Chromatographic column system
By designing a chromatographic column system with independent operation and gradient elution functions, the problems of low efficiency and poor applicability of existing high-pressure preparation chromatography systems are solved, and efficient and low-consumption product purification is achieved.
Patent Information
- Application Number
- CN202421235131.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-05-31
- Publication Date
- 2025-03-18
- Estimated Expiration
- 2034-05-31
AI Technical Summary
The existing high-pressure preparation chromatography systems have problems such as low efficiency, large solvent consumption and low product yield, while the dual-column system has problems such as poor applicability, inability to operate independently and inability to elute gradients.
A column system including a first column, a second column, an eluent line, a modification line, a loading line and a valve set is designed to allow the first column and the second column to operate independently and support gradient elution.
The efficient operation of the chromatographic column system is achieved, the solvent consumption is reduced, the product yield is improved, and the applicability is expanded, allowing the dual-column system to be used for more types of product purification.
Smart Images
Figure CN222623714U_ABST
Abstract
Description
Technical Field
[0001] The utility model relates to a high-pressure preparative chromatography system, in particular to a chromatography column system. Background Art
[0002] The existing single-column type of high-pressure preparative chromatography system can be applied to various products that require high-pressure preparation and purification, but it has defects such as low efficiency, large solvent consumption and low product yield. The existing dual-column type of high-pressure preparative chromatography system can overcome some or all of the defects of the single-column type, but it also has problems such as poor applicability, inability to operate two columns independently and inability to perform gradient elution, resulting in a very limited number of products that can be purified using the dual-column system. Utility Model Content
[0003] The technical problem to be solved by the utility model is to overcome the deficiencies of the prior art and provide a chromatographic column system which has a simple structure, good applicability, and can be independently operated and gradient eluted.
[0004] The utility model further provides a method for using the chromatographic column system.
[0005] In order to solve the above technical problems, the utility model adopts the following technical solutions:
[0006] A chromatographic column system comprises a first chromatographic column, a second chromatographic column, a first eluent pipeline, a second eluent pipeline, a third eluent pipeline, a fourth eluent pipeline, a modifying liquid pipeline and a sample loading pipeline, wherein the first eluent pipeline is connected to the liquid inlets of the first chromatographic column and the second chromatographic column through a first switching valve, the second eluent pipeline is connected to the liquid inlets of the first chromatographic column and the second chromatographic column through a second switching valve, the third eluent pipeline is connected to the liquid inlets of the first chromatographic column and the second chromatographic column through a third switching valve, the fourth eluent pipeline is connected to the liquid inlets of the first chromatographic column and the second chromatographic column through a fourth switching valve, the modifying liquid pipeline is connected to the liquid inlets of the first chromatographic column and the second chromatographic column through a fifth switching valve, the sample loading pipeline is connected to the liquid inlets of the first chromatographic column and the second chromatographic column through a sixth switching valve, the first chromatographic column and the second chromatographic column are provided with a first drain valve group and a second drain valve group respectively at the drain ports of the first chromatographic column and the second chromatographic column, the drain port of the first chromatographic column is connected to the liquid inlet of the second chromatographic column through a first series valve, and the drain port of the second chromatographic column is connected to the liquid inlet of the first chromatographic column through a second series valve.
[0007] As a further improvement of the above technical solution: the liquid discharge port of the first chromatographic column is provided with a first target substance detection component, and the liquid discharge port of the second chromatographic column is provided with a second target substance detection component.
[0008] As a further improvement of the above technical solution: a first eluent pump is provided on the first eluent pipeline.
[0009] As a further improvement of the above technical solution: a first pressure detection component is provided on the first eluent pipeline.
[0010] As a further improvement of the above technical solution: a first filter is also provided on the first eluent pipeline.
[0011] As a further improvement of the above technical solution: the first eluent pump, the first pressure detection component and the first filter are arranged in sequence.
[0012] As a further improvement of the above technical solution: a finishing liquid pump, a fifth pressure detection component and a fifth filter are sequentially arranged on the finishing liquid pipeline.
[0013] As a further improvement of the above technical solution: a sample loading pump, a sixth pressure detection component and a sixth filter are sequentially arranged on the sample loading pipeline.
[0014] As a further improvement of the above technical solution: the first liquid discharge valve group includes a first waste discharge valve, a first sample collection valve and a second waste discharge valve in parallel, and the second liquid discharge valve group includes a third waste discharge valve, a second sample collection valve and a fourth waste discharge valve in parallel.
