A three-pump four-valve liquid chromatography system

Abstract

The utility model discloses a three pump four valve liquid chromatography system, including sample injector for sucking sample, extraction flow channel group for conveying first mobile phase, and carrying out preliminary separation to sample, transfer flow channel group for transferring the substance captured on first chromatographic column to second chromatographic column and / third chromatographic column, analysis flow channel group for separating and detecting the captured substance, still include switching main valve, transfer valve, change-over valve and reversing valve, realize the sampling, extraction, transfer, analysis function of liquid chromatograph through the state switching cooperation of above -mentioned four valves, and because only through first connecting pipeline absorbs sample, has saved extraction pump and extraction mobile phase, has simplified the structure, has reduced the use of mobile phase, has reduced the influence that mass spectrometer receives subsequently, automatic to chromatographic column cleaning regeneration, has greatly prolonged the service life of chromatographic column.

Description

Technical Field

[0001] This utility model relates to the field of liquid chromatography, specifically to a three-pump four-valve liquid chromatography system. Background Technology

[0002] Liquid chromatography (LC) operates primarily on the principle of separating sample molecules through the partitioning and adsorption between the stationary and mobile phases, thereby enabling qualitative and quantitative analysis of the sample. LC uses a liquid as the mobile phase and a stationary phase (such as an adsorbent or partitioning agent) to separate different components in the sample. When the sample solution passes through the stationary phase, each component interacts with it. Due to the different partition coefficients of the components between the stationary and mobile phases, their migration velocities within the chromatographic column also differ, thus achieving component separation. Patent No. CN215894507U discloses a "Multidimensional Valve-Controlled Intelligent Liquid Chromatograph," comprising a first chromatographic column, a second chromatographic column, a third chromatographic column, and a fourth chromatographic column. A first chromatographic pump is connected to a first multi-port valve. The two ends of an injector are respectively connected to the first and second multi-port valves. The first chromatographic column is connected to any two ports of the second multi-port valve. The inlet end of the second chromatographic column is connected to the second multi-port valve, and the outlet end of the second chromatographic column is connected to the first and third multi-port valves via a three-way valve. The third chromatographic column is connected to any two ports of the third multi-port valve. The inlet end of the fourth chromatographic column is connected to the third multi-port valve, and the outlet end of the fourth chromatographic column is connected to a detector. The second chromatographic pump is connected to the fourth multi-port valve, and the fourth multi-port valve is connected to both the second and third multi-port valves. This chromatographic system is complex, with multiple mobile phases and corresponding pumps and channels. The mixing of multiple mobile phases increases impurities in the sample, intensifying the separation burden and affecting subsequent mass spectrometry analysis. Online extraction systems, while enriching the target analyte, often also enrich the matrix or impurities, accelerating matrix effects. The analytical columns, especially those with lower efficiency for larger molecular weight ions, are prone to matrix effects, leading to signal drops and rises during continuous analysis, severely impacting results. Furthermore, when analyzing heavily soiled samples online, substances in the sample can contaminate the secondary column, causing it to fail rapidly. The transfer efficiency is low, the chromatographic system is overly complex and redundant, and the scheme cannot automatically regenerate the column. The above-mentioned technical solutions only offer one extraction and transfer method, which is insufficient to meet the needs of complex samples requiring different extraction methods.

[0003] To address the aforementioned problems, this invention provides a three-pump, four-valve liquid chromatography system. Utility Model Content

[0004] In view of the shortcomings of the existing technology, the purpose of this utility model is: Reduce the number of extraction pumps and extraction mobile phases to simplify the structure of online extraction to the greatest extent and improve ease of use; 2. To address the problem in existing technologies that complex matrices may contaminate chromatographic columns and mass spectrometers, affecting the lifespan of chromatographic columns; 3. To address the limitation that existing online liquid chromatography systems offer only one transfer method, making it difficult to meet the extraction requirements of complex samples; 4. Solve the problems of existing liquid chromatography systems where reverse transfer easily leads to contamination and damage of the analytical column due to the enrichment of non-target substances, and the inability of the filtration mechanism to be automatically cleaned.

[0005] The technical solution of this utility model is: This utility model proposes a three-pump, four-valve liquid chromatography system, comprising: a switching main valve with multiple interfaces, a transfer valve with multiple ports, a switching valve with multiple ports, a directional valve with multiple ports, and multiple waste liquid terminals respectively connected to the switching main valve and the transfer valve; and further comprising: A first connecting line, which is connected to a sampling pump and an injector, is used to draw up a first mobile phase. The first connecting line is connected to an interface of a switching main valve. A fourth connecting line is connected to the detector, and the fourth connecting line is connected to one port of the transfer valve; A seventh connecting line is connected to the first chromatographic column, and the two ends of the seventh connecting line are respectively connected to any two ports of the reversing valve; A tenth connecting pipe with an arrestor is provided, the two ends of which are respectively connected to any two ports of the reversing valve; A twelfth connecting line, which is connected to a cleaning pump, is used to draw up the cleaning solution. The twelfth connecting line is connected to one port of the switching valve. A sixteenth connecting line is connected to a second chromatographic column, and the two ends of the sixteenth connecting line are respectively connected to any two ports of the switching valve; A seventeenth connecting line is connected to a third chromatographic column, and the two ends of the seventeenth connecting line are respectively connected to any two ports of the switching valve; And the fifth connecting pipe between the two ports of the switching main valve, the ninth and eleventh connecting pipes between the switching main valve and the transfer valve, the second and fourteenth connecting pipes between the switching main valve and the switching valve, the sixth and eighth connecting pipes between the switching main valve and the directional valve, the third connecting pipe between the transfer valve and the switching valve, and the thirteenth connecting pipe between the two ports of the switching valve.

[0006] Preferably, the switching main valve includes interface a; interface b; interface c; interface d; interface e; interface f; interface g; interface h; interface i; interface j; the transfer valve includes port a; port b; port c; port d; port e; port f; the switching valve includes port g; port h; port i; port j; port k; port l; port m; port n; port o; port p; and the reversing valve includes port q; port r; port s; port t; port u; port v.

