liquid chromatograph

Abstract

To provide a liquid chromatograph comprising a liquid feeding unit that can perform pre-compression at a predetermined pressure regardless of a material of a pump.SOLUTION: A liquid chromatograph 1 comprises a liquid feeding unit 20 that feeds a mobile phase in a retention part 11 to a column 14 at a predetermined pressure through a liquid feeding pipe 12. The liquid feeding unit 20 includes: a pump 21 that has a suction port 211 connected with the retention part 11, and a discharge port 212 connected with the liquid feeding pipe 12 directly or through the other pump; check valves 231, 232 that are provided in the suction port 211 and the discharge port 212, respectively; and a pressure application control unit 27 that controls the pressure applied to the mobile phase in the pump 21 before discharging the mobile phase sucked in from the suction port 211 from the discharge port 212, and based on the compressibility of the mobile phase and an amount of compression on an inner wall of the pump associated with the application of the pressure, controls the pressure to be a check valve opening pressure for opening the check valve 232 provided on the discharge port 212 side.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] The present invention relates to a liquid chromatograph. [Background technology]

[0002] Liquid chromatographs are widely used as devices for analyzing components contained in liquid samples. In liquid chromatographs, a liquid sample is introduced into a column along with a mobile phase flowing at a constant flow rate. The various components contained in the liquid sample are separated over time and then measured using a detector. During this process, the liquid delivery channel is subjected to pressure (several MPa to several tens of MPa) depending on the flow rate, the type of mobile phase, and its composition. If only one pump is used to deliver the mobile phase, there will be a period of time between the time the mobile phase is drawn in and the time it is discharged when no liquid can be delivered. Therefore, in order to deliver the mobile phase continuously at a constant flow rate, a liquid delivery unit combining two pumps has traditionally been used.

[0003] In the liquid delivery unit, the two pumps are connected in parallel or in series. In the parallel connection type, the two pumps are driven in the same cycle in opposite phases (when one pumps aspirates, the other pumps discharges) so that one of the pumps is always discharging. In the serial connection type, when the upstream pump is discharging mobile phase, the downstream pump aspirates some of the mobile phase discharged by the upstream pump while allowing the rest to pass through, and when the upstream pump is aspirating mobile phase (not discharging mobile phase), the downstream pump discharges the amount of mobile phase that it had previously aspirated.

[0004] In parallel-connected systems, check valves are provided at the suction and discharge ports of each of the two pumps. In series-connected systems, check valves are provided at the suction and discharge ports of the upstream pump. In parallel-connected systems, the check valve at one pump's suction port prevents backflow of mobile phase toward the suction port when that pump discharges it, while the check valve at the discharge port prevents mobile phase from flowing into the other pump's discharge port when the other pump discharges it. The check valve at the upstream pump in a series-connected system performs the same function. In a series-connected system, the downstream pump does not have a check valve at the discharge port because it allows half of the mobile phase to pass even during suction. Furthermore, a check valve at the suction side is also not provided because the check valve at the upstream pump's discharge port prevents backflow of mobile phase during discharge.

[0005] In a pump equipped with a check valve, when switching from the phase of aspirating the mobile phase to the phase of discharging the mobile phase, the check valve does not open until the pressure inside the pump reaches a predetermined value or higher. Therefore, in order to open the check valve simultaneously with the start of discharging, an operation called pre-pressurization is performed, in which the pressure of the mobile phase inside the pump is increased before discharging the mobile phase after the end of aspirating (see, for example, Patent Document 1).

[0006] The pressure of the mobile phase inside the pump when pre-pressurized (when the check valve is closed) is determined by the amount of change in volume inside the pump (corresponding to the amount of plunger movement) and the compressibility of the mobile phase. The compressibility of the mobile phase differs depending on the components of the mobile phase. Therefore, the amount of change in volume (amount of plunger movement) when pre-pressurized is determined for each mobile phase used. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Japanese Patent Application Laid-Open No. 2006-125367 [Patent Document 2] Japanese Patent Application Publication No. 07-077521 Summary of the Invention [Problem to be solved by the invention]

[0008] Traditionally, metals such as stainless steel have been used as materials for components of liquid delivery units. However, even small amounts of metal can dissolve in the mobile phase and cause metal ions to be detected, potentially affecting analytical results. For this reason, liquid chromatographs have been developed in recent years that use liquid delivery units made of resin, which barely dissolves in the mobile phase, for the parts of the liquid delivery unit that come into contact with the mobile phase. Pumps in liquid delivery units are either made entirely of resin, or the parts that come into contact with the mobile phase are made of resin with a metal periphery.

[0009] In pumps using these resins, the flow path expands when pressure is applied, resulting in insufficient pressure even when pre-pressurized under the same conditions as conventional metal pumps. Furthermore, the check valve only opens when the plunger is moved, which causes a delay in the timing of mobile phase discharge.

[0010] Furthermore, in a pump using such a resin, the following problems arise when performing low-pressure gradient control. Generally, gradient control refers to a control in which a mobile phase is supplied to a column while continuously changing its composition by continuously changing the mixing ratio of multiple solvents with different components. Low-pressure gradient control is a type of gradient control in which a mobile phase is obtained by mixing multiple solvents downstream of the pump using only one pumping unit. For example, in low-pressure gradient control, when a mobile phase containing a mixture of water and acetonitrile is supplied to a column, the mixing ratio of water to acetonitrile is continuously changed from 90:10 to 50:50 over 20 minutes. In this case, since a small amount of compressed solvent (compression residual liquid) remains in the pump when the pump has completed discharging the solvent, new solvent cannot be sucked in during the period from when the suction operation begins until the pressure of the compression residual liquid drops to a certain value (when depressurization is completed), and in consideration of this, the amount of movement of the plunger from when depressurization is completed to when suction is completed is divided according to the target value of the mixture ratio of each solvent, so that each solvent is sucked into the pump so that the mixture ratio becomes the target value (see Patent Document 2). However, when low-pressure gradient control is performed using a liquid delivery unit equipped with a resin pump, a problem occurs in that the actual mixture ratio of the mobile phase discharged from the pump deviates from the target value.