[0015] A method for using the above-mentioned chromatographic column system comprises the following steps:
[0016] S1, loading the first chromatographic column: the loading pipeline loads the first chromatographic column, and the first waste valve is opened to discharge waste;
[0017] S2, eluting the first chromatographic column: the first eluent pipeline and the second eluent pipeline elute the first chromatographic column, and the first waste valve is opened to discharge waste;
[0018] S3, the first chromatographic column and the second chromatographic column are connected in series: when the first target substance detection element detects that the target substance with the precursor is eluted from the first chromatographic column, the first waste valve is closed, and the first series valve is opened to allow the eluent to enter the second chromatographic column, and at the same time, the modifying liquid pipeline can enter the modifying liquid to enrich the sample at the head of the second chromatographic column;
[0019] S4, collecting samples from the first chromatographic column: when the first target substance detection component detects that the purity of the target substance eluted from the first chromatographic column meets the requirement, the first sample collection valve is opened to collect qualified products;
[0020] S5, the first chromatographic column and the second chromatographic column are connected in series: when the first target substance detection element detects that the target substance with impurities is eluted from the first chromatographic column, the first sample collection valve is closed to allow the eluent to enter the second chromatographic column, and at the same time, the modifying liquid pipeline can enter the modifying liquid to enrich the sample at the head of the second chromatographic column;
[0021] S6, the first chromatographic column and the second chromatographic column are operated in parallel: when the first target substance detection element detects that all the target substances are eluted from the first chromatographic column, the first eluent pipeline and the second eluent pipeline regenerate the first chromatographic column, and the second waste valve is opened to discharge waste; at the same time, the sample loading pipeline loads the sample on the second chromatographic column, and the third waste valve is opened to discharge waste;
[0022] S7, eluting the second chromatographic column: the third eluent pipeline and the fourth eluent pipeline elute the second chromatographic column, and the third waste valve is opened to discharge waste;
[0023] S8, the second chromatographic column is connected in series with the first chromatographic column: when the second target substance detection element detects that the target substance with the precursor is eluted from the second chromatographic column, the third waste valve is closed, and the second series valve is opened to allow the eluent to enter the first chromatographic column, and at the same time, the modifying liquid pipeline can be fed with the modifying liquid to enrich the sample at the head of the first chromatographic column;
[0024] S9, collecting samples from the second chromatographic column: when the second target substance detection component detects that the purity of the target substance eluted from the second chromatographic column meets the requirement, the second sample collection valve is opened to collect qualified products;
[0025] S10, the second chromatographic column is connected in series with the first chromatographic column: when the second target substance detection element detects that the target substance with impurities is eluted from the second chromatographic column, the second sample collection valve is closed to allow the eluent to enter the first chromatographic column, and at the same time, the modifying liquid pipeline can enter the modifying liquid to enrich the sample at the head of the first chromatographic column;
[0026] S11. The second chromatographic column is operated in parallel with the first chromatographic column: when the first target substance detection component detects that all the target substance has been eluted from the second chromatographic column, the third eluent pipeline and the fourth eluent pipeline regenerate the second chromatographic column, the fourth waste valve is opened to discharge waste, and at the same time the sample loading pipeline is opened to load the first chromatographic column, and the first waste valve is opened to discharge waste.
[0027] Compared with the prior art, the advantages of the utility model are:
[0028] The chromatographic column system disclosed in the utility model comprises a first chromatographic column, a second chromatographic column and corresponding eluent pipelines, modifying liquid pipelines, sample loading pipelines and valve groups, so that the first chromatographic column and the second chromatographic column can be operated independently or by gradient elution. The system has a simple structure and can adapt to the purification of various products.
[0029] The use method of the chromatographic column system disclosed in the utility model realizes the independent operation and gradient elution of the first chromatographic column and the second chromatographic column, so that the number of products that can be purified by using the double-column system is greatly increased, and the applicability is good.
[0030] Other features and advantages of the present invention will be described in detail in the subsequent specific implementation section. BRIEF DESCRIPTION OF THE DRAWINGS
[0031] Figure 1 It is a structural schematic diagram of the first chromatographic column of the utility model when loading samples.
[0032] Figure 2 It is a schematic structural diagram of the first chromatographic column of the utility model during gradient elution.
[0033] Figure 3 It is a schematic structural diagram of the utility model in which the impurities after the gradient elution of the first chromatographic column enter the second chromatographic column after dilution.
[0034] Figure 4 It is a schematic structural diagram of the utility model in which the second chromatographic column is diluted into the first chromatographic column after gradient elution.
[0035] Figure 5 It is a schematic diagram of the structure of the utility model in which the first chromatographic column is diluted with gradient elution and enters the second chromatographic column.
