Ultra-high performance liquid chromatography infusion system and pressure fluctuation control method

Abstract

The invention relates to an ultra-high performance liquid chromatography infusion system and a pressure fluctuation control method, the control method is applied to the ultra-high performance liquid chromatography infusion system, and the infusion system establishes a pipeline communication relationship among an inlet one-way valve, a liquid suction pump, an outlet one-way valve and a system pump; a pressure acquisition device is arranged on a pipeline for connecting the system pump and the after-pump system to acquire a pressure signal, the acquired pressure signal is transmitted to a controller, and the liquid suction pump and the system pump are controlled in a non-real-time manner through the controller according to pressure fluctuation; the effect of adjusting the compression volume of the liquid suction pump and the compensation volume after the liquid in the system pump is cooled is achieved, so that the actual non-ideal conditions such as one-way valve opening time, one-way valve closing time, motor starting delay, motor stopping delay and flow path delay do not need to be corrected one by one, and the control and manufacturing cost is saved.

Description

Technical Field

[0001] The present invention relates to the technical field of infusion control, and in particular to an ultra-high performance liquid chromatography infusion system and a pressure fluctuation control method. Background Art

[0002] As high performance liquid chromatography (HPLC) gradually develops towards ultra-high performance liquid chromatography (UHPLC), the operating pressure of the infusion system is getting higher and higher, and the required lag volume is getting lower and lower. As an infusion system, the traditional cam pump needs to be equipped with a large volume buffer to achieve the requirement of outputting a stable flow rate, and therefore it is no longer suitable for the needs of UHPLC.

[0003] The infusion system usually uses a plunger pump in series or parallel. Taking a series plunger pump as an example, a series plunger pump consists of a suction pump that draws liquid from the outside and a system pump that delivers liquid to the system behind the pump. The liquid sucked by the suction pump is a normal pressure liquid, while the liquid in the system pump is in a high pressure state. If the two liquids are directly mixed, the system pump will produce a pressure drop at the moment of mixing, which is often called pressure fluctuation.

[0004] In addition, even if the liquid in the suction pump chamber is pressurized in advance, the plunger rod will do work on the liquid in the main pump chamber (this process is similar to adiabatic compression), causing the temperature of the pre-pressurized liquid to be higher than room temperature. When the high-temperature liquid in the suction pump chamber enters the system pump, it mixes with the lower-temperature liquid in the system pump and heat transfer occurs. The temperature of the liquid entering the system from the suction pump decreases and the original pressure cannot be maintained. The result is still a decrease in system pressure - in other words, a fixed volume of liquid at room temperature is pressurized from one pressure to another by compressing the volume, and the volume required for adiabatic compression is smaller than that for isothermal compression. Therefore, after the liquid leaves the adiabatic environment, it is necessary to compensate for the reduced compression volume of adiabatic compression compared to isothermal compression, so that the liquid can maintain the target pressure after leaving the adiabatic environment.

[0005] Regarding the difference in compression volume caused by isothermal compression and adiabatic compression, patent CN103512986B proposes a correction method. After the liquid in the suction pump cavity is pre-pressurized, the pressure is monitored. According to the pressure monitoring situation, a function of the liquid temperature changing with time is obtained, and the pressure after the liquid temperature drops back to room temperature is inferred, so as to compensate after the liquid leaves the adiabatic environment according to the calculated value. However, this method requires the installation of an additional pressure collection and monitoring device in the suction pump cavity. The suction pump cavity is in a high-pressure state. The pressure collection and monitoring device that can withstand high pressure and whose contact volume, sensitivity, and collection frequency meet the requirements of the UHPLC system is expensive, which greatly increases the manufacturing and installation costs.

[0006] Patent US8535016B2 describes a high-pressure series plunger pump system, in which each plunger pump has a separate driver and pressure acquisition monitoring device, and performs instantaneous closed-loop feedback control on the pressure signal and the system pump to compensate for the secondary compression value in real time. Similarly, this method also adds additional pressure acquisition monitoring devices, resulting in increased costs, and the instantaneous closed-loop feedback control has poor anti-interference performance. For a high-pressure gradient infusion system that uses two sets of plunger pumps connected in the same flow path with a three-way connection, not only four pressure acquisition monitoring devices are required, but also a complex judgment process and cumbersome processing methods are required to avoid the two sets of plunger pumps from performing instantaneous closed-loop feedback control at the same time (patent US10060886B2), which greatly increases the difficulty of control.

[0007] Patent US9360006B2 describes a method for adjusting the speed of the suction pump according to the real-time feedback control of the system pressure during the suction pump infusion and system pump suction stages. The real-time feedback method is also used. As long as the real-time feedback is used, it is difficult to avoid unexpected situations. For example, when bubbles enter the system and cause a large pressure drop, the instantaneous speed compensation is too much and the motor has no time to accelerate, resulting in loss of step. It is also difficult to avoid mutual interference when the two sets of pumps in the high-pressure gradient infusion system enter feedback control at the same time, and the algorithm optimization is difficult. In addition, from the perspective of the system actually applied by the patent, it is recommended that the commonly used pressure is above 50 bar, which indirectly shows that the real-time feedback mode cannot achieve reliable stability at lower pressures. Summary of the invention

[0008] The technical problem to be solved by the present invention is how to reduce the pressure fluctuation of the infusion system while meeting the requirements of low cost, low control difficulty and high stability. In order to overcome the defects of the above-mentioned prior art, the present invention provides an ultra-high performance liquid chromatography infusion system and a pressure fluctuation control method, comprising an ultra-high performance liquid chromatography infusion system and a pressure fluctuation control method for the ultra-high performance liquid chromatography infusion system.

