Liquid chromatography autosampler, liquid chromatography system, and control method

Abstract

The application discloses a liquid chromatography automatic sampling device, a liquid chromatography system and a control method, and relates to the technical field of liquid chromatography, and can realize automatic sampling and automatic emptying of a sampling needle. The liquid chromatography automatic sampling device comprises a multi-channel rotary switching valve, a first channel of the multi-channel rotary switching valve being used for being connected to a transfusion unit, a second channel of the multi-channel rotary switching valve being used for being connected to an analysis unit, a sampling needle being connected to a third channel of the multi-channel rotary switching valve, and a needle sealing seat being connected to a fourth channel of the multi-channel rotary switching valve and being used for placing the sampling needle. The application also discloses a liquid chromatography system and a control method.

Description

Technical Field

[0001] This invention relates to the field of liquid chromatography instrument technology, and in particular to an automated liquid chromatography injection device, a liquid chromatography system, and a control method. Background Technology

[0002] Traditional liquid chromatography (LC) systems can be functionally divided into a solvent management unit, a delivery unit, an injection unit, an analysis unit, a detection unit, and a data processing and output unit. The delivery unit is responsible for delivering the solvent to the analysis unit at a specified ratio and flow rate (or a specified pressure), while the injection unit is responsible for introducing the sample into the analysis unit for separation and analysis. When the system is in operation, the delivery unit and subsequent flow paths are filled with air before the solvent enters from the reservoir. The delivery unit must be purged before the solvent can properly enter the system.

[0003] In traditional liquid chromatography, the vent valve is located within the infusion unit and is typically operated manually. As liquid chromatography systems become increasingly intelligent, automated, and integrated, vent valves have evolved from manual to automatic venting. Simultaneously, with the shift from high-performance liquid chromatography (HPLC) to ultra-high-performance liquid chromatography (UHPLC), the operating pressure of the infusion unit is increasing, and the tubing diameter is decreasing. Therefore, automatic vent valves are generally high-pressure (typically 18,000 ps i) rotary switching valves, similar to those used in autosamplers. These valves are expensive, and their location immediately after the infusion pump means the fluid does not pass through a filter (online filters are usually located at the mixer inlet, and both the mixer and filter have some flow resistance; therefore, to facilitate smooth venting and liquid intake, the mixer is usually located after the vent valve). Debris from the high-pressure seals worn from the infusion pump, or other solid impurities, will be carried into the vent valve along with the fluid, causing wear on the internal rotor and stator, potentially damaging the valve body and shortening its lifespan. Summary of the Invention

[0004] The purpose of this invention is to overcome the above-mentioned technical deficiencies and to propose an automatic liquid chromatography injection device, a liquid chromatography system and its control method, thereby solving the technical problems of easy failure of components and high component costs in the prior art.

[0005] To achieve the above-mentioned technical objectives, in a first aspect, the present invention provides an automated liquid chromatography sample injector, comprising:

[0006] A multi-channel rotary switching valve includes at least four channels. The first channel is connected to the infusion unit, and the second channel is used to connect to the analysis unit. The analysis unit is supplied with fluid through the second channel.

[0007] The sampling needle is connected to the third channel of the multi-channel rotary switching valve;

[0008] A needle sealing seat is connected to the fourth channel of the multi-channel rotary switching valve, and the needle sealing seat is used to hold the sampling needle;

[0009] A cleaning device includes a cleaning seat and a venting pump. The cleaning seat has a cylindrical structure and a partition ring inside, which divides the cleaning seat into an open space and an internal space. The venting pump is connected to the internal space through a pipe. When the tip of the sampling needle passes through the partition ring and enters the internal space, the venting pump operates to create a negative pressure environment in the internal space to vent the gas in the pipe before the sampling needle.

[0010] Compared with the prior art, the advantages of the automated liquid chromatography sample injector provided by the present invention include:

[0011] Traditional liquid chromatography systems can be functionally divided into solvent management, delivery, injection, analysis, detection, and data processing and output units. The delivery unit typically consists of a delivery pump, a vent valve, and a mixer. Vent valves are expensive and usually located after the delivery pump. Traditional venting methods only vent up to the delivery pump; the flow path from the mixer and injector to the analysis unit remains filled with air, which is then pumped into the subsequent analysis unit. This invention vents air up to the injection needle, limiting the volume of air present to only a small section of tubing after the needle hub, resulting in better venting. The cleaning device used is also cheaper, and the absence of a separate electric vent valve further reduces hardware costs. Furthermore, this invention integrates and combines components, reducing maintenance difficulty and improving ease of maintenance. Simultaneously, the vent valve and injection valve are combined and located after the filter and mixer. Fluid entering the vent valve has already passed through the filter, removing most solid impurities, thus reducing the probability of wear and failure of the rotary valve and extending the service life of components.

