WO2023218758A1 - Chromatograph liquid delivery system, and chromatograph liquid delivery method - Google Patents

Chromatograph liquid delivery system, and chromatograph liquid delivery method Download PDF

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Publication number
WO2023218758A1
WO2023218758A1 PCT/JP2023/010443 JP2023010443W WO2023218758A1 WO 2023218758 A1 WO2023218758 A1 WO 2023218758A1 JP 2023010443 W JP2023010443 W JP 2023010443W WO 2023218758 A1 WO2023218758 A1 WO 2023218758A1
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Prior art keywords
pressure
unit
liquid feeding
plunger pump
mobile phase
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PCT/JP2023/010443
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French (fr)
Japanese (ja)
Inventor
航太 亀井
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株式会社島津製作所
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Publication of WO2023218758A1 publication Critical patent/WO2023218758A1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/26—Conditioning of the fluid carrier; Flow patterns
    • G01N30/28—Control of physical parameters of the fluid carrier
    • G01N30/32—Control of physical parameters of the fluid carrier of pressure or speed

Definitions

  • the present invention relates to a chromatographic liquid feeding system and a chromatographic liquid feeding method.
  • a liquid delivery system for chromatography is sometimes equipped with a function to detect poor liquid delivery due to the generation of bubbles in the solvent, so that the solvent serving as the mobile phase can be delivered stably.
  • a liquid is continuously fed by a liquid feeding mechanism including two plunger pumps. Further, fluctuations in the liquid feeding pressure within one drive cycle of the liquid feeding mechanism are read.
  • the difference in liquid feeding pressure at the start point and end point of the discharge operation of one plunger pump is determined as the first fluctuation value
  • the difference in the liquid feeding pressure at the start point and end point of the discharge operation of the other plunger pump. is obtained as the second variation value.
  • the fluctuation range of the liquid feeding pressure is calculated based on the first fluctuation value and the second fluctuation value. If the number of consecutive cycles in which the calculated fluctuation range exceeds a predetermined reference value reaches a predetermined reference number, it is detected that a liquid delivery failure has occurred due to air bubbles entering the plunger pump. .
  • An object of the present invention is to provide a chromatographic liquid feeding system and a chromatographic liquid feeding method that can accurately detect liquid feeding defects.
  • One aspect of the present invention includes a liquid sending section that includes one or more plunger pumps and that sends a mobile phase by being driven periodically; a pressure acquisition unit that acquires pressure; a maximum value identification unit that identifies a maximum pressure among the pressures acquired by the pressure acquisition unit for each driving cycle of the liquid feeding unit; and each drive of the liquid feeding unit.
  • a minimum value specifying section that specifies the minimum pressure, the maximum pressure specified by the maximum value specifying section, and the minimum pressure specified by the minimum value specifying section.
  • the present invention relates to a liquid feeding system for chromatography, comprising: a detection unit that detects a liquid feeding failure due to air bubbles being mixed into the one or more plunger pumps based on the pressure of the plunger pump.
  • a liquid feeding unit including one or more plunger pumps periodically drives the mobile phase, and that the liquid feeding unit moves at a plurality of points within each driving cycle. obtaining the phase pressure; identifying the maximum pressure among the obtained pressures for each driving period of the liquid feeding section; and determining the maximum pressure of the obtained pressure for each driving period of the liquid feeding section. Among them, identifying the minimum pressure, and detecting a liquid feeding failure due to the inclusion of air bubbles in the one or more plunger pumps based on the identified maximum pressure and the identified minimum pressure.
  • the present invention relates to a liquid feeding method for chromatography, including:
  • a liquid feeding failure can be accurately detected.
  • FIG. 1 is a diagram showing the configuration of a chromatograph including a liquid feeding system according to an embodiment of the present invention.
  • FIG. 2 is a diagram for explaining the shape characteristics of the cam.
  • FIG. 3 is a diagram showing a change in the pressure of the mobile phase within one driving cycle of the liquid feeding section.
  • FIG. 4 is a diagram showing the configuration of the control section in FIG. 1.
  • FIG. 5 is a flowchart illustrating an example of a liquid feeding failure detection process performed by the control unit in FIG. 4.
  • FIG. 6 is a diagram for explaining a method for detecting liquid feeding failure in a reference example.
  • FIG. 1 is a diagram showing the configuration of a chromatograph including a liquid feeding system according to an embodiment of the present invention. Note that although the chromatograph 200 in this embodiment is a liquid chromatograph, it may be a supercritical fluid chromatograph.
  • the chromatograph 200 includes a liquid delivery system 100, a mobile phase container 110, a sample supply section 120, a separation column 130, a detector 140, and a processing device 150.
  • the mobile phase container 110 stores a solvent such as an aqueous solution or an organic solvent as a mobile phase.
  • the chromatograph 200 may include a plurality of mobile phase containers 110 each storing a plurality of different solvents.
  • the liquid feeding system 100 includes a liquid feeding section 10, a pressure sensor 20, and a control section 30.