[0011] The problem to be solved by the present invention is to provide a liquid chromatograph equipped with a liquid delivery unit that can apply pre-pressure at a predetermined pressure and perform low-pressure gradient control at a predetermined mixing ratio, regardless of the pump material. [Means for solving the problem]

[0012] A first aspect of the present invention, which has been made to solve the above problems, is a liquid chromatograph including a liquid delivery unit that delivers a mobile phase in a reservoir to a column through a liquid delivery tube at a predetermined pressure, the liquid chromatograph comprising: The liquid delivery unit a pump having a pump chamber, a plunger that reciprocates within the pump chamber, a suction port that is provided in the pump chamber and connected to the reservoir, and a discharge port that is provided in the pump chamber and connected to the liquid feed pipe directly or via another pump; a check valve connected to the discharge port; an input unit for inputting information regarding the compressibility of the mobile phase and the amount of change in the volume of the pump chamber due to a change in the pressure in the pump chamber; a pressure application control unit that controls the plunger based on the information input by the input unit so that a pressure applied to the mobile phase in the pump chamber becomes a check valve opening pressure that opens the check valve before the mobile phase sucked through the suction port is discharged from the discharge port; and Equipped with.

[0013] A second aspect of the present invention is a liquid chromatograph including a liquid delivery unit that delivers a mobile phase, which is a mixture of a plurality of solvents having different components, to a column through a liquid delivery tube at a predetermined pressure, the liquid chromatograph comprising: The liquid delivery unit is a solvent supply unit including a plurality of solvent supply flow paths and a switching mechanism for selectively switching one of the plurality of solvent supply flow paths to another; a pump having a pump chamber, a plunger reciprocating within the pump chamber, a suction port provided in the pump chamber and connected to the solvent supply unit, and a discharge port provided in the pump chamber and connected to the liquid delivery pipe directly or via another pump; an input unit for inputting information regarding the compressibility of the mobile phase and the amount of change in the volume of the pump chamber due to a change in the pressure in the pump chamber; a flow path switching control unit that controls the timing of switching the solvent supply flow path by the switching mechanism based on the information input by the input unit; Equipped with. [Effects of the Invention]

[0014] The pressure of the mobile phase in the pump chamber actually depends not only on the compressibility of the mobile phase, but also on the volume of the pump chamber, which changes as pressure is applied to the pump chamber walls, the plunger, the sealant between the plunger and the pump chamber walls, and the flow path from the pump chamber to the check valve. The amount of change in the volume of the pump chamber depends on the material of the pump chamber walls, etc., and is negligibly small when the material is metal, but cannot be ignored when the material is easily deformed by compression, such as resin. Therefore, in the liquid chromatograph of the first embodiment, the plunger is controlled based on the change in the volume of the pump chamber caused by changes in pressure, as well as the compressibility of the mobile phase, so that the pressure applied to the mobile phase in the pump chamber before discharging it from the inlet port through the outlet port is equal to the check valve opening pressure. Here, the plunger can be controlled by adjusting the plunger's position and movement speed over time, and the change in the volume of the pump chamber can be determined in advance through preliminary experiments, etc. By controlling the plunger in this manner, the mobile phase in the pump chamber reaches a pressure sufficient to open the check valve when the mobile phase is discharged from the discharge port, thereby enabling the mobile phase to be discharged from the pump at the appropriate timing. Furthermore, the operator uses the input unit to input information regarding the compressibility of the mobile phase and the amount of change in the volume of the pump chamber caused by compression of components such as the walls of the pump chamber due to changes in the pressure in the pump chamber, and the pressure application control unit controls the pressure, i.e., the pressure applied to the mobile phase in the pump, based on this information. Therefore, even if the compressibility of the mobile phase or the amount of change in the volume of the pump chamber changes due to changes in the mobile phase used or replacement of the pump, appropriate pressure control can be performed.

[0015] Furthermore, if the volume changes due to a change in the pressure in the pump chamber during low-pressure gradient control, the timing at which depressurization is completed and the solvent can be aspirated changes compared to when no change in volume occurs. Therefore, if the solvent introduced into the pump chamber is switched without considering this change in the timing at which depressurization is completed, the actual mixture ratio will deviate from the target value. Therefore, in the liquid chromatograph of the second embodiment, the timing at which the switching mechanism switches the solvent supply flow path is controlled based on not only the compressibility of the solvent in the pump chamber but also the change in the volume of the pump chamber due to a change in the pressure in the pump chamber. This allows the timing at which the solvent supply flow path is switched to correspond to the change in the timing at which depressurization is completed, thereby enabling multiple solvents to be mixed at the target mixture ratio. Furthermore, as with the liquid chromatograph of the first embodiment, the timing at which the solvent supply flow path is switched can be appropriately controlled even if the compressibility of the solvent or the volume of the pump chamber changes due to a change in the solvent used or replacement of the pump. [Brief explanation of the drawings]

[0016] [Figure 1] 1 is a schematic diagram showing the configuration of a first embodiment of a liquid chromatograph according to the present invention. [Figure 2] FIG. 2 is a diagram showing the configuration of a liquid delivery unit included in the liquid chromatograph of the first embodiment. [Figure 3] 3A to 3C are diagrams showing examples of a cam profile in the liquid delivery unit of the liquid chromatograph of the first embodiment, the operation of the pump when the cam rotates at a constant speed, and the rotation speed of the cam. [Figure 4] 5 is a flowchart showing a method for determining the amount of compression in consideration of the amount of compression of the inner wall of the pump in the liquid delivery unit of the liquid chromatograph of the first embodiment. [Figure 5] FIG. 1 is a schematic diagram showing a second embodiment of a liquid chromatograph according to the present invention. [Figure 6] 10A and 10B are diagrams for explaining a time period during which a solvent is to be aspirated and timing for switching the solution to be aspirated. [Figure 7]10 is a flowchart showing a method for determining the timing to switch the solution to be sucked into the pump, taking into consideration the amount of compression of the inner wall of the pump, in the liquid delivery unit of the liquid chromatograph of the second embodiment. [Figure 8] FIG. 10 is a diagram showing the configuration of a liquid delivery unit of a liquid chromatograph according to a modified example. DETAILED DESCRIPTION OF THE INVENTION

[0017] (1) First embodiment A first embodiment of a liquid chromatograph according to the present invention will be described with reference to FIGS. 1 to 4. FIG. 1 is a schematic diagram showing the configuration of a liquid chromatograph 1 according to this embodiment. The liquid chromatograph 1 includes a reservoir (reservoir) 11 for storing a mobile phase, a liquid delivery tube 12 connected at one end to the reservoir 11, a pump unit 20 provided in the liquid delivery tube 12, a sample injection unit (injector) 13 provided in the same tube downstream of the pump unit 20, a column 14 provided in the same tube downstream of the sample injection unit 13, and a detector 15 provided in the same tube downstream of the column 14. The sample injection unit 13 is a device for injecting a sample solution into the mobile phase. The column 14 separates various components contained in the sample solution injected into the mobile phase over time. The detector 15 is a device for sequentially detecting the various components separated by the column 14, and may be, for example, a mass spectrometer, a photodiode array (PDA) detector, or an ultraviolet-visible spectrophotometric detector. In the first embodiment, the liquid delivery unit corresponds to the pump unit 20. The components other than the pump unit 20 are the same as those used in conventional liquid chromatographs.

