Liquid delivery device and liquid delivery method

Abstract

A liquid delivery device capable of delivering liquids with high precision is provided. It comprises: a delivery unit (104) having cylinders (205, 206) for solvent intake and discharge via sliding plungers (207, 208); a pressure sensor (217) disposed downstream of the delivery unit (104) for detecting the pressure of the discharged solvent; switching valves (102a-102d) for switching between intake and discharge of multiple solvents; and a control unit (218) for controlling the operation of the delivery unit (104) and the switching valves (102a-102d). The control unit (218) synchronously controls the operation of the switching valves (102a-102d) with the intake action of the plungers (207, 208) to change the mixing ratio of the multiple solvents and controls the plungers (207, 208) to operate with at least two different accelerations (a first acceleration and a second acceleration) to suppress the oscillation of the solvent intakeed by the plungers (207, 208).

Description

Technical Field

[0001] This invention relates to a liquid delivery device and a liquid delivery method. Background Technology

[0002] As a liquid delivery device, it is used, for example, in a liquid chromatograph (LC). A liquid chromatograph is a chromatograph that uses a liquid as the mobile phase to deliver the sample to be measured. It consists of a liquid delivery device that delivers the solvent that becomes the mobile phase, an injection device that introduces the sample into the analytical flow path, a chromatographic column that separates the sample into structural components, and a detection device for detecting the separated components.

[0003] The separation column for separating the test sample is filled with a stationary phase containing a packing agent with physical or chemical properties. The difference in affinity between the stationary phase of the separation column and the mobile phase delivered by the liquid delivery device is used to separate the test sample by each component. The separated components are detected by detectors such as ultraviolet / visible spectrophotometer, fluorescence spectrophotometer, and mass spectrometer.

[0004] Liquid chromatograph outputs data as peak values ​​representing the relationship between the separation time (holding time) of the sample and the intensity of the detector signal. The holding time is the time of the peak. If the analytical conditions are the same, the value is approximately the same for each sample component, and therefore it is used as information for identifying the separated components.

[0005] In addition, when multiple components are involved, the separation degree is calculated based on the retention time between components, and is sometimes used as an indicator of separation performance.

[0006] In order to adjust the elution time of the sample and thus improve the separation time and resolution, analytical methods such as gradient elution are often used.

[0007] Gradient elution involves changing the composition ratio of the mobile phase delivered from the liquid delivery device over time while simultaneously delivering it to the analytical flow path and separation column. By altering the affinity between the stationary phase and the mobile phase (i.e., the solvent), the separation performance and separation time of the sample components can be adjusted.

[0008] In methods for implementing gradient elution, there are low-pressure gradient mixing methods where multiple mobile phases are mixed upstream of a single delivery device, and high-pressure gradient mixing methods where different mobile phases are delivered by two delivery devices, and the mobile phases are merged / mixed downstream of the delivery devices. Regarding these gradient mixing methods, based on their differences in characteristics, low-pressure gradient mixing is used when adjusting the composition of the mobile phase from multiple mobile phases, while high-pressure gradient mixing is used when it is desired to change the composition of two mobile phases with the earliest possible response.

[0009] In the low-pressure gradient mixing method, it is known that by opening and closing a switching valve, which is connected to each mobile phase and is called a proportional valve, in sync with the aspiration process of the liquid delivery device, a specified volume of mobile phase is drawn from multiple mobile phases and delivered, thereby achieving arbitrary concentration composition. The opening and closing control of the switching valve will affect the performance of the gradient elution method and the composition performance of the mixing ratio of the mobile phase.

[0010] Patent document 1 discloses the action control of the plunger in the opening and closing action range of the switching valve. In order to reduce the influence of the deviation in the opening and closing action time of the switching valve, a method is proposed to reduce the action speed of the plunger that draws in the mobile phase or to stop the plunger in the range of the switching valve's opening and closing action.

