A liquid chromatography high-pressure infusion pump head pressure grading system and control method thereof

Abstract

A liquid chromatography high-pressure infusion pump pump head pressure grading system and control method thereof, according to the flow direction of the cleaning liquid, sequentially including a solution bottle, a cleaning pump, an infusion pump, a pressure sensor, a back pressure device and a waste liquid bottle, the infusion pump including a rear plunger rod driving mechanism and a front pump head, a pump head seat and a plunger rod, a cleaning pump head is provided between the pump head and the pump head seat, a cleaning chamber is provided in the cleaning pump head, the cleaning chamber is connected to two cleaning joints, the front end of the plunger rod passes through the cleaning pump head and enters the pump head, a first sealing ring is provided between the cleaning pump head and the pump head, and a second sealing ring is provided in the cleaning pump head at the rear of the cleaning chamber. The present invention adopts a structural method of manufacturing a sealing ring pressure grading method to reduce the deformation of the first sealing ring during use, reduce the fatigue damage of the sealing ring under alternating stress, reduce leakage and delay the service life of the sealing ring. In addition, a high-pressure cleaning function is provided, which can effectively diffuse the buffer salt in the buffer salt solution into the cleaning liquid by increasing the pressure of the cleaning liquid, and protect the surface of the plunger rod and the sealing ring.

Description

Technical Field

[0001] The present invention belongs to the technical field of infusion pumps, and in particular relates to a pump head pressure grading system for a liquid chromatography high-pressure infusion pump and a control method thereof. Background Art

[0002] High-pressure infusion pumps are key components of high-performance liquid chromatography (HPLC) systems. The plunger and seals are core components that have extremely high processing requirements and are crucial to the proper functioning of the system. However, in actual use, due to their long-term contact with the mobile phase and constant movement during pump operation, the plunger and seals are also the most susceptible to damage. Therefore, in typical HPLC systems, these two components are considered consumables and require regular replacement, typically once a year. Under harsh conditions and in ultra-high-performance liquid chromatography (UHPLC) systems, replacement frequency is even higher.

[0003] Sealing rings are typically made of elastic materials. When the system pressure increases, the sealing rings deform under pressure. However, the plunger rod and pump sleeve that cooperate with the sealing ring are both made of hard materials and cannot absorb deformation. As a result, the sealing ring constantly switches between a normal state and a compressive and deformed state during the operation of the infusion pump, resulting in fatigue damage under alternating stress. In ultra-high performance liquid chromatography systems (UHPLC), the commonly used system pressure is much higher than that of ordinary high-performance liquid chromatography systems (HPLC). This means that during the alternating aspiration and infusion processes, the deformation of the sealing ring is greater. Deformation will cause changes in the internal volume of the sealing ring, resulting in unstable system pressure. If the deformation exceeds the limit, the sealing ring may not be able to completely clamp the plunger rod, causing the mobile phase to leak out of the gap between the two. The UHPLC system focuses on rapid separation and analysis. For rapid separation and analysis, even slight differences in the system can lead to significant differences in the results.

[0004] Currently, UHPLC typically addresses mobile phase leakage under ultrahigh pressure by programmatically compensating the flow rate to ensure accurate infusion. This approach requires individual calibration for different mobile phase compositions and extensive modeling to ensure data reliability. Furthermore, while addressing the issue of sample analysis reproducibility, mobile phase leakage and evaporation into the air can still occur, creating contamination.

[0005] Furthermore, when using a buffered salt as the mobile phase, the reciprocating motion of the plunger can carry a small amount of buffer outside the seal, exposing it to air. As the buffer evaporates, crystallized particles of buffer salt adhere to the plunger surface. These particles, rubbing against the inner surface of the seal as the plunger reciprocates, can cause irreversible damage.

[0006] The current method for reducing the wear of the sealing ring caused by buffer salt grains adhering to the surface of the plunger rod is to add a cleaning pump, using pure water or a solution with a majority of the aqueous phase as the cleaning fluid. While the infusion pump is delivering the buffer salt solution, the cleaning pump is turned on to flush the plunger rod. However, the contact area between the cleaning fluid and the plunger rod is limited, the gap between the circular hole of the cleaning pump head and the plunger rod is narrow, and the liquid surface tension makes it difficult for the cleaning fluid to enter between the sealing ring and the plunger rod and thoroughly clean the buffer salt solution between them.