[0007] Preferably, one end of the first connecting pipe is connected to the sampling pump, and the other end is connected to interface a; one end of the second connecting pipe is connected to interface j, and the other end is connected to port; one end of the third connecting pipe is connected to port n, and the other end is connected to port e; one end of the fourth connecting pipe is connected to port d, and the other end is connected to the detector; one end of the fifth connecting pipe is connected to interface b, and the other end is connected to interface g; one end of the sixth connecting pipe is connected to interface h, and the other end is connected to port v; one end of the seventh connecting pipe is connected to port q, and the other end is connected to port u; one end of the eighth connecting pipe is connected to port r, and the other end is connected to interface d; The ninth connecting pipe is connected at one end to interface c and at the other end to port a; the tenth connecting pipe is connected at one end to port s and at the other end to port t; the eleventh connecting pipe is connected at one end to port b and at the other end to interface i; the twelfth connecting pipe is connected at one end to the cleaning pump and at the other end to port l; the thirteenth connecting pipe is connected at one end to port k and at the other end to port p; the fourteenth connecting pipe is connected at one end to port g and at the other end to interface e; the sixteenth connecting pipe is connected at one end to port h and at the other end to port o; and the seventeenth connecting pipe is connected at one end to port j and at the other end to port m.

[0008] Preferably, it also includes a waste liquid end, wherein the interface f is connected to the waste liquid end, the port c is connected to the waste liquid end, and the port f is connected to the waste liquid end.

[0009] Preferably, the switching main valve includes a sampling state and an analysis state. When the switching main valve is in the sampling state, interface a and interface b are connected, interface c and interface d are connected, interface e and interface f are connected, interface g and interface h are connected, and interface i and interface j are connected. When the switching main valve is in the analysis state, interface b and interface c are connected, interface d and interface e are connected, interface f and interface g are connected, interface h and interface i are connected, and interface j and interface a are connected.

[0010] Preferably, the transfer valve includes an extraction state and a transfer state. When the transfer valve is in the extraction state, port b is connected to port c, port d is connected to port e, and port f is connected to port a. When the transfer valve is in the transfer state, port a is connected to port b, port c is connected to port d, and port e is connected to port f.

[0011] Preferably, the switching valve includes a first analysis and cleaning state and a second analysis and cleaning state. When the switching valve is in the first analysis and cleaning state, port h is connected to port i, port j is connected to port k, port l is connected to port m, port n is connected to port o, and port g is connected to port p. When the switching valve is in the second analysis and cleaning state, port g is connected to port h, port i is connected to port j, port k is connected to port l, port m is connected to port n, and port o is connected to port p.

[0012] Preferably, the reversing valve includes a forward state and a reverse state. When the reversing valve is in the forward state, port q is connected to port r, port s is connected to port t, and port u is connected to port v. When the reversing valve is in the reverse state, port r is connected to port s, port t is connected to port u, and port v is connected to port q.

[0013] Preferably, it further includes a fifteenth connecting pipe connected to an auxiliary pump for conveying the modulated solution; the fifteenth connecting pipe is connected to the fifth connecting pipe via a tee; the fifth connecting pipe is equipped with a mixer.

[0014] Preferably, the barrier is equipped with a weakly retaining filler or a non-retaining filler, which is mainly used to block particulate impurities or other non-target substances.

[0015] This invention also proposes a three-pump, four-valve liquid chromatography analysis method, applied to the aforementioned three-pump, four-valve liquid chromatography system, which includes the following functions: S1, Extraction function: The sampling pump draws the first mobile phase and passes it sequentially through the first connecting pipe, the fifth connecting pipe, the sixth connecting pipe, the seventh connecting pipe, the eighth connecting pipe, the ninth connecting pipe, and the waste liquid end. The target analyte in the first mobile phase is retained in the first chromatographic column, while non-target components are transported to the waste liquid end. S2, Forward Transfer Function: The first mobile phase is continuously drawn up by the sampling pump and passed sequentially through the first connecting pipe, the fifth connecting pipe, the sixth connecting pipe, the seventh connecting pipe, the eighth connecting pipe, the ninth connecting pipe, the eleventh connecting pipe, the second connecting pipe, the sixteenth connecting pipe, the third connecting pipe, and the waste liquid end. The target component retained in the first chromatographic column in step S1 is pushed by the first mobile phase to the second chromatographic column. S3, Reverse Transfer Function: The first mobile phase is drawn up by the sampling pump and sequentially passed through the first connecting pipe, the fifth connecting pipe, the sixth connecting pipe, the seventh connecting pipe, the tenth connecting pipe, the eighth connecting pipe, the ninth connecting pipe, the eleventh connecting pipe, the second connecting pipe, the sixteenth connecting pipe, the third connecting pipe, and the waste liquid end. The target component retained in the first chromatographic column in step S1 is pushed by the first mobile phase to reverse through the barrier and then transported to the second chromatographic column. S4, Analysis function: The sampling pump continues to draw the first mobile phase, which passes through the first connecting pipe, the second connecting pipe, the sixteenth connecting pipe, the third connecting pipe, and the fourth connecting pipe in sequence, pushing the target component delivered to the second chromatographic column in step S2 or S3 to the detector; S5, Alternating forward transfer function: The first mobile phase is drawn up by the sampling pump and passed sequentially through the first connecting pipe, the fifth connecting pipe, the sixth connecting pipe, the seventh connecting pipe, the eighth connecting pipe, the ninth connecting pipe, the eleventh connecting pipe, the second connecting pipe, the seventeenth connecting pipe, the third connecting pipe, and the waste liquid end. The target component retained in the first chromatographic column in step S1 is pushed by the first mobile phase to the third chromatographic column. S6. Alternating reverse transfer function: The first mobile phase is drawn by the sampling pump and sequentially passes through the first connecting pipe, the fifth connecting pipe, the sixth connecting pipe, the seventh connecting pipe, the tenth connecting pipe, the eighth connecting pipe, the ninth connecting pipe, the eleventh connecting pipe, the second connecting pipe, the seventeenth connecting pipe, the third connecting pipe, and the waste liquid end. The target component retained in the first chromatographic column in step S1 is pushed by the first mobile phase to reverse through the barrier and then transported to the third chromatographic column. S7, Alternating Analysis Function: The sampling pump draws the first mobile phase, which passes sequentially through the first connecting line, the second connecting line, the seventeenth connecting line, the third connecting line, and the fourth connecting line, pushing the target component delivered to the third chromatographic column in step S5 or S6 to the detector. S8. Cleaning function: First cleaning: The cleaning solution is drawn by the cleaning pump and sequentially passed through the twelfth, thirteenth, sixteenth, fourteenth, eighth, tenth, seventh, sixth, eleventh connecting pipes and the waste liquid end. The cleaning solution is pumped to clean the second or third chromatographic column, the barrier and the first chromatographic column. The second cleaning process involves pumping cleaning solution through the twelfth, thirteenth, sixteenth, fourteenth, eighth, seventh, sixth, eleventh connecting pipes and the waste liquid end to clean the second or third chromatographic column and the first chromatographic column.