[0011] Existing technical documents

[0012] Patent documents

[0013] Patent Document 1

[0014] Japanese Patent No. 5879280 Summary of the Invention

[0015] The problem that the invention aims to solve

[0016] As described in Patent Document 1, in order to reduce the deviation of the mixing composition of the mobile phase when using a low-pressure gradient mixing method and improve accuracy, it is considered important to improve the accuracy of the opening and closing control of the switching valve so that the opening and closing timing of the switching valve, which has been adjusted to supply the mobile phase to the cylinder, is consistent with the timing of the mobile phase being drawn in.

[0017] On the other hand, it is known that in the method of opening and closing the switching valve during the cylinder's suction action, there are often problems such as the pumping effect of the mobile phase moving back and forth due to the opening and closing action of the switching valve, or the time when the mobile phase is temporarily not flowing, which affect the accuracy of the mixing ratio. There are also problems that cannot be improved by controlling the opening and closing of the switching valve alone.

[0018] In addition, as one way to improve the correctness of the switching valve's operation, improving the driving performance of the switching valve in order to improve the mechanical opening and closing time can also be considered a method. However, it is actually difficult to completely eliminate mechanical deviations, and it also has the disadvantage of increased costs due to the performance verification and sorting of the switching valve.

[0019] Furthermore, based on microfluidic simulations and experimental results with altered switching valve timing, it was confirmed that even when the switching valve is opened and closed after the stop plunger for each pumped mobile phase, the pumped mobile phase takes a certain amount of time to completely stop due to the stop of the plunger, and may flow into the cylinder after the plunger stops, or may fail to pump the correct volume due to the resulting oscillation.

[0020] The purpose of this invention is to provide a liquid delivery device and method capable of delivering liquids with high precision.

[0021] Methods for solving problems

[0022] To achieve the above objectives, the present invention is configured as follows.

[0023] The liquid delivery device comprises: a delivery section having a cylinder for drawing in and discharging solvent by sliding a plunger; a pressure sensor disposed downstream of the delivery section for detecting the pressure of the discharged solvent; at least one switching valve for switching between drawing in and discharging multiple solvents; and a control section for controlling the operation of the delivery section and the switching valve, wherein the control section controls the operation of the switching valve synchronously with the drawing in action of the plunger, thereby changing the mixing ratio of the multiple solvents, and controls the plunger to operate with at least two different accelerations, namely a first acceleration and a second acceleration, to suppress the oscillation of the solvent drawn in by the plunger.

[0024] A liquid delivery method for a liquid delivery device, the liquid delivery device comprising: a delivery section having a cylinder for performing solvent suction and discharge actions by sliding a plunger; a pressure sensor disposed downstream of the delivery section for detecting the pressure of the discharged solvent; at least one switching valve for switching between suction and discharge of a plurality of solvents; and a control section for controlling the operation of the delivery section and the switching valve, wherein in the liquid delivery method of the liquid delivery device, the switching valve is activated synchronously with the suction action of the plunger, thereby changing the mixing ratio of the plurality of solvents.

[0025] Invention Effects

[0026] According to the present invention, a liquid delivery device and a liquid delivery method capable of delivering liquid with high precision can be realized. Attached Figure Description

[0027] Figure 1 This is a schematic structural diagram of a liquid chromatography apparatus using the liquid delivery device of Example 1.

[0028] Figure 2 express Figure 1 The internal structure of the delivery section is shown.

[0029] Figure 3 This is a schematic diagram illustrating the plunger speed and the opening and closing timing of the switching valve in a liquid delivery device with a low-pressure gradient mixing method, which is an example different from the present invention.

[0030] Figure 4 This describes the pulsation of the mobile phase generated in an absorption process that differs from that of the present invention.

[0031] Figure 5This is a schematic diagram of the plunger speed and the opening and closing timing of the switching valve in the liquid delivery device with low-pressure gradient mixing mode according to Embodiment 1 of the present invention.