[0009] The present invention provides an ultra-high performance liquid chromatography infusion system, comprising an inlet one-way valve, a suction pump, an outlet one-way valve, a system pump, a pressure collection device and a controller, wherein the system pump is connected to a post-pump system through a pipeline and is used to infuse liquid into the post-pump system, the inlet one-way valve, the suction pump, the outlet one-way valve and the system pump are connected in series through a pipeline, and the pressure collection device is arranged on a pipeline connecting the system pump and the post-pump system;

[0010] The controller is electrically connected to the suction pump, the system pump and the pressure acquisition device, respectively. The controller is configured to control the suction pump and / or the system pump according to the pressure fluctuation corresponding to the pressure information obtained by the pressure acquisition device in the current cycle or the current cycle and at least one cycle before the current cycle, so as to adjust the compression volume of the suction pump in the next cycle or the next multiple cycles and the compensation volume of the liquid in the system pump after cooling.

[0011] The ultra-high performance liquid chromatography infusion system disclosed in the present invention establishes a pipeline connection relationship between the inlet one-way valve, the suction pump, the outlet one-way valve, and the system pump, and arranges a pressure acquisition device on the pipeline connecting the system pump and the post-pump system to collect pressure signals, transmits the obtained pressure signal to the controller, and then controls the suction pump and the system pump according to the pressure fluctuation through the controller, so as to achieve the effect of adjusting the compression volume of the suction pump and the compensation volume of the liquid in the system pump after cooling, so that there is no need to correct the actual non-ideal conditions such as the one-way valve opening time, the one-way valve closing time, the motor start delay, the motor stop delay, the flow path delay, etc. one by one, but similar to the black box model, only according to the input and output results to obtain a suitable correction method. At the same time, the present invention adopts the method of arranging the pressure acquisition device on the pipeline, so that the specification requirements of the pressure acquisition device are relatively low, and only one pressure acquisition device is used as the pressure acquisition monitoring device, which saves costs.

[0012] In a possible implementation, the suction pump includes a first motor, a first plunger rod and a suction pump chamber, the first plunger rod is slidably arranged in the suction pump chamber to adjust the compression volume of the suction pump, and the first motor drives the first plunger rod to move through a screw transmission;

[0013] Compared with the prior art, the above technical solution can realize the control of the operation of the suction pump by the controller, thereby achieving the effect of adjusting the compression volume and infusion of the suction pump, thereby improving the operating efficiency of the system.

[0014] In a possible implementation, the system pump includes a second motor, a second plunger rod and a system pump chamber, the second plunger rod is slidably arranged in the system pump chamber to adjust the compression volume of the system pump, and the second motor drives the second plunger rod to move through a screw transmission;

[0015] Compared with the prior art, the above technical solution can realize the controller's control over the operation of the system pump, thereby adjusting the compression volume of the system pump to control the compensation volume effect after the liquid in the system pump is cooled, thereby further improving the operation efficiency of the system.

[0016] In a possible implementation, the controller is a programmable controller, thereby ensuring that the program can be edited while operating the suction pump and the system pump.

[0017] Another technical solution of the present invention is to provide a pressure fluctuation control method for an ultra-high performance liquid chromatography infusion system, which is applicable to the ultra-high performance liquid chromatography infusion system of the present invention, and comprises the following steps:

[0018] S1: Determine the scale standard of the infusion cycle, and specify the compression volume and compensation volume of the first cycle, wherein the compression volume is the compression volume of the suction pump during the pre-pressurization process, and the compensation volume is the compensation volume after the liquid in the system pump is cooled down;

[0019] S2: collecting pressure signals through the pressure collection device and transmitting them to the controller, and then entering the first cycle based on the infusion cycle scale standard;

[0020] S3: before the pre-pressurization moment of the current cycle, the controller obtains a pressure prediction model of the current cycle according to the previous pressure change, and obtains a pressure prediction value at a predetermined moment of the current cycle according to the pressure prediction model;

[0021] S4: from the pre-pressurization moment of the current cycle, the controller controls the liquid suction pump to perform pre-pressurization according to the compression volume of the current cycle;

[0022] S5: After the scheduled time of the current cycle, the controller calculates the difference between the predicted pressure value at the scheduled time of the current cycle and the actual pressure value at that time, and determines the compression volume of the next cycle according to the comparison between the difference and the first threshold value;

[0023] S6: from the infusion moment of the current cycle, according to the compensation volume of the current cycle, the controller controls the compression volume of the suction pump and / or the system pump to infuse the liquid through the suction pump;

[0024] S7: Starting from the end time of the infusion of the current cycle, the controller calculates the difference between the actual pressure value at the predetermined time of the current cycle and the actual pressure value at the end time of the infusion of the current cycle, and determines the compensation volume of the next cycle based on the comparison between the difference and the second threshold value, and then enters the next cycle and returns to execute the step S3.

