An ultra-high performance liquid chromatography auto-sampler and control method

Abstract

The present invention relates to an ultra-high performance liquid chromatography auto-sampler and a control method thereof. The device includes: a six-way rotary switching valve, and a first groove communicating with a mobile phase inlet valve port is provided on a stator of the six-way rotary switching valve, and the first groove is located at a circumferential position where the mobile phase inlet valve port is located. This solution can reduce the time of chromatographic column flow interruption.

Description

Technical Field

[0001] The present invention relates to the technical field of ultra-high performance liquid chromatography analysis, and particularly to an ultra-high performance liquid chromatography automatic sampling device and a control method therefor. Background Art

[0002] High performance liquid chromatography (hereinafter referred to as HPLC) is a common method for separating and analyzing samples. The sampling device is a module or structure for introducing a target sample into the chromatographic system for analysis. Since the rotary switching valve (US Patent 3411525) was invented in 1965, the sampling method and sampling device for introducing samples into the chromatographic system have been basically fixed. Although there have been structural expansions later, the basic methods have always been similar.

[0003] Currently, the switching valve used in the HPLC system is generally a two-position rotary valve, with two flow path states: LOAD and INJECT. When the valve flow path is in the LOAD state, the sample flow path is separated from the analysis flow path, and the mobile phase of the analysis flow path directly enters the chromatographic column. The sample flow path can be sampled separately by a syringe or other structures. When the valve flow path is in the INJECT state, the sample in the sample flow path enters the system flow path for separating and analyzing the target sample. Since the system flow path is connected to the valve port of the stator, when the valve flow path switches from one state to another, the flow paths on the stator of the switching valve are not connected during the switching process. That is to say, there must be a flow interruption during the valve switching. During this process, no liquid flows through the chromatographic column, and the instantaneous flow rate of the chromatographic column is 0. For example, when using a traditional automatic sampler, the six-way valve is in the INJECT state by default in the system, and the state during the sampling process is the LOAD state. During the entire sampling process, when sampling, the valve first switches from INJECT to LOAD, and there is a 60° chromatographic column flow interruption angle; when injecting the sample, the valve switches back from LOAD to INJECT, and there is still a 60° chromatographic column flow interruption angle. Adding the two together, during the entire sampling process, the total chromatographic column flow interruption angle is 120°.

[0004] Now, with the continuous development of technology, we have begun to gradually replace HPLC with an ultra-high performance liquid chromatography system (hereinafter referred to as UHPLC) with better separation and analysis effects for routine separation and analysis of samples. Although the UHPLC system has better analysis effects than the conventional HPLC, its operating pressure is also much higher than that of HPLC. The common pressure of HPLC is 5 - 20 MPa, while the common pressure of UHPLC is 40 - 80 MPa. Therefore, the problem of chromatographic column flow interruption has a more obvious impact on the UHPLC system.

[0005] Therefore, there is an urgent need for an ultra-high performance liquid chromatography automatic sampling device and method that can reduce the duration of chromatographic column flow interruption. Summary of the Invention

[0006] Based on this, it is necessary to provide an ultra-high performance liquid chromatography automatic sampling device and a control method for the problem of long column cut-off time.

[0007] An ultra-high performance liquid chromatography automatic sampling device, the device includes: a sampling device, a cleaning device, a waste liquid flow path, a syringe, a two-way three-way valve and a six-way rotary switching valve. The stator of the six-way rotary switching valve is provided with a first groove communicating with the mobile phase inlet valve port, and the first groove is located at the circumferential position where the mobile phase inlet valve port is located.

[0008] In one embodiment, the six-way rotary switching valve includes a stator and a rotor. The stator is provided with six valve ports and a first groove, which are the first valve port, the second valve port, the third valve port, the fourth valve port, the fifth valve port and the sixth valve port in sequence. The first valve port is the mobile phase inlet valve port. The first groove is located between the first valve port and the second valve port, communicates with the first valve port but does not communicate with the second valve port; the included angle between the second valve port and the third valve port is 60°, and the included angle between the third valve port and the fourth valve port is 60°; the rotor is provided with three grooves in the circumferential direction corresponding to the valve port positions, which are the second groove, the third groove and the fourth groove respectively. The arcs of the second groove and the third groove are 60°. The included angle between the fourth groove and the second groove is equal to the arc of the first groove. The sum of the arc of the fourth groove, the arc of the first groove and the included angle between the fourth valve port and the fifth valve port is 180°; wherein, the arc of the first groove is set as α, and the arc of the fourth groove is set as β, satisfying 0° < α < 60°, 120° - α < β < 180° - 2α.