[0016] Preferably, it further includes: S9, modulation function: in steps S1, S2, S3, S5 and S6, the modulation solution is simultaneously pumped by the auxiliary pump to the fifth connecting pipeline to mix with the first mobile phase, thereby modulating the first mobile phase.

[0017] Compared with the prior art, the beneficial effects of this utility model are: 1. This invention utilizes a flow channel design to achieve a shared analytical mobile phase (first mobile phase) for both extraction and analysis functions. The analytical mobile phase can flow through the extraction column alone or simultaneously and sequentially through both the extraction and analysis columns, enabling collinear use of the mobile phase. Existing technologies typically use different mobile phases for extraction and analysis, preventing the analytical mobile phase from simultaneously flowing through both columns. This invention eliminates the need for an extraction pump and extraction mobile phase, requiring only one pump to perform conventional extraction and analysis functions. This invention significantly simplifies the system structure, reduces the types of solvents used, mitigates the instability caused by solvent alternation, and uses only one analytical mobile phase, resulting in fewer impurities and further reducing instability to subsequent mass spectrometry detection. This invention uses only the analytical mobile phase and the modulation mobile phase, significantly reducing the number of flow channels and resulting in a more indirect structure.

[0018] 2. This invention features a dual-column structure (a second and a third column), which can be used automatically and alternately, allowing analysis and regeneration to be performed separately. Compared to existing single-column technologies, this provides significantly stronger analytical and regeneration capabilities. In complex samples, the matrix is ​​separated using the analytical mobile phase in conjunction with a modulation pump for primary matrix separation. After the co-eluted substances enter the analytical column, substances retained on the secondary / analytical column are transferred to the cleaning channel and regenerated by the cleaning system, reducing matrix effects. Both analytical columns are housed within the same valve body structure, significantly reducing the increase in physical size and complexity caused by increasing the number of valve bodies.

[0019] 3. The cleaning channel of this utility model can sequentially pass through the analytical chromatographic column (second and third chromatographic columns), the barrier, and the extraction chromatographic column (first chromatographic column). When the second chromatographic column is working and analyzing, the third and first chromatographic columns can be cleaned simultaneously, achieving the purpose of two-stage cleaning. At the same time, the rapid regeneration of the third chromatographic column is realized without hindering the analysis process. Similarly, when the third chromatographic column is working and analyzing, the rapid regeneration of the second chromatographic column can also be realized simultaneously, which greatly enhances the matrix resistance of the analytical chromatographic column and extends its service life.

[0020] 4. This invention allows for parallel operation of analysis and cleaning processes, further improving work efficiency. It also features a regeneration function, enabling automatic cleaning of the analytical column, barrier, and extraction column within a single analysis cycle. The cleaning flow channel of this invention sequentially passes through the analytical column, barrier, and extraction column, achieving a two-stage cleaning process.

[0021] 5. This utility model is equipped with a reversing valve, which can control the transfer mode of the target object. Forward or reverse transfer can be switched as needed, which can match the transfer requirements of existing complex samples and improve transfer efficiency and transfer quality.

[0022] 6. This invention incorporates a reverse transfer barrier in the transfer channel to intercept non-target substances and strongly retained substances from the first chromatographic column from transferring to the second chromatographic column. This prevents increased load on the second chromatographic column, avoids contamination and damage due to the accumulation of non-target substances and strongly retained substances, and significantly extends the service life of the second chromatographic column. It also has the function of cleaning and regenerating the barrier.

[0023] 7. This utility model uses only one auxiliary flow path to modulate the mobile phase, realizing online extraction. At the same time, it uses the same auxiliary flow path to realize one-dimensional column separation, reducing the number of key components used in the instrument, reducing costs, and realizing the multi-functionality of a single component.

[0024] This invention realizes the functions of sampling, extraction, transfer, analysis, and cleaning of liquid chromatograph. It is a highly automated liquid chromatography-mass spectrometry system that integrates forward and reverse transfer online extraction, dual analytical column alternating analysis, extraction analysis transfer channel strong retention substance interception system, online desalting, and automatic regeneration.

[0025] The detailed structure of this utility model will be further described below with reference to the accompanying drawings and specific embodiments. Attached Figure Description

[0026] Figure 1 This is a schematic diagram of the structure of Embodiment 1 of the present utility model; Figure 2 This is a schematic diagram of the first analytical cleaning state and extraction function operation state in Embodiment 1 of this utility model; Figure 3 This is a schematic diagram of the operation state of the first analysis and cleaning state forward transfer function in Embodiment 1 of this utility model; Figure 4 This is a schematic diagram of the reverse transfer function of the first analysis and cleaning state in Embodiment 1 of this utility model. Figure 5 This is a schematic diagram of the first analysis and cleaning state analysis function and the first cleaning parallel operation state in the cleaning function of Embodiment 1 of this utility model; Figure 6This is a schematic diagram of the parallel operation of the first analysis and cleaning state analysis function and the second cleaning function in Embodiment 1 of this utility model; Figure 7 This is a schematic diagram of the operation state of the forward transfer function of the second analysis and cleaning state in Embodiment 1 of this utility model; Figure 8 This is a schematic diagram of the operation of the reverse transfer function of the second analysis and cleaning state in Embodiment 1 of this utility model; Figure 9 This is a schematic diagram of the parallel operation state of the first cleaning function in the second analysis and cleaning state analysis function and the cleaning function in Embodiment 1 of this utility model; Figure 10 This is a schematic diagram of the second analysis and cleaning state analysis function and the second cleaning parallel operation state in the cleaning function of Embodiment 1 of this utility model; Figure 11 This is a schematic diagram showing the parallel operation of the modulation and extraction functions in Embodiment 2 of this utility model; Figure 12 This is a schematic diagram of the parallel operation of the first analysis and cleaning state modulation function and the forward transfer function in Embodiment 2 of this utility model; Figure 13 This is a schematic diagram of the parallel operation of the first analysis and cleaning state modulation function and the reverse transfer function in Embodiment 2 of this utility model; Figure 14 This is a schematic diagram of the parallel operation of the second analysis and cleaning state modulation function and the forward transfer function in Embodiment 2 of this utility model; Figure 15 This is a schematic diagram of the parallel operation of the second analysis and cleaning state modulation function and the reverse transfer function in Embodiment 2 of this utility model.