[0025] The pressure fluctuation control method of the ultra-high performance liquid chromatography infusion system disclosed in the present invention is a method of using the ultra-high performance liquid chromatography infusion system of the present invention. It is based on the cycle scale standard and the pressure signal obtained by the pressure acquisition device, and the controller predicts the operating speed of the current cycle according to the pressure fluctuation of the previous cycle, and the mode of short-term compensation of the preset speed in the same cycle, so as to ensure the acquisition and realization of the compression volume and the compensation volume, and the fault is discovered quickly, the error probability is low, and the anti-interference ability is strong, which can ensure stable operation under low pressure conditions. At the same time, the pressure acquisition depends on the pressure acquisition device, and the control depends on the controller. There is no need to calibrate the actual non-ideal situations such as the one-way valve opening time, the one-way valve closing time, the motor start delay, the motor stop delay, the flow path delay, etc. one by one, and the overall cost and control cost are reduced.

[0026] In a possible implementation, the infusion cycle scale standard in step S1 is:

[0027] The time interval between two consecutive uniform speed start times of the second motor in the system pump is an infusion cycle;

[0028] This solution can avoid the technical defect that the infusion cycle is difficult to grasp due to the complexity of the pressure change law of the suction pump and the system pump, thereby ensuring the efficient and orderly pre-pressurization and infusion.

[0029] In a possible implementation, in step S3, the pressure prediction model of any period is expressed as follows:

[0030]

[0031] P s (t) = P s,2 +k s t,

[0032] in,

[0033] P s,1 Represents the pressure value obtained by the pressure acquisition device at the time interval Δt0 before the pre-pressurization time of the sth cycle;

[0034] P s,2 Represents the pressure value obtained by the pressure acquisition device at the pre-pressurization moment of the sth cycle;

[0035] P s (t) represents the predicted value of the pressure obtained by the pressure acquisition device at time t in the sth cycle;

[0036] The model set up in this scheme can predict the target pressure based on the changes in system pressure in each infusion cycle. Due to the short duration, the model is accurate in predicting the target pressure.

[0037] In a possible implementation manner, the predetermined time of each cycle is determined by: determining a δ time interval according to the installation position of the pressure collection device and the specification of the pipeline in front of the pressure collection device, and the predetermined time of each cycle is the time of the δ time interval after the pre-pressurization time of the current cycle;

[0038] The duration of the pre-pressurization phase of each cycle is the time interval between the infusion time and the pre-pressurization time of the cycle;

[0039] The duration of the infusion phase of each cycle is the time interval between the end of infusion and the infusion time of the cycle;

[0040] The duration of the pre-pressurization phase of each cycle is the same as that of the infusion phase, ranging from (50 to 500) ms;

[0041] By making the duration of the pre-pressurization phase of each cycle the same as the duration of the infusion phase, factors affecting pressure fluctuations can be reduced to a greater extent.

[0042] In a possible implementation manner, in step S5, the compression volume of the next cycle is determined as follows:

[0043] If the difference between the predicted pressure value at a predetermined time of the current cycle and the actual pressure value at that time is less than or equal to the first threshold, the compressed volume of the next cycle is the compressed volume of the current cycle;

[0044] If the difference between the predicted pressure value at the scheduled time of the current cycle and the actual pressure value at the time is greater than the first threshold, the compression volume of the next cycle is:

[0045] V s+1,1 =V s,1 -αΔP s,1 ,

[0046] in,

[0047] V s+1,1 representing said compression volume for the next cycle;

[0048] V s,1 represents the compression volume of the current cycle;

[0049] α represents the compression factor;

[0050] ΔP s,1 Represents the difference between the predicted pressure value at the scheduled time of the current cycle and the actual pressure value at that time;

[0051] This scheme can arrange the compression volume of the next cycle according to the fluctuation of the actual value and the predicted value of the pressure in the pre-pressurization stage of the current cycle, ensuring the controllability of the compression volume of each cycle.

[0052] In a possible implementation manner, in step S7, the compensation volume of the next cycle is determined as follows:

[0053] If the difference between the actual pressure value at the scheduled time of the current cycle and the actual pressure value at the end time of the infusion of the current cycle is less than or equal to the second threshold, the compensation volume of the next cycle is the compensation volume of the current cycle;

[0054] If the difference between the actual pressure value at the scheduled time of the current cycle and the actual pressure value at the end of the infusion of the current cycle is greater than the second threshold, the compensation volume of the next cycle is:

[0055] V s+1,2 =Vs,2 -βΔP s,2 ,

[0056] in,

[0057] V s+1,2 representing the compensation volume for the next cycle;

[0058] V s,2 represents the compensation volume of the current cycle;

[0059] β represents the adjustment factor;

[0060] ΔP s,2 Represents the difference between the predicted pressure value at the scheduled time of the current cycle and the actual pressure value at the end of the infusion of the current cycle;

[0061] This solution not only ensures the compensation volume of each cycle, but also combines with the compression volume control to ensure the high-efficiency operation of the system infusion while reducing the range of pressure drop of the entire system. BRIEF DESCRIPTION OF THE DRAWINGS

[0062] Figure 1 It is a schematic diagram of the structure of the ultra-high performance liquid chromatography infusion system disclosed in an embodiment of the present invention;

[0063] Figure 2 is a flow chart of the method disclosed in the embodiment of the present invention;

[0064] Figure 3 The image of the speed change of the output shafts of the first motor and the second motor in one infusion cycle in the embodiment of the present invention;

[0065] Figure 4 is a pressure fluctuation image in an embodiment of the present invention;

[0066] Figure 5 FIG. 4 is another pressure fluctuation image in an embodiment of the present invention.