[0032] Figure 6 This is a schematic diagram of the plunger speed and the opening and closing timing of the switching valve in the liquid delivery device with low-pressure gradient mixing mode according to Embodiment 2 of the present invention.

[0033] Figure 7 This is a schematic diagram of the plunger speed and the opening and closing timing of the switching valve in the liquid delivery device with low-pressure gradient mixing mode according to Embodiment 3 of the present invention. Detailed Implementation

[0034] The following describes the liquid delivery device and delivery method for a liquid chromatography apparatus with a low-pressure gradient system according to the present invention.

[0035] This invention is not limited to the embodiments. For example, it can be applied regardless of the type and number of switching valves used as proportional valves, or the type of liquid delivery device that connects the cylinders of the liquid delivery device in series or in parallel. This invention can be applied within the scope of its technical concept.

[0036] [Example]

[0037] (Example 1)

[0038] Figure 1 This is a schematic structural diagram of a liquid chromatography apparatus that uses the liquid delivery device of Embodiment 1. Figure 1 The liquid chromatography apparatus shown has a low-pressure gradient delivery device that can deliver one or more mobile phases (solvents) in a low-pressure gradient mixing manner by a single delivery device 105.

[0039] The liquid chromatography apparatus includes: a liquid delivery device 105 having a delivery section (liquid delivery section) 104, which draws in multiple mobile phases 10101a, 101b, 101c, and 101d used in sample delivery and separation, compresses them under high pressure, and discharges them; a sample introduction device 106; a separation column 107 connected to the downstream side of the sample introduction device 106 via a flow path, which separates the analyte sample introduced from the sample introduction device 106 into individual components; a column temperature control device 108 that houses the separation column 107 and controls it to a constant temperature; and a detection device 109 connected to the downstream side of the column temperature control device 108 for detecting the individual components of the separated sample.

[0040] Furthermore, the liquid delivery device 105 is connected to multiple mobile phases 101a to 101d respectively, and has switching valves 102a, 102b, 102c, and 102d for switching multiple mobile phases and a confluence point 103 for each mobile phase.

[0041] In addition, although Figure 1Although not shown, the liquid delivery device 105 has a control unit (control section) 218. The liquid delivery device 105 is a liquid delivery device for low-pressure gradient applications.

[0042] Figure 2 express Figure 1 The internal structure of the output section 104 shown.

[0043] Figure 2 The delivery section 104 shown is an example of a delivery section in a low-pressure gradient liquid delivery device. It is a series-type device in which two cylinders, a first cylinder 205 and a second cylinder 206, which are responsible for the absorption and delivery of the mobile phase by sliding reciprocating motion of plungers 207 and 208, are connected in series.

[0044] exist Figure 2 In this process, linear motion mechanisms 213 and 214, which convert rotary motion into linear motion, are connected to motors 215 and 216. Plungers 207 and 208, fixed to the linear motion mechanisms 213 and 214, reciprocate repeatedly within the first cylinder 205 and the second cylinder 206, which are sealed by seals 211 and 212. As a result, the delivery section 104 draws in and delivers the mobile phases 101a to 101d.

[0045] Check valves 209 and 210, used to restrict the flow direction of mobile phases 101a to 101d, are connected to the first cylinder 205. A pressure sensor 217, used to detect the pressure of the discharged mobile phase, is installed downstream of the second cylinder 206. The control unit 218 adjusts the motor speeds of motors 215 and 216 based on the discharge pressure detected by the pressure sensor 217 and the set discharge flow rate, thereby discharging the mobile phases 101a to 101d.

[0046] In a low-pressure gradient mixing method in which the mixing ratio of multiple mobile phases 101a to 101d changes over time, during the process of the first cylinder 205 drawing in mobile phases 101a to 101d, the set arbitrary mixing ratio is achieved by switching the opening and closing states of switching valves 102a to 102d connected to mobile phases 101a to 101d.