[0007] Taking pure water as an example, at room temperature (20°C), the contact angle of water on stainless steel is θ=75°, and the contact angle with the plunger rod (calculated based on a smooth glass surface) is also less than 90°. Therefore, when the cleaning fluid enters the gap between the cleaning pump head and the plunger rod, the liquid surface appears concave, cleaning only a limited area of ​​the plunger rod and failing to thoroughly clean it. The buffer salt precipitates near the sealing ring, so cleaning only a limited area of ​​the plunger rod will not remove all the buffer salt. Instead, the precipitated buffer salt will gradually accumulate as the infusion pump operates, limiting its effectiveness in cleaning the plunger rod surface and protecting the sealing ring. Summary of the Invention

[0008] The purpose of the present invention is to overcome the shortcomings of the prior art, provide a liquid chromatography high-pressure plunger infusion pump head pressure distribution system and its control method, and design a system that can extend the life of the plunger rod and the sealing ring so that both are no longer consumable parts that need to be frequently replaced.

[0009] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0010] A liquid chromatography high-pressure infusion pump head pressure grading system comprises, in order of the flow direction of the cleaning fluid, a solution bottle, a cleaning pump, an infusion pump, a pressure sensor, a backpressure device, and a waste liquid bottle. The infusion pump comprises a rear plunger drive mechanism and a front pump head, a pump head seat, and a plunger rod. A cleaning pump head is provided between the pump head and the pump head seat. A cleaning chamber is provided within the cleaning pump head, which is connected to two cleaning connectors. The front end of the plunger rod passes through the cleaning pump head and enters the pump head. A first sealing ring is provided between the cleaning pump head and the pump head, and a second sealing ring is provided within the cleaning pump head at the rear of the cleaning chamber. The backpressure device ensures that the cleaning fluid flow path where the infusion pump is located has a higher pressure to improve the cleaning effect. The first sealing ring and the second sealing ring are both high-pressure sealing rings, and the cleaning pump is a high-pressure cleaning pump.

[0011] Preferably, the back pressure device may be a back pressure pipe, a back pressure valve, etc.

[0012] Preferably, a bypass valve is provided on the pipeline between the back pressure device and the waste liquid bottle, and the bypass valve is connected to the solution bottle. The bypass valve allows the cleaning liquid to flow back to the solution bottle, allowing the cleaning liquid to be recycled.

[0013] Preferably, the grading system further comprises a controller for controlling the operation of the system.

[0014] Preferably, the front end of the cleaning chamber has a gradually tapering conical structure, making it easier for cleaning liquid to enter the cleaning pump head. Previously, the behavior of cleaning liquid entering the gap was similar to that of two pipes of different diameters directly contacting each other, with the diameters suddenly decreasing. Due to the extremely small gap, the local resistance coefficient was close to 1. However, due to the presence of the chamfered corners of the conical structure, the behavior of cleaning liquid entering the gap is similar to that of a rounded inlet, with a local resistance coefficient of 0.25, making it easier for cleaning liquid to enter and increasing the cleaning area.

[0015] A method for controlling a pump head pressure grading system of a liquid chromatography high-pressure infusion pump comprises the following steps:

[0016] S001. Before the grading system starts working, set the partial pressure ratio of the cleaning liquid flow path or the pressure value of the first sealing ring according to the use requirements.

[0017] S002. Read the mobile phase flow path pressure and send it to the controller. This is the pressure detected by the pressure sensor in the pipeline used by the infusion pump to deliver the mobile phase when the infusion pump is running and the cleaning pump is not running. The controller calculates the operating pressure of the cleaning fluid in the grading system based on the mobile phase flow path pressure and the set partial pressure ratio or pressure value. It also calculates the default flow rate of the cleaning pump using a pressure-flow model.

[0018] S003. The cleaning pump starts at the default flow rate. The cleaning liquid flows out of the solution bottle and is delivered to the cleaning pump head and back pressure device of the infusion pump through the cleaning pump. The cleaning liquid between the cleaning pump and the back pressure device is pressurized, and the plunger rod is cleaned under a certain pressure. Then, the liquid flows into the waste liquid bottle through the back pressure device.

[0019] S004. The pressure sensor reads the actual pressure of the cleaning fluid flow path and sends it to the controller. The actual pressure of the cleaning fluid flow path is often inconsistent with the set working pressure.