[0018] 2, the pump unit 20 has a first pump 21 and a second pump 22. The liquid feed pipe 12 has, within the pump unit 20 and before and after the pump unit 20, a first liquid feed pipe 121 connecting the reservoir 11 and a suction port (first suction port) 211 of the first pump 21, a second liquid feed pipe 122 connecting a discharge port (first discharge port) 212 of the first pump 21 and a suction port (second suction port) 221 of the second pump 22, and a third liquid feed pipe 123 connecting a discharge port (second discharge port) 222 of the second pump 22 and the sample injection section 13. In this way, the first pump 21 and the second pump 22 are connected in series via the second liquid feed pipe 122.

[0019] A first check valve 231 is provided at the first suction port 211, and a second check valve 232 is provided at the first discharge port 212. Both the first check valve 231 and the second check valve 232 have the role of preventing the mobile phase from flowing back toward the reservoir tank 11.

[0020] It should be noted that check valves are not provided at the second suction port 221 and the second discharge port 222 of the second pump 22. This is because the second check valve 232 provided at the first discharge port 212 of the first pump 21 can prevent backflow of the mobile phase at the second suction port 221, and because half of the mobile phase sucked from the second suction port 221 needs to pass through the second discharge port 222 even during suction, as will be described later.

[0021] As shown in FIG. 2 , the first pump 21 includes a first cylinder (first pump chamber) 213 that communicates with the first suction port 211 and the first discharge port 212, and a first plunger 214 that reciprocates within the first cylinder 213. In this embodiment, the wall of the first cylinder 213 and the first plunger 214 are made of a resin, polyether ether ketone (PEEK). PEEK has the advantage of being almost soluble in the mobile phase. On the other hand, when the first plunger 214 is pressed, pressure is applied to the mobile phase within the first cylinder 213, and the mobile phase is compressed, thereby changing the volume within the first cylinder 213. The wall of the first cylinder 213 and / or the first plunger 214 may be entirely made of PEEK, or only the surface in contact with the mobile phase may be made of PEEK and the remaining portions may be made of metal. Resins other than PEEK may also be used.

[0022] In addition, a seal material (not shown) is provided in the gap between the wall of the first cylinder 213 and the first plunger 214 to prevent the mobile phase from leaking from the gap.

[0023] The second pump 22 includes a second cylinder (second pump chamber) 223 and a second plunger 224 that are similar in structure, volume, and material to the first cylinder 213 and the first plunger 214 of the first pump 21.

[0024] 2, the pump unit 20 further includes a camshaft 24, a first cam 251 and a second cam 252 fixed to the camshaft 24, a stepping motor 26 that rotates the camshaft 24, and a control unit 27 that controls the rotation speed of the stepping motor 26. The liquid chromatograph 1 is also provided with input devices (input unit 28) such as a keyboard and a mouse, and a display (display unit 29), and the conditions for control by the control unit 27 can be input from the input unit 28 and displayed on the display unit 29.

[0025] The first cam 251 comes into contact with the rear end of the first plunger 214, and rotates in conjunction with the rotation of the camshaft 24, thereby reciprocating the first plunger 214. The second cam 252 comes into contact with the rear end of the second plunger 224, and reciprocates the second plunger 224 in a manner similar to that of the first cam 251. The shapes of the first cam 251 and the second cam 252 are set so that the speed of the second plunger 224 is half the speed of the first plunger 214. Furthermore, in principle, the first plunger 214 and the second plunger 224 move in opposite directions (as a result, when the first pump 21 draws in the mobile phase, the second pump 22 discharges the mobile phase, and when the first pump 21 discharges the mobile phase, the second pump 22 draws in the mobile phase). However, when switching between the first pump 21 and the second pump 22 which discharges the mobile phase, and when pre-pressurization is performed as described below, both the first plunger 214 and the second plunger 224 move in the pushing direction.

[0026] The operation of the pump unit 20 will now be described. Rotation of the camshaft 24 causes the first cam 251 and the second cam 252 to rotate, causing the first plunger 214 and the second plunger 224 to reciprocate. When the first pump 21 discharges the mobile phase from the first outlet 212 (the first plunger 214 advances), the second pump 22 draws the mobile phase discharged from the first outlet 212 through the second suction port 221 (the second plunger 224 retreats). The second pump 22 draws in only half of the mobile phase discharged by the first pump 21 and allows the remaining half to pass and flow out from the second outlet 222. On the other hand, when the first pump 21 draws in the mobile phase from the first suction port 211, the second pump 22 discharges the half of the mobile phase it had previously drawn in from the second outlet 222. This ensures that the mobile phase is always delivered at a substantially constant pressure and flow rate, regardless of the suction / discharge phase of each pump.

[0027] When the first pump 21 discharges the mobile phase, the mobile phase in the first pump 21 is pushed not only toward the first discharge port 212 but also toward the first suction port 211, but the provision of the first check valve 231 prevents the mobile phase from flowing back into the storage tank 11. Furthermore, when the first pump 21 sucks the mobile phase, the provision of the second check valve 232 prevents the mobile phase in the second liquid feed pipe 122 and the second pump 22 from flowing back into the first pump 21. When the second pump 22 discharges the mobile phase, the mobile phase in the second pump 22 is pushed not only toward the second discharge port 222 but also toward the second suction port 221, but the provision of the second check valve 232 prevents the mobile phase from flowing back into the first pump 21.

[0028] Pre-pressure will be described below. When the first pump 21 discharges the mobile phase, the second check valve 232 does not open until the pressure inside the first pump 21 reaches or exceeds a predetermined value (the check valve opening pressure described above), and therefore the mobile phase cannot be discharged. Therefore, in the pump unit 20 of this embodiment, after the first pump 21 has finished suctioning the mobile phase and before it starts discharging, a pre-pressure operation is performed as described below to increase the pressure of the mobile phase inside the first pump 21 to or above the check valve opening pressure. Note that the second pump 22 does not need to be pre-pressurized because it is not provided with a check valve.

[0029] Let V be the volume of the space that contains the mobile phase in the first pump 21 at the end of suction, ΔV be the change in the volume of the first pump 21 (corresponding to the distance traveled by the plunger) from the state in which suction has ended until the second check valve 232 is opened (during the pre-pressure period), ΔP be the change in pressure of the mobile phase in the first pump 21 during the pre-pressure period (ΔP is determined by the structure of the second check valve 232), and β be the compressibility of the mobile phase.