  • the liquid feeding section 10 is configured by a serial double plunger system, and includes two plunger pumps 11 and 12, two check valves 13 and 14, a camshaft 15, and an actuator 16.
  • the check valves 13 and 14 are arranged upstream and downstream of the plunger pump 11, respectively.
  • Plunger pump 12 is arranged downstream of check valve 14 .
  • the cam shaft 15 is provided with two cams 15a and 15b.
  • the cams 15a and 15b are connected to the plungers of the plunger pumps 11 and 12, respectively, and convert the rotational driving force of the actuator 16 into reciprocating motion of the plungers. This drives the plunger pumps 11 and 12.
  • the actuator 16 is, for example, a stepping motor.
  • the plunger pumps 11, 12 are driven by one actuator 16 via a common camshaft 15, but they may be driven by separate actuators.
  • the plunger pump 11 and the plunger pump 12 are driven complementary to each other. Therefore, basically, the plunger pump 12 performs a suction operation during the period when the plunger pump 11 performs a discharge operation, and the plunger pump 12 performs a discharge operation during a period when the plunger pump 11 performs a suction operation. Thereby, the mobile phase stored in the mobile phase container 110 is stably sent downstream. Details of the liquid feeding section 10 will be described later.
  • the pressure sensor 20 is arranged downstream of the liquid sending unit 10 and detects the pressure of the mobile phase sent by the liquid sending unit 10.
  • the control unit 30 includes, for example, a CPU (central processing unit) and memory. The control unit 30 detects, based on the pressure of the mobile phase detected by the pressure sensor 20, that a liquid feeding failure has occurred due to the inclusion of air bubbles in the plunger pump 11. Details of the control unit 30 will be described later.
  • the sample supply unit 120 is, for example, a sample injector, and supplies a sample to be analyzed to the mobile phase sent by the liquid delivery unit 10.
  • the sample supplied by the sample supply section 120 is mixed with a mobile phase and introduced into the separation column 130. Further, in this example, the sample supply section 120 is connected to a waste liquid section 201 (not shown).
  • the control unit 30 detects a liquid feeding failure, the sample supply unit 120 discards the mobile phase fed by the liquid feeding unit 10 to the waste liquid unit 201.
  • the separation column 130 is housed inside a column constant temperature bath (not shown), and is adjusted to a predetermined constant temperature.
  • the separation column 130 separates the introduced sample into components based on differences in chemical properties or composition.
  • the detector 140 is, for example, a UV (ultraviolet-visible spectroscopy) detector, an absorbance detector, or an RI (differential refractive index) detector.
  • the detector 140 detects the components of the sample separated by the separation column 130 and provides a detection signal indicating the detection intensity to the processing device 150.
  • the processing device 150 includes, for example, a CPU and a memory, and controls the operations of the liquid feeding system 100, the sample supply section 120, the separation column 130 (column constant temperature bath), and the detector 140. Further, the processing device 150 generates a chromatogram showing the relationship between the retention time of each component of the sample by the separation column 130 and the detection intensity by processing the detection signal provided by the detector 140.
  • FIG. 2 is a diagram for explaining the shape characteristics of the cams 15a and 15b.
  • the horizontal axis in FIG. 2 indicates the rotation angle of the camshaft 15, and the vertical axis indicates the amount of movement of the plunger.
  • the amount of movement of the plunger of the upstream plunger pump 11 is shown by a dotted line
  • the amount of movement of the plunger of the downstream plunger pump 12 is shown by a dashed line
  • the combined amount of movement of the plunger is shown by a solid line. It will be done.
  • the shape of the cam 15a is formed so that the change in the amount of movement of the plunger shown by the dotted line in FIG. 2 is realized.
  • the shape of the cam 15b is formed so that the change in the amount of movement of the plunger shown by the dashed line in FIG. 2 is realized.
  • the amount of movement of the plunger is positive, liquid is fed in an amount corresponding to the amount of movement.
  • the details of the operation of the liquid feeding section 10 will be described below.
  • the check valve 14 is not opened until the pressure inside the plunger pump 11 becomes higher than the pressure inside the downstream flow path. , mobile phase dispensing does not start. Therefore, before the discharge operation of the downstream plunger pump 12 is completed, as shown by the dotted line in FIG. 2, the plunger pump 11 performs a pre-pressure operation to compress the mobile phase.
  • the pressure within the plunger pump 11 becomes higher than the pressure within the downstream flow path, and the check valve 14 is opened. Thereby, the discharge operation of the plunger pump 11 is performed. After the discharge operation is completed, the plunger pump 11 performs the suction operation. Thereafter, the plunger pump 11 returns to preload operation.
  • the discharge operation of the plunger pump 12 is performed. Thereafter, while the plunger pump 11 performs the discharge operation, the plunger pump 12 performs the suction operation.
  • the period during which the plunger pump 11 performs the discharge operation and the period during which the plunger pump 12 performs the discharge operation may partially overlap.