[0012] According to some embodiments of the present invention, the cleaning device further includes a cleaning pump, which is connected to the opening space via a pipe, and is used to clean the outer wall of the sampling needle and the interior of the cleaning device.

[0013] This application is equipped with a control module that enables intelligent one-click venting. Operators only need to operate it on a workstation with control functions, without having to manually open the vent valve at the instrument site. It can realize remote control and batch operation, which can reduce the difficulty of operation for operators, increase the number of instruments that can be controlled at the same time, and improve work efficiency.

[0014] According to some embodiments of the present invention, the cleaning pump is any one of a peristaltic pump, a diaphragm pump, a syringe, or a metering pump; the evacuation pump is a diaphragm pump or a vacuum pump.

[0015] According to some embodiments of the present invention, the separator ring is a resin sealing gasket, and the material of the sealing gasket can be any one of FFKM, PTFE and PEEK. When the tip of the sampling needle passes through the separator ring and enters the internal space, the outer wall of the needle tip and the separator ring are in a sealed state.

[0016] According to some embodiments of the present invention, the separator ring is made of any one of PEEK material, stainless steel material, and titanium alloy material. The separator ring is provided with a straight hole or a tapered hole slightly larger than the outer diameter of the sampling needle. When the tip of the sampling needle passes through the straight hole or tapered hole of the separator ring and enters the internal space, the venting pump works to create a negative pressure environment in the internal space.

[0017] Secondly, the technical solution of the present invention provides a liquid chromatography system, comprising:

[0018] The liquid storage device, the liquid delivery unit, the automatic liquid chromatography sample injector as described in any one of the first aspects, the analysis unit, the detection unit, and the data processing and output unit are connected in sequence.

[0019] According to some embodiments of the present invention, the infusion unit includes an infusion pump, which is composed of a system pump and a suction pump paired together, and the system pump and the suction pump are driven and controlled separately by their respective motors.

[0020] Thirdly, the technical solution of the present invention provides a control method for a liquid chromatography system, applied to the liquid chromatography system as described in the second aspect, characterized by comprising the following steps:

[0021] Start the liquid chromatography system and execute the system flow path purging action;

[0022] When the multi-channel rotary switching valve is in the injection state, it controls the sampling needle to leave the needle sealing seat;

[0023] The sampling needle tip is controlled to pass through the separator ring and enter the internal space of the cleaning device;

[0024] The venting pump operates to create a negative pressure environment in the internal space, while simultaneously controlling the infusion pump of the infusion unit to enter the venting operation mode to vent the gas in the pipeline before the sampling needle.

[0025] After purging is complete, shut down the purging pump and the infusion pump, and control the sampling needle to enter the needle sealing seat.

[0026] According to some embodiments of the present invention, the infusion pump of the infusion unit enters the evacuation operation mode, including the following steps:

[0027] S1. Control the plunger rod of the suction pump and the plunger rod of the system pump to run to the position with the largest pump chamber volume, and stay for a preset time to allow the empty pump to fully reduce the air pressure in the system.

[0028] S2. Control the plunger rod of the suction pump to run at the venting flow rate to the position where the pump cavity volume is the smallest, and then control the plunger rod of the system pump to run at the venting flow rate to the position where the pump cavity volume is the smallest.

[0029] S3. Control the plunger rod of the suction pump to run at the venting flow rate to the position where the pump chamber volume is the largest, and then control the plunger rod of the system pump to run at the venting flow rate to the position where the pump chamber volume is the largest, and stay for a preset time to allow the venting pump to fully reduce the air pressure in the system.

[0030] S4. Repeat S2 and S3 until the emptying process is complete.

[0031] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Attached Figure Description

[0032] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, wherein the abstract drawings are to be completely consistent with one of the drawings in the specification:

[0033] Figure 1 This is a schematic diagram of a traditional liquid chromatography system;

[0034] Figure 2 This is a schematic diagram of the structure of an automated liquid chromatography sample injector provided in one embodiment of the present invention;

[0035] Figure 3 This is a schematic diagram of the cleaning seat structure of an automated liquid chromatography sample injector provided in one embodiment of the present invention;

[0036] Figure 4 This is a schematic diagram of the cleaning seat structure of an automated liquid chromatography sample injector provided in one embodiment of the present invention;

[0037] Figure 5 This is a schematic diagram of the pressure distribution of the delivery unit of a liquid chromatography system according to an embodiment of the present invention;

[0038] Figure 6 A flowchart of a control method for a liquid chromatography system provided in one embodiment of the present invention;

[0039] Figure 7 This is a structural diagram of the infusion pump of a liquid chromatography system provided in one embodiment of the present invention.