[0009] In one embodiment, for the ultra-high performance liquid chromatography automatic sampling device, the outlet of the infusion pump is connected to the first valve port, the chromatographic column is connected to the second valve port, the needle seat is connected to the third valve port, the waste liquid flow path is connected to the fourth valve port, the two-way three-way valve is connected to the fifth valve port, and the sampling needle is connected to the sixth valve port.

[0010] In one embodiment, the sampling device includes a needle seat and a sampling needle, which are hermetically connected.

[0011] In one embodiment, the ultra-high performance liquid chromatography automatic sampling device further includes a controller for controlling the actions of the six-way rotary switching valve, the sampling needle, the two-way three-way valve, the syringe or the cleaning device.

[0012] In one embodiment, the diameter value range of the first groove in the circumferential direction is 3mm - 5mm, the diameter of the six valve ports provided by the stator is 0.1mm - 0.3mm, and the arc distance between the first groove and the second valve port is not less than 15°, that is, 15° ≤ α ≤ 45°, 135° - α ≤ β ≤ 165° - 2α.

[0013] In one embodiment, 15° ≤ α ≤ 45° and β = 135° - α.

[0014] In one embodiment, the radian α of the first groove is 15°, and the radian β of the fourth groove is 120°.

[0015] A method for controlling ultra-high performance liquid chromatography auto-sampler applied to the above ultra-high performance liquid chromatography auto-sampler device includes:

[0016] Receiving a signal for preparing to inject a sample;

[0017] Controlling the six-way rotary switching valve to enter the INJECT state and keeping the sampling needle sealed in the needle seat; wherein, in the INJECT state, the fourth groove of the rotor of the six-way rotary switching valve communicates with the first valve port and the sixth valve port of the stator, the second groove communicates with the second valve port and the third valve port, and the third groove communicates with the fourth valve port and the fifth valve port;

[0018] Judging whether the drainage and cleaning duration of the sampling device is reached;

[0019] If the drainage and cleaning duration of the sampling device is reached, controlling the six-way rotary switching valve to enter the LAOD state; wherein, in the LAOD state, the second groove of the rotor of the six-way rotary switching valve communicates with the first valve port and the second valve port of the stator, the third groove communicates with the third valve port and the fourth valve port, and the fourth groove communicates with the fifth valve port and the sixth valve port;

[0020] Controlling the sampling needle to move to the cleaning seat for cleaning, after cleaning, moving to the sample vial to aspirate a target amount of sample, then moving the sampling needle to the cleaning seat for cleaning again, and after the second cleaning is completed, controlling the sampling needle to move to the needle seat for sealing;

[0021] Controlling the six-way rotary switching valve to enter the PRE state and maintaining it for a preset time length; wherein, in the PRE state, the second groove of the rotor of the six-way rotary switching valve communicates with the second valve port and the first groove of the stator, and the fourth groove communicates with the first valve port and the sixth valve port.

[0022] Controlling the six-way rotary switching valve to enter the INJECT state again to end the sample injection.

[0023] In one embodiment, after judging whether the drainage and cleaning duration of the sampling device is reached, it includes: if the drainage and cleaning duration of the sampling device is not reached, controlling the two-way three-way valve to switch to the injection liquid path and controlling the syringe to aspirate liquid; controlling the two-way three-way valve to switch to the six-way rotary switching valve path and controlling the syringe to drain and clean.

[0024] The above-mentioned ultra-high performance liquid chromatography automatic sampling device and control method set a first groove in the six-way rotary switching valve 110, and the mobile phase inlet is communicated with the first groove, increasing the angle of the mobile phase flowing into the valve. During the switching process of each flow path state, the rotor rotates to ensure that it is communicated with other valve ports, the mobile phase inlet and the first groove within a large range, thereby reducing the system dead time; only a single six-way rotary switching valve 110 can achieve the switching of three states, and the overall structure of the device is simple and the pipeline connection is simple. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 FIG. is a schematic structural diagram of an ultra-high performance liquid chromatography automatic sampling device in an embodiment;

[0026] Figure 2 FIG. is a schematic structural diagram of a stator of a six-way rotary switching valve in an embodiment;

[0027] Figure 3 FIG. is a schematic structural diagram of a rotor of a six-way rotary switching valve in an embodiment;