[0036] Figure 6 It is a schematic diagram of the structure of the utility model in which the first chromatographic column is used for elution and sample collection, and the second chromatographic column is used for gradient regeneration. DETAILED DESCRIPTION
[0037] In the description of the present invention, it should be understood that the terms "length", "width", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", etc., indicating the orientation or position relationship, are based on the orientation or position relationship shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on the present invention.
[0038] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of the present utility model, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.
[0039] In the present invention, unless otherwise clearly specified and limited, the terms "assemble", "connect", "connect", "fix" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.
[0040] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments.
[0041] Embodiment 1
[0042] Figures 1 to 6 An embodiment of the chromatographic column system of the utility model is shown. The chromatographic column system of this embodiment comprises a first chromatographic column ( Figure 1 Column 1 in the second column ( Figure 1 Column 2), the first eluent pipeline ( Figure 1 The pipeline for the eluent A1 in the middle), the second eluent pipeline ( Figure 1 The pipeline for the eluent B1 in the middle is located below the first eluent pipeline), the third eluent pipeline ( Figure 1 The pipeline for the eluent A2 is located below the second eluent pipeline), the fourth eluent pipeline ( Figure 1 The pipeline for the eluent B2 in the middle is located below the third eluent pipeline), the modifying liquid pipeline ( Figure 1 Located below the fourth eluent line) and the sample line ( Figure 1The first eluent pipeline is connected to the liquid inlet of the first chromatographic column and the second chromatographic column through the first switching valve (valve PBV201, preferably a solenoid valve, etc., for remote automatic control), the second eluent pipeline is connected to the liquid inlet of the first chromatographic column and the second chromatographic column through the second switching valve (valve PBV202), the third eluent pipeline is connected to the liquid inlet of the first chromatographic column and the second chromatographic column through the third switching valve (valve PBV203), the fourth eluent pipeline is connected to the liquid inlet of the first chromatographic column and the second chromatographic column through the fourth switching valve (valve PBV204), and the modifying liquid pipeline is connected to the liquid inlet of the first chromatographic column and the second chromatographic column through the fifth switching valve (valve PBV205). ) connects the liquid inlet of the first chromatographic column and the second chromatographic column, the sample loading pipeline connects the liquid inlet of the first chromatographic column and the second chromatographic column through the sixth switching valve (valve PBV206), the discharge ports of the first chromatographic column and the second chromatographic column are respectively provided with a first discharge valve group (including valves PBV301, PBV302 and PBV303) and a second discharge valve group (including valves PBV304, PBV305 and PBV306), the discharge port of the first chromatographic column is connected to the liquid inlet of the second chromatographic column through a first series valve (valve PBV207), and the discharge port of the second chromatographic column is connected to the liquid inlet of the first chromatographic column through a second series valve (valve PBV208).
[0043] The chromatographic column system of this embodiment includes a first chromatographic column, a second chromatographic column and corresponding eluent pipelines, modification liquid pipelines, sample loading pipelines and valve groups, so that the first chromatographic column and the second chromatographic column can be operated independently or by gradient elution. It has a simple structure and can adapt to the purification of various products.
[0044] Furthermore, in this embodiment, the discharge port of the first chromatographic column is provided with a first target substance detection element ( Figure 1 A201 in the second chromatographic column), the discharge port of the second chromatographic column is provided with a second target substance detection member ( Figure 1 Preferably, the first target substance detection element and the second target substance detection element are UV detection elements, or ultraviolet light detection elements, which are convenient for accurately detecting whether the target substance is discharged from the discharge port of the chromatographic column and controlling the opening and closing of the corresponding pipeline and the opening and closing of the valve group.
[0045] Furthermore, in this embodiment, a first eluent pump ( Figure 1 The pump P201 in is used to pump the eluent A1).
[0046] Furthermore, in this embodiment, a first pressure detection member ( Figure 1 The pressure sensor 201 is used to detect the pressure of the first eluent pipeline).
[0047] Furthermore, in this embodiment, a first filter ( Figure 1 The filter 201 in the filter is used to filter the eluent A1 to prevent impurities from entering the first chromatographic column and the second chromatographic column. As a preferred embodiment, the first eluent pump, the first pressure detection element and the first filter are arranged in sequence.
[0048] Among them, the second eluent pipeline, the third eluent pipeline and the fourth eluent pipeline have the same structure as the first eluent pipeline, and will not be repeated herein.