[0030] In a conventional liquid delivery unit, ΔV is ΔV=βVΔP …(1) The plunger movement distance during the preload period was determined so as to satisfy the following relationship. Since the compressibility β differs depending on the components of the mobile phase, ΔV is determined for each component of the mobile phase.

[0031] However, when using a pump (first pump 21) made of a material that is compressed by the application of pressure as in this embodiment, it is necessary to consider not only the compression of the mobile phase shown in equation (1) but also the change in pump volume due to the compression of each component of the pump, such as the wall of the pump chamber, the plunger, and the seal material. Therefore, in this embodiment, the amount of change in pump volume due to deformation caused by the application of pressure to the mobile phase in the first pump 21 is defined as αΔP, and ΔV is ΔV=(βV+α)ΔP …(2) The moving distance of the plunger during the preload period is specified so as to satisfy the relationship:

[0032] The value of α depends on the pump material, and therefore does not need to be changed unless the first pump 21 is replaced with a pump made of a different material. Therefore, the value of α is usually kept as an unchanging constant, and ΔV can be determined by inputting only the compressibility β depending on the components of the mobile phase. When the first pump 21 is replaced, α should be changed to a value determined by the material of the new first pump 21.

[0033] Next, with reference to FIG. 3, the operation of the first cam 251 and the second cam 252 will be described, focusing on the time when preload is applied. The graph labeled "Cam Profile" in the upper part of FIG. 3 shows the relationship between the rotation angle θ of the camshaft 24 (and the first cam 251 and the second cam 252) and the moving speed dr / dθ of the plungers (first plunger 214 and second plunger 224). Here, the moving speed dr / dθ of the plungers is the speed at which the plungers move when the camshaft 24 rotates by a unit angle (1°) (note that this is different from the speed, which is the value obtained by dividing the distance by the time). This relationship between θ and dr / dθ is set by the shape of the cam. When dr / dθ is positive, it means that the plungers move in the pushing direction, and when dr / dθ is negative, it means that the plungers move in the pulling direction.

[0034] By setting the cam profile in this way, when the camshaft 24 rotates at a constant speed, as shown in the middle of Figure 3, the first pump 21 discharges the mobile phase when the rotation angle θ is between 96° and 264°, sucks the mobile phase when the rotation angle θ is between 264° and 360° (0°), and preloads the mobile phase when the rotation angle θ is between 0° and 96°. Here, when the camshaft 24 rotates at a constant speed, the preload is completed. angle The 96° set as the reference rotation angle corresponds to the "reference rotation angle" described later. During preloading, dr / dθ is set to be smaller than during discharge. Meanwhile, the second pump 22 discharges the mobile phase when the rotation angle θ passes through 360° (0°) from 240° and reaches 120°, and aspirates the mobile phase when the rotation angle θ is between 120° and 240°. Note that within the range of the rotation angle θ between 96° and 120°, the second pump 22 continues to discharge the mobile phase while decreasing the moving speed dr / dθ of the second plunger 224 in accordance with the rotation of the camshaft 24. Therefore, the first pump 21 maintains the moving speed dr / dθ of the first plunger 214 during preloading (making it smaller than dr / dθ when θ is 120° or greater), thereby suppressing the discharge amount of the mobile phase. Furthermore, when the rotation angle θ is between 240° and 120°, 264 When θ is 0.5°, both the first pump 21 and the second pump are discharging the mobile phase, so the movement speed dr / dθ of the first plunger 214 and the second plunger 224 is adjusted so that the flow rate of the mobile phase supplied to the third liquid delivery pipe 123 is constant.

[0035] The timing of preload termination (switching from preload to discharge) of the first pump 21 when the camshaft 24 rotates at a constant speed is set to match the timing when a specific pump is used as the first pump 21 to deliver a specific mobile phase. In practice, the timing of preload termination differs depending on the pump material and the mobile phase components, as shown in equation (2). In this embodiment, the shapes of the first cam 251 and the second cam 252 (the cam profile in the upper part of FIG. 3 ) are the same regardless of the material and mobile phase components of the first pump 21. The rotational speed of the camshaft 24 is set using the following method to adjust the preload termination timing for each material and mobile phase component of the first pump 21. The control unit 27 controls the stepping motor 26 to rotate the camshaft 24 at the set rotational speed.

[0036] If the material of the first pump 21 is harder than the material of the specific pump or if the compressibility of the mobile phase is smaller than that of the specific mobile phase, the value of ΔV in equation (2) will be smaller, and preloading will be completed earlier than the timing set when the camshaft 24 rotates at a constant speed. In this case, the mobile phase will be discharged from the first pump 21 even at a rotation angle θ of 120° or less, at which preloading is still being applied in the case of constant speed rotation. Therefore, in accordance with pattern 1 of the rotation speed examples shown in the lower part of FIG. 3, the rotation speed is slowed from the rotation angle at which preloading is completed (the angle indicated by the reference numeral 51 in the figure, which will be described later as the "rotation angle when the check valve is open"; in the example shown in the figure, this is 48°) to the angle at which preloading is completed in the case of constant speed rotation (96°). The rotation speed at this time is set so that the sum of the flow rate of the mobile phase discharged from the first pump 21 and passing through the second pump 22 and the flow rate of the mobile phase discharged from the second pump 22 by the operation of the second pump 22 matches the original discharge rate of the second pump 22. As a result, after the completion of pre-pressurization, the sum of the mobile phase discharged from the first pump 21 and passing through the second pump 22 and the mobile phase discharged from the second pump 22 is supplied to the third liquid delivery pipe 123, and the flow rate of the mobile phase becomes the same value as before the completion of pre-pressurization.

[0037] If the material of the first pump 21 is softer than the material of the specific pump or if the compressibility of the mobile phase is greater than the compressibility of the specific mobile phase, the value of ΔV in equation (2) becomes larger, and preload completion occurs later than the timing set when the camshaft 24 rotates at a constant speed. In this case, the rotation speed is increased so that the rotation angle θ of the first pump 21 at which preload completion occurs is reached earlier at a rotation angle θ of 120° or greater, at which preload completion occurs in the case of constant speed rotation.

[0038] 3, when the rotation angle of the first pump 21 at the completion of preload (the angle indicated by reference numeral 52 in the figure) is between 96° and 120°, i.e., when both the first pump 21 and the second pump 22 are discharging mobile phase, the rotation speed of the camshaft 24 is made faster than that during uniform rotation from 96° to the rotation angle at the completion of preload, and then the rotation speed is made slower than that during uniform rotation up to 120°. This allows the rotation angle at the completion of preload to be reached quickly, and prevents the mobile phase from being supplied at an excessive flow rate after the rotation angle is reached.

