A reversible on-line extraction liquid chromatography system

Abstract

The utility model discloses a kind of reversible online extraction liquid chromatography systems, comprising: the switching main valve of multiple interfaces is equipped with, the transfer valve of multiple ports is equipped with, the reversing valve of multiple ports is equipped with and multiple waste liquid ends respectively connected on switching main valve and transfer valve;Still including multiple connecting pipelines between switching main valve, transfer valve or switching valve, multiple connecting pipelines are respectively connected with sampling pump, sample injector, detector, first chromatographic column, second chromatographic column, blocker and cleaning pump;The utility model is realized by the state switching cooperation of switching main valve, transfer valve and reversing valve, the sampling of liquid chromatograph, extraction, transfer, fractionation function, it is a kind of with forward and reverse transfer online extraction, extraction analysis transfer flow channel's particle interception system, extraction analysis transfer flow channel's strong retention material interception system, on-line desalting, automatic regeneration integrated highly automated liquid chromatography mass spectrometry system.

Description

Technical Field

[0001] This utility model relates to the field of liquid chromatography, specifically to a reversible online extraction liquid chromatography system. Background Technology

[0002] Liquid chromatography (LC) is a chemical technique used to separate, purify, and analyze mixtures. Its core principle is to separate components by utilizing the differences in the distribution of different substances between the "mobile phase" (liquid solvent) and the "stationary phase" (packing material in the chromatographic column).

[0003] Online extraction is the most common method for automating chromatography-mass spectrometry (GC-MS). For simultaneous analysis of multi-component substances and analysis of single-component substances, online extraction often requires different extraction methods. When the target analyte transfers from the extraction column to the analytical column, there are usually two methods: forward transfer and reverse transfer. Current online GC-MS systems typically lack the capability to support both transfer methods. Even if they do, the following problems exist: In reverse transfer, due to the simultaneous elution of strongly and weakly retained substances at the column head to the analytical column, the analytical column becomes heavily loaded, increasing contamination. Therefore, the amount of substance transferred from the extraction column to the analytical column needs to be reduced. Thus, during reverse transfer, the highly enriched non-target substances and particles on the extraction column can easily damage the analytical column. Current systems typically add a filtration mechanism between the extraction and analytical columns, but this mechanism lacks automatic cleaning capabilities, often leading to uncertainties in the current analytical process.

[0004] Patent No. CN206330945U discloses "A Liquid Chromatography Analyzer," which includes: a first flow channel connected to a first chromatographic column for transporting a mixed mobile phase, wherein a stirrer, an injector, and a protector are respectively provided on the first flow channel; a multi-flow channel switching valve having seven ports, wherein any four ports on the multi-flow channel switching valve are respectively connected to the ports of the first flow channel, the second flow channel, the waste liquid flow channel, and the analytical flow channel, and any two ports of the remaining three ports are respectively connected to the two ports of a three-way valve through pipes A and B; a storage valve having a second chromatographic column connected between any two ports, and any two ports of the storage valve being respectively connected to the last port on the multi-flow channel switching valve and the three-way valve through connecting pipes A and B; a third chromatographic column disposed on the analytical flow channel; and a detector disposed at the end of the analytical flow channel. The above technical solution requires transferring the target substance from the first chromatographic column to the third chromatographic column for analysis, and then temporarily storing it in the second chromatographic column. The chromatographic system structure is too complex and redundant, the transfer efficiency is low, and there is only one forward transfer method, which is too limited to meet the current demand for extraction methods for complex samples.

[0005] To address the aforementioned problems, this invention provides a reversible online extraction liquid chromatography system. Utility Model Content

[0006] In view of the shortcomings of the existing technology, the purpose of this utility model is: 1. 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 limitation of existing online liquid chromatography systems with their single transfer method, which makes it difficult to meet the extraction requirements of complex samples; 3. 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.