[0027] Component names and corresponding serial numbers: 1. Interface a; 2. Interface b; 3. Interface c; 4. Interface d; 5. Interface e; 6. Interface f; 7. Interface g; 8. Interface h; 9. Interface i; 10. Interface j; 11. Port a; 12. Port b; 13. Port c; 14. Port d; 15. Port e; 16. Port f; 17. Port g; 18. Port h; 19. Port i; 20. Port j; 21. Port k; 22. Port l; 23. Port m; 24. Port n; 25. Port o; 26. Port p; 27. Port q; 28. Port r; 29. ​​Port s; 30. Port t; 31. Port u; 32. Port v; A1, First mobile phase; A2, Washing solution; A3, Preparation solution; P1, Injection pump; AS, Injector; P2, Washing pump; P3, Auxiliary pump; M, Mixer; F, Waste end; T1, T-connector; C1, First column; C2, Second column; DE, Detector; V1, Switching valve; V2, Transfer valve; V3, Switching valve; V4, Directional valve; L1, First connecting line; L2, Second connecting line; L3, Third connecting line; L4, Fourth connecting pipe; L5, Fifth connecting pipe; L6, Sixth connecting pipe; L7, Seventh connecting pipe; L8, Eighth connecting pipe; L9, Ninth connecting pipe; L10, Tenth connecting pipe; L11, Eleventh connecting pipe; L12, Twelfth connecting pipe; L13, Thirteenth connecting pipe; L14, Fourteenth connecting pipe; L15, Fifteenth connecting pipe; L16, Sixteenth connecting pipe; L17, Seventeenth connecting pipe. Detailed Implementation

[0028] 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. The components of the embodiments of this utility model described and shown in the accompanying drawings can be arranged and designed in various different configurations. The following detailed description of the embodiments of this utility model provided in the accompanying drawings is not intended to limit the scope of the claimed utility model, but merely to illustrate selected embodiments of the utility model. All other embodiments obtained by those skilled in the art based on the embodiments of this utility model without inventive effort are within the scope of protection of this utility model.

[0029] Unless otherwise defined, the technical or scientific terms used in this disclosure shall have the ordinary meaning understood by a person skilled in the art to which this disclosure pertains. The words “comprising” or “including” and similar terms used in this disclosure mean that the element or object preceding the word covers the element or object listed after the word and its equivalents, without excluding other elements or objects. The words “connected” or “linked” and similar terms are not limited to physical or mechanical connections, but may also include electrical connections, whether direct or indirect. “Up,” “down,” “left,” “right,” etc., are used only to indicate relative positional relationships. When the absolute position of the described object changes, the relative positional relationship may also change accordingly.

[0030] Example 1

[0031] Please see Figure 1A three-pump, four-valve liquid chromatography system includes: a switching main valve V1 with multiple interfaces, a transfer valve V2 with multiple ports, a switching valve V3 with multiple ports, a directional valve V4 with multiple ports, and multiple waste liquid terminals F respectively connected to the switching main valve V1 and the transfer valve V2; characterized in that: it further includes: A first connecting line L1, which is connected to a sampling pump P1 and an injector AS, is used to draw the first mobile phase A1. The first connecting line L1 is connected to an interface of the switching main valve V1. A fourth connecting pipe L4 is connected to the detector DE, and the fourth connecting pipe L4 is connected to one port of the transfer valve V2; A seventh connecting pipe L7 is connected to the first chromatographic column C1, and the two ends of the seventh connecting pipe L7 are respectively connected to any two ports of the reversing valve V4; The tenth connecting pipe L10 is connected to the blocker Z1, and the two ends of the tenth connecting pipe L10 are respectively connected to any two ports of the reversing valve V4. The twelfth connecting pipe L12, which is connected to the cleaning pump P2, is used to draw the cleaning solution A3. The twelfth connecting pipe L12 is connected to one port of the switching valve V3. The sixteenth connecting pipe L16 is connected to the second chromatographic column C2, and the two ends of the sixteenth connecting pipe L16 are respectively connected to any two ports of the switching valve V3; The seventeenth connecting line L17 is connected to the third chromatographic column C3, and the two ends of the seventeenth connecting line L17 are respectively connected to any two ports of the switching valve V3; And the fifth connecting pipe L5 connecting the two ports of the switching main valve V1, the ninth connecting pipe L9 and the eleventh connecting pipe L11 connecting the switching main valve V1 and the transfer valve V2, the second connecting pipe L2 and the fourteenth connecting pipe L14 connecting the switching main valve V1 and the directional valve V3, the sixth connecting pipe L6 and the eighth connecting pipe L8 connecting the switching main valve V1 and the directional valve V4, the third connecting pipe L3 connecting the transfer valve V2 and the switching valve V3, and the thirteenth connecting pipe L13 connecting the two ports of the switching valve V3.

[0032] The switching main valve V1 has multiple interfaces, which are connected to the sampling channel, extraction channel, analysis channel and transfer channel. It is configured to selectively switch between sampling mode and analysis mode. In sampling mode, it is used to connect the sampling channel with the extraction channel and the transfer channel. In analysis mode, it is used to connect the sampling channel with the analysis channel. Its interfaces include interface a1, interface b2, interface c3, interface d4, interface e5, interface f6, interface g7, interface h8, interface i9 and interface j10.

[0033] The transfer valve V2 has multiple ports, which are connected to the extraction channel, the transfer channel and the analysis channel, and are configured to selectively switch between extraction mode and transfer mode. In the extraction mode, the extraction channel is used to connect to the waste liquid end F, and in the transfer mode, the extraction channel, the second chromatographic column C2 and / or the third chromatographic column C3 and the waste liquid end F are connected. Its ports include port a11, port b12, port c13, port d14, port e15 and port f16.