[0039] 3, when the rotation angle of the first pump 21 at the completion of preload (the angle indicated by reference numeral 53 in the figure) is 120° or greater, the rotation speed of the camshaft 24 is made faster than that during constant speed rotation from 96° to the rotation angle at the completion of preload, thereby enabling the camshaft 24 to reach that rotation angle quickly. At this time, by gradually increasing the rotation speed between 96° and 120°, the supply of mobile phase at an excessive flow rate is prevented.

[0040] The timing of completion of pre-pressurization described above is preferably set automatically by the software when a maintenance person or user of the liquid chromatograph 1 (hereinafter referred to as the "operator") inputs information about the pump material and mobile phase from the input unit 28. An example of the operation of such software will be described with reference to the flowchart in FIG. 4. In this embodiment, pre-pressurization is performed in the first pump 21 equipped with the first plunger 214, but in the following description of the operation of the software, these will be generally referred to as the "plunger" and the "pump."

[0041] First, the operator performs a predetermined operation using the input unit 28, which causes the control unit 27 to start the operation of the software. The software accepts input of values ​​for α and β as follows (step 1). First, an input screen for allowing the operator to input information regarding the pump material and mobile phase is displayed on the display unit 29. Here, as this information, the operator may be prompted to input the values ​​of α and β in equation (2), or the operator may be prompted to input or select from options the name of the mobile phase to be used and the name of the pump material, and then the control unit 27 may retrieve from the memory the values ​​of α and β that have been previously stored in a memory unit (not shown) for each mobile phase and pump material.

[0042] Next, the control unit 27 calculates the amount of change ΔV in the volume of the pump until pre-loading is complete, using equation (2) based on the acquired values ​​of α and β (step 2). Note that the volume V in equation (2) is a value determined by the structure of the pump, and therefore this value is used without requiring input by the operator.

[0043] Next, the value of n is set to 1 (Step 3), and the movement distance of the plunger when the stepping motor 26 is rotated by n pulses (1 pulse at this point, since n=1), from the preload start position, is calculated based on the cam profile (Step 4). Then, the change in the volume inside the pump when the plunger is moved by this movement distance, ΔV n (Step 5) The calculated ΔV nIf is smaller than ΔV (NO in step 6), the volume inside the pump has not yet changed enough to complete preloading. 、 The value of n is increased by 1 (step 7), and steps 4 to 6 are performed again.

[0044] On the other hand, ΔV calculated in step 5 n If ΔV is equal to or greater than ΔV (YES in step 6), this means that preloading will be completed when the stepping motor 26 has rotated by n pulses. Therefore, the position where the stepping motor 26 has rotated by n pulses from the preload start position is set as the preload completion position (step 8). Then, the rotational speed of the camshaft 24 after the preload completion position until the discharge state of the mobile phase from the pump reaches a normal state (in the example of FIG. 3, the rotational angle θ is 144° or more) is set so that the flow rate of the mobile phase delivered to the third liquid delivery pipe 123 becomes as constant as possible (step 9). The above software operation completes the setting of the timing of preload completion (and the subsequent rotational speed of the camshaft 24).

[0045] A plurality of conditions set in this way, such as the timing of completion of pre-pressure, may be stored in the memory unit, and when starting to use the liquid chromatograph 1, the plurality of conditions may be displayed on the display unit 29 and the user may select one of them. In this case, since the value of α (or the type of pump corresponding to it) is changed only when the pump is replaced, the user may be allowed to select only the value of β or the type of mobile phase corresponding to it when starting to use the liquid chromatograph 1 normally (even in this case, of course, the value of α is set to a value determined according to the pump being used).

[0046] (2) Second embodiment A second embodiment of the liquid chromatograph according to the present invention will be described with reference to FIGS. 5 to 7. 51 is a schematic diagram showing the configuration of a liquid chromatograph 4 of the second embodiment. This liquid chromatograph 4 includes a first reservoir 411, a second reservoir 412, a solvent supply unit 42, a liquid delivery tube 12, a pump unit 20, a mixer 46, a sample injection unit (injector) 13, a column 14, and a detector 15. The liquid delivery tube 12, the sample injection unit 13, the column 14, and the detector 15 have the same configurations as those in the first embodiment, and therefore detailed description thereof will be omitted.

[0047] First reservoir 411 and second reservoir 412 are reservoirs that store different components. Hereinafter, the solvent stored in first reservoir 411 will be referred to as a first solvent, and the solvent stored in second reservoir 412 will be referred to as a second solvent. In this embodiment, two reservoirs, namely, first reservoir 411 and second reservoir 412, are provided, but three or more reservoirs may be provided when analysis is performed using a mobile phase in which three or more solvents are mixed.

[0048] solvent The supply unit 42 includes a first supply flow path 4221 and a second supply flow path 4222 extending from the first storage unit 411 and the second storage unit 412, respectively, a switching valve (switching mechanism) 423, and a flow path switching control unit 424. The switching valve 423 is a valve that switches the supply flow path that supplies the solvent introduced into the liquid feed tube 12 between the first supply flow path 4221 and the second supply flow path 4222. The flow path switching control unit 424 controls the switching valve 423 to switch the supply flow path at a predetermined timing, as will be described later.

[0049] The pump unit 20 has a configuration similar to that of the first embodiment (see Figure 2 above), in which a first pump 21 and a second pump 22, whose cylinder walls and plungers are made of resin (PEEK), are connected in series, and check valves (first check valve 231 and second check valve 232) are connected to the first suction port 211 and first discharge port 212 of the first pump 21, respectively.

[0050] In the second embodiment, solventThe supply section 42, the liquid delivery tube 12, and the pump unit 20 combine to form a liquid delivery unit 40 (different from the first embodiment in which the liquid delivery unit is formed only by the pump unit 20).

[0051] The mixer 46 mixes and delivers the first and second solvents that flow in with a time lag from the pump unit 20. The liquid obtained by mixing the first and second solvents in the mixer 46 is supplied to the sample injection section 13 as a mobile phase.

[0052] The operation of the liquid delivery unit 40 in the liquid chromatograph 4 of the second embodiment will be described below. The basic operation of the pump unit 20 in the liquid delivery unit 40 is the same as that of the first embodiment. That is, the first cam 251 and the second cam 252 rotate in accordance with the rotation of the camshaft 24, causing the first plunger 214 and the second plunger 224 to reciprocate, respectively. When the first pump 21 discharges the solvent from the first outlet 212, the second pump 22 aspirates half of the discharged solvent from the second suction port 221, and passes the remaining half of the solvent through to flow out from the second outlet 222. When the first pump 21 aspirates the mobile phase from the first suction port 211, the second pump 22 aspirates half of the solvent that it had previously aspirated from the second outlet 222.