[0020] S005. The controller determines whether the actual pressure in the cleaning fluid flow path is within the set operating pressure threshold range. If so, the cleaning pump operating flow rate remains unchanged. If not, the controller calculates the appropriate operating flow rate and controls the cleaning pump to adjust it. The operating pressure has an upper and lower critical value range. If the actual pressure is within the critical value range, the cleaning pump operates normally. If the actual pressure is below the minimum critical value, the controller controls the cleaning pump to increase the flow rate to increase the actual pressure. If the actual pressure is above the maximum critical value, the controller controls the cleaning pump to decrease the flow rate to reduce the actual pressure.

[0021] As the cleaning fluid's pressure increases, it overcomes the liquid's surface tension and enters the gap between the plunger and the cleaning pump head. There, it fully contacts the buffer solution carried by the plunger's surface, causing diffusion to occur at the contact surface. Diffusion is essentially an increase in entropy. In a solution, this manifests itself as the transfer of solute molecules from areas of higher concentration to areas of lower concentration. The buffer salt concentration in the cleaning fluid is much lower than that in the buffer solution. Therefore, the buffer salt in the buffer solution diffuses into the cleaning fluid. However, the buffer salt concentration in the plunger decreases, failing to reach saturation. This prevents the precipitation of buffer salt crystals and the resulting wear on the seal. This ensures a thorough cleaning of the plunger's surface and extends the life of the seal.

[0022] For the first seal ring, on the one hand, the pressure differential that causes deformation in the existing technology is between the mobile phase system pressure and atmospheric pressure. A large pressure differential results in large deformation of the first seal ring. On the other hand, gradient injection is the mainstream method for chromatographic systems, and during gradient injection, the mobile phase composition changes, and the system pressure also changes with the changes in the mobile phase composition. In this case, the deformation of the first seal ring in the existing constant pressure cleaning technology also changes accordingly. Therefore, variable pressure cleaning is required. The pressure differential generated now is between the mobile phase system pressure and the cleaning liquid pressure, so that the pressure difference between the two ends of the first seal ring is always stable at a similar value. This reduces the pressure differential, reduces the deformation change, reduces alternating fatigue, and extends the lifespan. The controllable cleaning liquid pressure is beneficial for cleaning HPLC and UHPLC systems under gradient conditions.

[0023] Preferably, after the grading system is operational, the pressure of the mobile phase flow path is constantly read and transmitted to a controller. The controller then calculates the corresponding operating pressure of the cleaning pump based on the mobile phase flow path pressure and controls the cleaning pump to adjust the pressure. This ensures that the pressure differential across the first sealing ring is always stable at a similar value, and the deformation of the first sealing ring remains stable.

[0024] Preferably, in step S003, the controller controls the bypass valve to select the cleaning liquid to flow into the waste liquid bottle or the solution bottle, depending on the cleaning liquid situation. For example, when the cleaning liquid in the solution bottle is insufficient, the solution bottle enters a reflux circulation mode.

[0025] Beneficial effects of the present invention:

[0026] 1. Accurately control the pressure of the cleaning fluid to share the system pressure and avoid the problem of poor repeatability caused by trace leakage of the sealing ring under high pressure in the UHPLC system.

[0027] 2. Fix the pressure difference between the two ends of the first sealing ring, reduce the alternating fatigue of the sealing ring due to periodic deformation, and extend its service life.

[0028] 3. Use high-pressure cleaning method in conjunction with cleaning chamber design to improve solvent replacement efficiency by increasing cleaning liquid pressure and contact area between cleaning liquid and plunger rod, making it easier for cleaning liquid to enter the gap between plunger rod and cleaning pump head, fully cleaning the buffer solution on the surface of plunger rod, preventing the precipitation of buffer salt crystal particles, protecting the surface of plunger rod and sealing ring, and extending the service life of infusion pump system. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 Schematic diagram of the structure of the grading system of the present invention;

[0030] Figure 2 A perspective view of an infusion pump in the grading system of the present invention;

[0031] Figure 3 A partial cross-sectional view of an infusion pump in the grading system of the present invention;

[0032] Figure 4 Schematic diagram of the process of the grading system control method of the present invention;

[0033] Figure 5 Schematic diagram of the cleaning solution of the present invention.