[0040] Explanation of reference numerals in the attached drawings: multi-channel rotary switching valve 110, first channel 111, second channel 112, third channel 113, fourth channel 114, fifth channel 115, sixth channel 116, sampling needle 120, needle sealing seat 130, cleaning device 140, cleaning pump 141, cleaning seat 142, evacuation pump 143, partition ring 144, internal space 145, opening space 146, control module 150, metering device 160. Detailed Implementation

[0041] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0042] It should be noted that although functional modules are divided in the system diagram and the logical order is shown in the flowchart, in some cases, the steps shown or described may be executed in a different order than the module division in the system or the order in the flowchart. The terms "first," "second," etc., in the specification, claims, and the aforementioned figures are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence.

[0043] Patent US6012487 discloses a method that combines an infusion pump purging valve and an injector injection valve, employing an atypical rotary switching valve that can switch between three different positions: inject, load, and purge. In the purging state, the infusion pump is directly connected to the waste port on the injector to achieve the purging function, eliminating the need for an infusion pump purging valve compared to traditional liquid chromatography.

[0044] However, the patent uses an atypical rotary switching valve with three states (a typical rotary switching valve only has two states: "injection" and "loading"). Both the hardware and software control require custom customization. Moreover, the use of a quantitative loop injection method results in sample loss during the injection process. In addition, when the system is filled with air, according to pressure calculations, if the flow resistance in the pump's internal flow path increases to a critical point, the air in the pump's internal flow path will not generate negative pressure as it moves back and forth with the plunger rod. The system cannot expel air bubbles, and new fluid cannot enter the infusion unit, thus failing to achieve the purpose of purging.

[0045] It should be noted that the inner diameter of the flow path tube used in liquid chromatography is typically 0.25 mm, and the typical flow rate is 1 mL / min (approximately 1.67 × 10⁻⁶). -8 m 3 The flow rate ( / s) is a microfluidic flow, which is far below the Reynolds number required for turbulent flow. Therefore, the following calculations will be performed on a smooth, straight circular tube as a laminar flow.

[0046] Assume the pipe flow resistance is λ, the fluid viscosity is μ, the pipe length is L, the pipe inner diameter is d, and the system flow rate is Q, all in SI units.

[0047] The following formulas are given:

[0048]

[0049] For an ideal gas, under constant temperature conditions, the product of the pressure and volume of a given amount of ideal gas is a fixed value, that is, the gas pressure is inversely proportional to the gas volume.

[0050] For ease of explanation, the viscosity of the low-pressure gas can be considered constant. Define ΔV as the volume decrease, ΔP as the pressure increase, P0 as the initial air pressure in the cavity, and V0 as the total volume of the pump cavity and pipeline. We can then obtain:

[0051]

[0052] When the above inequality holds, that is, when the volume change caused by compressed air is less than the volume change caused by the pressure generated by the flow resistance at that flow rate, the air in the infusion unit will be repeatedly compressed and expanded during operation, and will not draw in new fluid, thus failing to achieve the purpose of discharging air.

[0053] Substituting the physical properties of air at normal temperature and pressure into the calculation, P0 = 101325 Pa, μ = 1.79 × 10 -5 Pa·s, pump chamber and pipeline volume V0 is approximately 400 μL, ΔV is approximately 40 μL, and venting flow rate is Q = 3 mL / min = 5 × 10⁻⁶. -8 m 3 / s, pipe inner diameter d=0.25mm=2.5×10 -4 Substituting m into the equation yields the critical value: L≥1.21(m).

[0054] In ultra-high performance liquid chromatography systems with even higher requirements for system volume, the inner diameter of commonly used tubing is even smaller at 0.18 mm, and the calculated critical value is only 0.33 m. This tubing length is almost impossible to complete the connection of all components within the infusion unit and between the infusion unit and the injection unit.

[0055] It should also be noted that the actual tubing used is not straight and the inner wall is not completely smooth, so the actual flow resistance will only be greater than the calculated value. At the same time, components such as mixers, buffers, pressure sensors and online filters that may exist in the infusion system also have flow resistance. Therefore, the actual length of tubing that can be used to successfully perform the evacuation operation will only be much shorter than the calculated value.

[0056] Considering all the above factors, the purging method described in patent US6012487 is virtually impossible to implement, as confirmed by actual test results. Precisely because of the excessive flow resistance, current liquid chromatographs on the market do not adopt this patented method. Instead, they operate like traditional liquid chromatography systems, placing the purging valve within the delivery unit and using a large-diameter pipe (typically a 1 / 32" inner diameter pipe, approximately 0.79 mm) for one purging outlet. Furthermore, components with high flow resistance, such as mixers, are not included in the purging process.

[0057] The embodiments of the present invention will be further described below with reference to the accompanying drawings.

[0058] Reference Figures 1 to 4 , Figure 1 This is a schematic diagram of a traditional liquid chromatography system; Figure 2 This is a schematic diagram of the structure of an automated liquid chromatography sample injector provided in one embodiment of the present invention; Figure 3 This is a schematic diagram of the cleaning seat structure of an automated liquid chromatography sample injector provided in one embodiment of the present invention; Figure 4 This is a schematic diagram of the cleaning seat structure of an automated liquid chromatography sample injector provided in one embodiment of the present invention.