  • the period during which the plunger pump 12 performs the suction operation with the maximum amount of liquid sent is referred to as the maximum suction period.
  • the plunger pumps 11 and 12 Through the operations of the plunger pumps 11 and 12 described above, a fixed amount of mobile phase is delivered, as shown by the solid line in FIG. 2, except for the period in which the plunger pump 11 performs a pre-pressure operation. In the preload operation, the plunger is driven at high speed. This promotes compression and completes the preload operation in a short time.
  • FIG. 3 is a diagram showing changes in the pressure of the mobile phase within one drive cycle of the liquid feeding section 10.
  • the horizontal axis in FIG. 3 indicates the number of drive pulses given to the actuator 16, and the vertical axis indicates the pressure of the mobile phase.
  • the number of drive pulses given to the actuator 16 corresponds to the rotation angle of the camshaft 15.
  • the maximum suction period of the plunger pump 12 is shown by a dashed line.
  • the prepressure operation of the plunger pump 11 is performed during the period in which the drive pulses P1 and P2 are applied to the actuator 16, thereby increasing the pressure of the mobile phase.
  • compression of the mobile phase ends at the time corresponding to the drive pulse P2.
  • the time point at which compression of the mobile phase ends in an ideal state where no air bubbles are mixed in the plunger pump 11 is known, and can be calculated based on preset mobile phase information and the shape characteristics of the cam 15a.
  • the plunger In the preload operation, the plunger is driven at high speed so that the compression of the mobile phase is completed in a short time. After the end of the compression of the mobile phase, ie after the time corresponding to the drive pulse P2, the drive speed of the plunger is reduced. In this state, by further applying a drive pulse to the actuator 16, the check valve 14 is opened without decreasing the pressure of the mobile phase, and the plunger pump 11 performs a discharge operation.
  • the pressure of the mobile phase reaches its maximum near the time corresponding to the drive pulse P2. Thereafter, when further driving pulses are applied to the actuator 16, the pressure of the mobile phase decreases until the plunger is pushed in by an amount equal to or more than the volume of the gas. Further, after the pre-pressure operation of the plunger pump 11 is completed, the suction operation of the plunger pump 12 is started, and therefore, depending on the amount of air bubbles mixed in, the pressure of the mobile phase decreases rapidly.
  • a plurality of drive pulses are sequentially applied to the actuator 16.
  • the check valve 14 is opened at a time corresponding to the drive pulse P3.
  • the discharge operation of the plunger pump 11 is started, and the pressure of the mobile phase becomes the minimum during the maximum suction period of the plunger pump 12. Thereafter, the pressure of the mobile phase increases linearly in proportion to the number of drive pulses, and at the time corresponding to drive pulse P4, the check valve 14 is closed. This completes the discharge operation of the plunger pump 11.
  • FIG. 4 is a diagram showing the configuration of the control unit 30 in FIG. 1.
  • the control unit 30 includes a pressure acquisition unit 31, a maximum value identification unit 32, a minimum value identification unit 33, a fluctuation range acquisition unit 34, a determination unit 35, a counting unit 36, and a detection unit 37 as functional units. and an output section 38.
  • the functional units of the control unit 30 are realized by the CPU of the control unit 30 executing a liquid feeding failure detection program stored in a memory or the like.
  • a part or all of the functional units of the control unit 30 may be realized by hardware such as an electronic circuit. Alternatively, some or all of the functional units of the control unit 30 may be realized by the processing device 150.
  • the pressure acquisition unit 31 acquires the pressure of the mobile phase detected by the pressure sensor 20 at a predetermined period.
  • the cycle of pressure acquisition by the pressure acquisition unit 31 is sufficiently shorter than the driving cycle of the liquid feeding unit 10 in FIG. 1 . Therefore, the pressure acquisition unit 31 acquires the pressure at multiple points in time within each driving cycle of the liquid feeding unit 10 .
  • the cycle of pressure acquisition by the pressure acquisition unit 31 may be 1/10 or less of the drive cycle of the liquid feeding unit 10.
  • the maximum value identifying unit 32 identifies the maximum pressure among the pressures at a plurality of times within each drive cycle acquired by the pressure acquiring unit 31.
  • the maximum pressure specified by the maximum value specifying section 32 is indicated by a circle A.
  • the maximum value specifying unit 32 may specify the maximum pressure within a predetermined period including the time when compression of the mobile phase ends in each drive cycle.
  • the minimum value identifying unit 33 identifies the minimum pressure among the pressures at a plurality of times within each drive cycle acquired by the pressure acquiring unit 31.
  • the minimum pressure specified by the minimum value specifying section 33 is indicated by a circle B.
  • the minimum value specifying unit 33 may specify the minimum pressure within the maximum suction period of the plunger pump 12 in each drive cycle.