[0053] solvent The supply unit 42 switches the solvent supplied to the first pump 21 between the first solvent and the second solvent at a predetermined timing described below. To explain this, first, the operation of the liquid delivery unit 40 in a conventional liquid chromatograph will be described.

[0054] In conventional liquid chromatographs, the liquid delivery unit 40 switches the time period during which the first pump 21 attempts to aspirate the solvent (the time period marked "Aspiration" in FIG. 6 ) so as to distribute the solvent in the same ratio as the mixture ratio of the first and second solvents. For example, if the first pump 21 is to aspirate the solvent in two cycles, and the first and second solvents are mixed in a 20:80 mixture ratio, 40% of the first solvent and 60% of the second solvent are aspirated during the aspirating period of the first cycle, and 100% of the second solvent is aspirated during the aspirating period of the second cycle. (Note that the cycle unit for setting the mixture ratio is not limited to two cycles, but may be one cycle or three or more cycles.) However, during each aspirating period, the solvent cannot actually be aspirated from the start of the aspirating operation (retraction of the first plunger 214) until the pressure in the first pump 21 is reduced to a predetermined value and depressurization is completed (referred to as the "depletion period"). Therefore, by setting the ratio of the suction volumes of the first and second solvents during the remaining period excluding the loss period, it is possible to aspirate the first and second solvents at the target mixture ratio. For example, if the loss period in the example mixture ratio above is 20% of the entire suction cycle, the remaining 80% of the suction period in the first cycle can be divided into 40% first solvent and 60% second solvent. In this case, the timing for switching the solvent to be aspirated should be (100% - 20%) x 40% = 32% from the end of the loss period ((20% + 32%) = 52% from the start of the suction operation) (see "Pump compression deformation not considered (conventional)" in Figure 6).

[0055] However, if the components of the first pump 21 are made of a material that deforms under pressure, such as resin, the pressure applied to the remaining solvent at the completion of discharge before the start of the suction operation will cause deformation of the first cylinder 213. As a result, the position of the first plunger 214 at the completion of depressurization will be different from that in the case where deformation under pressure does not occur, and the timing at which suction of the solvent actually begins will also be different. Therefore, the timing for switching the solvent to be suctioned must be changed from that in the case where deformation under pressure does not occur (see "Consideration of pump compression deformation" in Figure 6).

[0056] The volume inside the first pump 21 at the start of the suction operation is V m , the difference in volume and pressure from the start of the suction operation to the completion of decompression is ΔV m and ΔP m The compressibility of the solvent remaining in the first pump 21 at the start of the suction operation is β m , the amount of change in the volume of the first pump 21 due to deformation caused by a change in pressure inside the first pump 21 is defined as α m ΔP m Since there is no solvent flowing into or out of the first pump 21 from the start of the suction operation until the completion of depressurization, if deformation due to pressure changes is not taken into consideration, the same as during pre-pressurization during the discharge operation, ΔV m =β m V m ΔP m …(3) When deformation due to pressure change is taken into consideration, the same as when preloading, ΔV m =(β m V m +α m )ΔP m …(4) In this embodiment, based on the relationship (4), ΔV m and ΔP m Then, when the pressure in the first pump 21 drops to a value that allows the solvent to be sucked (i.e., when depressurization is completed), ΔP m ΔV corresponding to m The time when the first plunger 214 has moved until the pressure reaches the pressure-relief value is determined as the time when decompression is completed.

[0057] α m The value of α depends on the material of the pump, and therefore does not need to be changed unless the first pump 21 is replaced with a pump made of a different material. m The value of is set as a constant, and the compressibility β depends on the components of the solvent remaining in the first pump 21 (the solvent sucked in during the previous suction, and if multiple types of solvents were sucked in during that suction, the solvent is mixed). m By inputting only ΔV at the time of completion of decompressionm When the first pump 21 is replaced, α m is changed to a value determined by the material of the new first pump 21. m Once the position of the first plunger 214 is identified, the timing for switching between the first solvent and the second solvent can be determined by setting the ratio of the amounts of the first solvent and the second solvent to be aspirated during the remaining period of movement of the first plunger 214 from the position of the first plunger 214 at that time, in a manner similar to that of the conventional method.

[0058] As in the first embodiment, it is preferable that the software automatically sets the pump material and solvent when the operator inputs the information about the pump material and solvent through the input unit 28. An example of the operation of such software will be described with reference to the flowchart in Figure 7. In the explanation of the second embodiment up to this point, the operation of the first pump 21 equipped with the first plunger 214 has been described as an example, but in the following explanation, the terms "plunger" and "pump" will be used in general terms.

[0059] When the operator performs a predetermined operation using the input unit 28 to start the operation of the software, the control unit 27 m and β m The value of α is input (step 11). m and β m The value of α may be input directly by the operator, or the name of the mobile phase (plural solvents and their mixing ratio) to be used and the name of the pump material may be input by the operator or selected from options, and then the value of α may be stored in a storage unit (not shown) in advance for each mobile phase and pump material. m and β m The control unit 27 may acquire the value of from the storage unit.

[0060] Next, the control unit 27 calculates the obtained α m and β m Based on the value of ΔV at the completion of decompression, using equation (4) m (Step 12) In equation (4), the volume of the pump at the start of the suction operation, V mSince is a value determined by the structure of the pump, this value is used without requiring the operator to input it.

[0061] Next, the value of n is set to 1 (step 13), and the movement distance of the plunger when the stepping motor 26 is rotated by n pulses (1 pulse at this point, since n=1), from the position where the suction operation starts, is calculated based on the cam profile (step 14). Then, the change in the volume inside the pump when the plunger is moved by this movement distance, ΔV mn (Step 15) The calculated ΔV mn is ΔV m If it is smaller than (NO in step 16), decompression has not yet been completed. 、 Increment the value of n by 1 (step 17) and then 14 ~ 16 Execute the operation again.

[0062] On the other hand, ΔV calculated in step 15 mn is ΔV m If the value is equal to or greater than (YES in step 16), this means that decompression will be completed when the stepping motor 26 has rotated by n pulses. Therefore, the position where the stepping motor 26 has rotated by n pulses from the start position of the suction operation is set as the decompression completion position (step 18).

[0063] Next, the change in volume within the pump from the completion of depressurization to the end of the suction operation is divided according to the mixture ratio of the first and second solvents to be mixed, thereby determining the suction volume V1 of the first solvent from the completion of depressurization to the time the solvents are switched (step 19).