[0067] Description of reference numerals:

[0068] 1. Inlet check valve, 2. Suction pump, 21. First motor, 22. First plunger rod, 23. Suction pump pump cabin, 3. Outlet check valve, 4. System pump, 41. Second motor, 42. Second plunger rod, 43. System pump pump cabin, 5. Pressure collection device, 6. Controller, 7. Post-pump system. DETAILED DESCRIPTION

[0069] First, those skilled in the art should understand that these implementations are only used to explain the technical principles of the embodiments of the present application, and are not intended to limit the protection scope of the embodiments of the present application. Those skilled in the art can make adjustments to them as needed to adapt to specific application scenarios.

[0070] In the description of the embodiments of the present application, it should be noted that, unless otherwise clearly specified and limited, the terms "electrical connection" and "electrical connection relationship" should be understood in a broad sense, that is, referring to a connection method with an electrical relationship, for example, it can be a circuit connection through a wire, or it can be an electrical connection through a radio signal channel (channel), or a combination of the two. In addition, "electrical connection" and "electrical connection relationship" can be based on mechanical connection (such as a wire set in a connection key); it can be a direct connection or an indirect connection through an intermediate medium. For ordinary technicians in this field, the specific meanings of the above terms in the embodiments of the present application can be understood according to specific circumstances.

[0071] In the embodiments of the present application, unless otherwise clearly specified and limited, a first feature being "above" or "below" a second feature may mean that the first and second features are in direct contact, or the first and second features are in indirect contact through an intermediate medium. Moreover, a first feature being "above", "above" or "above" a second feature may mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is higher in level than the second feature. A first feature being "below", "below" or "below" a second feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the first feature is lower in level than the second feature.

[0072] The present application is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0073] See also Figure 1 to Figure 4 As shown, the present application embodiment discloses an ultra-high performance liquid chromatography infusion system, see Figure 1 As shown, the system includes an inlet one-way valve 1, a suction pump 2, an outlet one-way valve 3, a system pump 4, a pressure collection device 5 and a controller 6. The output end of the system pump 4 is connected to the input end of the post-pump system 7 through a pipeline, and is used for infusing liquid into the post-pump system 7, wherein the input end of the suction pump 2 is connected to the output end of the inlet one-way valve 1 through a pipeline in sequence, the input end of the outlet one-way valve 3 is connected to the output end of the suction pump 2 through a pipeline, and the input end of the system pump 4 is connected to the output end of the outlet one-way valve 3 through a pipeline, and the pressure collection device 5 is arranged on the pipeline connecting the output end of the system pump 4 and the input end of the post-pump system 7.

[0074] Please continue to see Figure 1As shown, in this embodiment, the suction pump 2 includes a first motor 21, a first plunger rod 22 and a suction pump chamber 23. The first plunger rod 22 is slidably arranged in the suction pump chamber 23 to adjust the compression volume of the suction pump 2. The first motor 21 drives the first plunger rod 22 to move through a screw transmission. The first motor 21 is electrically connected to the controller 6. The system pump 4 includes a second motor 41, a second plunger rod 42 and a system pump chamber 43. The second plunger rod 42 is slidably arranged in the system pump chamber 43 to adjust the compression volume of the system pump 4. The second motor 41 drives the second plunger rod 42 to move through a screw transmission. The second motor 41 is electrically connected to the controller 6. Sensors for obtaining the rotation speed of their respective output shafts are provided on the first motor 21 and the second motor 41, so that the controller 6 can conveniently obtain the output shaft rotation speed information of the two motors at any time.

[0075] Please continue to see Figure 1 As shown, in this embodiment, the controller 6 is a programmable controller. The controller 6 is configured to control the suction pump 2 and / or the system pump 4 according to the pressure fluctuation corresponding to the pressure information obtained by the pressure acquisition device 5, so as to adjust the compression volume of the suction pump 2 and the compensation volume of the liquid in the system pump 4 after the temperature is reduced.

[0076] The following provides a pressure fluctuation control method for an ultra-high performance liquid chromatography infusion system led by the controller 6, see Figure 2 As shown, the method comprises the following steps:

[0077] S1: Determine the scale standard of the infusion cycle, and specify the compression volume and compensation volume of the first cycle, wherein the compression volume is the compression volume of the suction pump 2 during the pre-pressurization process, and the compensation volume is the compensation volume after the liquid in the system pump 4 is cooled down.

[0078] See also Figure 3 As shown, in this embodiment, the infusion cycle scale standard in step S1 is: the time interval between two adjacent uniform speed start moments of the second motor 41 in the system pump 4 is an infusion cycle. Figure 3 A distribution image of a cycle of the rotational speed of the output shaft of the first motor 21 (referred to as the suction pump 2 rotational speed in the figure) and the rotational speed of the output shaft of the second motor 41 (referred to as the system pump 4 rotational speed in the figure) is drawn. The output rotational speed in the figure is the vector sum of the rotational speed of the suction pump 2 and the rotational speed of the system pump 4, Δt1 represents the duration of the pre-pressurization phase of this cycle, and Δt2 represents the duration of the infusion phase of this cycle.