[0047] If the suction process of mobile phases 101a to 101d begins, the plunger 207 begins suction operation along with the linear motion mechanism 213, which is operated by the motor 215, and the pressure in the first cylinder 205 is reduced from the delivery pressure to atmospheric pressure. As a result, the closed suction-side check valve 209 opens, and the mobile phases 101a to 101d begin to be drawn into the first cylinder 205.

[0048] The control unit 218 determines the opening and closing timing and opening and closing time of the switching valves 102a to 102d according to the set mixing ratio of the flowing phases 101a to 101d, and switches the opening and closing states of the switching valves 102a to 102d according to the determined results.

[0049] Thus, the mobile phase is drawn into the first cylinder 205 in a manner that achieves any mixing ratio.

[0050] The drawn-in mobile phases 101a to 101d flow into the first cylinder 205 via the confluence point 103. When the drawing-in process of mobile phases 101a to 101d is completed, the first cylinder 205 begins the compression process of compressing mobile phases 101a to 101d to the delivery pressure.

[0051] Then, when the pressure of the mobile phases 101a to 101d in the first cylinder 205 reaches the delivery pressure detected by the pressure sensor 217, the discharge side check valve 210 opens, and the delivery process of the mobile phases 101a to 101d in the first cylinder 205 begins.

[0052] The plunger 208 in the second cylinder 206 actuates to supplement the operation of the first cylinder 205. While the first cylinder 205 is in the intake process of the mobile phases 101a to 101d and the compression process of the mobile phases 101a to 101d up to the delivery pressure, the second cylinder 206 is responsible for the delivery process. When the first cylinder 205 starts delivering the mobile phases 101a to 101d, the second cylinder 206 becomes idle until the mobile phases 101a to 101d are filled into the second cylinder 206 and the next cycle of delivery begins.

[0053] Figure 3 This is a schematic diagram illustrating the plunger speed and the opening and closing timing of the switching valve in a liquid delivery device with a low-pressure gradient mixing method, which is an example different from the present invention.

[0054] exist Figure 3 In the process, switching valve A changes from the closed state to the open state, and then closes after a certain period of time. Next, switching valve B changes from the closed state to the open state, and then closes after a certain period of time. Switching valve C changes from the closed state to the open state, and then closes after a certain period of time. Switching valve D remains closed.

[0055] exist Figure 3 In the liquid delivery device shown, which differs from the present invention, during the suction process of the plunger that suctions the mobile phase at a constant speed, the opening and closing states of switching valves A, B, C, and D are switched according to a set mixing ratio. Thus, the mobile phase corresponding to the set mixing ratio is suctioned into the cylinder.

[0056] Figure 4This describes the pulsation (oscillation) of the mobile phase generated in an absorption process that differs from that of the present invention. Figure 4 The waveforms shown represent the plunger's operating speed during mobile phase absorption, the change in solvent flow rate during absorption, and the switching timing of the switching valve, all obtained from microfluidic simulation.

[0057] exist Figure 4 In the process, as the switching valve changes from closed to open, the plunger is accelerated and moves, and when it reaches a constant speed, the flowing phase oscillates. Furthermore, as the plunger decelerates from the constant speed and comes to a stop, the flowing phase also oscillates. Since the absolute values ​​of the plunger's acceleration and deceleration are approximately the same, they produce equal oscillations in the flowing phase.

[0058] Large oscillations in the mobile phase can affect the accuracy of the gradient mixing ratio.

[0059] Figure 5 This is a schematic diagram of the plunger speed and the opening and closing timing of switching valves 102a, 102b, 102c, and 102d in the liquid delivery device with a low-pressure gradient mixing method according to Embodiment 1 of the present invention.

[0060] exist Figure 5 In this process, when the suction process of each flow phase 101a, 101b, 101c, and 101d begins, the control unit 218 synchronously controls the switching valves 102a, 102b, 102c, and 102d to open them. After sufficient standby time required for the switching valves 102a, 102b, 102c, and 102d to be fully opened, the suction action of the plungers 207 and 208 begins. When the suction process of each flow phase 101a, 101b, 101c, and 101d ends, the plunger action speed is decelerated by an acceleration below a certain value, thereby stopping the suction action.