[0007] To achieve the purpose of this utility model, the technical solution of this utility model is as follows: This utility model provides a reversible online extraction liquid chromatography system, comprising: a switching main valve with multiple interfaces, a transfer valve with multiple ports, a reversing 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 second connecting line is connected to a second chromatographic column, and the two ends of the second connecting line are respectively connected to an interface of the switching main valve and a port of the transfer valve; A third connection line connected to the detector is connected to one port of the transfer valve; A sixth connecting line is connected to the first chromatographic column, and the two ends of the sixth connecting line are respectively connected to any two ports of the reversing valve; A seventh connecting pipe with an arrestor is provided, the two ends of which are respectively connected to any two ports of the reversing valve; An eleventh connecting line, which is connected to a cleaning pump, is used to draw up the cleaning solution. The eleventh connecting line is connected to an interface of the switching main valve. And a fourth connecting pipe connecting the two ports of the switching main valve, a fifth and an eighth connecting pipe connecting the switching main valve and the directional valve, and a ninth and a tenth connecting pipe connecting the switching main valve and the transfer valve.

[0008] 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.

[0009] 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; and the directional valve includes port q; port r; port s; port t; port u; and port v.

[0010] 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 e; one end of the third connecting pipe is connected to port d, and the other end is connected to the detector; one end of the fourth connecting pipe is connected to interface b, and the other end is connected to interface g; one end of the fifth connecting pipe is connected to interface h, and the other end is connected to port v; one end of the sixth connecting pipe is connected to port q, and the other end is connected to port u; one end of the seventh connecting pipe is connected to port s, and the other end is connected to port t; one end of the eighth connecting pipe is connected to port r, and the other end is connected to interface d; one end of the ninth connecting pipe is connected to interface c, and the other end is connected to port a; one end of the tenth connecting pipe is connected to interface i, and the other end is connected to port b; one end of the eleventh connecting pipe is connected to the cleaning pump, and the other end is connected to interface e.

[0011] Preferably, 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.

[0012] 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.

[0013] 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.

[0014] 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.

[0015] Preferably, it further includes a twelfth connecting pipe connected to an auxiliary pump for conveying the modulating solution; the twelfth connecting pipe is connected to the fourth connecting pipe via a tee; the fourth connecting pipe is equipped with a mixer.

[0016] This invention also provides a reversible online extraction liquid chromatography analysis method, applied to the aforementioned reversible online extraction liquid chromatography system, including the following functions: S1. Extraction: The first mobile phase is drawn up by the sampling pump and passed sequentially through the first connecting pipe, the fourth connecting pipe, the fifth connecting pipe, the sixth connecting pipe, the eighth connecting pipe, the ninth connecting pipe, and the waste liquid end. The target substance in the first mobile phase is retained in the first chromatographic column, and the non-target substance is transported to the waste liquid end. S2. Forward transfer: The first mobile phase is continuously drawn up by the sampling pump and passed sequentially through the first connecting pipe, the fourth connecting pipe, the fifth connecting pipe, the sixth connecting pipe, the eighth connecting pipe, the ninth connecting pipe, the tenth connecting pipe, the second connecting pipe, and the waste liquid end. The target substance retained in the first chromatographic column in step S1 is pushed by the first mobile phase to the second chromatographic column. S3. Reverse transfer: The first mobile phase is drawn up by the sampling pump and passed sequentially through the first connecting pipe, the fourth connecting pipe, the fifth connecting pipe, the sixth connecting pipe, the seventh connecting pipe, the eighth connecting pipe, the ninth connecting pipe, the tenth connecting pipe, the second connecting pipe, and the waste liquid end. The target substance retained in the first chromatographic column in step S1 is pushed by the first mobile phase through the barrier to the second chromatographic column. S4. Analysis: The sampling pump draws up the first mobile phase, which passes through the first connecting pipe, the second connecting pipe and the third connecting pipe in sequence, and pushes the target analyte sent to the second chromatographic column in step S2 or S3 to the detector. S5. First cleaning: The cleaning solution is drawn up by the cleaning pump and sequentially passed through the eleventh connecting pipe, the eighth connecting pipe, the seventh connecting pipe, the sixth connecting pipe, the fifth connecting pipe, the tenth connecting pipe, and the waste liquid end. The cleaning solution is then pumped to clean the barrier and the first chromatographic column. S6. Second cleaning: After step S5, the cleaning solution is continuously drawn up by the cleaning pump and sequentially passed through the eleventh connecting pipe, the eighth connecting pipe, the sixth connecting pipe, the fifth connecting pipe, the tenth connecting pipe, and the waste liquid end to clean the first chromatographic column.