[0034] A switching valve V3 with multiple ports has ports connected to an extraction channel, a transfer channel, and an analysis channel, and is configured to selectively switch between a first analytical cleaning state and a second analytical cleaning state. The first analytical cleaning state is used for the analysis channel to connect with the second chromatographic column C2, and the second analytical cleaning state is used for the analysis channel to connect with the third chromatographic column C3. Its ports include port g17, port h18, port i19, port j20, port k21, port l22, port m23, port n24, port o25, and port p26.

[0035] The reversing valve V4 has multiple ports, which are connected to the extraction channel, the transfer channel and the cleaning channel, and are configured to selectively switch between a forward state and a reverse state. The forward state is used to connect the first chromatographic column C1 in the forward direction, and the reverse state is used to connect the first chromatographic column C1 and the blocker Z1 in the reverse direction. Its ports include port q27, port r28, port s29, port t30, port u31 and port v32.

[0036] Specifically, one end of the first connecting pipe L1 is connected to the sampling pump P1, and the other end is connected to interface a1; one end of the second connecting pipe L2 is connected to interface j10, and the other end is connected to port 17; one end of the third connecting pipe L3 is connected to port n24, and the other end is connected to port e15; one end of the fourth connecting pipe L4 is connected to port d14, and the other end is connected to detector DE; one end of the fifth connecting pipe L5 is connected to interface b2, and the other end is connected to interface g7; one end of the sixth connecting pipe L6 is connected to interface h8, and the other end is connected to port v32; one end of the seventh connecting pipe L7 is connected to port q27, and the other end is connected to port u31; the first The eighth connecting pipe L8 is connected to port r28 at one end and to interface d4 at the other end; the ninth connecting pipe L9 is connected to interface c3 at one end and to port a11 at the other end; the tenth connecting pipe L10 is connected to port s29 at one end and to port t30 at the other end; the eleventh connecting pipe L11 is connected to port b12 at one end and to interface i9 at the other end; the twelfth connecting pipe L12 is connected to cleaning pump P2 at one end and to port l22 at the other end; the thirteenth connecting pipe L13 is connected to port k21 at one end and to port p26 at the other end; the fourteenth connecting pipe L14 is connected to port g17 at one end and to interface e5 at the other end. The sixteenth connecting pipe L16 is connected to port h18 at one end and to port o25 at the other end; the seventeenth connecting pipe L17 is connected to port j20 at one end and to port m23 at the other end.

[0037] Specifically, it also includes waste liquid terminal F, with interface f6 connected to waste liquid terminal F, port c13 connected to waste liquid terminal F, and port f16 connected to waste liquid terminal F.

[0038] A three-pump, four-valve liquid chromatography system, comprising: The sampling channel is used to pick up the sample and the first mobile phase A1. An extraction channel connected to the first chromatographic column C1 is used to deliver the first mobile phase A1 and to perform preliminary separation of the sample; Simultaneously connected to the transfer channel of the first chromatographic column C1, the second chromatographic column C2 and / or the third chromatographic column C3, for transferring substances captured on the first chromatographic column C1 to the second chromatographic column C2 and / or the third chromatographic column C3; An analytical flow channel connected to a second chromatographic column C2 and / or a third chromatographic column C3 is used for the separation and detection of captured substances; Specifically, it also includes a cleaning channel for reverse cleaning of the first chromatographic column C1, the second chromatographic column C2, the third chromatographic column C3 and / or the blocker Z1; the cleaning channel is connected to a cleaning pump for pumping the cleaning solution A2.

[0039] Specifically, the flow channel for implementing the sampling function includes a first connecting pipe L1, the front end of which is connected to the injection pump P1, and the rear end of the first connecting pipe L1 passes through the injector AS and is connected to the interface a1 of the switching main valve V1.

[0040] Specifically, the flow channel for implementing the analysis function includes a first connecting pipe L1 that is collinear with the flow channel for implementing the sampling function, and also includes a second connecting pipe L2, a third connecting pipe L3, and a fourth connecting pipe L4. The front end of the second connecting pipe L2 is connected to the interface j10 of the switching main valve V1, and the rear end of the second connecting pipe L2 is connected to the port i19 of the switching valve V3. The front end of the third connecting pipe L3 is connected to the port n24 of the switching valve V3. The switching valve V3 has a second chromatographic column C2 and a third chromatographic column C3 arranged in parallel. The front end of the second chromatographic column C2 is connected to the port h18 and port o25 of the switching valve V3, respectively. The front and rear ends of the third chromatographic column C3 are connected to the port j20 and port m23 of the switching valve V3, respectively. The rear end of the third connecting pipe L3 is connected to the port e15 of the transfer valve V2. The front end of the fourth connecting pipe L4 is connected to the port d14 of the transfer valve V2, and the rear end of the fourth connecting pipe L4 is connected to the detector DE.

[0041] Specifically, the flow channel assembly for achieving the extraction function includes a first connecting pipe L1, a fifth connecting pipe L5, a sixth connecting pipe L6, a seventh connecting pipe L7, an eighth connecting pipe L8, and a ninth connecting pipe L9. The front end of the fifth connecting pipe L5 is connected to interface b2 of the switching main valve V1, and the rear end of the fifth connecting pipe L5 passes through the mixer M and connects to interface g7 of the switching main valve V1. The front end of the sixth connecting pipe L6 is connected to interface h8 of the switching main valve V1, and the rear end of the sixth connecting pipe L6 is connected to port v32 of the reversing valve V4. The front end of the seventh connecting pipe L7 is connected to port u31 of the reversing valve V4, and the rear end of the seventh connecting pipe L7 is connected to port q27 of the reversing valve V4 after connecting to the first chromatographic column C1. The front end of the eighth connecting pipe L8 is connected to port r28 of the reversing valve V4, and the rear end of the eighth connecting pipe L8 is connected to interface d4 of the switching main valve V1. The front end of the ninth connecting pipe L9 is connected to the switching main valve V1 and is adjacent to the rear end of the eighth connecting pipe L8. The rear end of the ninth connecting pipe L9 is connected to the transfer valve V2 and is adjacent to the waste liquid end.