  • the fluctuation range acquisition unit 34 acquires the pressure fluctuation range within each drive cycle. In this example, by calculating the difference between the maximum pressure within each drive period specified by the maximum value specifying section 32 and the minimum pressure within the same drive period specified by the minimum value specifying section 33, The pressure fluctuation range is obtained. In FIG. 3, the fluctuation range acquired by the fluctuation range acquisition unit 34 is shown by a dotted line.
  • the determination unit 35 determines whether the pressure fluctuation range acquired by the fluctuation range acquisition unit 34 is larger than the reference value for each drive cycle.
  • the reference value may be a predetermined value or a value specified by the user.
  • the counting unit 36 counts the number of consecutive driving cycles in which the determining unit 35 determines that the pressure fluctuation width is larger than the reference value.
  • the detection unit 37 detects that a liquid feeding failure has occurred due to air bubbles entering the plunger pump 11. Detect.
  • the reference number of times may be a predetermined number of times, or may be a number of times specified by the user.
  • the output unit 38 outputs the detection result of poor liquid feeding by the detection unit 37 to the processing device 150.
  • the processing device 150 may control the sample supply unit 120 to discard the mobile phase sent by the liquid delivery unit 10 to the waste liquid unit 201 in FIG. 1 when a detection result of poor liquid delivery is output. .
  • the processing device 150 may interrupt the analysis of the sample when a detection result of poor liquid delivery is output.
  • the processing device 150 may notify the user to that effect.
  • the processing device 150 if the chromatograph 200 in FIG. 1 includes a display device, a character string indicating that a liquid feeding failure has occurred may be displayed.
  • the chromatograph 200 includes an audio output device, audio indicating the same content may be output, or a warning sound such as a buzzer may be output.
  • the chromatograph 200 includes an indicator light such as a lamp, the indicator light may be turned on, turned off, or blinked in a manner corresponding to the content of the notification.
  • the fluctuation range acquisition unit 34 in each driving cycle of the liquid feeding unit 10 it may be determined whether the pressure of the mobile phase is normally monotonically increasing or decreasing. For example, in FIG. 3, after the end of the maximum suction period of the plunger pump 12, the difference in mobile phase pressure between the time when two drive pulses are given to the actuator 16 and the time when the drive pulse P5 is given to the actuator 16 is be obtained. If this pressure difference is larger than a certain value, it may be determined that the mobile phase pressure is normally monotonically increasing or monotonically decreasing.
  • FIG. 5 is a flowchart showing an example of liquid feeding failure detection processing performed by the control unit 30 of FIG. 4.
  • the liquid feeding failure detection process in FIG. 5 is performed by the CPU of the control unit 30 executing a liquid feeding failure detection program stored in a memory or the like.
  • a liquid feeding failure detection program stored in a memory or the like.
  • the counting unit 36 sets the value of the variable n to 0 (step S1).
  • the variable n indicates the number of driving cycles of the liquid feeding unit 10 in which the range of fluctuation in the pressure of the mobile phase exceeds a predetermined reference number of times.
  • the pressure acquisition section 31 acquires the pressure of the mobile phase detected by the pressure sensor 20 at a cycle sufficiently shorter than the drive cycle of the liquid feeding section 10 (step S2).
  • the pressure acquisition unit 31 determines whether the driving cycle of the liquid feeding unit 10 has ended (step S3). If the drive cycle of the liquid feeding section 10 has not ended, the pressure acquisition section 31 returns to step S2. Steps S2 and S3 are repeated until the driving cycle of the liquid feeding section 10 ends. Thereby, pressures at multiple points in time within one drive cycle of the liquid feeding section 10 are acquired.
  • the maximum value specifying unit 32 specifies the maximum pressure among the pressures at the plurality of times acquired in step S2 (step S4).
  • the minimum value specifying unit 33 specifies the minimum pressure among the pressures at the plurality of times acquired in step S2 (step S5). Steps S4 and S5 may be executed either first or at the same time.
  • step S4 the maximum value identifying unit 32 may identify the maximum pressure within a predetermined period including the time when compression of the mobile phase ends. Further, in step S5, the minimum value specifying unit 33 may specify the minimum pressure within the maximum suction period of the plunger pump 12. In these cases, steps S4 and S5 may be executed before the end of step S3. Further, in this case, step S4 may be executed before step S5.
  • the variation range acquisition unit 34 obtains the pressure variation range by calculating the difference between the maximum pressure identified in step S4 and the minimum pressure identified in step S5 (step S6). Subsequently, the determining unit 35 determines whether the pressure fluctuation range acquired in step S6 is larger than a predetermined reference value (step S7).
  • step S8 determines whether the variable n in step S8 is larger than the reference number of times.
  • the reference number of times is an integer greater than or equal to 2, and is 5 in this example.
  • step S10 If the variable n is less than or equal to the reference number of times, the detection unit 37 returns to step S2. As a result, the process from step S2 onwards is repeated while the variable n is maintained. If the variable n is larger than the reference number of times, the detection unit 37 detects that a liquid feeding failure has occurred due to the inclusion of air bubbles in the plunger pump 11 (step S10). The output unit 38 outputs the detection result of the liquid feeding failure in step S10 to the processing device 150 (step S11), and ends the liquid feeding failure detection process.