[0017] The first or second cleaning function can be run independently after the analysis function, or it can be run in parallel with the analysis function.

[0018] Preferably, the method further includes step S7: S7, modulation: In steps S1, S2 and S3, the modulation solution is synchronously pumped by the auxiliary pump to the fourth connecting pipeline to mix with the first mobile phase.

[0019] Compared with the prior art, the beneficial effects of this utility model are: 1. This invention utilizes a flow channel design to enable the extraction column and analytical column to share the same analytical mobile phase (i.e., the first mobile phase). The analytical mobile phase can flow through the extraction column alone or simultaneously and sequentially through both columns, achieving co-linear use of the mobile phase. Existing technologies typically use different mobile phases for the extraction and analytical columns, preventing the analytical mobile phase from flowing through both simultaneously. This invention eliminates the need for an extraction pump and extraction mobile phase, requiring only one pump to achieve conventional extraction and analysis functions. This invention significantly simplifies the system structure, reduces the types of solvents used, lowers 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.

[0020] 2. This utility model is equipped with a reversing valve, which can control the transfer mode of the target object (forward transfer / reverse transfer), and can match the transfer requirements of existing complex samples, thereby improving transfer efficiency and transfer quality.

[0021] 3. This utility model incorporates a reverse transfer barrier in the transfer channel to intercept non-target substances and strongly retained substances in the first chromatographic column from transferring to the second chromatographic column. This prevents an increase in the load on the second chromatographic column, avoids contamination and damage caused by the enrichment of non-target substances and strongly retained substances, and significantly extends the service life of the second chromatographic column.

[0022] 4. This utility model can quickly remove non-target substances retained in the barrier and the first chromatographic column during extraction and transfer by cleaning the flow channel online, thereby achieving rapid regeneration and efficient operation of the first chromatographic column, ensuring cleanliness, and significantly improving the service life of the barrier and the first chromatographic column.

[0023] 5. The analysis and cleaning processes of this invention can be run in parallel, allowing the automatic cleaning of the first chromatographic column and the reverse transfer blocker to be completed automatically within one analysis cycle, further improving work efficiency.

[0024] 6. This utility model uses only one auxiliary modulation channel to modulate the mobile phase, enabling online extraction while using the same auxiliary flow path to achieve one-dimensional column separation. This reduces the number of key components used in the instrument, lowers costs, and achieves multi-functionality of a single component.

[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 extraction function operation status in Embodiment 1 of this utility model; Figure 3 This is a schematic diagram of the forward transfer function operation state in Embodiment 1 of this utility model; Figure 4 This is a schematic diagram of the reverse transfer function operation status in Embodiment 1 of this utility model; Figure 5 This is a schematic diagram of the operation status of the analysis function in Embodiment 1 of this utility model; Figure 6 This is a schematic diagram of the parallel operation of the analysis function and the first cleaning function in Embodiment 1 of this utility model; Figure 7 This is a schematic diagram of the parallel operation of the analysis function and the second cleaning (opposite to the first cleaning direction) in Embodiment 1 of this utility model. Figure 8 This is a schematic diagram showing the parallel operation of the modulation and extraction functions in Embodiment 2 of this utility model; Figure 9 This is a schematic diagram showing the parallel operation of the modulation function and the forward transfer function in Embodiment 2 of this utility model; Figure 10 This is a schematic diagram showing the parallel operation of the modulation function and the reverse transfer function in Embodiment 2 of this utility model; 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; 27. Port q; 28. Port r; 29. ​​Port s; 30. Port t; 31. Port u; 32. Port v; A1, First mobile phase; A2, Preparation solution; A3, Washing solution; P1, Sampling pump; AS, Injector; P2, Washing pump; P3, Auxiliary pump; M, Mixer; F, Waste end; T1, T-connector; C1, First column; C2, Second column; Z1, Barrier; DE, Detector; V1, Switching main valve; V2, Transfer valve; V4, Directional valve; L1, First connecting line; L2, Second connecting line; L3, Third connecting line; L4, Fourth connecting line; L5, Fifth connecting line; L6, Sixth connecting line; L7, Seventh connecting line; L8, Eighth connecting line; L9, Ninth connecting line; L10, Tenth connecting line; L11, Eleventh connecting line; L12, Twelfth connecting line. Detailed Implementation

[0027] 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.