[0042] Specifically, the flow channel group that realizes the transfer function includes a first connecting pipe L1, a second connecting pipe L2, a third connecting pipe L3, a fifth connecting pipe L5, a sixth connecting pipe L6, a seventh connecting pipe L7, an eighth connecting pipe L8, and a ninth connecting pipe L9, as well as a tenth connecting pipe L10 and an eleventh connecting pipe L11. The front end of the tenth connecting pipe L10 is connected to port t30 of the reversing valve V4, and the rear end of the tenth connecting pipe L10 passes through the blocker Z1 and is connected to port s29 of the reversing valve V4. The rear end of the eleventh connecting pipe L11 is connected to interface i9 of the switching main valve V1, and the front end of the eleventh connecting pipe L11 is connected to port b12 of the transfer valve V2.

[0043] Specifically, the flow channel assembly for achieving the cleaning function includes the sixth connecting pipe L6, the seventh connecting pipe L7, the eighth connecting pipe L8, the tenth connecting pipe L10, and the eleventh connecting pipe L11, as well as the twelfth connecting pipe L12, the thirteenth connecting pipe L13, and the fourteenth connecting pipe L14. The front end of the twelfth connecting pipe L12 is connected to the cleaning pump P2, and the rear end of the twelfth connecting pipe L12 is connected to port l22 of the switching valve V3. The front end of the thirteenth connecting pipe L13 is connected to port k21 of the switching valve V3, and the rear end of the thirteenth connecting pipe L13 is connected to port p26 of the switching valve V3. The front end of the fourteenth connecting pipe L14 is connected to port g17 of the switching valve V3, and the rear end of the fourteenth connecting pipe L14 is connected to interface e5 of the switching main valve V1.

[0044] Function Description: Please see Figure 2 Extraction function: Turn on the injection pump P1, switch the main valve V1 to the sampling state, switch the transfer valve V2 to the extraction state, and switch the reversing valve V4 to the forward state, so that the first mobile phase A1 moves downstream under the push of the injection pump P1. The sample is introduced into the first mobile phase A1 through the injector AS. The first mobile phase A1 containing the sample enters the first chromatographic column C1 through the first connecting pipe L1, the fifth connecting pipe L5 and the sixth connecting pipe L6 in sequence. The components in the sample begin to separate under the chromatographic separation mechanism of the first mobile phase A1 and the first chromatographic column. The first mobile phase A1 passing through the first chromatographic column C1 enters the transfer valve V2 port f16 through the seventh connecting pipe L7, the eighth connecting pipe L8 and the ninth connecting pipe L9 and is discharged to the waste liquid end F.

[0045] Transfer function: Users can freely choose between two modes: forward transfer and reverse transfer; Forward transfer: Please refer to Figure 3 ,and Figure 7Turn on the injection pump P1, switch the main valve V1 to the sampling state, and deliver the first mobile phase A1 downstream. The sample is introduced into the first mobile phase A1 through the injector AS. The first mobile phase A1 containing the sample enters the first chromatographic column C1 in the forward direction through the first connecting line L1, the fifth connecting line L5, and the sixth connecting line L6 (entering from the front end of the seventh connecting line L7 and exiting from the rear end of the seventh connecting line L7). The components in the sample begin to separate under the chromatographic separation mechanism of the first mobile phase A1 and the first chromatographic column C1. The target component in the sample... As the first mobile phase A1 is about to flow out of the first column C1, the transfer valve V2 is switched to the transfer state, and the ninth connecting line L9 and the eleventh connecting line L11 are connected. This allows the first mobile phase A1 containing the target component to enter the second column C2 or the third column C3 through the eleventh connecting line L11 and the second connecting line L2. The target component that has a strong interaction with the second column C2 and the third column C3 can be captured by the second column C2 and the third column C3. The uncaptured component enters the transfer valve V2 port f16 with the first mobile phase A1 and is discharged to the waste liquid end F.

[0046] Reverse transfer: Please refer to Figure 4 and Figure 8 Turn on the injection pump P1, switch the main valve V1 to the sampling state, and deliver the first mobile phase A1 downstream. The sample is introduced into the first mobile phase A1 through the injector AS. The first mobile phase A1 containing the sample is guided sequentially through the first connecting pipe L1, the fifth connecting pipe L5, and the sixth connecting pipe L6 to enter the first chromatographic column C1 in reverse (entering from the rear end of the seventh connecting pipe L7 and exiting from the front end of the seventh connecting pipe L7). This pushes the impurities retained in the first chromatographic column C1 during the extraction function out of the first chromatographic column C1 in reverse and delivers them to the barrier Z1. The matrix is ​​further intercepted by the barrier Z1, and the transfer valve V2 is switched to the transfer state, opening the ninth connecting pipe L9 and the eleventh connecting pipe L11. This allows the first mobile phase A1 containing the target component to enter the second chromatographic column C2 or the third chromatographic column C3 through the eleventh connecting pipe L11 and the second connecting pipe L2. The target component that has a strong interaction with the second chromatographic column C2 and the third chromatographic column C3 can be captured by the second chromatographic column C2 and the third chromatographic column C3. The uncaptured component enters the transfer valve V2 port f16 with the first mobile phase A1 and is discharged to the waste liquid end F.

[0047] Please see Figure 5 , Figure 6 , Figure 9 and Figure 10Analysis Function: The injection pump P1 is activated, the main valve V1 is switched to analysis mode, and the transfer valve V2 is switched back to extraction mode. The first mobile phase A1 containing the sample is directly connected to the second column C2 and / or the third column C3 via the first connecting line L1 and the second connecting line L2. The target components captured by the second column C2 and / or the third column C3 in the transfer function are propelled by the first mobile phase A1 and then through the third connecting line L3 to the detector DE. The user can freely switch which analytical column (second column C2 / third column C3) is used for the analysis function. When the switching valve V3 is switched to the first analytical cleaning mode, the analysis is completed by the second column C2; when the switching valve V3 is switched to the second analytical cleaning mode, the analysis is completed by the third column C3. The second column C2 and the third column C3 are used alternately for analysis.