[0028] Figure 4 FIG. is a schematic structural diagram of the INJECT state of a six-way rotary switching valve in an embodiment;

[0029] Figure 5 FIG. is a schematic structural diagram of the LAOD state of a six-way rotary switching valve in an embodiment;

[0030] Figure 6 FIG. is a schematic structural diagram of the PRE state of a six-way rotary switching valve in an embodiment;

[0031] Figure 7 FIG. is a schematic connection structure diagram of an ultra-high performance liquid chromatography automatic sampling device in the LAOD state in an embodiment;

[0032] Figure 8 FIG. is a schematic connection structure diagram of an ultra-high performance liquid chromatography automatic sampling device in the PRE state in an embodiment;

[0033] Figure 9 FIG. is a schematic flow diagram of an ultra-high performance liquid chromatography automatic sampling control method in an embodiment.

[0034] Reference numerals: ultra-high performance liquid chromatography auto-sampler 100; six-port rotary switching valve 110; stator 101; first valve port 111; second valve port 112; third valve port 113; fourth valve port 114; fifth valve port 115; sixth valve port 116; first groove 117; rotor 102; second groove 1011; third groove 1012; fourth groove 1013; sampling needle 120; needle seat 130; waste liquid flow path 140; two-position three-way valve 150; syringe 160; cleaning device 170; cleaning seat 171; cleaning pump 172; solvent selection valve 173; controller 180; infusion pump 200; chromatographic column 300; detector 400. Detailed implementation manners

[0035] In order to enable those skilled in the art to better understand the technical solutions in this application, the technical solutions in the embodiments of this application will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of this application. Obviously, the described embodiments are only a part of the embodiments of this application, rather than all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by those of ordinary skill in the art without making creative efforts shall fall within the scope of protection of this application.

[0036] It should be noted that when an element is referred to as being "fixed to" or "disposed on" another element, it can be directly disposed on the other element or indirectly disposed on the other element; when an element is referred to as being "connected to" another element, it can be directly connected to the other element or indirectly connected to the other element.

[0037] It should be understood that the orientation or positional relationship indicated by the terms "length", "width", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc. is based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing this application and simplifying the description, rather than indicating or implying 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 to this application.

[0038] In addition, the terms "first" and "second" are only used for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, the features defined with "first" and "second" may explicitly or implicitly include one or more of such features. In the description of this application, the meaning of "a plurality" or "several" is two or more, unless otherwise specifically defined.

[0039] It should be noted that the structures, proportions, sizes, etc. shown in the attached drawings of this specification are only used to cooperate with the content disclosed in the specification for those familiar with this technology to understand and read, and are not used to limit the implementation conditions of this application. Therefore, they do not have any substantial technical significance. Any modification of the structure, change in the proportional relationship, or adjustment of the size, without affecting the efficacy that this application can produce and the purpose that can be achieved, should still fall within the scope covered by the technical content disclosed in this application.

[0040] Currently, the pressure of the chromatographic column is generated by the system mobile phase flowing through the chromatographic column. If the flow is interrupted, that is, no mobile phase passes through the chromatographic column, the system instantaneous pressure is 0. Of course, due to the existence of the pipeline and the volume of the chromatographic column, there is a certain buffer, and there is a certain time difference in the actual pressure drop speed and it is not instantaneous. However, there is indeed a relatively large pressure drop during the valve switching process, which impacts the packing at the head of the chromatographic column. After multiple impacts, it often leads to the collapse of the packing, resulting in a deterioration of the chromatographic peak shape and separation effect of the sample after entering the system (such as typical split peaks). Therefore, the life of the chromatographic column is usually characterized by the number of sample injections. To reduce the chromatographic column flow interruption time, this application provides an ultra-high performance liquid chromatography automatic sampling device 100. By setting a first groove in the six-way rotary switching valve 110, the first valve port is connected to the first groove, increasing the angle of the mobile phase flowing into the valve. At the same time, three grooves are set on the rotor, and the distance and arc of the three grooves are set to ensure the normal operation of various flow path states and reduce the system flow interruption duration.

[0041] In one embodiment, as Figure 1 and Figure 2 shown, an ultra-high performance liquid chromatography automatic sampling device 100 is provided. The device includes: a sampling device, a cleaning device 170, a waste liquid flow path 140, a syringe 160, a two-way three-way valve 150, and a six-way rotary switching valve 110. The stator 101 of the six-way rotary switching valve 110 is provided with a first groove 117 connected to the mobile phase inlet valve port, and the first groove 117 is located at the circumferential position where the mobile phase inlet valve port is located.