[0028] 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. Example 1

[0029] Please see Figure 1 A reversible online extraction liquid chromatography system includes: a switching main valve V1 with multiple interfaces, a transfer valve V2 with multiple ports, a reversing 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 second connecting pipe L2 is connected to a second chromatographic column C2. The two ends of the second connecting pipe L2 are respectively connected to an interface of the switching main valve V1 and a port of the transfer valve V2. A third connecting pipe L3 is connected to the detector DE, and the third connecting pipe L3 is connected to one port of the transfer valve V2; A sixth connecting pipe L6 is connected to the first chromatographic column C1, and the two ends of the sixth connecting pipe L6 are respectively connected to any two ports of the reversing valve V4; A seventh connecting pipe L7 is connected to the blocker Z1, and the two ends of the seventh connecting pipe L7 are respectively connected to any two ports of the reversing valve V4. The eleventh connecting pipe L11, which is connected to the cleaning pump P2, is used to draw the cleaning solution A3. The eleventh connecting pipe L11 is connected to an interface of the switching main valve V1. And the fourth connecting pipe L4 connecting the two ports of the switching main valve V1, the fifth connecting pipe L5 and the eighth connecting pipe L8 connecting the switching main valve V1 and the reversing valve V4, and the ninth connecting pipe L9 and the tenth connecting pipe L10 connecting the switching main valve V1 and the transfer valve V2.

[0030] The switching main valve V1 includes ports a1, b2, c3, d4, e5, f6, g7, h8, i9, and j10; the transfer valve V2 includes ports a11, b12, c13, d14, e15, and f16; and the directional valve V4 includes ports q27, r28, s29, t30, u31, and v32.

[0031] One end of the first connecting pipe L1 is connected to the sampling pump P1, and the other end is connected to the interface a1; One end of the second connecting pipe L2 is connected to interface j10, and the other end is connected to port e15; One end of the third connecting pipe L3 is connected to port d14, and the other end is connected to detector DE; One end of the fourth connecting pipe L4 is connected to interface b2, and the other end is connected to interface g7; One end of the fifth connecting pipe L5 is connected to interface h8, and the other end is connected to port v32; One end of the sixth connecting pipe L6 is connected to port q27, and the other end is connected to port u31; One end of the seventh connecting pipe L7 is connected to port s29, and the other end is connected to port t30; One end of the eighth connecting pipe L8 is connected to port r28, and the other end is connected to interface d4; One end of the ninth connecting pipe L9 is connected to interface c3, and the other end is connected to port a11; One end of the tenth connecting pipe L10 is connected to interface i9, and the other end is connected to port b12; One end of the eleventh connecting pipe L11 is connected to the cleaning pump P2, and the other end is connected to the interface e5.

[0032] The interface f6 is connected to the waste liquid end F, the port c13 is connected to the waste liquid end F, and the port f16 is connected to the waste liquid end F.

[0033] 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 a1 and interface b2 are connected, interface c3 and interface d4 are connected, interface e5 and interface f6 are connected, interface g7 and interface h8 are connected, and interface i9 and interface j10 are connected. When the switching main valve V1 is in the analysis state, interface b2 and interface c3 are connected, interface d4 and interface e5 are connected, interface f6 and interface g7 are connected, interface h8 and interface i9 are connected, and interface j10 and interface a1 are connected.

[0034] The transfer valve V2 includes an extraction state and a transfer state. When the transfer valve V2 is in the extraction state, port b12 is connected to port c13, port d14 is connected to port e15, and port f16 is connected to port a1. When the transfer valve V2 is in the transfer state, port a11 is connected to port b12, port c13 is connected to port d14, and port e15 is connected to port f16.