[0064] Next, the value of k is set to 1 (step 20), and the movement distance of the plunger when the stepping motor 26 is rotated by k pulses (1 pulse at this point, since k=1), from the position at the completion of decompression, is calculated based on the cam profile (step 21). Then, the change in the volume inside the pump, ΔV, when the plunger is moved by this movement distance from the position at the completion of decompression is calculated. mk(Step 22). mk If ΔV is smaller than the amount of suction of the first solvent V1 (NO in step 23), the value of k is increased by 1 (step 24), and the operations of steps 21 to 23 are performed again. mk If V is equal to or greater than V1 (YES in step 23), this means that the timing for switching the solvent is when the stepping motor 26 has rotated k pulses from the completion of depressurization. Therefore, the timing for switching the solvent is set to when the stepping motor 26 has rotated k pulses from the completion of depressurization (step 25). This completes the series of operations.

[0065] The present invention is not limited to the above-described embodiment, and various modifications are possible within the scope of the present invention.

[0066] For example, while the above-described embodiments use a pump unit 20 in which a first pump 21 and a second pump 22 are connected in series, a pump unit 30 in which a first pump 31 and a second pump 32 are connected in parallel may be used instead, as shown in FIG. 8 . When the pumps are connected in parallel in this manner, a first check valve 331 and a second check valve 332 are provided corresponding to the first suction port 311 and the first discharge port 312 of the first pump 31, respectively, and a third check valve 333 and a fourth check valve 334 are provided corresponding to the second suction port 321 and the second discharge port 322 of the second pump 32, respectively. Furthermore, the first pump 31 and the second pump 32 each include a first cylinder 313 and a second cylinder 323, and a first plunger 314 and a second plunger 324, similar to the first pump 21 and the second pump 22 in the above-described embodiments. Although the first pump 31 and the second pump 32 are both entirely made of resin, a pump in which the portion in contact with the mobile phase is made of resin and the other portions are made of metal may also be used. In this modification, since the fourth check valve 334 is provided not only in the first pump 31 but also in the second pump 32, pre-pressurization is performed before discharging the mobile phase. As in the first embodiment, the timing of pre-pressurization of the second pump 32 can be determined based on equation (2) taking into account the change in capacity of each pump due to a change in pressure, αΔP, and the compressibility of the mobile phase, β. The same applies to the first pump 31. The shapes of the first cam 351 and the second cam 352 are determined appropriately depending on the operation of the pumps when connected in parallel. Low-pressure gradient control conduct In this case, as in the second embodiment, the change amount α of the displacement of each pump due to the change in pressure is m ΔP m and the compressibility of the solvent in the pump β m The completion time of decompression can be determined by taking into consideration the above.

[0067] [Note] It will be understood by those skilled in the art that the exemplary embodiments described above are specific examples of the following additional aspects.

[0068] (Section 1) The liquid chromatograph according to claim 1 is a liquid chromatograph including a liquid delivery unit that delivers a mobile phase in a reservoir to a column through a liquid delivery tube at a predetermined pressure, The liquid delivery unit is a pump having a pump chamber, a plunger that reciprocates within the pump chamber, a suction port that is provided in the pump chamber and connected to the reservoir, and a discharge port that is provided in the pump chamber and connected to the liquid feed pipe directly or via another pump; a check valve connected to the discharge port; an input unit for inputting information regarding the compressibility of the mobile phase and the amount of change in the volume of the pump chamber due to a change in the pressure in the pump chamber; a pressure application control unit that controls the plunger based on the information input by the input unit so that a pressure applied to the mobile phase in the pump chamber becomes a check valve opening pressure that opens the check valve before the mobile phase sucked through the suction port is discharged from the discharge port; and Equipped with.

[0069] The pressure of the mobile phase in the pump chamber actually depends not only on the compressibility of the mobile phase, but also on the volume of the pump chamber, which changes as the pump chamber wall compresses with applied pressure. The change in volume of the pump chamber depends on the material of the pump chamber wall. If the material is metal, the change is negligible, but if the material is easily deformed by compression, such as resin, the change cannot be ignored. Therefore, in the liquid chromatograph described in paragraph 1, the plunger is controlled based on the change in volume of the pump chamber caused by changes in pressure, as well as the compressibility of the mobile phase, so that the pressure applied to the mobile phase in the pump chamber before it is drawn in through the intake port and discharged from the outlet port is equal to the check valve opening pressure. The plunger can be controlled by adjusting the plunger's position and movement speed over time, and the change in volume of the pump chamber can be determined through preliminary experiments, etc. By controlling the plunger in this way, the mobile phase in the pump chamber is at a pressure sufficient to open the check valve when it is discharged from the outlet port, allowing the mobile phase to be discharged from the pump at the appropriate time.

[0070] Furthermore, the operator uses the input unit to input information regarding the compressibility of the mobile phase and the amount of change in the volume of the pump chamber caused by components such as the walls of the pump chamber being compressed as the pressure in the pump chamber changes.Based on this information, the pressure application control unit controls the pressure, i.e., the pressure applied to the mobile phase in the pump.Therefore, even if the compressibility of the mobile phase or the amount of change in the volume of the pump chamber changes due to changing the mobile phase used or replacing the pump, appropriate pressure control can be performed.

[0071] The liquid chromatograph according to paragraph 1 can be applied to both parallel-connected and serial-connected liquid delivery units. In the case of a parallel-connected type, both of the two pumps correspond to the "pump" in paragraph 1 (as well as paragraphs 2 and 3). In this case, a check valve is connected to the suction port and discharge port of each of the two pumps, and the pressure of each of the two pumps is controlled by a pressure application control unit. In the case of a serial-connected type, the upstream pump of the two pumps corresponds to the "pump" in paragraph 1 (as well as paragraphs 2 and 3). In this case, a check valve is connected to the suction port and discharge port of the upstream pump, and the pressure of that pump is controlled by a pressure application control unit, but no check valve is connected to either the suction port or discharge port of the downstream pump.

[0072] (Section 2) A liquid chromatograph according to a second aspect is the liquid chromatograph according to the first aspect, wherein the information relating to the amount of change is information relating to the amount of deformation of a material used in the pump chamber.

[0073] According to the liquid chromatograph according to the second aspect, even if the amount of deformation differs due to differences in the materials used in the pump chamber, the pressure can be appropriately controlled.

[0074] (Section 3) The liquid chromatograph according to paragraph 3 is a liquid chromatograph according to paragraph 1 or 2, the pump further comprising: a cam that converts rotational motion into reciprocating motion of the plunger; a rotation mechanism that rotates the cam; Equipped with When the check valve opening rotation angle, which is the rotation angle of the cam when the pressure reaches the check valve opening pressure, is smaller than a predetermined reference rotation angle, the pressure application control unit controls to reduce the rotation speed of the cam from the check valve opening rotation angle to the reference rotation angle, and when the check valve opening rotation angle is larger than the reference rotation angle, to increase the rotation speed of the cam from the reference rotation angle to the check valve opening rotation angle.