  • the mobile phase is fed by periodically driving the serial double plunger type liquid feeding unit 10 including the plunger pumps 11 and 12.
  • the pressure of the mobile phase at a plurality of times within each driving cycle of the liquid feeding section 10 is acquired by the pressure acquisition section 31 .
  • the maximum pressure among the pressures acquired by the pressure acquisition section 31 is specified by the maximum value specifying section 32. Further, for each drive cycle of the liquid feeding section 10, the minimum pressure among the pressures acquired by the pressure acquisition section 31 is specified by the minimum value specifying section 33. Based on the maximum pressure specified by the maximum value specification section 32 and the minimum pressure specified by the minimum value specification section 33, the detection section 37 detects a liquid feeding failure due to the inclusion of air bubbles in the plunger pump 11. Ru.
  • the maximum pressure and minimum pressure of the mobile phase in each driving cycle of the liquid feeding section 10 are specified. Therefore, even when the amount of air bubbles mixed into the plunger pump 11 is small, it is possible to easily detect a change in the pressure of the mobile phase caused by the air bubbles mixed in. This makes it possible to accurately detect liquid feeding failures caused by the inclusion of air bubbles.
  • the fluctuation width acquisition unit 34 determines each drive of the liquid feeding unit 10 based on the maximum pressure specified by the maximum value specification unit 32 and the minimum pressure specified by the minimum value specification unit 33. Obtain the pressure fluctuation range within the period.
  • the determination unit 35 determines whether or not the pressure fluctuation range acquired by the fluctuation range acquisition unit 34 is larger than a reference value for each driving cycle of the liquid feeding unit 10 .
  • the counting unit 36 counts the number of consecutive drive cycles in which the determining unit 35 determines that the pressure fluctuation width is larger than the reference value.
  • the detection unit 37 detects a liquid feeding failure when the number of consecutive driving cycles counted by the counting unit 36 is greater than a predetermined number. This makes it possible to more accurately detect liquid feeding failures caused by the inclusion of air bubbles.
  • the maximum value identifying unit 32 acquires the maximum pressure among the pressures acquired by the pressure acquiring unit 31 within a predetermined period including a predetermined time point at which the check valve 14 should be opened. It's okay. In this case, even if the maximum pressure of the mobile phase due to noise is acquired by the pressure acquisition unit 31 outside the predetermined period, the maximum pressure is excluded from the identification target by the maximum value identification unit 32.
  • the minimum value identifying unit 33 may acquire the minimum pressure among the pressures acquired by the pressure acquiring unit 31 within the maximum suction period of the plunger pump 12. In this case, even if the minimum pressure of the mobile phase due to noise is acquired by the pressure acquisition unit 31 outside the maximum suction period of the plunger pump 12, the minimum pressure is excluded from the identification target by the minimum value identification unit 33. be done. According to these configurations, it is possible to more accurately detect liquid feeding failure caused by the inclusion of air bubbles.
  • FIG. 6 is a diagram for explaining a method for detecting liquid feeding failure in a reference example.
  • the change in mobile phase pressure shown in FIG. 6 is the same as the change in mobile phase pressure in FIG. 3.
  • the discharge operation of the plunger pump 11 starts at a time corresponding to the drive pulse P3.
  • the liquid feeding pressure at this time is indicated by circle C.
  • the end point of the discharge operation of the plunger pump 11 is a time point corresponding to the drive pulse P4.
  • the liquid feeding pressure at this time is indicated by circle D. That is, the difference between the liquid feeding pressure of circle C and the liquid feeding pressure of circle D is determined as the first fluctuation value.
  • the maximum value of the first fluctuation value determined by this method is smaller than the maximum value of the pressure in this embodiment shown in FIG. Further, the minimum value of the first fluctuation value is larger than the minimum value of the pressure in the present embodiment shown in FIG. Therefore, the first fluctuation value is smaller than the pressure fluctuation width in this embodiment shown in FIG. Therefore, when the amount of bubbles mixed into the plunger pump 11 is small, a sufficiently large first fluctuation value is not obtained, and it is difficult to accurately detect a liquid feeding failure.
  • a liquid feeding failure is detected based on the range of pressure fluctuation within each drive cycle of the liquid feeding unit 10, but the embodiment is limited to this. Not done.
  • a liquid feeding failure may be detected based on an arbitrary evaluation value determined based on the maximum pressure and minimum pressure within each drive cycle.
  • the liquid feeding section 10 is configured with a serial double plunger system, but the embodiment is not limited to this.
  • the liquid feeding section 10 may be configured with a parallel double plunger system.
  • the maximum value identifying unit 32 identifies the first maximum pressure resulting from the mobile phase discharge operation by the plunger pump 11 for each driving cycle of the liquid feeding unit 10. Further, the maximum value specifying unit 32 specifies the second maximum pressure caused by the discharge operation of the mobile phase by the plunger pump 12 for each drive cycle of the liquid feeding unit 10 .