[0048] Cleaning function, first cleaning, please refer to [link / reference]. Figure 5 The cleaning pump P2 is turned on, the main valve V1 is switched to maintain the analysis state, the transfer valve V2 is switched to maintain the extraction state, and the reversing valve V4 is in the reverse state. When the switching valve V3 is switched to the first analysis cleaning state, the cleaning solution A3, driven by the cleaning pump P2, flows in the reverse direction through the twelfth connecting pipe L12 through the third chromatographic column C3 (entering from the rear end of the third chromatographic column C3 and flowing out from the front end of the third chromatographic column C3), and then through the thirteenth connecting pipe L13, the fourteenth connecting pipe L14 and the eighth connecting pipe L8, flows in the reverse direction through the barrier Z1 and the first chromatographic column C1 in sequence, realizing the cleaning of the third chromatographic column C3, the barrier Z1 and the first chromatographic column C1, and achieving rapid regeneration. The cleaning solution A2 carrying impurities is discharged to the waste liquid end F through the sixth connecting pipe L6 and the eleventh connecting pipe L11 to the port c13 of the transfer valve V2. The first cleaning is mainly used to clean soluble impurities.

[0049] Second cleaning: Since the large particulate impurities in the blocker Z1 are intercepted by the first chromatographic column during the first cleaning process, a second cleaning is required after the first cleaning. The cleaning pump P2 is turned on, the main valve V1 is switched to analytical mode, the transfer valve V2 is switched to extraction mode, and the reversing valve V4 is switched to forward mode. The cleaning solution A3, driven by the cleaning pump P2, flows in reverse through the twelfth connecting pipe L12 through the third chromatographic column C3, and then, guided by the thirteenth connecting pipe L13, the fourteenth connecting pipe L14, and the eighth connecting pipe L8, flows forward through the first chromatographic column C1, flushing the particulate impurities accumulated at the head of the first chromatographic column C1 to the waste liquid end F, completing the cleaning process. The second cleaning is mainly used to remove particulate impurities.

[0050] Please see Figure 9 and Figure 10This refers to the process of cleaning the second chromatographic column C2 when the switching valve V3 is switched to the second analytical cleaning state. The cleaning process is the same as the cleaning process described above, and will not be repeated here.

[0051] It is worth noting that the cleaning function can run either after the analysis function or in parallel with the analysis function.

[0052] The device of this utility model has a forward transfer operation mode, and the steps of the forward transfer operation mode include: 1) Preparatory steps: Routine analysis function runs; 2) Extraction step: Extraction function runs as described above; 3) Forward transfer step: Forward transfer function runs as described above (if transfer to the third column C3 is selected at this time); 4) Analysis step: Analysis function runs as described above (third column C3); 5) First cleaning step: Cleaning function runs as described above. Cleaning solution A3 passes through the second column C2 (cleansing the second column C2 during analysis on the third column C3), the barrier Z1, and the first column C1 to achieve two-stage and simultaneous cleaning; 6) Second cleaning step: Cleaning solution A3 reverses direction and passes through the second column C2 and the first column C1 to clean and intercept large particles intercepted at the front end of the first column C1, which are carried to the waste liquid end F.

[0053] The device of this utility model has a reverse transfer operation mode, and the steps of the reverse transfer operation mode include: 1) Preparatory steps: Standard analysis function is run; 2) Extraction step: The extraction function is run as described above; 3) Reverse transfer step: The reverse transfer function is run as described above (if transfer to the second column C2 is selected at this time); 4) Analysis step: The analysis function is run as described above (second column C2); 5) First cleaning step: The cleaning function is run as described above, and the cleaning solution A3 passes through the third column C3, the barrier Z1, and the first column C1 to achieve secondary and simultaneous cleaning; 6) Second cleaning step: The cleaning solution A3 passes through the reversed third column C3 and the first column C1, and the large particles intercepted at the front end of the first column C1 are carried to the waste liquid end F.

[0054] Example 2

[0055] A three-pump, four-valve liquid chromatography system, based on Example 1, further includes a modulation channel for conveying modulation solution A3; a tee T1 is provided on the fifth connecting pipe L5, and the modulation channel is connected to the fifth connecting pipe L5 through the tee T1.

[0056] Specifically, the modulation channel includes a fifteenth connecting pipe L15, one end of which is connected to the auxiliary pump P3, and the other end of which is connected to a tee T1.

[0057] Function Description: Please see Figures 11-15Modulation function: During extraction and transfer functions, auxiliary pump P3 can be activated simultaneously to deliver modulation solution A3 to the fifth connecting pipe L5, where it merges with the first mobile phase A1. Modification solution A3 alters the pH, ionic strength, or organic phase ratio of the first mobile phase A1, thereby enhancing the retention of the target component on the first column C1, second column C2, and third column C3, preventing efflux of the target component during extraction and transfer functions. Figure 11 In order to be in Figure 2 A schematic diagram showing the addition of a modulation function to the extraction function; Figure 12 In order to be in Figure 3 A schematic diagram showing the state of adding a modulation function to the forward transfer function of the second chromatographic column C2; Figure 13 In order to be in Figure 4 A schematic diagram showing the state of adding a modulation function to the reverse transfer function of the second chromatographic column C2; Figure 14 In order to be in Figure 7 A schematic diagram showing the addition of a modulation function to the forward transfer function of the third chromatographic column C3; Figure 15 In order to be in Figure 8 A schematic diagram showing the state of adding modulation function to the reverse transfer function of the third chromatographic column C2.

[0058] The above are specific embodiments of this utility model, but the protection scope of this utility model is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the technical scope disclosed in this utility model, based on the technical solution and concept of this utility model, should be covered within the protection scope of the claims of this utility model.