[0034] Explanation of the main component symbols in the figure: 10. Solution bottle, 20. Cleaning pump, 30. Infusion pump, 31. Pump head, 31.1. Connector, 31.2. One-way valve, 32. Pump head seat, 33. Plunger rod, 34. Spring seat, 35. Compression spring, 36. Cleaning pump head, 36.1. Cleaning chamber, 36.2. Cleaning connector, 37. First sealing ring, 38. Second sealing ring, 39. Guide ring, 310. Screw cap, 311. Locking ring, 40. Back pressure device, 50. Pressure sensor, 60. Waste liquid bottle, 70. Controller, 80. Bypass valve. DETAILED DESCRIPTION

[0035] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0036] The implementation method is as follows: Figure 1-3The figure shows a pressure grading system for a liquid chromatography high-pressure infusion pump head. The system comprises, in order of the flow direction of the cleaning fluid, a solution bottle 10, a cleaning pump 20, an infusion pump 30, a pressure sensor 50, a backpressure device 40, a bypass valve 80, and a waste liquid bottle 60. The bypass valve 80 is also connected to the solution bottle 10. The grading system also includes a controller 70. The infusion pump 30 comprises a rear plunger drive mechanism and a front pump head 31, a pump head seat 32, and a plunger rod 33. A cleaning pump head 36 is disposed between the pump head 31 and the pump head seat 32. A cleaning chamber 36.1 is disposed within the cleaning pump head 36. Two cleaning connectors 36.2 are connected to the cleaning chamber 36. The front end of the cleaning chamber 36.1 has a gradually tapering structure. The front end of the plunger rod 33 passes through the cleaning pump head 36 and enters the pump head 31. A first sealing ring 37 is disposed between the cleaning pump head 36 and the pump head 31. A second sealing ring 38 is disposed within the cleaning pump head 36 at the rear of the cleaning chamber 36.1.

[0037] Combine Figure 4-5 As shown, a method for controlling a pump head pressure grading system of a liquid chromatography high-pressure infusion pump comprises the following steps:

[0038] S001. Before the grading system starts working, set the partial pressure ratio of the cleaning liquid flow path or the pressure value of the first sealing ring 37 according to the use requirements;

[0039] S002, read the pressure of the mobile phase flow path and send it to the controller 70, the controller 70 calculates the working pressure of the cleaning liquid in the grading system based on the mobile phase flow path pressure and the set partial pressure ratio or pressure value, and calculates the default flow rate of the cleaning pump 20 through the pressure-flow model;

[0040] S003: The cleaning pump 20 is started at the default flow rate. The cleaning liquid flows out of the solution bottle 10 and is delivered to the cleaning pump head 36 of the infusion pump 30 and the back pressure device 40 through the cleaning pump 20. The cleaning liquid between the cleaning pump 20 and the back pressure device 40 is pressurized, cleaning the plunger rod 33 under a certain pressure, and then flows into the waste liquid bottle 60 through the back pressure device 40;

[0041] S004, the pressure sensor 50 reads the actual pressure of the cleaning fluid flow path and sends it to the controller 70;

[0042] S005. The controller 70 determines whether the actual pressure of the cleaning liquid flow path is within the set working pressure threshold range. If it is within the threshold range, the working flow rate of the cleaning pump 20 is kept unchanged. If it is outside the threshold range, the controller 70 calculates the appropriate working flow rate and controls the cleaning pump 20 to adjust.

[0043] For example, if the partial pressure ratio of the cleaning liquid flow path is set to 40%, if the pressure of the mobile phase flow path is 100 MPa, then the pressure of the cleaning liquid flow path between the first sealing ring 37 and the second sealing ring 38 is 40 MPa; or if the pressure value of the first sealing ring 37 is set to 60 MPa, if the pressure of the mobile phase flow path is 100 MPa, then when the cleaning liquid flow path between the first sealing ring 37 and the second sealing ring 38 is 40 MPa, the pressure value of the first sealing ring 37 is the set 60 MPa, and the second sealing ring 38 withstands a pressure of 40 MPa.

[0044] It should be noted that after the classification system is working, the pressure of the mobile phase flow path is read from time to time and sent to the controller 70. The controller 70 calculates the corresponding working pressure of the cleaning pump 20 according to the mobile phase flow path pressure and controls the cleaning pump 20 to adjust.