  • the minimum value identifying unit 33 identifies the first minimum pressure resulting from the mobile phase discharge operation by the plunger pump 11 for each driving cycle of the liquid feeding unit 10. Further, the minimum value specifying unit 33 specifies the second minimum pressure caused by the discharge operation of the mobile phase by the plunger pump 12 for each driving cycle of the liquid feeding unit 10 .
  • the detection unit 37 detects the first maximum pressure specified by the maximum value specification unit 32 and the first minimum pressure specified by the minimum value specification unit 33 for each drive period of the liquid feeding unit 10, A liquid feeding failure caused by air bubbles entering the plunger pump 11 is detected.
  • the detection unit 37 also detects the second maximum pressure specified by the maximum value specification unit 32 and the second minimum pressure specified by the minimum value specification unit 33 for each drive period of the liquid feeding unit 10. Then, a liquid feeding failure caused by air bubbles entering the plunger pump 12 is detected.
  • the liquid feeding section 10 includes two plunger pumps 11 and 12, but the embodiment is not limited to this.
  • the liquid feeding section 10 may be configured with a single plunger system including one plunger pump 11.
  • the maximum value specifying unit 32 specifies the maximum pressure during the discharge operation of the plunger pump 11 for each driving cycle of the liquid feeding unit 10.
  • the minimum value identifying unit 33 identifies the minimum pressure during the discharge operation of the plunger pump 11 for each drive cycle of the liquid feeding unit 10 .
  • the detection unit 37 detects a liquid feeding failure based on the maximum pressure specified by the maximum value identification unit 32 and the minimum pressure specified by the minimum value identification unit 33 for each drive period of the liquid feeding unit 10.
  • the chromatographic liquid delivery system includes: a liquid sending section that includes one or more plunger pumps and that sends the mobile phase by being driven periodically; a pressure acquisition unit that acquires the pressure of the mobile phase at a plurality of times within each driving cycle of the liquid feeding unit; a maximum value identifying unit that identifies a maximum pressure among the pressures acquired by the pressure acquiring unit for each driving cycle of the liquid feeding unit; a minimum value identifying unit that identifies a minimum pressure among the pressures acquired by the pressure acquiring unit for each driving cycle of the liquid feeding unit; Detection of a liquid feeding failure caused by air bubbles being mixed into the one or more plunger pumps based on the maximum pressure specified by the maximum value specifying section and the minimum pressure specified by the minimum value specifying section. It may also include a section.
  • (Section 2) The chromatographic liquid delivery system described in Section 1, a fluctuation range for obtaining a pressure fluctuation range within each drive cycle of the liquid feeding unit based on the maximum pressure identified by the maximum value identification unit and the minimum pressure identified by the minimum value identification unit; It further includes an acquisition section, The detection unit may detect a liquid feeding failure based on the pressure fluctuation range acquired by the fluctuation range acquisition unit.
  • the chromatographic liquid delivery system described in Section 3 further comprising a counting unit that counts the number of consecutive driving cycles in which the pressure fluctuation width is determined to be larger than a reference value by the determining unit,
  • the detection unit may detect a liquid feeding failure when the number of consecutive driving cycles counted by the counting unit is greater than a predetermined number of times.
  • the liquid feeding unit includes a first plunger pump and a second plunger pump that are connected in series and driven complementary to each other as the one or more plunger pumps,
  • the second plunger pump is arranged downstream of the first plunger pump, and a check valve is arranged between the first plunger pump and the second plunger pump,
  • the first plunger pump compresses the mobile phase to a predetermined time point at which the check valve is to be opened, before discharging the mobile phase
  • the maximum value identifying section may acquire the maximum pressure among the pressures acquired by the pressure acquiring section within a predetermined period including the predetermined time.
  • the liquid feeding section is configured with an in-line double plunger system.
  • the maximum pressure of the mobile phase due to noise is acquired by the pressure acquisition unit outside the above-mentioned predetermined period, the maximum pressure is excluded from the identification target by the maximum value identification unit. This makes it possible to more accurately detect liquid feeding failures caused by the inclusion of air bubbles.
  • the liquid feeding unit includes a first plunger pump and a second plunger pump that are connected in series and driven complementary to each other as the one or more plunger pumps, the second plunger pump is located downstream of the first plunger pump,
  • the minimum value identifying section may acquire the minimum pressure among the pressures acquired by the pressure acquiring section within a period in which the second plunger pump is performing a suction operation.
  • the liquid feeding section is configured with an in-line double plunger system.
  • the minimum pressure of the mobile phase due to noise is acquired by the pressure acquisition section outside the period when the suction operation is performed by the second plunger pump, the minimum pressure is determined by the minimum value identification section. excluded from specific targets. This makes it possible to more accurately detect liquid feeding failures caused by the inclusion of air bubbles.