[0075] In the liquid chromatograph according to paragraph 3, when the check valve opening rotation angle is smaller than the reference rotation angle, pre-pressurization is completed early and mobile phase is discharged simultaneously from the pre-pressurized pump and the other pumps. Therefore, by reducing the cam rotation speed, the supply of mobile phase at an excessive flow rate is prevented. On the other hand, when the check valve opening rotation angle is larger than the reference rotation angle, the completion of pre-pressurization is delayed at the current rotation speed. Therefore, the cam rotation speed is increased so that the check valve opening rotation angle is reached more quickly. By controlling the cam rotation speed in this way, mobile phase can be supplied with appropriate pre-pressurization timing and discharge rate, even if the check valve opening rotation angle changes depending on the compressibility of the mobile phase and the compression amount of the pump inner wall.

[0076] (Section 4) A liquid chromatograph according to claim 4 is a liquid chromatograph equipped with a liquid delivery unit that delivers a mobile phase, which is a mixture of multiple solvents having different components, to a column through a liquid delivery tube at a predetermined pressure, The liquid delivery unit is a solvent supply unit including a plurality of solvent supply flow paths and a switching mechanism for selectively switching one of the plurality of solvent supply flow paths to another; a pump chamber, a plunger that reciprocates within the pump chamber, and a Solvent Supply a pump having a suction port connected to the pump chamber and a discharge port provided in the pump chamber and connected to the liquid supply pipe directly or via another pump; an input unit for inputting information regarding the compressibility of the mobile phase and the amount of change in the volume of the pump chamber due to a change in the pressure in the pump chamber; a flow path switching control unit that controls the timing of switching the solvent supply flow path by the switching mechanism based on the information input by the input unit; Equipped with.

[0077] If the volume changes due to a change in pressure in the pump chamber during low-pressure gradient control, the timing at which depressurization is completed and the solvent can be aspirated changes compared to when no change in volume occurs. Therefore, if the solvent introduced into the pump chamber is switched without considering this change in the timing at which depressurization is completed, the actual mixing ratio will deviate from the target value. Therefore, in the liquid chromatograph according to paragraph 4, the timing at which the switching mechanism switches the solvent supply flow path is controlled based on the change in the volume of the pump chamber due to a change in pressure in the pump chamber, in addition to the compressibility of the solvent in the pump chamber. This makes it possible to determine the timing at which the solvent supply flow path is switched in response to the change in the timing at which depressurization is completed, thereby allowing multiple solvents to be mixed at the target mixing ratio.

[0078] Also, 4 In the liquid chromatograph according to paragraph 1, as in the liquid chromatograph according to paragraph 1, even if the compressibility of the solvent or the volume of the pump chamber changes due to a change in the solvent used or replacement of the pump, the timing of switching the solvent supply flow path can be appropriately controlled. [Explanation of symbols]

[0079] 1, 4... Liquid chromatograph 11...Storage tank 12...liquid supply pipe 121...First liquid supply pipe 122...Second liquid supply pipe 123...Third liquid supply pipe 13...Sample injection section (injector) 14...Column 15...Detector 20, 30... Pump unit (liquid delivery unit in the first embodiment) 21, 31...First pump 211, 311...1st suction port 212, 312...1st discharge port 213, 313...First cylinder (first pump chamber) 214, 314...First plunger 22, 32...Second pump 221, 321...Second suction port 222, 322...Second discharge port 223, 323...Second cylinder (second pump chamber) 224, 324...Second plunger 231, 331...First check valve 232, 332...Second check valve 24...Camshaft 251, 351...1st cam 252, 352...Second cam 26...Stepping motor 27...Control unit 28...Input section 29...Display section 333...Third check valve 334...Fourth check valve 40... Liquid delivery unit 411...First storage section 412...Second storage Department 4 2...Solvent supply section 4221...First supply flow path (one of multiple solvent supply flow paths) 4222...Second supply flow path (same as above) 423...Switching valve 424...Switching control unit 46...Mixer 51, 52, 53...Rotation angle when preload is complete (Rotation angle when check valve is open)

Claims

1. A liquid chromatograph including a liquid delivery unit that delivers a mobile phase in a reservoir to a column through a liquid delivery tube at a predetermined pressure, The liquid delivery unit a pump having a pump chamber, a plunger that reciprocates within the pump chamber, a suction port that is provided in the pump chamber and connected to the reservoir, and a discharge port that is provided in the pump chamber and connected to the liquid feed pipe directly or via another pump; a check valve connected to the discharge port; an input unit for inputting information regarding the compressibility of the mobile phase and the amount of change in the volume of the pump chamber due to a change in the pressure in the pump chamber; a pressure application control unit that controls the plunger based on the information input by the input unit so that a pressure applied to the mobile phase in the pump chamber becomes a check valve opening pressure that opens the check valve before the mobile phase sucked through the suction port is discharged from the discharge port; and A liquid chromatograph comprising:

2. 2. The liquid chromatograph according to claim 1, wherein the information about the amount of change is information about the amount of deformation of a material used in the pump chamber.

3. the pump further comprising: a cam that converts rotational motion into reciprocating motion of the plunger; a rotation mechanism that rotates the cam; Equipped with the pressure application control unit controls to reduce the rotation speed of the cam from the check valve opening rotation angle to the reference rotation angle when the check valve opening rotation angle, which is the rotation angle of the cam when the pressure reaches the check valve opening pressure, is smaller than a predetermined reference rotation angle, and controls to increase the rotation speed of the cam from the reference rotation angle to the check valve opening rotation angle when the check valve opening rotation angle is larger than the reference rotation angle.

3. The liquid chromatograph according to claim 1 or 2.

4. A liquid chromatograph having a liquid delivery unit that delivers a mobile phase, which is a mixture of a plurality of solvents having different components, to a column through a liquid delivery tube at a predetermined pressure, The liquid delivery unit is a solvent supply unit including a plurality of solvent supply flow paths and a switching mechanism for selectively switching one of the plurality of solvent supply flow paths to another; a pump having a pump chamber, a plunger reciprocating within the pump chamber, a suction port provided in the pump chamber and connected to the solvent supply unit, and a discharge port provided in the pump chamber and connected to the liquid delivery pipe directly or via another pump; an input unit for inputting information regarding the compressibility of the solvent in the pump chamber and the amount of change in the volume of the pump chamber due to a change in the pressure in the pump chamber; a flow path switching control unit that controls the timing of switching the solvent supply flow path by the switching mechanism based on the information input by the input unit; A liquid chromatograph comprising:

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