[0059] In one embodiment, the automated liquid chromatography (HPLC) sample injector includes: a multi-channel rotary switching valve 110, comprising at least four channels; a first channel 111 connected to a delivery unit, supplying liquid to an analysis unit via a second channel 112, the second channel 112 being used to connect to the analysis unit; a sampling needle 120 connected to a third channel 113 of the multi-channel rotary switching valve 110; and a needle seal 130 connected to a fourth channel 114 of the multi-channel rotary switching valve 110, the needle seal 130 being used to hold the sampling needle 120. 0; Cleaning device 140, including: cleaning seat 142 and venting pump 143. The cleaning seat 142 is provided with a partition ring 144, which divides the cleaning seat 142 into an open space 146 and an internal space 145. The venting pump 143 is connected to the internal space 145 through a pipe. When the tip of the sampling needle 120 passes through the partition ring 144 and enters the internal space 145, the venting pump 143 works to create a negative pressure environment in the internal space 145 to vent the gas in the pipe before the sampling needle 120.

[0060] In one embodiment, the automated liquid chromatography (HPLC) sample injector includes: a multi-channel rotary switching valve 110, comprising at least four channels, a first channel 111 connected to a delivery unit, and a second channel 112 supplying liquid to an analysis unit; a sampling needle 120 connected to a third channel 113 of the multi-channel rotary switching valve 110; a needle seal 130 connected to a fourth channel 114 of the multi-channel rotary switching valve 110, the needle seal 130 being used to hold the sampling needle 120; and a cleaning device 140, including a cleaning pump 141. The cleaning seat 142 and the venting pump 143 are provided. The cleaning seat 142 has a cylindrical structure and a partition ring 144 is provided inside the cleaning seat 142. The partition ring 144 divides the cleaning seat 142 into an open space 146 and an internal space 145. The cleaning pump 141 is connected to the open space 146 through a pipe, and the venting pump 143 is connected to the internal space 145 through a pipe. When the tip of the sampling needle 120 passes through the partition ring 144 and enters the internal space 145, the venting pump 143 works to create a negative pressure environment in the internal space 145 to vent the gas in the pipe before the sampling needle 120.

[0061] The infusion unit is connected to the first channel 111. The infusion unit can directly include an infusion pump and a mixer. The infusion unit does not contain a drain valve, which can reduce hardware costs and reduce maintenance difficulty.

[0062] The sampling needle 120 is connected to the third channel 113 of the multi-channel rotary switching valve 110. In the sampling state, the sampling needle 120 is placed in the needle sealing seat 130, which is connected to the fourth channel 114 of the multi-channel rotary switching valve 110. The present invention is provided with a cleaning device 140, including a cleaning seat 142 and a venting pump 143. The cleaning seat 142 has a cylindrical structure and a partition ring 144 is provided inside the cleaning seat 142. The partition ring 144 divides the cleaning seat 142 into an open space 146 and an internal space 145. The venting pump 143 is connected to the internal space 145 through a pipe. When the tip of the sampling needle 120 passes through the partition ring 144 and enters the internal space 145, the venting pump 143 works to create a negative pressure environment in the internal space 145 to vent the gas in the pipeline before the sampling needle 120. After the purging operation of the cleaning device 140 in this invention, the gas is vented to the injection needle position. The volume of air present is only a small section of the tubing behind the needle seat, which improves the purging effect. Moreover, the purging pump 143 of the cleaning device 140 in this application is located at the rear end of the mixer. The fluid entering the purging pump 143 has been filtered, and there are very few impurities in the liquid. This can effectively reduce the probability of wear and failure of the rotary switching valve, and improve the reliability and service life of the equipment.

[0063] In one embodiment, the automated liquid chromatography (HPLC) injection device includes: a multi-channel rotary switching valve 110, comprising at least four channels; a first channel 111 connected to a delivery unit for supplying liquid to the injection unit; a second channel 112 for connecting to an analysis unit; a sampling needle 120 connected to a third channel 113 of the multi-channel rotary switching valve 110; a needle seal 130 connected to a fourth channel 114 of the multi-channel rotary switching valve 110 for housing the sampling needle 120; and a cleaning device. 140 includes: a cleaning seat 142 and a venting pump 143. The cleaning seat 142 has a cylindrical structure and a partition ring 144 inside, dividing the cleaning seat 142 into an open space 146 and an internal space 145. The venting pump 143 is connected to the internal space 145 through a pipe. When the tip of the sampling needle 120 passes through the partition ring 144 and enters the internal space 145, the venting pump 143 operates to create a negative pressure environment in the internal space 145 to vent the gas in the pipe before the sampling needle 120. A control module 150 is connected to the sampling needle 120. The control module 150 includes a motor and a positioning device. The motor controls the movement of the sampling needle 120, and the positioning device is used to position the movement of the sampling needle 120.