  • the liquid feeding unit includes a first plunger pump and a second plunger pump that are connected in parallel and driven complementary to each other as the one or more plunger pumps,
  • the maximum value specifying unit specifies, for each driving cycle of the liquid feeding unit, a first maximum pressure caused by the mobile phase discharging operation by the first plunger pump, and a first maximum pressure caused by the mobile phase discharging operation by the second plunger pump.
  • the minimum value specifying unit specifies, for each drive cycle of the liquid feeding unit, a first minimum pressure caused by the mobile phase discharging operation by the first plunger pump, and a first minimum pressure caused by the mobile phase discharging operation by the second plunger pump. identifying a second minimum pressure resulting from a dispensing operation of the mobile phase;
  • the detection unit detects air bubbles to the first plunger pump based on the first maximum pressure specified by the maximum value specification unit and the first minimum pressure specified by the minimum value specification unit. Detecting a liquid feeding failure due to contamination, the second maximum pressure specified by the maximum value specifying section and the second minimum pressure specified by the minimum value specifying section A liquid feeding failure caused by air bubbles entering the plunger pump may also be detected.
  • a chromatographic liquid feeding method includes: Sending the mobile phase by periodically driving a liquid feeding section including one or more plunger pumps; Obtaining the pressure of the mobile phase at a plurality of times within each driving cycle of the liquid feeding section; Identifying the maximum pressure among the acquired pressures for each drive cycle of the liquid feeding section; Identifying the minimum pressure among the acquired pressures for each drive cycle of the liquid feeding section; The method may also include detecting a liquid feeding failure due to air bubbles being mixed into the one or more plunger pumps based on the specified maximum pressure and the specified minimum pressure.
  • the maximum pressure and minimum pressure of the mobile phase in each drive cycle of the liquid feeding section are specified. Therefore, even if the amount of air bubbles mixed into the plunger pump is small, it is possible to easily detect a change in the pressure of the mobile phase caused by the air bubbles mixed in. This makes it possible to accurately detect liquid feeding failures caused by the inclusion of air bubbles.

Abstract

This chromatograph liquid delivery system includes a liquid delivery unit, a pressure acquiring unit, a maximum value identifying unit, a minimum value identifying unit, and a detecting unit. The liquid delivery unit includes one or more plunger pumps, and is periodically driven to deliver a mobile phase. The pressure acquiring unit acquires a pressure of the mobile phase at a plurality of time points during each drive cycle of the liquid delivery unit. The maximum value identifying unit identifies a maximum pressure, among the pressures acquired by the pressure acquiring unit, for each drive cycle of the liquid delivery unit. The minimum value identifying unit identifies a minimum pressure, among the pressures acquired by the pressure acquiring unit, for each drive cycle of the liquid delivery unit. The detecting unit detects a liquid feed failure resulting from contamination of bubbles into the one or more plunger pumps, on the basis of the identified maximum pressure and minimum pressure.

Description

クロマトグラフ用送液システムおよびクロマトグラフ用送液方法Chromatograph liquid delivery system and chromatograph liquid delivery method
　本発明は、クロマトグラフ用送液システムおよびクロマトグラフ用送液方法に関する。 The present invention relates to a chromatographic liquid feeding system and a chromatographic liquid feeding method.
　クロマトグラフ用送液システムには、移動相となる溶媒を安定的に送液できるように、溶媒中の気泡の発生に起因する送液不良を検知する機能が設けられることがある。例えば、特許文献１に記載された液体クロマトグラフ用送液システムにおいては、２つのプランジャポンプを含む送液機構により液が連続的に送液される。また、送液機構の１駆動周期内における送液圧力の変動が読み取られる。 A liquid delivery system for chromatography is sometimes equipped with a function to detect poor liquid delivery due to the generation of bubbles in the solvent, so that the solvent serving as the mobile phase can be delivered stably. For example, in a liquid chromatograph liquid feeding system described in Patent Document 1, a liquid is continuously fed by a liquid feeding mechanism including two plunger pumps. Further, fluctuations in the liquid feeding pressure within one drive cycle of the liquid feeding mechanism are read.
　ここで、一方のプランジャポンプの吐出動作の開始点および終了点における送液圧力の差が第１変動値として求められ、他方のプランジャポンプの吐出動作の開始点および終了点における送液圧力の差が第２変動値として求められる。第１変動値および第２変動値のいずれか一方のみが正の値である場合、第１変動値および第２変動値に基づいて送液圧力の変動幅が算出される。算出された変動幅が所定の基準値を超えた周期の連続数が所定の基準回数に達した場合、プランジャポンプへの気泡の混入に起因した送液不良が発生していることが検知される。 Here, the difference in liquid feeding pressure at the start point and end point of the discharge operation of one plunger pump is determined as the first fluctuation value, and the difference in the liquid feeding pressure at the start point and end point of the discharge operation of the other plunger pump. is obtained as the second variation value. When only one of the first fluctuation value and the second fluctuation value is a positive value, the fluctuation range of the liquid feeding pressure is calculated based on the first fluctuation value and the second fluctuation value. If the number of consecutive cycles in which the calculated fluctuation range exceeds a predetermined reference value reaches a predetermined reference number, it is detected that a liquid delivery failure has occurred due to air bubbles entering the plunger pump. .