[0079] In such Figure 1 In the system shown in FIG. 1 , there are two compression volumes during the operation of the system. One is the compression volume of the suction pump 2 during the near-adiabatic compression during pre-pressurization, i.e., the compression volume of the suction pump 2 during the pre-pressurization process (hereinafter referred to as the compression volume). Figure 3 From the distribution image, the volume is Figure 3 The other is the compensation volume corresponding to the pressure loss of the liquid in the system pump chamber 43 after cooling, that is, the compensation volume of the liquid in the system pump 4 after cooling (hereinafter referred to as the compensation volume), from Figure 3 From the distribution image, this volume is the difference between the system infusion volume in this period when the output speed of the output shaft of the second motor 41 is adjusted to fluctuate to a suitable value in the Δt2 period and the infusion volume when the speed is not adjusted. These two volumes can be set arbitrarily at the initial stage.

[0080] S2: The pressure signal is collected by the pressure collection device 5 and transmitted to the controller 6, and then the first cycle is entered based on the infusion cycle scale standard.

[0081] S3: Before the pre-pressurization moment of the current cycle, the controller 6 obtains the pressure prediction model of the current cycle according to the previous pressure change, and obtains the pressure prediction value at the predetermined moment of the current cycle according to the pressure prediction model.

[0082] Assuming that the current cycle is the sth cycle, in step S3 of this embodiment, the pressure prediction model of the sth cycle is expressed as follows:

[0083]

[0084] P s (t) = P s,2 +k s t,

[0085] in,

[0086] P s,1 represents the pressure value obtained by the pressure acquisition device 5 at the time interval Δt0 before the pre-pressurization time of the s-th cycle;

[0087] P s,2 represents the pressure value obtained by the pressure acquisition device 5 at the pre-pressurization moment of the sth cycle;

[0088] P s (t) represents the predicted value of the pressure obtained by the pressure acquisition device 5 at time t in the sth cycle.

[0089] At the same time, in this embodiment, the predetermined time of each cycle is determined by: determining the δ time interval according to the installation position of the pressure collection device 5 and the specifications of the pipeline in front of the pressure collection device 5, and the predetermined time of each cycle is the time of the δ time interval after the pre-pressurization time of the current cycle, δ is generally (20-100) ms, which needs to be obtained by actual measurement. The specific measurement method is the existing technology and will not be expanded here. The duration Δt1 of the pre-pressurization stage of each cycle is the time interval between the infusion time and the pre-pressurization time of the current cycle; the duration Δt2 of the infusion stage of each cycle is the time interval between the end of the infusion and the infusion time of the current cycle; the duration Δt1 of the pre-pressurization stage of each cycle is the same as the duration Δt2 of the infusion stage, and its range is (50-500) ms.

[0090] from Figure 3 It can be seen that when the suction pump 2 starts infusing (infusion time), the system pump 4 ends the uniform speed infusion. For the sth cycle, the pre-pressurization stage of the suction pump 2 requires a relatively wide flow range. It starts Δt1 before the system pump 4 ends the uniform speed infusion. During this period, the first motor 21 in the suction pump 2 runs at a fixed speed for V s,1 The volume of the suction pump 2 is , and the infusion phase lasts for Δt2.

[0091] The size of Δt1 and Δt2 can be determined according to the flow segment of the infusion fluid. For example, the flow range of (0-6) mL / min is divided into (0-3) mL / min and (3-6) mL / min. Different flow segments take different Δt1 and Δt2 values, but the Δt1 and Δt2 values ​​in the same flow segment are the same. Δt1 needs to be short enough, such as (50-500) ms, typically (100-300) ms, and typically 200 ms. The value of Δt2 also needs to be short enough, such as (50-500) ms, typically (100-300) ms, and typically 200 ms. The two times are the same in order to reduce the factors that affect pressure fluctuations.

[0092] When the flow rate range is limited, no matter how the flow rate changes, the near-adiabatic compression time of the suction pump 2 and the heat transfer time of the same two liquids remain unchanged, that is, the influence of the thermal effect is consistent during this period, and the only variables that affect the compression volume of the suction pump 2 and the system pump 4 are the solvent type and the current system pressure.

[0093] S4: From the pre-pressurization moment of the current cycle, the controller 6 controls the suction pump 2 to perform pre-pressurization according to the compression volume of the current cycle.

[0094] S5: After the scheduled time of the current cycle, the controller 6 calculates the difference between the predicted pressure value at the scheduled time of the current cycle and the actual pressure value at that time, and determines the compression volume of the next cycle based on the comparison between the difference and the first threshold.

[0095] Specifically, in step S5, the compression volume of the next cycle is determined as follows:

[0096] If the difference between the predicted pressure value at a predetermined time of the current cycle and the actual pressure value at that time is less than or equal to the first threshold, the compression volume of the next cycle is the compression volume of the current cycle.