[0042] Among them, an ultra-high performance liquid chromatography automatic sampling device 100 can be applied to HPLC systems and UHPLC systems. The infusion pump 200 transports the system mobile phase, the ultra-high performance liquid chromatography automatic sampling device 100 automatically introduces the sample, the chromatographic column 300 analyzes the sample, and the detector 400 connected to the chromatographic column 300 is responsible for detecting the sample.

[0043] The above-mentioned ultra-high performance liquid chromatography auto-sampler 100 sets a first groove in the six-way rotary switching valve 110. The mobile phase inlet port is connected to the first groove, increasing the angle at which the mobile phase flows into the valve. During the switching process of each flow path state, the rotor rotates to ensure that it communicates with other valve ports, the mobile phase inlet port, and the first groove within a large range, thereby reducing the system dead flow angle. Only a single six-way rotary switching valve 110 can achieve the switching of three states, and the overall structure of the device is simple, and the pipeline connection is simple.

[0044] In one embodiment, as Figures 1-8 shown, the six-way rotary switching valve 110 includes a stator 101 and a rotor 102. The stator 101 is provided with six valve ports and a first groove 117, which are the first valve port 111, the second valve port 112, the third valve port 113, the fourth valve port 114, the fifth valve port 115, and the sixth valve port 116 in sequence. The first valve port 111 is the mobile phase inlet port. The first groove 117 is located between the first valve port 111 and the second valve port 112, is connected to the first valve port, and is not connected to the second valve port. The included angle between the second valve port 112 and the third valve port 113 is 60°, and the included angle between the third valve port 113 and the fourth valve port 114 is 60°. The rotor 102 is provided with three grooves in the circumferential direction corresponding to the positions of the valve ports, namely the second groove 1011, the third groove 1012, and the fourth groove 1013. The arcs of the second groove 1011 and the third groove 1012 are 60°. The included angle between the fourth groove 1013 and the second groove 1011 is equal to the arc of the first groove 117. The sum of the arc of the fourth groove 1013, the arc of the first groove 117, and the included angle between the fourth valve port 114 and the fifth valve port 115 is 180°. Among them, the arc of the first groove 117 is set as α, and the arc of the fourth groove 1013 is set as β, satisfying 0° < α < 60°, 120° - α < β < 180° - 2α.

[0045] Among them, the first valve port 111, the second valve port 112, the third valve port 113, the fourth valve port 114, the fifth valve port 115, and the sixth valve port 116 are non-circularly evenly distributed. The arcs of the second groove 1011, the third groove 1012, and the fourth groove 1013 on the rotor are not equal. As Figure 3 shown, the rotor 102 has 3 grooves with different lengths. The arcs of the second groove 1011 and the third groove 1012 are 60°. The arc of the fourth groove 1013 is denoted as β. The included angles between the fourth groove 1013 and the other two grooves are α and 180° - α - β respectively. As Figure 2 shown, the first valve port 111 is connected to the first groove 117. The angle of the first groove 117 in the circumferential direction is α, and the included angle between the fourth valve port 114 and the fifth valve port 115 is 180° - α - β.

[0046] In one embodiment, for the ultra-high performance liquid chromatography auto-sampler 100, the outlet of the infusion pump 200 is connected to the first valve port 111, the chromatographic column 300 is connected to the second valve port 112, the needle seat 130 is connected to the third valve port 113, the waste liquid flow path 140 is connected to the fourth valve port 114, the two-way three-way valve 150 is connected to the fifth valve port 115, and the sampling needle 120 is connected to the sixth valve port 116.

[0047] For the above-mentioned ultra-high performance liquid chromatography auto-sampler, the six valve ports are respectively connected to the infusion pump, the chromatographic column, the needle seat, the waste liquid flow path, the two-way three-way valve and the sampling needle, which can clean the ultra-high performance liquid chromatography auto-sampler to ensure the purity of the sample and make the sample analysis more accurate.

[0048] In one embodiment, as Figure 1 、 Figure 7 and Figure 8 shown, the sampling device includes a needle seat 130 and a sampling needle 120, and the needle seat 130 is hermetically connected to the sampling needle 120.