[0064] The control module 150 in this application can control the movement of the sampling needle 120. Specifically, when an emptying operation is required, the control module 150 controls the sampling needle 120 to leave the needle sealing seat 130, moves the needle to the position of the cleaning device 140, and then the tip of the sampling needle 120 passes through the separator ring 144 into the internal space 145. After the emptying operation is completed, the control module 150 controls the sampling needle 120 to leave the cleaning device 140 and return to the position of the needle sealing seat 130 for subsequent liquid chromatography analysis.

[0065] Furthermore, since a control module 150 is provided in this embodiment, multiple instruments can be emptied at once through the control platform, enabling intelligent one-click emptying. Operators only need to operate on a workstation with control functions, without having to manually open the emptying valve at the instrument site. This allows for remote control and batch operation, reducing the difficulty of operation for operators, increasing the number of instruments that can be controlled simultaneously, and improving work efficiency.

[0066] In one embodiment, the automated liquid chromatography (HPLC) sample injector includes: a multi-channel rotary switching valve 110, with a first channel 111 connected to a delivery unit and a second channel 112 for supplying liquid to an analysis unit; a sampling needle 120 connected to a third channel 113 of the multi-channel rotary switching valve 110; a needle seal 130 connected to a fourth channel 114 of the multi-channel rotary switching valve 110, the needle seal 130 for holding the sampling needle 120; and a cleaning device. The device 140 includes a cleaning seat 142 and an emptying pump 143. The cleaning seat 142 has a partition ring 144 inside, dividing it into an open space 146 and an internal space 145. The emptying pump 143 is connected to the internal space 145 via a pipe. When the tip of the sampling needle 120 passes through the partition ring 144 and enters the internal space 145, the emptying pump 143 operates to create a negative pressure environment in the internal space 145, thereby emptying the gas in the pipe before the sampling needle 120. The multi-channel rotary switching valve 110 also has a fifth channel 115 and a sixth channel 116. The fifth channel 115 is connected to a waste liquid pipe, through which waste liquid is discharged. The sixth channel 116 is connected to the first port of the metering device 160 via a pipe, and the second port of the metering device 160 is connected to the metering device cleaning fluid delivery device.

[0067] In one embodiment, the automated liquid chromatography (HPLC) injection device includes: a multi-channel rotary switching valve 110, with a first channel 111 connected to a liquid delivery unit for supplying liquid to the injection unit, and a second channel 112 for connecting to an analysis unit; a sampling needle 120 connected to a third channel 113 of the multi-channel rotary switching valve 110; a needle seal 130 connected to a fourth channel 114 of the multi-channel rotary switching valve 110 for housing the sampling needle 120; and a cleaning device. The device 140 includes a cleaning seat 142 and an air venting pump 143. The cleaning seat 142 is provided with a partition ring 144, which divides the cleaning seat 142 into an open space 146 and an internal space 145. The air venting pump 143 is connected to the internal space 145 through a pipe. When the tip of the sampling needle 120 passes through the partition ring 144 and enters the internal space 145, the air venting pump 143 works to create a negative pressure environment in the internal space 145 to vent the gas in the pipe before the sampling needle 120.

[0068] Furthermore, the cleaning pump 141 is any one of a peristaltic pump, a diaphragm pump, a syringe, or a metering pump; the evacuation pump 143 is a diaphragm pump or a vacuum pump.

[0069] Furthermore, the separator ring 144 is a resin sealing gasket, and the material of the sealing gasket can be any one of FFKM sealing ring, PTFE sealing ring and PEEK sealing ring. When the needle tip of the sampling needle 120 passes through the separator ring 144 and enters the internal space 145, the outer wall of the needle tip and the separator ring 144 are in a sealed state.

[0070] Furthermore, the separator ring 144 can be made of any of the following materials: PEEK, stainless steel, and titanium alloy. The separator ring 144 is provided with a straight hole or a conical hole that is slightly larger than the outer diameter of the sampling needle 120. When the tip of the sampling needle 120 passes through the straight hole or conical hole of the separator ring 144 and enters the internal space 145, the venting pump 143 works to create a negative pressure environment in the internal space 145.

[0071] Reference Figure 5 , Figure 5 This is a schematic diagram of the pressure distribution of the delivery unit of a liquid chromatography system provided in one embodiment of the present invention.

[0072] In one embodiment, a liquid chromatography system includes: a liquid storage device, a liquid delivery unit, an automatic liquid chromatography sample injector as described above, an analysis unit, a detection unit, and a data processing and output unit connected in sequence.

[0073] Furthermore, the infusion unit includes: a first check valve, a suction pump, a second check valve, and a system pump. One end of the first check valve is connected to the liquid storage device, and the other end is connected to the inlet of the suction pump. The outlet of the suction pump is connected to the first end of the second check valve. The second end of the second check valve is connected to the inlet of the system pump. The outlet of the system pump is connected to the automatic liquid chromatography sample injector.