[0097] If the difference between the predicted pressure value at the scheduled time of the current cycle and the actual pressure value at that time is greater than the first threshold, the compression volume of the next cycle is:

[0098] V s+1,1 =V s,1 -αΔP s,1 ,

[0099] in,

[0100] V s+1,1 Represents the compressed volume of the next cycle;

[0101] V s,1 Represents the compression volume of the current cycle;

[0102] α represents the compression factor;

[0103] ΔP s,1 Represents the difference between the predicted pressure value at the scheduled time of the current cycle and the actual pressure value at that time, that is, the actual value minus the predicted value; Figure 2 P1(Δt1+δ) in is the true value of pressure at that moment in a certain cycle.

[0104] S6: From the infusion moment of the current cycle, the compression volume of the system pump 4 is controlled by the controller (6) according to the compensation volume of the current cycle to infuse the liquid through the suction pump 2.

[0105] S7: Starting from the end time of the infusion of the current cycle, the controller 6 calculates the difference between the actual pressure value at the predetermined time of the current cycle and the actual pressure value at the end time of the infusion of the current cycle, and determines the compensation volume of the next cycle based on the comparison between the difference and the second threshold value, and then enters the next cycle and returns to execute step S3.

[0106] Specifically, in step S7, the compensation volume of the next cycle is determined as follows:

[0107] If the difference between the actual pressure value at the scheduled time of the current cycle and the actual pressure value at the end time of the infusion of the current cycle is less than or equal to the second threshold, the compensation volume of the next cycle is the compensation volume of the current cycle.

[0108] If the difference between the actual pressure value at the scheduled time of the current cycle and the actual pressure value at the end of the infusion of the current cycle is greater than the second threshold, the compensation volume of the next cycle is:

[0109] V s+1,2 =V s,2 -βΔP s,2 ,

[0110] in,

[0111] V s+1,2 Represents the compensation volume for the next cycle;

[0112] V s,2 Represents the compensation volume of the current cycle;

[0113] β represents the adjustment factor;

[0114] ΔP s,2 represents the difference between the actual pressure value at the scheduled time of the current cycle and the actual pressure value at the end of the infusion of the current cycle, that is, the actual value minus the predicted value; Figure 2 P1(Δt1+Δt2) in is the true value of the pressure at the end of the infusion in the previous cycle of a certain cycle.

[0115] In addition, in this embodiment, the controller 6 drives the first and second motors 41 to adjust the corresponding pump chamber compression volumes of the motors according to the formula:

[0116] Infusion volume = output flow rate × time = (plunger rod cross-sectional area × motor output speed × screw lead) × time.

[0117] The specific application of the ultra-high performance liquid chromatography infusion system in this embodiment is further described below with a specific example.

[0118] Example 1:

[0119] For an isocratic fluid system with a fixed liquid composition and constant flow rate in the system pump chamber 43, the operating state and pressure state of each cycle of the ultra-high performance liquid chromatography infusion system are basically the same, and the parameters of the previous one or more cycles are used as reference to determine the V of the current cycle. s,1 and V s,2 There is no problem with the value.

[0120] For a high-pressure gradient fluid system with a fixed liquid composition and a variable flow rate in the system pump chamber 43, the pressure state is different in different cycles but the liquid does not change, and the same Δt1 and Δt2 values ​​in a certain flow interval mean that the liquid thermal effect is the same when the flow rate changes in this flow interval, and the adjustment factors α and β remain unchanged. Therefore, it is only necessary to adjust the pressure according to P s (t) The target pressure of this cycle is obtained by calculation.

[0121] However, for low-pressure gradient fluid systems where the liquid in each pump chamber changes but the flow rate does not change, there may be a lag problem. First of all, it is necessary to make it clear that there are large volumes in the pump chamber and the connecting pipelines. For low-pressure gradient fluids, the periodic volumes of proportional changes are 50μL and 20μL, while the corresponding volumes of the suction pump chamber 23 and the connecting pipeline in front of the pump may be 250μL and 100μL. In other words, when the fluid switches from pure water to pure methanol, without considering liquid diffusion, the changes in the suction pump chamber 23 are 100% pure water → 80% pure water → 64% pure water → 51% pure water... The actual changes in fluid composition are not as large as in the ideal situation. The compression volume V of the pre-pressurization stage of this cycle is executed according to the operating results of the previous cycle. s,1 It will not significantly affect the system pressure fluctuation.

[0122] In addition, the pressure data of the previous multiple cycles can be used to execute the compression volume of the pre-pressurization stage of this cycle. For example, if the difference between the theoretical pressure value and the actual pressure value of the first cycle is greater than the threshold, the compression volume of the pre-pressurization stage of this cycle is recorded as V s,1 , according to the pressure of the first cycle, we can get the second cycle V s+1,1 , after execution, the difference between the theoretical value and the actual value is still greater than the threshold. At this time, V s+2,1 The changing trend needs to be taken into account when calculating.

[0123] Assume that the compression volume of the pre-pressurization stage calculated according to the second cycle is V′ s+2,1 , the difference between the theoretical value and the actual value of pressure in the first cycle is ΔP s,1 , the difference between the theoretical value and the actual value of pressure in the second cycle is ΔP s+1,1 .

