mechanical arm.

21. The chromatography purification device according to any one of claims 1-4, 7, 9-11, 13, 16, 19-20, characterized in that: The on-off valve group is a solenoid valve, and / or the intersection body (1) is an eight-way valve.

22. The chromatography purification device 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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