[0061] Then, after plungers 207 and 208 have completely stopped, object switching valves 102a, 102b, 102c, and 102d are closed. When the next switching valve 102a, 102b, 102c, or 102d is to be opened, object switching valves 102a, 102b, 102c, and 102d are opened, and the mobile phase is drawn in through the same process.

[0062] Figure 5 A, B, C, and D represent switching valves 102a, 102b, 102c, and 102d, respectively.

[0063] Figure 5 The movement control of the plungers 207 and 208 shown is performed by the control unit 218.

[0064] exist Figure 5In the process, from time point t0 to time point t1, switching valve A changes from the closed state to the open state. Then, from time point t1 to time point t2, plunger 207 or 208 moves while accelerating, reaching a constant speed. This acceleration is set as the first acceleration.

[0065] Next, the vehicle moves while decelerating from time point t3 to time point t4, and then stops. The acceleration at this point is designated as the second acceleration. In this case, due to the deceleration of plunger 207 or 208, the second acceleration becomes a negative acceleration. Therefore, the second acceleration is synonymous with deceleration.

[0066] The time from time point t1 to time point t2 for the first acceleration is shorter than the time from time point t3 to time point t4 for the second acceleration. That is, the absolute value of the first acceleration is greater than the absolute value of the second acceleration. Figure 5 As shown, the tilt angle of the first acceleration is larger than the tilt angle of the second acceleration. Preferably, the tilt angle of the second acceleration is approximately half the tilt angle of the first acceleration.

[0067] By reducing the deceleration of plungers 207 and 208, the oscillation that occurs when plungers 207 and 208 stop can be suppressed. This, in turn, suppresses the impact on the accuracy of the gradient mixing ratio.

[0068] Next, the actions of switching valve A and plunger 207 or 208 are used to switch valves B and C and plunger 207 or 208. Switching valve C remains closed.

[0069] The switching valve C operates in the same way as switching valves A and B, with plunger 207 or 208 changing from a constant speed to a second acceleration instead of a constant speed.

[0070] The action of drawing in is followed by the action of ejecting, but detailed explanations are omitted.

[0071] According to Embodiment 1 of the present invention, when repeatedly performing the suction and stopping actions of the plungers 207 and 208 on each mobile phase, more accurate suction of the mobile phase can be achieved by setting the acceleration in a manner that does not produce oscillation of the mobile phase.

[0072] Furthermore, even if the suction operation is not stopped according to the switching of the mobile phase, as in the prior art, the acceleration of the plungers 207 and 208 can be set at the end of the final suction process in a way that prevents the mobile phase from oscillating, so that the mobile phase sucked in during the second half of the suction process can be accurately sucked up.

[0073] That is, according to Embodiment 1 of the present invention, a liquid delivery device and a liquid delivery method capable of delivering liquid with high precision can be realized.

[0074] Furthermore, according to Embodiment 1 of the present invention, a liquid chromatography apparatus having a liquid delivery device capable of delivering liquid with high precision can be realized.

[0075] (Example 2)

[0076] Next, Example 2 will be described.

[0077] Example 2 is similar to Example 1, and is an example of a low-pressure gradient liquid delivery device using a low-pressure gradient mixing method.

[0078] In addition, in Example 2, similarly to Example 1, when the suction process of each mobile phase begins, the switching valve to be targeted is opened, and after sufficient standby time required until the switching valve is fully open, the plunger suction operation begins.

[0079] Then, at the end of the suction process of each mobile phase, in order to shorten the time until the plunger stops, the acceleration is changed in stages or continuously, and finally the plunger's operating speed is reduced to a certain value below the acceleration, thereby stopping the suction operation.