[0035] The reversing valve V4 includes a forward state and a reverse state. When the reversing valve V4 is in the forward state, port q27 is connected to port r28, port s29 is connected to port t30, and port u31 is connected to port v32. When the reversing valve V4 is in the reverse state, port r28 is connected to port s29, port t30 is connected to port u31, and port v32 is connected to port q27.

[0036] Specifically, it also includes a cleaning channel assembly connected to the first chromatographic column C1 and the blocker Z1, used to perform reverse cleaning of the first chromatographic column C1 and the blocker Z1; the cleaning channel assembly is connected to the cleaning pump P2, the switching main valve V1 and the transfer valve V2. When the cleaning channel assembly is connected, the switching main valve V1 is in the analysis state and the transfer valve V2 is in the extraction state.

[0037] Specifically, the sampling channel includes a first connecting pipe L1, one end of which is connected to the sampling pump P1, and the other end of which is connected to the interface a1 of the switching main valve V1.

[0038] Specifically, the flow channel for implementing the analysis function includes a first connecting pipe L1 that is collinear with the flow channel used for sampling, and also includes a second connecting pipe L2 and a third connecting pipe L3. One end of the second connecting pipe L2 is connected to the interface j10 of the switching main valve V1, and the other end of the second connecting pipe L2 is connected to the port e15 of the transfer valve V2. One end of the third connecting pipe L3 is connected to the port d14 of the transfer valve V2, and one end of the third connecting pipe L3 is connected to the detector DE.

[0039] Specifically, the flow channel for realizing the extraction function includes a first connecting pipe L1 collinear with the flow channel used for sampling, and also includes a fourth connecting pipe L4, a fifth connecting pipe L5, a sixth connecting pipe L6, an eighth connecting pipe L8, and a ninth connecting pipe L9. One end of the fourth connecting pipe L4 is connected to the interface b2 of the switching main valve V1, and the other end of the fourth connecting pipe L4 is connected to the interface g7 of the switching main valve V1; one end of the fifth connecting pipe L5 is connected to the interface h8 of the switching main valve V1, and the other end of the fifth connecting pipe L5 is connected to the end of the reversing valve V4. The front end of the sixth connecting pipe L6 is connected to port u31 of the reversing valve V4, and the rear end of the sixth connecting pipe L6 passes through the first chromatographic column C1 and is connected to port q27 of the reversing valve V4; 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 interface c3 of the switching main valve V1, and the rear end of the ninth connecting pipe L9 is connected to port a11 on the transfer valve V2, and port f16 is connected to the waste liquid end F.

[0040] Specifically, the flow channel for realizing the transfer function includes a first connecting pipe L1, a second connecting pipe L2, a fourth connecting pipe L4, a fifth connecting pipe L5, and a sixth connecting pipe L6 that are collinear with the flow channel for realizing the extraction function and the flow channel for realizing the analysis function. It also includes a seventh connecting pipe L7 and a tenth connecting pipe L10. The front end of the seventh connecting pipe L7 is connected to port t30 of the reversing valve V4, and the rear end of the seventh connecting pipe L7 is connected to port s29 of the reversing valve V4. One end of the tenth connecting pipe L10 is connected to interface i9 of the switching main valve V1, and the other end of the tenth connecting pipe L10 is connected to port b12 of the transfer valve V2, and port c13 is connected to the waste liquid end F.

[0041] Specifically, the flow channel that realizes the cleaning function includes the fifth connecting pipe L5 and the seventh connecting pipe L7, which are collinear with the flow channel that realizes the transfer function, and also includes the eleventh connecting pipe L11. One end of the eleventh connecting pipe L11 is connected to the cleaning pump P2, and the other end of the eleventh connecting pipe L11 is connected to the interface e5 of the switching main valve V1. The interface f6 of the switching main valve V1 is connected to the waste liquid end F to form the waste liquid end.

[0042] Function Description: Please see Figure 2 Extraction function: When the sampling pump P1 is turned on, the main valve V1 is switched to the sampling state and the transfer valve V2 is switched to the extraction state, so that the first mobile phase A1 moves downstream under the push of the sampling 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 fourth connecting pipe L4, 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 C1. The first mobile phase A1 passing through the first chromatographic column C1 enters the transfer valve V2 port f16 through the eighth connecting pipe L8 and the ninth connecting pipe L9 and is discharged to the waste liquid end F.