[0074] Infusion pumps in infusion units typically employ parallel or series plunger pump structures. Both a set of parallel plunger pumps and a set of series plunger pumps consist of two pumps. Based on their functions, these two pumps can be defined as a suction pump and a system pump. In a series plunger pump, the two pumps will be fixed to perform the functions of either a suction pump or a system pump, while in a parallel plunger pump, the two pumps will take turns performing the functions of a suction pump and a system pump.

[0075] Both the inlet and outlet of the suction pump have check valves. At the inlet, external fluid can only enter when the external fluid pressure is greater than the fluid pressure at the inlet of the suction pump; at the outlet, fluid can only enter the subsequent flow path when the fluid pressure inside the suction pump is greater than the fluid pressure in the subsequent flow path.

[0076] When the infusion pump is required to deliver fluid at a fixed flow rate, the suction pump draws fluid while the system pump is delivering fluid. At this time, the system pump pressure is greater than the suction pump pressure, and the outlet check valve is closed. When the system pump draws fluid, the suction pump delivers fluid at (set flow rate + system pump suction flow rate). At this time, the system pump pressure is momentarily less than the suction pump pressure, and the outlet check valve opens. In the long run, after the outlet check valve opens, the pressure inside the system pump and the suction pump are equal.

[0077] from Figure 5As can be seen, the total internal cavity volume V0 is fixed. When the infusion pump delivers fluid, the plunger moves forward, resulting in a volume reduction of ΔV. This volume reduction generates a corresponding pressure increase of ΔP1. The negative pressure at the outlet carries away some gas, so the actual pressure increase (ΔP1-ΔP2) is less than the ΔP1 caused by the volume reduction ΔV. (If the flow path resistance is small, the resulting pressure rise may be lower than the pressure difference between the outlet negative pressure and atmospheric pressure; in this case, (ΔP1-ΔP2) may be negative, meaning the system pressure is lower than atmospheric pressure, resulting in better venting.)

[0078] At this point, the infusion pump draws in liquid, the plunger rod retracts, and the total volume of the internal cavity returns to V0. However, due to the presence of ΔP2, the pressure inside the infusion pump cavity is no longer P0 but is less than P0. The external atmospheric pressure is normal, which is P0, and is greater than the current pressure inside the infusion pump. The inlet check valve opens, allowing external gas or liquid from the storage bottle to smoothly enter the infusion pump. Because the evacuation pump 143 runs continuously, the negative pressure inside the cleaning seat 142 remains at a relatively constant value. Therefore, a portion of the gas in the system is always carried away by the evacuation pump 143 at the outlet of the sampling needle 120.

[0079] This process is repeated multiple times to successfully expel gas from the system until the liquid in the storage bottle enters the infusion pump, thus achieving the purpose of emptying the system.

[0080] Reference Figure 6 and Figure 7 , Figure 6 A flowchart of a control method for a liquid chromatography system provided in one embodiment of the present invention; Figure 7 This is a structural diagram of the infusion pump of a liquid chromatography system provided in one embodiment of the present invention.

[0081] The control methods for the liquid chromatography system include, but are not limited to, steps S110 to S130.

[0082] Step S110: Start the liquid chromatography system and purge the system flow path;

[0083] Step S120: When the multi-channel rotary switching valve 110 is in the injection state, control the sampling needle 120 to leave the needle sealing seat 130;

[0084] Step S130: Control the tip of the sampling needle 120 to pass through the separator ring 144 and enter the internal space 145 of the cleaning device 140;

[0085] In step S140, the venting pump 143 operates to create a negative pressure environment in the internal space 145, while controlling the infusion pump of the infusion unit to operate at a venting flow rate to vent the gas in the pipeline before the sampling needle 120.

[0086] Step S150: After purging is completed, turn off the purging pump 143 and the infusion pump, and control the sampling needle 120 to move and enter the needle sealing seat 130.

[0087] In one embodiment, the control method of the liquid chromatography system includes the following steps: starting the liquid chromatography system and purging the system flow path; when the multi-channel rotary switching valve 110 is in the injection state, controlling the sampling needle 120 to leave the needle seal seat 130; controlling the tip of the sampling needle 120 to pass through the separator ring 144 and enter the internal space 145 of the cleaning device 140; the purging pump 143 operates to create a negative pressure environment in the internal space 145, and at the same time controls the infusion pump of the infusion unit to enter the purging operation mode to purge the gas in the pipeline before the sampling needle 120; after purging is completed, the purging pump 143 and the infusion pump are turned off, and the sampling needle 120 is controlled to enter the needle seal seat 130.