[0049] In one embodiment, as Figure 1 、 Figure 7 and Figure 8 shown, the ultra-high performance liquid chromatography auto-sampler further includes: a syringe 160 connected to the two-way three-way valve 150.

[0050] In one embodiment, as Figure 1 、 Figure 7 and Figure 8 shown, the ultra-high performance liquid chromatography auto-sampler further includes a cleaning device 170.

[0051] Among them, the cleaning device 170 includes a cleaning seat 171, a cleaning pump 172 and a solvent selection valve 173. The solvent selection valve 173 can be connected to various cleaning solvents, such as strong cleaning liquid, medium cleaning liquid and weak cleaning liquid. The cleaning solvent selection valve 173 can be connected to three different cleaning solvent storage bottles. The controller 180 controls the valve position of the cleaning solvent selection valve 173 to allow the cleaning pump 172 to introduce the corresponding cleaning solvent into the cleaning seat 171 according to the set cleaning process to clean the outer wall of the sampling needle 120.

[0052] In one embodiment, as Figure 1 、 Figure 7 and Figure 8 shown, the ultra-high performance liquid chromatography auto-sampler further includes a controller 180 for controlling the actions of the six-way rotary switching valve 110, the sampling needle 120, the two-way three-way valve 150, the syringe 160 or the cleaning device 170.

[0053] In one embodiment, the commonly used value range of the diameter of the first groove 117 in the circumferential direction is 3 mm - 5 mm, the diameters of the six valve ports provided on the stator are 0.1 mm - 0.3 mm, the typical diameter is 0.2 mm, the arc range of each valve port in the circumferential direction is 3° - 11.5°, and to ensure that the first groove is not connected to the second valve port, the arc distance between the first groove 117 and the second valve port 112 is not less than 15°, that is, 15° ≤ α ≤ 45°, 135° - α ≤ β ≤ 165° - 2α.

[0054] Specifically, considering the volume, the smaller the volume of the fourth groove 1013, the better the sample injection effect, that is, the smaller the arc, the better the sample injection effect, so 15° ≤ α ≤ 45°, β = 135° - α. As an alternative embodiment, the arc α of the first groove 117 is taken as 15°, and the arc β of the fourth groove 1013 is taken as 120°.

[0055] In a specific embodiment, as Figure 1 shown, the two-way three-way valve 150 is connected to the syringe 160; when the two-way three-way valve 150 is connected to the liquid storage bottle, the syringe communicates with the liquid storage bottle storing the injection liquid, and the syringe can suck the injection liquid in the liquid storage bottle; when the two-way three-way valve 150 is connected to the fifth valve port 115, the syringe communicates with the fifth valve port 115, and when the six-way rotary switching valve 110 is in the INJECT state, the syringe can push out the syringe to discharge its own air or replace the old injection liquid.

[0056] In a specific embodiment, as Figures 4-6 shown, the controller 180 controls the rotation of the rotor 102, and the six-way rotary switching valve 110 can be switched at any position to reach the three position states of LOAD, INJECT, and PRE, where the PRE state is the pre-pressurization state. Combining the stator and the rotor, as Figures 4-6 shown, the thin line represents the stator and the thick line represents the rotor. Figure 4 The positions of the rotor and the stator in the INJECT state are shown in Figure 5 The positions of the rotor and the stator in the LOAD state are shown in Figure 6 The positions of the rotor and the stator in the PRE state are shown in

[0057] In a specific embodiment, the theoretical value range of α is 0° < α < 60°, and the allowable value range of β needs to refer to the three states of the six-way rotary switching valve 110:

[0058] In the INJECT state, it satisfies:

[0059]

[0060] Also, ∵ 0° < α < 60°

[0061] ∴ 60° < 90° - (α / 2) < 90°

[0062] ∴ The above conditions can be summarized as β > 90° - (α / 2);

[0063] When in the LOAD state, it is necessary to satisfy:

[0064] β > 120° - (180° - α - β), that is, β > (α - 60°). Also, since 0° < α < 60°, this equation always holds;

[0065] When in the PRE state, it is necessary to satisfy: (180° - α - β) > α, that is, β < 180° - 2α;

[0066] The angular difference between the fourth valve port 114 and the fifth valve port 115 needs to satisfy: (180° - α - β) > α, that is, β < 180° - 2α;

[0067] Combining the above conditions, we have: 0° < α < 60°, 120° - α < β < 180° - 2α.