[0049] Furthermore, in this embodiment, a finishing liquid pump ( Figure 1 The pump P205 in the pump is used to pump the finishing liquid), the fifth pressure detection part ( Figure 1 The pressure sensor P205 in the trimming liquid pipeline is used to detect the pressure of the trimming liquid pipeline) and the fifth filter ( Figure 1 The filter 205 is used to filter the modification solution to prevent impurities from entering the first chromatographic column and the second chromatographic column).
[0050] Further, in this embodiment, the sample loading pipeline is provided with a sample loading pump ( Figure 1 The middle pump 206 is used to pump the sample), the sixth pressure detection member ( Figure 1 The pressure sensor P206 in the sample loading pipeline is used to detect the pressure of the sample loading pipeline) and the sixth filter ( Figure 1 The filter 206 is used to filter the sample to prevent impurities from entering the first chromatographic column and the second chromatographic column).
[0051] Further, in this embodiment, the first liquid discharge valve group includes a first waste discharge valve ( Figure 1 Valve PBV301 in), first sample receiving valve ( Figure 1 Valve PBV302 in the second exhaust valve ( Figure 1 The valve PBV303 in the first column), different waste liquids and qualified products discharged from the first chromatographic column can be discharged and collected from different waste valves, the structure is simple and reasonable, and the second liquid discharge valve group includes a third waste valve ( Figure 1 Valve PBV304 in the middle), the second sample receiving valve ( Figure 1 Valve PBV305) and the fourth exhaust valve ( Figure 1 The valve PBV306 in the middle), different waste liquids and qualified products discharged from the second chromatographic column can be discharged and collected from different waste valves, and the structure is simple and reasonable.
[0052] Embodiment 2
[0053] Figures 1 to 6 An embodiment of a method for using a chromatographic column system of the utility model is shown. The method for using a chromatographic column system of this embodiment comprises the following steps:
[0054] S1, loading the first chromatographic column: the loading pipeline loads the first chromatographic column (the sixth switching valve PBV206 connects the loading pipeline and the liquid inlet of the first chromatographic column), and the first waste valve (valve PBV301) is opened for waste discharge;
[0055] S2, elution of the first chromatographic column: the first eluent pipeline and the second eluent pipeline elute the first chromatographic column, and the first waste valve is opened to discharge waste (the first switching valve PBV201 and the second switching valve PBV202 connect the first eluent pipeline and the second eluent pipeline with the liquid inlet of the first chromatographic column);
[0056] S3, the first chromatographic column and the second chromatographic column are connected in series: when the first target substance detection element (detection element A201) detects that the target substance with the precursor is eluted from the first chromatographic column, the first waste valve is closed, and the first series valve (valve PBV207) is opened to allow the eluent to enter the second chromatographic column, and at the same time, the modification liquid pipeline can enter the modification liquid to enrich the sample at the head of the second chromatographic column (the fifth switching valve PBV205 connects the modification liquid pipeline and the second chromatographic column);
[0057] S4, first chromatographic column sample collection: when the first target substance detection element detects that the purity of the target substance eluted from the first chromatographic column meets the requirement, the first sample collection valve (valve PBV302) is opened to collect qualified products;
[0058] S5, the first chromatographic column and the second chromatographic column are connected in series: when the first target substance detection element detects that the target substance with impurities is eluted from the first chromatographic column, the first sample collection valve is closed to allow the eluent to enter the second chromatographic column, and at the same time, the modifying liquid pipeline can enter the modifying liquid to enrich the sample at the head of the second chromatographic column;
[0059] S6, the first chromatographic column and the second chromatographic column are operated in parallel: when the first target substance detection component detects that all the target substances are eluted from the first chromatographic column, the first eluent pipeline and the second eluent pipeline regenerate the first chromatographic column (the first switching valve PBV201 and the second switching valve PBV202 connect the first eluent pipeline and the second eluent pipeline with the liquid inlet of the first chromatographic column), and the second waste valve (valve PBV302) is opened for waste discharge; at the same time, the sample loading pipeline loads the second chromatographic column (the sixth switching valve connects the sample loading pipeline with the second chromatographic column), and the third waste valve (valve PBV304) is opened for waste discharge;
[0060] S7, elution of the second chromatographic column: the third eluent pipeline and the fourth eluent pipeline elute the second chromatographic column (the third switching valve PBV203 and the fourth switching valve PBV204 connect the third eluent pipeline and the fourth eluent pipeline with the liquid inlet of the second chromatographic column), and the third waste valve is opened to discharge waste;
[0061] S8, the second chromatographic column is connected in series with the first chromatographic column: when the second target substance detection element (detection element A202) detects that the target substance with the precursor is eluted from the second chromatographic column, the third waste valve is closed, and the second series valve (valve PBV208) is opened to allow the eluent to enter the first chromatographic column, and at the same time, the modification liquid pipeline can enter the modification liquid to enrich the sample at the head of the first chromatographic column (the fifth switching valve PBV205 connects the modification liquid pipeline with the first chromatographic column);