[0043] Please see Figure 3 and Figure 4Transfer function: Sampling pump P1 is activated, and main valve V1 is switched to sampling mode. The first mobile phase A1 is delivered downstream. The sample is introduced into the first mobile phase A1 through injector AS. The first mobile phase A1 containing the sample is guided sequentially through the first connecting line L1, the fourth connecting line L4, the fifth connecting line L5, and the sixth connecting line L6 into the first chromatographic column C1. 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. When the target component in the sample is about to elute from the first chromatographic column C1, the reversing valve V4 can be switched to either forward or reverse mode. When the reversing valve V4 is in the forward mode, the first mobile phase A1 passes forward through the first chromatographic column C1 (entering from the front end of the sixth connecting line L6 and exiting from the rear end), and the target component is sequentially delivered through the sixth connecting line L6, the eighth connecting line L8, the ninth connecting line L9, the tenth connecting line L10, and the second connecting line L2 to the second chromatographic column C2, where it is separated from the first chromatographic column C1. Target components with strong interaction with the second column C2 are captured by the second column C2. Non-target substances are discharged to the waste liquid end F via the first mobile phase A1 and enter the transfer valve V2 port f16. When the reversing valve V4 is in the reverse state, the first mobile phase A1 flows in reverse through the first column C1 (entering from the rear end of the sixth connecting pipe L6 and exiting from the front end), and delivers the target components sequentially through the sixth connecting pipe L6, the seventh connecting pipe L7 and the blocker Z1, the eighth connecting pipe L8, the ninth connecting pipe L9, the tenth connecting pipe L10 and the second connecting pipe L2 to the second column C2. Target components with strong interaction with the second column C2 are captured by the second column C2. Non-target substances are discharged to the waste liquid end F via the first mobile phase A1 passing through the second column C2 and enter the transfer valve V2 port f16. The blocker Z1 can intercept particulate matter and strongly retained substances in the non-target substances to prevent them from eluting into the second column C2 and to prevent the second column C2 from being overloaded.

[0044] Please see Figure 5 Analysis function: Turn on the sampling pump P1, switch the main valve V1 to the analysis state, switch the transfer valve V2 back to the extraction state, and the first mobile phase A1 containing the sample is directly connected to the second chromatographic column C2 through the first connecting line L1 and the second connecting line L2. The target component captured by the second chromatographic column C2 in the transfer function is pushed by the first mobile phase A1 and then connected to the detector DE through the third connecting line L3 for analysis and detection.

[0045] Cleaning function: Please refer to Figure 6The first cleaning process involves starting the cleaning pump P2, switching the main valve V1 to the analysis state, the transfer valve V2 to the extraction state, and the reversing valve V4 to the reverse state. The cleaning solution A3, driven by the cleaning pump P2, passes through the eleventh connecting pipe L11, the eighth connecting pipe L8, and the seventh connecting pipe L7, sequentially cleaning the blocker Z1 and the first chromatographic column C1 in reverse. Large molecular particulate impurities in the blocker Z1 are intercepted by the first chromatographic column C1, while non-target substances in the first chromatographic column C1 are pushed through the fifth connecting pipe L5 and the tenth connecting pipe L10 to the port c13 of the transfer valve V2 and discharged to the waste liquid end F.

[0046] Please see Figure 7 The second cleaning process involves maintaining the cleaning pump P2 in the open state after the first cleaning, switching the main valve V1 to the analysis state, the transfer valve V2 to the extraction state, and switching the reversing valve V4 to the forward state. This allows the cleaning solution A3 to pass through the eleventh connecting pipe L11, the eighth connecting pipe L8, the sixth connecting pipe L6, and the tenth connecting pipe L10 under the push of the cleaning pump P2, and then separately cleaning the first chromatographic column C1 again. This process removes the large molecular particulate impurities that were flushed out by the barrier Z1 and intercepted by the first chromatographic column C1 during the first cleaning process, cleaning them to the waste liquid end F, thus completing the cleaning process.