[0124] Then the compression volume of the third cycle in the pre-pressurization stage can be executed as:

[0125] V S+2,1 =V S+1,1 -α·(ΔP S+2,1 +ΔP S+1,1 ),

[0126] or

[0127] V S+2,1 =V S+1,1 -α·ΔP S+2,1 -γ·ΔP S+1,1 .

[0128] Figure 4It is a pressure fluctuation image of the test (low-pressure gradient fluid system) using the method in this embodiment. The compression factor α is 0.12 when the fluid pressure is below 8 MPa, 0.18 when the pressure is (8-12) MPa, and 0.25 when the pressure is 12 MPa and above; the adjustment factor β is 0.08 when the fluid pressure is below 8 MPa, 0.12 when the pressure is (8-12) MPa, and 0.16 when the pressure is 12 MPa and above.

[0129] The post-pump system 7 uses a C18 fully porous packing column with an inner diameter of 4.6 mm, a length of 250 mm, and a particle size of 5 μm. Under the condition of a total fluid flow rate of 1.0 mL / min, the pressure change (single change time 5 min) from 95% methanol water to 5% methanol water and then back to 95% methanol water is shown in the figure below. Figure 4 As shown in the figure, the pressure range is (7.6~15.6)MPa, and the pressure fluctuation does not exceed 0.1MPa throughout the process. Using a C18 fully porous packing column with an inner diameter of 4.6, a length of 30mm, and a particle size of 5μm, under the condition of a total flow rate of 1.0mL / min, the pressure changes from 95% methanol water to 5% methanol water and then back to 95% methanol water (single change time 5min), the pressure changes in the range of (0.9~2.0)MPa, and the pressure fluctuation does not exceed 0.1MPa throughout the process, see Figure 5 The stability of pressure correction under normal and low pressure (below 5 MPa) conditions is further demonstrated.

[0130] The ultra-high performance liquid chromatography infusion system disclosed in this embodiment does not need to calibrate the non-ideal situations that actually exist, such as the one-way valve opening time, the one-way valve closing time, the motor start delay, the motor stop delay, the flow path delay, etc., one by one. Instead, it is similar to a black box model, and only obtains a suitable correction method based on the input and output results. The method in this embodiment adopts a mode of predicting the operating speed of this cycle based on the pressure fluctuation of the previous cycle and short-term compensation of the preset speed in the same cycle. It detects faults quickly, has a low probability of error, has strong anti-interference, and can still operate stably at low pressures below 50 bar. At the same time, only one pressure acquisition and monitoring device is used to save costs.

[0131] In the description of the embodiments of the present application, it should be noted that in the description of the present application, terms such as "inside" and "outside" indicating directions or positional relationships are based on the directions or positional relationships shown in the drawings. This is only for the convenience of description, and does not indicate or imply that the device or component must have a specific orientation, be constructed and operated in a specific orientation. Therefore, it cannot be understood as a limitation on the present application.

[0132] In the description of the present application, the description with reference to the terms "one embodiment", "some embodiments", "in the present embodiment", "specific example", or "some examples" etc. means that the specific features, mechanisms, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present application. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, mechanisms, materials or characteristics described may be combined in a suitable manner in any one or more embodiments or examples. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0133] The above is only a specific implementation of the present application, but the protection scope of the present application is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed in the present application should be included in the protection scope of the present application. Therefore, the protection scope of the present application shall be based on the protection scope of the claims.

Claims

1. An ultra-high performance liquid chromatography infusion system, comprising an inlet check valve (1) and an outlet check valve (3), characterized in that: It also comprises a liquid suction pump (2), a system pump (4), a pressure collection device (5) and a controller (6); the system pump (4) is connected to the post-pump system (7) via a pipeline and is used to infuse liquid into the post-pump system (7); the inlet one-way valve (1), the liquid suction pump (2), the outlet one-way valve (3) and the system pump (4) are connected in series via a pipeline; the liquid suction pump (2) and the system pump (4) are respectively controlled by independent motors; the pressure collection device (5) is arranged on the pipeline connecting the system pump (4) and the post-pump system (7), and the number of the pressure collection device (5) is one; The controller (6) is electrically connected to the suction pump (2), the system pump (4) and the pressure acquisition device (5) respectively. The controller (6) is configured to control the suction pump (2) and / or the system pump (4) according to the pressure fluctuation corresponding to the pressure information obtained by the pressure acquisition device (5) in the current cycle or the current cycle and at least one cycle before the current cycle, so as to adjust the compression volume of the suction pump (2) in the next cycle or the next multiple cycles and the compensation volume of the liquid in the system pump (4) after cooling.

2. The ultra-high performance liquid chromatography infusion system according to claim 1, characterized in that: The suction pump (2) comprises a first motor (21), a first plunger rod (22) and a suction pump chamber (23); the first plunger rod (22) is slidably arranged on the suction pump chamber (23) to adjust the compression volume of the suction pump (2); the first motor (21) drives the first plunger rod (22) to move via a screw transmission.

3. The ultra-high performance liquid chromatography infusion system according to claim 2, characterized in that: The system pump (4) comprises a second motor (41), a second plunger rod (42) and a system pump chamber (43); the second plunger rod (42) is slidably arranged in the system pump chamber (43) to adjust the compression volume of the system pump (4); the second motor (41) drives the second plunger rod (42) to move through a screw transmission.