[0045] The cleaning principle of the present invention is as follows: initially, there is no cleaning liquid in the cleaning pump head 36, and there is only a small amount of buffer salt solution and air on the surface of the plunger rod 33. After the cleaning pump 20 is started, the cleaning liquid is delivered to the back pressure device 40 via the cleaning pump 20. The cleaning liquid between the cleaning pump 20 and the back pressure device 40 is pressurized. The cleaning liquid pressure increases, overcomes the surface tension of the liquid, enters the gap between the plunger rod 33 and the cleaning pump head 36, and fully contacts with the buffer salt solution brought out from the surface of the plunger rod 33. A diffusion process occurs at the contact liquid surface. The essence of the diffusion process is an entropy increase process. In the solution, the solute molecules are transferred from the area with higher concentration to the area with lower solute concentration. The buffer salt concentration in the cleaning liquid is much lower than the buffer salt concentration in the buffer salt solution. Therefore, the buffer salt in the buffer salt solution will diffuse into the cleaning liquid, while the concentration of the buffer salt solution in the plunger rod 33 decreases and does not reach the saturation concentration. Buffer salt crystalline particles will not precipitate, and the phenomenon of grain wear of the first sealing ring 37 will not occur. At the same time, the system uses the pressure sensor 50 as an aid to accurately control the pressure of the cleaning liquid, ensuring that the pressure difference between the mobile phase system pressure of the buffered salt solution and the cleaning liquid system remains stable, and the deformation of the first sealing ring 37 remains stable.

[0046] Although the present invention has been described in detail with reference to the aforementioned embodiments, it is still possible for those skilled in the art to modify the technical solutions described in the aforementioned embodiments, or to make equivalent substitutions for some of the technical features therein. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for controlling a pump head pressure classification system of a liquid chromatography high-pressure infusion pump, characterized in that: The grading system comprises a solution bottle (10), a cleaning pump (20), an infusion pump (30), a pressure sensor (50), a back pressure device (40) and a waste liquid bottle (60) in order of the flow direction of the cleaning liquid. The infusion pump (30) comprises a plunger rod driving mechanism at the rear and a pump head (31), a pump head seat (32) and a plunger rod (33) at the front. A cleaning pump head (36) is provided between the pump head (31) and the pump head seat (32). A cleaning chamber (36.1) is provided in the cleaning pump head (36). The cleaning chamber (36.1) is connected to two cleaning connectors (36.2). The front end of the plunger rod (33) passes through the cleaning pump head (36) and enters the pump head (31). A first sealing ring (37) is provided between the cleaning pump head (36) and the pump head (31). A second sealing ring (38) is provided in the cleaning pump head (36) at the rear of the cleaning chamber (36.1). A bypass valve (80) is provided on the pipeline between the back pressure device (40) and the waste liquid bottle (60), and the bypass valve (80) is connected to the solution bottle (10); the grading system further comprises a controller (70); The control method of the grading system comprises the following steps: S001. Before the system starts working, the partial pressure ratio of the cleaning liquid flow path or the pressure value of the first sealing ring (37) is set according to the use requirements; S002, reading the pressure of the mobile phase flow path and sending it to the controller (70), the controller (70) calculating the working pressure of the cleaning liquid in the classification system according to the mobile phase flow path pressure and the set partial pressure ratio or pressure value, and calculating the default flow rate of the cleaning pump (20) through the pressure-flow model; S003, the cleaning pump (20) is started at a default flow rate, the cleaning liquid flows out from the solution bottle (10), and is delivered to the cleaning pump head (36) and the back pressure device (40) of the infusion pump (30) through the cleaning pump (20), the cleaning liquid between the cleaning pump (20) and the back pressure device (40) is pressurized, and the plunger rod (33) is cleaned under a certain pressure, and then flows into the waste liquid bottle (60) through the back pressure device (40); S004, the pressure sensor (50) reads the actual pressure of the cleaning liquid flow path and sends it to the controller (70); S005. The controller (70) determines whether the actual pressure of the cleaning liquid flow path is within a set working pressure threshold range. If it is within the threshold range, the working flow rate of the cleaning pump (20) is kept unchanged. If it is outside the threshold range, the controller (70) calculates a suitable working flow rate and controls the cleaning pump (20) to adjust.

2. A method for controlling a pump head pressure classification system of a liquid chromatography high-pressure infusion pump according to claim 1, characterized in that: The front end of the cleaning chamber (36.1) is in a gradually shrinking conical structure.

3. A method for controlling a pump head pressure classification system of a liquid chromatography high-pressure infusion pump according to claim 1, characterized in that: After the system is in operation, the pressure of the mobile phase flow path is read from time to time and sent to the controller (70). The controller (70) calculates the corresponding working pressure of the cleaning pump (20) according to the pressure of the mobile phase flow path and controls the adjustment of the cleaning pump (20).

4. A method for controlling a pump head pressure classification system of a liquid chromatography high-pressure infusion pump according to claim 1, characterized in that: In step S003, the controller (70) controls the bypass valve (80) to select whether the cleaning liquid flows into the waste liquid bottle (60) or the solution bottle (10).

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