[0047] It is worth noting that the cleaning function can be run independently after the analysis function, or it can be run in parallel with the analysis function. Example 2

[0048] A reversible online extraction liquid chromatography system, based on Example 1, further includes a modulation channel for conveying modulation solution A2; a tee T1 is provided on the fourth connecting pipe L4, and the modulation channel is connected to the fourth connecting pipe L4 through the tee T1; a mixer M is also provided on the fourth connecting pipe L4 for mixing the modulation solution A2 and the first mobile phase A1.

[0049] Specifically, the modulation channel includes a twelfth connecting pipe L12, one end of which is connected to the auxiliary pump P3, and the other end of which is connected to the tee T1.

[0050] Function Description: Please see Figure 8-10 Modulation function: During extraction and transfer functions, auxiliary pump P3 can be activated simultaneously to pump the modulation solution A2 into the fourth connecting pipe L4 to mix with the first mobile phase A1. By modifying the pH, ionic strength, or organic phase ratio of the first mobile phase A1 through the modulation solution A2, the retention capacity of the target component on the first column C1 and the second column C2 is enhanced, preventing the target component from eluting during extraction and transfer functions; wherein, Figure 8 In order to be in Figure 2In addition to the extraction function, a modulation function for the first chromatographic column C1 is added. Figure 9 In order to be in Figure 3 Based on the positive transfer function, the modulation function of the first chromatographic column C1 and the second chromatographic column C2 is added; Figure 10 In order to be in Figure 4 Based on the reverse transfer function, the modulation function for the first chromatographic column C1 and the third chromatographic column C3 is added.

[0051] 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 reversible online extraction liquid chromatography system, comprising: The system comprises a switching main valve (V1) with multiple interfaces, a transfer valve (V2) 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 second connecting line (L2) is connected to a second chromatographic column (C2), and the two ends of the second connecting line (L2) are respectively connected to one port of the switching main valve (V1) and one port of the transfer valve (V2); A third connection line (L3) is connected to the detector (DE), and the third connection line (L3) is connected to one port of the transfer valve (V2); A sixth connecting line (L6) is connected to the first chromatographic column (C1), and the two ends of the sixth connecting line (L6) are respectively connected to any two ports of the reversing valve (V4); A seventh connecting pipe (L7) is connected to a stopper (Z1), and the two ends of the seventh connecting pipe (L7) are respectively connected to any two ports of the reversing valve (V4); An eleventh connecting line (L11) connected to a cleaning pump (P2) is used to draw up the cleaning solution (A3), and the eleventh connecting line (L11) is connected to an interface of the switching main valve (V1); And the fourth connecting line (L4) connecting the two ports of the switching main valve (V1), the fifth connecting line (L5) and the eighth connecting line (L8) connecting the switching main valve (V1) and the reversing valve (V4), and the ninth connecting line (L9) and the tenth connecting line (L10) connecting the switching main valve (V1) and the transfer valve (V2).

2. The reversible online extraction 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); and the reversing valve (V4) includes ports q (27); r (28); s (29); t (30); u (31); and v (32).

3. The reversible online extraction 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 e (15); One end of the third connecting pipe (L3) is connected to port d (14), and the other end is connected to the detector (DE). The fourth connecting pipe (L4) is connected to interface b (2) at one end and to interface g (7) at the other end; The fifth connecting pipe (L5) is connected at one end to interface h (8) and at the other end to port v (32); The sixth connecting pipe (L6) is connected to port q (27) at one end and to port u (31) at the other end; The seventh connecting pipe (L7) is connected at one end to port s (29) and at the other end to port t (30); 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 interface i (9) and at the other end to port b (12); One end of the eleventh connecting pipe (L11) is connected to the cleaning pump (P2), and the other end is connected to the interface e (5).

4. The reversible online extraction liquid chromatography system according to claim 2, characterized in that: 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 reversible online extraction 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 reversible online extraction 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 reversible online extraction 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).

8. A reversible online extraction liquid chromatography system according to any one of claims 1-4, characterized in that: It also includes a twelfth connecting line (L12) connected to an auxiliary pump (P3) for conveying the conditioning solution (A2); the twelfth connecting line (L12) is connected to the fourth connecting line (L4) via a tee (T1); the fourth connecting line (L4) is equipped with a mixer (M).

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