[0068] Specifically, for further optimized values: Considering that the diameter of the first groove 117 in the circumferential direction is generally 3 - 5 mm, the valve port diameter is generally 0.1 - 0.3 mm, and the maximum radian of the valve port in the circumferential direction is 11.5° (taking 3 mm and 0.3 mm), therefore, to ensure that the first groove is not connected to the second valve port, it is recommended to reserve a margin of 15° between the groove and the non - connected valve port. The process of further optimizing the value range of α and β is as follows:

[0069] Preferably, α ∈ [15°, 45°];

[0070] The angular difference between the fourth valve port 114 and the fifth valve port 115 also needs to satisfy: 15° + α ≤ (180° - α - β) ≤ 45°;

[0071] ∴ 15° + α ≤ 45°

[0072] ∴ α has a more precise value range, α ∈ [15°, 30°]

[0073] ∴ (180° - α - β) ≥ 15° + α, that is, β ≤ 165° - 2α

[0074] ∴ (180° - α - β) ≤ 45°, that is, β ≥ 135° - α

[0075] ∴ 135° - α ≤ β ≤ 165° - 2α

[0076] Combining the above conditions, we have: 15° ≤ α ≤ 45°, 135° - α ≤ β ≤ 165° - 2α.

[0077] More specifically, considering the volume, the smaller the volume of the grooving, the better. The smaller the volume, the smaller the diffusion of the sample in the flow path. Therefore, β takes the minimum value and satisfies:

[0078]

[0079] For example, when taking values, α = 15° and β = 120°, which meet the optimal conditions.

[0080] In one embodiment, as Figure 9 shown, a method for controlling ultra-high performance liquid chromatography auto-sampler applied to the ultra-high performance liquid chromatography auto-sampler device described in the above embodiment is provided, including:

[0081] S510, receiving a signal for preparing to inject a sample.

[0082] S520, controlling the six-port rotary switching valve to enter the INJECT state and keeping the sampling needle sealed in the needle seat; wherein, in the INJECT state, the fourth groove of the rotor of the six-port rotary switching valve communicates with the first valve port and the sixth valve port of the stator, the second groove communicates with the second valve port and the third valve port, and the third groove communicates with the fourth valve port and the fifth valve port.

[0083] Among them, the system defaults to the INJECT state. As Figure 1 shown, at this time, the sampling needle is in the needle seat and the two are completely sealed. The mobile phase output by the infusion pump enters the sixth valve port through the first valve port, flows through the sampling needle and the needle seat, then enters the third valve port of the valve, and finally flows out from the second valve port and enters the chromatographic column. At this time, the drainage and cleaning duration of the syringe is set to discharge the air bubbles in the syringe.

[0084] S530, determining whether the drainage and cleaning duration of the sampling device is reached.

[0085] S540, if the drainage and cleaning duration of the sampling device is reached, controlling the six-port rotary switching valve to enter the LAOD state; wherein, in the LAOD state, the second groove of the rotor of the six-port rotary switching valve communicates with the first valve port and the second valve port of the stator, the third groove communicates with the third valve port and the fourth valve port, and the fourth groove communicates with the fifth valve port and the sixth valve port.

[0086] Specifically, as Figure 7 shown, the system enters the LOAD state from the INJECT state, and the rotor 102 rotates counterclockwise by 60°. During the switching process, the angle at which the chromatographic column 300 is cut off from the flow is α. After switching to the LOAD state, the liquid with the preset system pressure in the sampling needle 120 releases the excess pressure from the waste liquid port connecting the fourth valve port 114 to the waste liquid flow path 140. In this state, the syringe 160 is connected to the fifth valve port 115 of the six-port rotary switching valve 110 through the two-way three-way valve 150, and then connected to the sampling needle 120 through the sixth valve port 116.

[0087] S550 controls the sampling needle to move to the cleaning seat for cleaning. After cleaning, it moves to the sample bottle to aspirate the target amount of sample. Then, the sampling needle is moved to the cleaning seat for cleaning again. After the second cleaning is completed, the sampling needle is controlled to move into the needle seat for sealing.