Claims

1. A three-pump, four-valve liquid chromatography system, comprising: The system comprises a switching main valve (V1) with multiple interfaces, a transfer valve (V2) with multiple ports, a switching valve (V3) with multiple ports, a directional valve (V4) with multiple ports, and multiple waste liquid terminals (F) respectively connected to the switching main valve (V1) and the transfer valve (V2); characterized in that it further comprises: A first connecting line (L1) connected to a sampling pump (P1) and an injector (AS) is used to draw up a first mobile phase (A1). The first connecting line (L1) is connected to an interface of a switching main valve (V1). A fourth connection line (L4) is connected to a detector (DE), and the fourth connection line (L4) is connected to one port of the transfer valve (V2); A seventh connecting line (L7) is connected to the first chromatographic column (C1), and the two ends of the seventh connecting line (L7) are respectively connected to any two ports of the reversing valve (V4); A tenth connecting pipe (L10) connected to a stopper (Z1) has its two ends connected to any two ports of a reversing valve (V4). A twelfth connecting line (L12) connected to the cleaning pump (P2) is used to draw the cleaning solution (A2), and the twelfth connecting line (L12) is connected to one port of the switching valve (V3); A sixteenth connecting line (L16) is connected to the second chromatographic column (C2), and the two ends of the sixteenth connecting line (L16) are respectively connected to any two ports of the switching valve (V3); The seventeenth connecting line (L17) is connected to the third chromatographic column (C3), and the two ends of the seventeenth connecting line (L17) are respectively connected to any two ports of the switching valve (V3); The fifth connecting line (L5) connects the two ports of the switching main valve (V1), the ninth connecting line (L9) and the eleventh connecting line (L11) connect the switching main valve (V1) and the transfer valve (V2), the second connecting line (L2) and the fourteenth connecting line (L14) connect the switching main valve (V1) and the switching valve (V3), the sixth connecting line (L6) and the eighth connecting line (L8) connect the switching main valve (V1) and the directional valve (V4), the third connecting line (L3) connects the transfer valve (V2) and the switching valve (V3), and the thirteenth connecting line (L13) connects the two ports of the switching valve (V3).

2. The three-pump, four-valve liquid chromatography system according to claim 1, characterized in that: The switching main valve (V1) includes ports a (1); b (2); c (3); d (4); e (5); f (6); g (7); h (8); i (9); j (10); the transfer valve (V2) includes ports a (11); b (12); c (13); d (14); e (15); f (16); the switching valve (V3) includes ports g (17); h (18); i (19); j (20); k (21); l (22); m (23); n (24); o (25); p (26); the reversing valve (V4) includes ports q (27); r (28); s (29); t (30); u (31); v (32).

3. The three-pump four-valve liquid chromatography system according to claim 2, characterized in that: One end of the first connecting pipe (L1) is connected to the sampling pump (P1), and the other end is connected to the interface a (1); One end of the second connecting pipe (L2) is connected to interface j (10), and the other end is connected to port i (19); The third connecting pipe (L3) is connected to port n (24) at one end and to port e (15) at the other end; One end of the fourth connecting pipe (L4) is connected to port d (14), and the other end is connected to the detector (DE). The fifth connecting pipe (L5) is connected to interface b (2) at one end and to interface g (7) at the other end; The sixth connecting pipe (L6) is connected at one end to interface h (8) and at the other end to port v (32); The seventh connecting pipe (L7) is connected to port q (27) at one end and to port u (31) at the other end; The eighth connecting pipe (L8) is connected at one end to port r (28) and at the other end to interface d (4); One end of the ninth connecting pipe (L9) is connected to interface c (3), and the other end is connected to port a (11); The tenth connecting pipe (L10) is connected at one end to port s (29) and at the other end to port t (30); The eleventh connecting pipe (L11) is connected at one end to port b (12) and at the other end to interface i (9); One end of the twelfth connecting pipe (L12) is connected to the cleaning pump (P2), and the other end is connected to port l (22); The thirteenth connecting pipe (L13) is connected at one end to port k (21) and at the other end to port p (26); The fourteenth connecting pipe (L14) is connected at one end to port g (17) and at the other end to interface e (5); The sixteenth connecting pipe (L16) is connected at one end to port h (18) and at the other end to port o (25); The seventeenth connecting pipe (L17) is connected to port j (20) at one end and to port m (23) at the other end.

4. The three-pump, four-valve liquid chromatography system according to claim 2, characterized in that: It also includes a waste liquid end (F), the interface f (6) is connected to the waste liquid end (F), the port c (13) is connected to the waste liquid end (F), and the port f (16) is connected to the waste liquid end (F).

5. A three-pump, four-valve liquid chromatography system according to any one of claims 2-4, characterized in that: The switching main valve (V1) includes a sampling state and an analysis state. When the switching main valve (V1) is in the sampling state, interface a (1) and interface b (2) are connected, interface c (3) and interface d (4) are connected; interface e (5) and interface f (6) are connected, interface g (7) and interface h (8) are connected, and interface i (9) and interface j (10) are connected. When the switching main valve (V1) is in the analysis state, interface b (2) and interface c (3) are connected; interface d (4) and interface e (5) are connected, interface f (6) and interface g (7) are connected, interface h (8) and interface i (9) are connected, and interface j (10) and interface a (1) are connected.

6. A three-pump four-valve liquid chromatography system according to any one of claims 2-4, characterized in that: The transfer valve (V2) includes an extraction state and a transfer state. When the transfer valve (V2) is in the extraction state, port b (12) is connected to port c (13), port d (14) is connected to port e (15), and port f (16) is connected to port a (11). When the transfer valve (V2) is in the transfer state, port a (11) is connected to port b (12), port c (13) is connected to port d (14), and port e (15) and port f (16) are connected.

7. A three-pump four-valve liquid chromatography system according to any one of claims 2-4, characterized in that: The switching valve (V3) includes a first analysis cleaning state and a second analysis cleaning state. When the switching valve (V3) is in the first analysis cleaning state, port h (18) is connected to port i (19), port j (20) is connected to port k (21), port l (22) is connected to port m (23), port n (24) is connected to port o (25), and port g (17) is connected to port p (26). When the switching valve (V3) is in the second analysis cleaning state, port g (17) is connected to port h (18), port i (19) is connected to port j (20), port k (21) is connected to port l (22), port m (23) is connected to port n (24), and port o (25) is connected to port p (26).

8. A three-pump four-valve liquid chromatography system according to any one of claims 2-4, characterized in that: The reversing valve (V4) includes a forward state and a reverse state. When the reversing valve (V4) is in the forward state, port q (27) is connected to port r (28), port s (29) is connected to port t (30), and port u (31) is connected to port v (32). When the reversing valve (V4) is in the reverse state, port r (28) is connected to port s (29), port t (30) is connected to port u (31), and port v (32) is connected to port q (27).

9. A three-pump four-valve liquid chromatography system according to any one of claims 1-4, characterized in that: It also includes a fifteenth connecting line (L15) connected to an auxiliary pump (P3) for conveying the conditioning solution (A3); the fifteenth connecting line (L15) is connected to the fifth connecting line (L5) via a tee (T1); the fifth connecting line (L5) is equipped with a mixer (M).

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