[0088] The emptying process is as follows:

[0089] When the system receives the instruction to "empty the system flow path", the sampling needle 120 control module 150 moves the opening of the sampling needle 120 into the emptying module of the cleaning seat 142. Note that when controlling the descent depth of the sampling needle 120, the opening of the sampling needle 120 must be located inside the emptying module, and the opening must be in contact with the air inside the emptying module, and cannot be sealed or blocked (the sampling needle 120 has various types such as side opening and end face opening).

[0090] Upon receiving the instruction to "empty the system flow path", first check whether the autosampler rotary switching valve is in the injection state. If not, switch to the injection state. Then, the sampling needle 120 control module 150 controls the sampling needle 120 to leave the needle seat, move to the cleaning seat 142, and enter the sealing structure or slit of the cleaning seat 142.

[0091] The evacuation pump 143 is started, continuously drawing air out of the cleaning seat 142 to create negative pressure in the cavity. At the same time, the infusion pump enters the evacuation operation mode. The operating speed of the evacuation pump 143 can be 0.01 to 3.0 L / min, more preferably 0.1 to 2.0 L / min, and in a more preferred example, 0.7 L / min.

[0092] After the sampling needle 120 leaves the cleaning seat 142, the system is filled with air at normal pressure. Therefore, after a negative pressure is formed in the cleaning seat 142, the normal pressure gas in the system escapes from the outlet of the sampling needle 120, and the air pressure at the outlet of the sampling needle 120 is lower than normal pressure.

[0093] Taking a straight circular pipe as an example, with a fixed flow rate Q, the system pressure drop is proportional to the pipe length, so the absolute pressure in the pipe decreases.

[0094] According to the flow resistance formula When the flow resistance λ and the flow rate remain constant, the pressure drop of the entire flow path is fixed.

[0095] Therefore, when the outlet pressure decreases, the internal pressure of the system will also decrease proportionally. After purging is complete, shut down the purging pump 143 and the infusion pump, and control the sampling needle 120 to enter the needle seal seat 130.

[0096] The emptying process can also be:

[0097] The stroke of the variable stroke tandem piston pump can be controlled independently for both the system pump and the suction pump.

[0098] Regarding assisting / optimizing the emptying effect:

[0099] 1. When the system enters the venting state, the sampling needle control module causes the sampling needle to enter the venting module of the cleaning seat. At this time, the motor controls the plunger rod of the suction pump and the plunger rod of the system pump to run to the position with the largest pump chamber volume, and the venting pump is turned on. A negative pressure is formed inside the venting module. After a certain period of time, the venting pump can reduce the air pressure in the system more fully.

[0100] 2. Control the plunger rod of the suction pump to move to the position where the pump cavity volume is minimized at a certain flow rate, and then control the plunger rod of the system pump to move to the position where the pump cavity volume is minimized at a certain flow rate;

[0101] 3. Control the plunger rod of the suction pump to move to the position with the largest pump chamber volume at a certain flow rate, and then control the plunger rod of the system pump to move to the position with the largest pump chamber volume at a certain flow rate, and stay for a certain period of time to allow the empty pump to reduce the air pressure in the system more fully;

[0102] 4. Repeat steps 2 and 3 until the emptying process is complete.

[0103] 5. After the purging process is complete, first return the plunger rod of the aspiration pump and the plunger rod of the system pump to their initial positions, then turn off the purging pump and control the sampling needle to leave the purging module and return to the needle seat. The flow rate mentioned above can be 0.1–10 mL / min, more preferably 3–7 mL / min, and in a more preferred example, 5 mL / min; the residence time can be 0.1–5.0 s, more preferably 0.5–3.0 s, and in a more preferred example, 1.0 s.

[0104] The device embodiments described above are merely illustrative. The units described as separate components may or may not be physically separate; they may be located in one place or distributed across multiple network units. Some or all of the modules can be selected to achieve the purpose of this embodiment according to actual needs.

[0105] Furthermore, one embodiment of the present invention provides a computer-readable storage medium storing computer-executable instructions that are executed by a processor or controller, for example, by a processor in the above-described terminal embodiment, such that the processor performs the control method of the liquid chromatography system in the above-described embodiment.

[0106] Those skilled in the art will understand that all or some of the steps and systems in the methods disclosed above can be implemented as software, firmware, hardware, and suitable combinations thereof. Some or all of the physical components can be implemented as software executed by a processor, such as a central processing unit, digital signal processor, or microprocessor, or as hardware, or as an integrated circuit, such as an application-specific integrated circuit. Such software can be distributed on a computer-readable medium, which can include computer storage media (or non-transitory media) and communication media (or transient media). As is known to those skilled in the art, the term computer storage media includes volatile and non-volatile, removable and non-removable media implemented in any method or technology for storing information (such as computer-readable instructions, data structures, program modules, or other data). Computer storage media includes, but is not limited to, RAM, ROM, EEPROM, flash memory or other memory technologies, CD-ROM, digital versatile disc (DVD) or other optical disc storage, magnetic cartridges, magnetic tape, disk storage or other magnetic storage devices, or any other medium that can be used to store desired information and is accessible to a computer. Furthermore, as is known to those skilled in the art, communication media typically contain computer-readable instructions, data structures, program modules, or other data in modulated data signals such as carrier waves or other transmission mechanisms, and may include any information transmission medium.