[0088] Specifically, the motor controls and moves the sampling needle, moves the sampling needle out of the needle seat, moves to the position of the cleaning seat, and inserts it. The solvent selection valve of the cleaning pump selects the set cleaning liquid, and according to the set cleaning time of the cleaning pump, generally, the outer wall of the sampling needle is cleaned in the order of strong, medium, and weak. For samples that are not likely to leave residues, medium or weak cleaning liquid can also be directly used. Among them, the cleaning seat and the needle seat can also be combined into one, and structures such as a waste liquid port can be added at the bottom of the needle seat. The motor controls the sampling needle, moves the sampling needle out of the cleaning seat, moves to the position of the sample bottle 190, and then the syringe aspirates the sample in the sample bottle according to the set amount. The motor controls the sampling needle, moves the sampling needle out of the sample bottle, moves to the position of the cleaning seat, and inserts it. The solvent selection valve of the cleaning pump selects the set cleaning liquid, and according to the set cleaning time of the cleaning pump, generally, the outer wall of the sampling needle is cleaned in the order of strong, medium, and weak. The motor controls the sampling needle, moves the sampling needle out of the cleaning seat, moves to the needle seat, and inserts it for sealing.

[0089] S560 controls the six-way rotary switching valve to enter the PRE state and maintain the preset time length. Among them, in the PRE state, the second groove of the rotor of the six-way rotary switching valve communicates with the second valve port and the first groove of the stator, and the fourth groove communicates with the first valve port and the sixth valve port.

[0090] Specifically, as Figure 8 shown, the rotor rotates counterclockwise by an angle α to enter the PRE state. In the PRE state, the infusion pump, the sampling needle, the needle seat, and the chromatographic column are all in the same flow path, and the chromatographic column will not be interrupted. The system can switch to the PRE state and stay for a period of time. Because the infusion pump is always running and the chromatographic column and the sampling needle are in the same flow path, the system fluid will actively pressurize the sample in the sampling needle at this time. The volume of the sample taken by the sampling needle is generally half of the volume of the sampling needle. Therefore, in this state, the sample is in the front end of the sampling needle, the needle seat, and the third valve port, and no additional diffusion will occur. The injection system waits for a certain time, such as 1 second, in the PRE state. After the sample is pressurized, it is switched to the INJECT state. At this time, the pressure of the sample entering the chromatographic column is the same as the system pressure, and reverse diffusion caused by the pressure difference between the sample and the system will not occur. Among them, the PRE state is the pre-pressurization state.

[0091] S570 controls the six-way rotary switching valve to enter the INJECT state again, and the injection is completed.

[0092] Among them, the system switches to the INJECT state, and the sample enters the chromatographic column through the sampling needle, needle seat, third valve port, and second valve port for separation and analysis.

[0093] During the entire process from S510 to S570, the angle of chromatographic column flow interruption is 2α. For example, taking α = 15° as an example, the theoretical flow interruption during the entire process is 30°, which is reduced to 1 / 4 of the original flow interruption time compared with 120° in the prior art; if considering extreme conditions, using a grooved arc with a circumferential diameter of 5 mm and a grooved diameter of 0.1 mm, α can be minimized to 3°, and the flow interruption time is only 1 / 20 of the prior art.

[0094] In the above ultra-high performance liquid chromatography automatic injection control method, through the setting of the first groove and control mode in the six-way rotary switching valve, the chromatographic column has a short flow interruption time, reducing the impact of pressure shock on the chromatographic column; and, the PRE state is added to pressurize the sample entering the injection needle, avoiding reverse diffusion of the sample caused by the pressure difference when entering the chromatographic column.

[0095] In one of the embodiments, after determining whether the drainage and cleaning duration of the sampling device is reached, it includes: S580, if the drainage and cleaning duration of the sampling device is not reached, controlling the two-way three-way valve to switch to the injection liquid path and controlling the syringe to aspirate liquid; S590, controlling the two-way three-way valve to switch to the six-way rotary switching valve path and controlling the syringe to drain and clean the sampling needle.

[0096] The technical features of the above-described embodiments can be combined arbitrarily. For the sake of brevity of description, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, it should be considered as the scope described in this specification.

[0097] The above-described embodiments only represent several implementation manners of the present invention, and their descriptions are relatively specific and detailed, but they should not be construed as limiting the scope of the invention patent. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several deformations and improvements can still be made, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the invention patent should be subject to the appended claims.