4. The ultra-high performance liquid chromatography infusion system according to any one of claims 1 to 3, characterized in that: The controller (6) is a programmable controller.

5. A method for controlling pressure fluctuations in an ultra-high performance liquid chromatography infusion system, characterized in that: The ultra-high performance liquid chromatography infusion system according to any one of claims 1 to 4 comprises the following steps: S1: Determine the scale standard of the infusion cycle, and specify the compression volume and compensation volume of the first cycle, wherein the compression volume is the compression volume of the suction pump (2) during the pre-pressurization process, and the compensation volume is the compensation volume after the liquid entering the system pump (4) is cooled; S2: collecting pressure signals through the pressure collection device (5) and transmitting them to the controller (6), and then entering the first cycle based on the infusion cycle scale standard; S3: before the pre-pressurization moment of the current cycle, the controller (6) obtains a pressure prediction model of the current cycle according to the previous pressure change, and obtains a pressure prediction value at a predetermined moment of the current cycle according to the pressure prediction model; S4: from the pre-pressurization moment of the current cycle, the controller (6) controls the liquid suction pump (2) to perform pre-pressurization according to the compression volume of the current cycle; S5: After the scheduled time of the current cycle, the controller (6) calculates the difference between the predicted pressure value at the scheduled time of the current cycle and the actual pressure value at that time, and determines the compression volume of the next cycle according to the comparison between the difference and the first threshold value; S6: from the infusion moment of the current cycle, according to the compensation volume of the current cycle, the controller (6) controls the compression volume of the suction pump (2) and / or the system pump (4) to infuse the liquid through the suction pump (2); S7: Starting from the end time of the infusion of the current cycle, the controller (6) calculates the difference between the actual pressure value at the predetermined time of the current cycle and the actual pressure value at the end time of the infusion of the current cycle, and determines the compensation volume of the next cycle based on the comparison between the difference and the second threshold value, and then enters the next cycle and returns to execute step S3.

6. The method for controlling pressure fluctuations in an ultra-high performance liquid chromatography infusion system according to claim 5, characterized in that: The infusion cycle scale standard in step S1 is: The time interval between two adjacent uniform speed start moments of the second motor (41) in the system pump (4) is an infusion cycle.

7. The method for controlling pressure fluctuations in an ultra-high performance liquid chromatography infusion system according to claim 6, characterized in that: In step S3, the pressure prediction model of any period is expressed as follows: P s (t)=P s,2 +k s t, in, P s,1 represents the pressure value obtained by the pressure acquisition device (5) at the time interval Δt0 before the pre-pressurization time of the sth cycle; P s,2 represents the pressure value obtained by the pressure acquisition device (5) at the pre-pressurization moment of the sth cycle; P s (t) represents the predicted value of the pressure obtained by the pressure acquisition device (5) at time t in the sth cycle.

8. The method for controlling pressure fluctuations in an ultra-high performance liquid chromatography infusion system according to claim 7, characterized in that: The predetermined time of each cycle is determined by: determining a time interval of δ according to the installation position of the pressure collection device (5) and the specifications of the pipeline in front of the pressure collection device (5), and the predetermined time of each cycle is the time of δ time interval after the pre-pressurization time of the current cycle; The duration of the pre-pressurization phase of each cycle is the time interval between the infusion time and the pre-pressurization time of the cycle; The duration of the infusion phase of each cycle is the time interval between the end of infusion and the infusion time of the cycle; The duration of the pre-pressurization phase of each cycle is the same as that of the infusion phase, ranging from (50 to 500) ms.

9. The method for controlling pressure fluctuations in an ultra-high performance liquid chromatography infusion system according to claim 8, characterized in that: In step S5, the compression volume of the next cycle is determined in the following manner: If the difference between the predicted pressure value at a predetermined time of the current cycle and the actual pressure value at that time is less than or equal to the first threshold, the compressed volume of the next cycle is the compressed volume of the current cycle; If the difference between the predicted pressure value at the scheduled time of the current cycle and the actual pressure value at the time is greater than the first threshold, the compression volume of the next cycle is: V s+1,1 =V s,1 -αΔP s,1 , in, V s+1,1 representing said compression volume for the next cycle; V s,1 represents the compression volume of the current cycle; α represents the compression factor; ΔP s,1 Represents the difference between the predicted pressure value at the scheduled time of the current cycle and the actual pressure value at that time.

10. The method for controlling pressure fluctuations in an ultra-high performance liquid chromatography infusion system according to claim 9, characterized in that: In step S7, the compensation volume of the next cycle is determined as follows: If the difference between the actual pressure value at the scheduled time of the current cycle and the actual pressure value at the end time of the infusion of the current cycle is less than or equal to the second threshold, the compensation volume of the next cycle is the compensation volume of the current cycle; If the difference between the actual pressure value at the scheduled time of the current cycle and the actual pressure value at the end of the infusion of the current cycle is greater than the second threshold, the compensation volume of the next cycle is: V s+1,2 =V s,2 -βΔP s,2 , in, V s+1,2 representing the compensation volume for the next cycle; V s,2 represents the compensation volume of the current cycle; β represents the adjustment factor; ΔP s,2 Represents the difference between the predicted pressure value at the scheduled time of the current cycle and the actual pressure value at the end of the infusion of the current cycle.

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