[0107] The above is a detailed description of the preferred embodiments of the present invention. However, the present invention is not limited to the above embodiments. Those skilled in the art can make various equivalent modifications or substitutions without departing from the spirit of the present invention. All such equivalent modifications or substitutions are included within the scope defined by the claims of the present invention.

[0108] The specific embodiments of the present invention described above do not constitute a limitation on the scope of protection of the present invention. Any other corresponding changes and modifications made in accordance with the technical concept of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. An automated liquid chromatography (HPLC) sample injector, comprising a multi-channel rotary switching valve, a sampling needle, a needle seal, and a cleaning device, wherein the multi-channel rotary switching valve comprises at least four channels, a first channel for connecting to an infusion unit, and a second channel for connecting to an analysis unit, characterized in that: The sampling needle is connected to the third channel of the multi-channel rotary switching valve; A needle sealing seat is connected to the fourth channel of the multi-channel rotary switching valve, and the needle sealing seat is used to place and seal the sampling needle; The cleaning device includes a cleaning seat and an air venting pump. The cleaning seat is provided with a partition ring inside, which divides the cleaning seat into an open space and an internal space. The air venting pump is connected to the internal space through a pipe. When the tip of the sampling needle enters the internal space through the partition ring, the air venting pump operates to create a negative pressure environment in the internal space to vent the gas in the pipe before the sampling needle.

2. The automated liquid chromatography sample injector according to claim 1, characterized in that, The cleaning device also includes a cleaning pump, which is connected to the opening space via a pipe, and is used to clean the outer wall of the sampling needle and the interior of the cleaning device.

3. The automated liquid chromatography sample injector according to claim 2, characterized in that, The cleaning pump is any one of a peristaltic pump, diaphragm pump, syringe, or metering pump; the evacuation pump is a diaphragm pump or a vacuum pump.

4. The automated liquid chromatography sample injector according to claim 1, characterized in that, The separator ring is a resin sealing gasket, and the material of the sealing gasket is any one of FFKM, PTFE and PEEK. When the tip of the sampling needle passes through the separator ring and enters the internal space, the outer wall of the needle tip and the separator ring are in a sealed state.

5. The automated liquid chromatography sample injector according to claim 1, characterized in that, The separator ring is made of any one of PEEK, stainless steel, or titanium alloy. The separator ring has a straight or tapered hole slightly larger than the outer diameter of the sampling needle. When the tip of the sampling needle passes through the straight or tapered hole of the separator ring and enters the internal space, the venting pump operates to create a negative pressure environment in the internal space.

6. A liquid chromatography system, characterized in that, include: The liquid storage device, the liquid delivery unit, the automatic liquid chromatography sample injector as described in any one of claims 1 to 5, the analysis unit, the detection unit, and the data processing and output unit are connected in sequence.

7. The liquid chromatography system according to claim 6, characterized in that, The infusion unit includes an infusion pump, which consists of a system pump and a suction pump paired together, and the system pump and the suction pump are driven and controlled separately by their respective motors.

8. A control method for a liquid chromatography system, applied to the liquid chromatography system as described in claim 6, characterized in that, Includes the following steps: Start the liquid chromatography system and execute the system flow path purging action; When the multi-channel rotary switching valve is in the injection state, it controls the sampling needle to leave the needle sealing seat; The sampling needle tip is controlled to pass through the separator ring and enter the internal space of the cleaning device; The venting pump operates to create a negative pressure environment in the internal space, while simultaneously controlling the infusion pump of the infusion unit to enter the venting operation mode to vent the gas in the pipeline before the sampling needle. After purging is complete, shut down the purging pump and the infusion pump, and control the sampling needle to enter the needle sealing seat.

9. The control method for the liquid chromatography system according to claim 8, characterized in that, The infusion pump of the infusion unit enters the evacuation operation mode, including the following steps: S1. Control the plunger rod of the suction pump and the plunger rod of the system pump to run to the position with the largest pump chamber volume, and stay for a preset time to allow the empty pump to fully reduce the air pressure in the system. S2. Control the plunger rod of the suction pump to run at the venting flow rate to the position where the pump cavity volume is the smallest, and then control the plunger rod of the system pump to run at the venting flow rate to the position where the pump cavity volume is the smallest. S3. Control the plunger rod of the suction pump to run at the venting flow rate to the position where the pump chamber volume is the largest, and then control the plunger rod of the system pump to run at the venting flow rate to the position where the pump chamber volume is the largest, and stay for a preset time to allow the venting pump to fully reduce the air pressure in the system. S4. Repeat S2 and S3 until the emptying process is complete.

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