[0080] Then, close the object switching valve after the plunger has completely stopped. When the next switching valve to be opened is available, open the object switching valve and perform the same process to draw in the mobile phase.

[0081] The liquid chromatography apparatus and liquid delivery device of Application Example 2 have the same structure as those of Example 1, therefore, the illustrations and detailed descriptions are omitted.

[0082] The difference between Example 2 and Example 1 is the acceleration of the plungers 207 and 208.

[0083] Figure 6 This is a schematic diagram of the plunger speed and the opening and closing timing of switching valves 102a, 102b, 102c, and 102d in the liquid delivery device with low-pressure gradient mixing mode according to Embodiment 2 of the present invention.

[0084] exist Figure 6 In the process, the action of plunger 207 or 208 from time point t0 to time point t3 becomes related to... Figure 5 The example shown is the same action.

[0085] In Example 2, plunger 207 or 208 travels from time point t3 to time point t4. 31 Moving with a third acceleration, from time point t 31 At time t4, the vehicle moves with the same second acceleration as in Example 1. Because plunger 207 or 208 decelerates, the third acceleration becomes negative. The absolute value of the third acceleration is greater than the absolute value of the second acceleration.

[0086] That is, to cause the plunger 207 or 208 to decelerate in stages.

[0087] The action of plunger 207 or 208 in the opening and closing action of switching valve B is the same as that of plunger 207 or 208 in the opening and closing action of switching valve A.

[0088] Next, the operation of plunger 207 or 208 in the opening and closing action of switching valve C will be explained.

[0089] Actions from time point t5 to time point t6 and Figure 5 The example is similar. From time point t6 to time point t7, plunger 207 or 208 moves with a third acceleration, and from time point t7 to time point t8, it moves with a second acceleration. There are states where plunger 207 or 208 decelerates, and the second and third accelerations become negative. Therefore, the second and third accelerations can also be defined as the second and third decelerations.

[0090] According to Example 2, in addition to achieving the same effects as in Example 1, the following effects can also be obtained.

[0091] That is, Example 2 is an example of changing the deceleration of plunger 207 or 208 in stages. The deceleration of plunger 207 or 208 at the beginning of deceleration is set to be large. When the speed of plunger 207 or 208 becomes below a certain value, by reducing the deceleration, the oscillation of the flowing phase when plunger 207 or 208 stops can be suppressed. Compared with the case of Example 1, the time required for plunger 207 or 208 to stop can be shortened. In the flowing phase suction process with time constraints, the opening and closing time of the switching valve can be appropriately determined.

[0092] (Example 3)

[0093] Next, Example 3 will be described.

[0094] Example 3, like Examples 1 and 2, is an example of a low-pressure gradient liquid delivery device using a low-pressure gradient mixing method.

[0095] In addition, in Example 3, similarly to Example 1 and Example 2, when the suction process of each mobile phase is started, the switching valve to be targeted is opened, and after sufficient standby time required until the switching valve is fully open, the suction action of the plunger is started.

[0096] Furthermore, at the end of the suction process of each mobile phase, in order to shorten the time until the plunger stops, the acceleration is changed in stages or continuously, and finally the plunger speed is reduced to an acceleration below a certain value, thereby stopping the suction operation.

[0097] Then, close the object switching valve after the plunger has completely stopped. When the next switching valve to be opened is available, open the object switching valve and perform the same process to draw in the mobile phase.

[0098] The liquid chromatography apparatus and liquid delivery device used in Example 3 have the same structure as those in Example 1, therefore, illustrations and detailed descriptions are omitted.

[0099] Similar to Example 2, in Example 3, the acceleration of the plunger 207 or 208 varies with a first acceleration, a second acceleration, and a third acceleration.

[0100] The difference between Example 3 and Example 2 is the setting time of the acceleration of the plungers 207 and 208.