[0062] S9, collecting samples from the second chromatographic column: When the second target substance detection component detects that the purity of the target substance eluted from the second chromatographic column meets the requirement, the second sample collection valve (valve PBV305) is opened to collect qualified products;
[0063] S10, the second chromatographic column is connected in series with the first chromatographic column: when the second target substance detection element detects that the target substance with impurities is eluted from the second chromatographic column, the second sample collection valve is closed to allow the eluent to enter the first chromatographic column, and at the same time, the modifying liquid pipeline can enter the modifying liquid to enrich the sample at the head of the first chromatographic column;
[0064] S11. The second chromatographic column is operated in parallel with the first chromatographic column: when the first target substance detection component detects that all the target substance has been eluted from the second chromatographic column, the third eluent pipeline and the fourth eluent pipeline regenerate the second chromatographic column (the third switching valve PBV203 and the fourth switching valve PBV204 connect the third eluent pipeline and the fourth eluent pipeline to the liquid inlet of the second chromatographic column), the fourth waste valve (valve PBV306) is opened for waste discharge, and at the same time the sample loading pipeline is opened to load the first chromatographic column, and the first waste valve is opened for waste discharge.
[0065] Although the present invention has been disclosed as a preferred embodiment, it is not intended to limit the present invention. Any technician familiar with the art can use the above disclosed technical content to make many possible changes and modifications to the technical solution of the present invention without departing from the scope of the technical solution of the present invention, or modify it into an equivalent embodiment of equivalent changes. Therefore, any simple modification, equivalent change and modification made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention should fall within the scope of protection of the technical solution of the present invention.
Claims
1. A chromatographic column system, characterized in that: The invention comprises a first chromatographic column, a second chromatographic column, a first eluent pipeline, a second eluent pipeline, a third eluent pipeline, a fourth eluent pipeline, a modifying liquid pipeline and a sample loading pipeline, wherein the first eluent pipeline is connected to the liquid inlets of the first chromatographic column and the second chromatographic column through a first switching valve, the second eluent pipeline is connected to the liquid inlets of the first chromatographic column and the second chromatographic column through a second switching valve, the third eluent pipeline is connected to the liquid inlets of the first chromatographic column and the second chromatographic column through a third switching valve, the fourth eluent pipeline is connected to the liquid inlets of the first chromatographic column and the second chromatographic column through a fourth switching valve, the modifying liquid pipeline is connected to the liquid inlets of the first chromatographic column and the second chromatographic column through a fifth switching valve, the sample loading pipeline is connected to the liquid inlets of the first chromatographic column and the second chromatographic column through a sixth switching valve, the drain ports of the first chromatographic column and the second chromatographic column are respectively provided with a first drain valve group and a second drain valve group, the drain port of the first chromatographic column is connected to the liquid inlet of the second chromatographic column through a first series valve, and the drain port of the second chromatographic column is connected to the liquid inlet of the first chromatographic column through a second series valve.
2. The chromatographic column system according to claim 1, characterized in that: The liquid discharge port of the first chromatographic column is provided with a first target substance detection component, and the liquid discharge port of the second chromatographic column is provided with a second target substance detection component.
3. The chromatographic column system according to claim 1, characterized in that: The first eluent pipeline is provided with a first eluent pump.
4. The chromatographic column system according to claim 3, characterized in that: The first eluent pipeline is provided with a first pressure detection component.
5. The chromatographic column system according to claim 4, characterized in that: The first eluent pipeline is also provided with a first filter.
6. The chromatographic column system according to claim 5, characterized in that: The first eluent pump, the first pressure detection member and the first filter are arranged in sequence.
7. The chromatographic column system according to any one of claims 1 to 6, characterized in that: The finishing liquid pipeline is provided with a finishing liquid pump, a fifth pressure detecting component and a fifth filter in sequence.
8. The chromatographic column system according to any one of claims 1 to 6, characterized in that: The sample loading pipeline is provided with a sample loading pump, a sixth pressure detection component and a sixth filter in sequence.
9. The chromatographic column system according to any one of claims 1 to 6, characterized in that: The first liquid discharge valve group includes a first waste discharge valve, a first sample collection valve, and a second waste discharge valve connected in parallel, and the second liquid discharge valve group includes a third waste discharge valve, a second sample collection valve, and a fourth waste discharge valve connected in parallel.
Citation Information
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