Claims

1. An ultra-high performance liquid chromatography automatic sampling device, characterized in that, The device includes: a sampling device, a cleaning device, a waste liquid flow path, a syringe, a two-way three-way valve, and a six-way rotary switching valve. The stator of the six-way rotary switching valve is provided with a first groove communicating with the mobile phase inlet valve port, and the first groove is located at the circumferential position where the mobile phase inlet valve port is located; The six-way rotary switching valve includes a stator and a rotor. The stator is provided with six valve ports and a first groove, which are the first valve port, the second valve port, the third valve port, the fourth valve port, the fifth valve port, and the sixth valve port in sequence. The first valve port is the mobile phase inlet valve port. The first groove is located between the first valve port and the second valve port, communicates with the first valve port, and does not communicate with the second valve port. The included angle between the second valve port and the third valve port is 60°, and the included angle between the third valve port and the fourth valve port is 60°; The rotor is provided with three grooves in the circumferential direction corresponding to the valve port positions, namely the second groove, the third groove, and the fourth groove. The arcs of the second groove and the third groove are 60°. The included angle between the fourth groove and the second groove is equal to the arc of the first groove. The sum of the arc of the fourth groove, the arc of the first groove, and the included angle between the fourth valve port and the fifth valve port is 180°. Among them, the arc of the first groove is set as α, and the arc of the fourth groove is set as β; The diameter of the first groove in the circumferential direction ranges from 3 mm to 5 mm. The diameters of the six valve ports provided on the stator are from 0.1 mm to 0.3 mm. The arc distance between the first groove and the second valve port is not less than 15°, that is, 15° ≤ α ≤ 45°, 135° - α ≤ β ≤ 165° - 2α.

2. The ultra-high performance liquid chromatography automatic sampling device according to claim 1, characterized in that, The outlet of the infusion pump is connected to the first valve port, the chromatographic column is connected to the second valve port, the needle seat is connected to the third valve port, the waste liquid flow path is connected to the fourth valve port, the two-way three-way valve is connected to the fifth valve port, and the sampling needle is connected to the sixth valve port.

3. The ultra-high performance liquid chromatography automatic sampling device according to claim 1, characterized in that, The sampling device includes a needle seat and a sampling needle, which are hermetically connected.

4. The ultra-high performance liquid chromatography automatic sampling device according to any one of claims 1-3, characterized in that, It further includes a controller for controlling the actions of the six-way rotary switching valve, the sampling needle, the two-way three-way valve, the syringe, or the cleaning device.

5. The ultra-high performance liquid chromatography automatic sampling device according to claim 1, characterized in that, 15°≤α≤45°，β=135°-α。 6. The ultra-high performance liquid chromatography automatic sampling device according to claim 5, characterized in that, The arc α of the first groove is 15°, and the arc β of the fourth groove is 120°.

7. An ultra-high performance liquid chromatography automatic sampling control method applied to the ultra-high performance liquid chromatography automatic sampling device according to any one of claims 1-6, characterized in that, Including: Receiving a signal for preparing to inject a sample; Controlling the six-way rotary switching valve to enter the INJECT state, and keeping the sampling needle sealed in the needle seat; where, in the INJECT state, the fourth groove of the rotor of the six-way rotary switching valve communicates with the first valve port and the sixth valve port of the stator, the second groove communicates with the second valve port and the third valve port, and the third groove communicates with the fourth valve port and the fifth valve port; Judging whether the drainage and cleaning duration of the sampling device is reached; If the drainage and cleaning duration of the sampling device is reached, controlling the six-way rotary switching valve to enter the LAOD state; where, in the LAOD state, the second groove of the rotor of the six-way rotary switching valve communicates with the first valve port and the second valve port of the stator, the third groove communicates with the third valve port and the fourth valve port, and the fourth groove communicates with the fifth valve port and the sixth valve port; Controlling the sampling needle to move to the cleaning seat for cleaning, after cleaning, moving to the sample bottle to aspirate the target amount of sample, then moving the sampling needle to the cleaning seat for cleaning again, and after the second cleaning, controlling the sampling needle to move to the needle seat for sealing; Control the six-way rotary switching valve to enter the PRE state and maintain a preset time length; wherein, in the PRE state, the second groove of the rotor of the six-way rotary switching valve communicates with the second valve port and the first groove of the stator, and the fourth groove communicates with the first valve port and the sixth valve port; Control the six-way rotary switching valve to enter the INJECT state again, and the sample injection ends.

8. The method according to claim 7, characterized in that, After judging whether the liquid discharge cleaning duration of the sampling device is reached, it includes: If the liquid discharge cleaning duration of the sampling device is not reached, control the two-way three-way valve to switch to the injection liquid path and control the syringe to suck liquid; Control the two-way three-way valve to switch to the six-way rotary switching valve path and control the syringe to discharge and clean the liquid.

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