[0101] In Example 3, under the control of the control unit 218 of the liquid delivery device 105 with a low-pressure gradient mixing mode, when the aspiration process of each mobile phase 101a, 101b, 101c, 101d is started, the switching valve that is targeted in the switching valves 102a, 102b, 102c, 102d is opened. After sufficient standby time required until the switching valve is fully open, the aspiration operation of the plunger 207 or 208 is started.

[0102] Furthermore, regarding the operating speed of plungers 207 or 208, based on the opening and closing times of switching valves 102a, 102b, 102c, and 102d calculated according to the mixing ratio of each flowing phase 101a, 101b, 101c, and 101d, the operating speed of plungers 207 or 208 is set faster when the mixing ratio is high (= large suction volume) and slower when the mixing ratio is low (= small suction volume).

[0103] Furthermore, at the end of the suction process for each mobile phase 101a, 101b, 101c, and 101d, in order to shorten the time until plunger 207 or 208 stops, the acceleration is varied in stages or continuously, ultimately reducing the operating speed of plunger 207 or 208 to below a certain acceleration value, thereby stopping the suction operation. After plunger 207 or 208 has completely stopped, the target switching valve in switching valves 102a, 102b, 102c, and 102d is closed. When the next switching valve to be opened is available, the target switching valve is opened, and the suction of the mobile phase is performed in the same manner.

[0104] Figure 7 This is a schematic diagram of the plunger action speed and the opening and closing timing of switching valves 102a, 102b, 102c, and 102d in the liquid delivery device with low-pressure gradient mixing mode according to Embodiment 3 of the present invention.

[0105] exist Figure 7In the middle, the time from time point t1 to time point t2 is set to be more than Figure 6 The example is long, and the time from time point t2 to time point t3 is set more than... Figure 6 The example is shorter. Also, the time frame from t5 to t6 is set shorter than... Figure 6 The example is short, from time point t6 to time point t. 61 The range of constant operating speed for plunger 207 or 208 is set.

[0106] like Figure 7 As shown, the suction speed of plunger 207 or 208 is set according to the mixing ratio, and the acceleration of plunger 207 or 208 during deceleration is changed in stages. Moreover, the acceleration (third acceleration) at the beginning of deceleration of plunger 207 or 208 is set to be large, the operating speed of plunger 207 or 208 becomes below a certain value, and then the acceleration is reduced to the second acceleration.

[0107] That is, in Examples 1 and 2, the constant speed and the speed at which the first acceleration changes to the second or third acceleration are the same during the absorption action of any of the solvents 101a, 101b, 101c, and 101d. However, in Example 3, the constant speed is changed according to the type of solvent, and the absorption time of the switching valve C is set to a longer period than that in Examples 1 and 2.

[0108] Therefore, even in switching valves with small mixing ratios where sufficient suction time is difficult to ensure in suction processes with time constraints, the opening and closing time can be ensured to take into account the acceleration changes when the plunger stops, thus suppressing the oscillation of the flowing phase when the plunger stops.

[0109] According to Embodiment 3 of the present invention, in addition to achieving the same effects as in Embodiment 2, the aforementioned effects can also be obtained.

[0110] In addition, in embodiments 2 and 3 above, the operating speed of plunger 207 or 208 is set to three accelerations: first acceleration, second acceleration, and third acceleration, but a fourth acceleration can also be set.

[0111] In addition, in embodiments 2 and 3 above, the operating speed of plunger 207 or 208 can be varied in multiple stages of acceleration, but the acceleration curve can also be varied continuously (modified).

[0112] In addition, the above example is configured to have multiple switching valves, but it can also be a structure that uses a single switching valve to switch multiple mobile phases (solvents).

[0113] Explanation of reference numerals in the attached figures

[0114] 101a, 101b, 101c, 101d...Mobile phase; 102a, 102b, 102c, 102d...Switching valves; 103...Merging point; 104...Output section; 105...Liquid delivery device; 106...Sample introduction device; 107...Separation column; 108...Column temperature control device; 109...Detection device; 205...First cylinder; 206...Second cylinder; 207, 208...Plungers; 209...Inhalation side check valve; 210...Discharge side check valve; 211, 212...Seals; 213, 214...Linear motion mechanism; 215, 216...Motor; 217...Pressure sensor; 218...Control unit.

Claims

1. A liquid delivery device, comprising: The liquid delivery section has a cylinder that performs solvent suction and discharge actions by sliding a plunger; A pressure sensor, disposed downstream of the liquid delivery section, detects the pressure of the discharged solvent; At least one switching valve that switches between the aspirated and discharged solvents; and The control unit controls the operation of the liquid delivery unit and the switching valve. Its features are, The control unit synchronously controls the switching valve's operation with the plunger's suction action, causing the mixing ratio of the multiple solvents to change, and controls the plunger to operate with different first, second, and third accelerations to suppress the oscillation of the solvent drawn in by the plunger. The second and third accelerations are negative, while the first acceleration is positive and its absolute value is greater than that of the second acceleration. The absolute value of the third acceleration is also greater than that of the second acceleration. Through the solvent absorption action, after the plunger accelerates with the first acceleration, it decelerates with the third acceleration, and then stops with the second acceleration. The solvent is a plurality of solvents. The control unit determines the absorption volume of each solvent based on the mixing ratio of the plurality of solvents. When the determined absorption volume is large, the operating speed of the plunger that absorbs each solvent is set to be fast. When the determined absorption volume is small, the operating speed of the plunger that absorbs each solvent is set to be slow.

2. The liquid delivery device according to claim 1, characterized in that, The control unit stops the plunger by causing it to change in stages or continuously through the solvent absorption action.

3. The liquid delivery device according to claim 2, characterized in that, The cylinders are multiple.

4. The liquid delivery device according to claim 3, characterized in that, When the control unit opens the switching valve, it sets a sufficient standby time for the opening action to end. After the standby time, it starts the plunger's suction action. When the switching valve is closed at the end of the suction action, it starts the closing action of the switching valve when the plunger's suction action has ended and the plunger has completely stopped.

5. The liquid delivery device according to claim 1, characterized in that, The liquid delivery device is the liquid delivery device of the liquid chromatography apparatus.

6. A liquid delivery method for a liquid delivery device, the liquid delivery device comprising: a delivery section having a cylinder for performing solvent suction and discharge operations by sliding a plunger; a pressure sensor disposed downstream of the delivery section for detecting the pressure of the discharged solvent; at least one switching valve for switching between suction and discharge of a plurality of solvents; and a control section for controlling the operation of the delivery section and the switching valve. Its features are, In the liquid delivery method, the switching valve is activated synchronously with the plunger's suction action, causing a change in the mixing ratio of the multiple solvents. The plunger is actuated with different first, second, and third accelerations to suppress the oscillation of the solvent drawn in by the plunger. The second and third accelerations are negative, while the first acceleration is positive and its absolute value is greater than that of the second acceleration. The absolute value of the third acceleration is also greater than that of the second acceleration. Through the solvent absorption action, after the plunger accelerates with the first acceleration, it decelerates with the third acceleration, and then stops with the second acceleration. The solvent is a plurality of solvents. The control unit determines the absorption volume of each solvent based on the mixing ratio of the plurality of solvents. When the determined absorption volume is large, the operating speed of the plunger that absorbs each solvent is set to be fast. When the determined absorption volume is small, the operating speed of the plunger that absorbs each solvent is set to be slow.

7. The liquid delivery method according to claim 6, characterized in that, The plunger is stopped by the solvent absorption action, which causes the plunger to change in stages or continuously.

8. The liquid delivery method according to claim 7, characterized in that, When the switching valve is opened, a sufficient standby time is set for the opening action to end. After the standby time, the plunger's suction action begins. When the switching valve is closed at the end of the suction action, the closing action of the switching valve begins when the plunger's suction action has ended and the plunger has completely stopped.

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