国際公開第２０２０／１８３７７４号International Publication No. 2020/183774
　特許文献１に記載の方法においては、プランジャポンプに混入する気泡量が比較的大きい場合には、送液不良を検知することができる。しかしながら、プランジャポンプに混入する気泡量が小さい場合には、送液不良を検知することは困難である。そのため、送液不良をより正確に検知することが求められる。 In the method described in Patent Document 1, if the amount of air bubbles entering the plunger pump is relatively large, a liquid feeding failure can be detected. However, if the amount of bubbles that enter the plunger pump is small, it is difficult to detect a liquid feeding failure. Therefore, it is required to detect liquid feeding failures more accurately.
　本発明の目的は、送液不良を正確に検知することが可能なクロマトグラフ用送液システムおよびクロマトグラフ用送液方法を提供することである。 An object of the present invention is to provide a chromatographic liquid feeding system and a chromatographic liquid feeding method that can accurately detect liquid feeding defects.
　本発明の一態様は、１以上のプランジャポンプを含み、周期的に駆動することにより移動相を送液する送液部と、前記送液部の各駆動周期内における複数の時点の移動相の圧力を取得する圧力取得部と、前記送液部の各駆動周期について、前記圧力取得部により取得された圧力のうち、最大の圧力を特定する最大値特定部と、前記送液部の各駆動周期について、前記圧力取得部により取得された圧力のうち、最小の圧力を特定する最小値特定部と、前記最大値特定部により特定された最大の圧力および前記最小値特定部により特定された最小の圧力に基づいて、前記１以上のプランジャポンプへの気泡の混入に起因した送液不良を検知する検知部とを備える、クロマトグラフ用送液システムに関する。 One aspect of the present invention includes a liquid sending section that includes one or more plunger pumps and that sends a mobile phase by being driven periodically; a pressure acquisition unit that acquires pressure; a maximum value identification unit that identifies a maximum pressure among the pressures acquired by the pressure acquisition unit for each driving cycle of the liquid feeding unit; and each drive of the liquid feeding unit. Regarding the period, among the pressures acquired by the pressure acquisition section, there is a minimum value specifying section that specifies the minimum pressure, the maximum pressure specified by the maximum value specifying section, and the minimum pressure specified by the minimum value specifying section. The present invention relates to a liquid feeding system for chromatography, comprising: a detection unit that detects a liquid feeding failure due to air bubbles being mixed into the one or more plunger pumps based on the pressure of the plunger pump.
　本発明の他の態様は、１以上のプランジャポンプを含む送液部が周期的に駆動することにより移動相を送液することと、前記送液部の各駆動周期内における複数の時点の移動相の圧力を取得することと、前記送液部の各駆動周期について、取得された圧力のうち、最大の圧力を特定することと、前記送液部の各駆動周期について、取得された圧力のうち、最小の圧力を特定することと、特定された最大の圧力および特定された最小の圧力に基づいて、前記１以上のプランジャポンプへの気泡の混入に起因した送液不良を検知することとを含む、クロマトグラフ用送液方法に関する。 Another aspect of the present invention is that a liquid feeding unit including one or more plunger pumps periodically drives the mobile phase, and that the liquid feeding unit moves at a plurality of points within each driving cycle. obtaining the phase pressure; identifying the maximum pressure among the obtained pressures for each driving period of the liquid feeding section; and determining the maximum pressure of the obtained pressure for each driving period of the liquid feeding section. Among them, identifying the minimum pressure, and detecting a liquid feeding failure due to the inclusion of air bubbles in the one or more plunger pumps based on the identified maximum pressure and the identified minimum pressure. The present invention relates to a liquid feeding method for chromatography, including:
　本発明によれば、送液不良を正確に検知することができる。 According to the present invention, a liquid feeding failure can be accurately detected.
図１は本発明の一実施の形態に係る送液システムを含むクロマトグラフの構成を示す図である。FIG. 1 is a diagram showing the configuration of a chromatograph including a liquid feeding system according to an embodiment of the present invention. 図２はカムの形状特性を説明するための図である。FIG. 2 is a diagram for explaining the shape characteristics of the cam. 図３は送液部の１つの駆動周期内における移動相の圧力の変化を示す図である。FIG. 3 is a diagram showing a change in the pressure of the mobile phase within one driving cycle of the liquid feeding section. 図４は図１の制御部の構成を示す図である。FIG. 4 is a diagram showing the configuration of the control section in FIG. 1. 図５は図４の制御部による送液不良検知処理の一例を示すフローチャートである。FIG. 5 is a flowchart illustrating an example of a liquid feeding failure detection process performed by the control unit in FIG. 4. 図６は参考例における送液不良の検知方法を説明するための図である。FIG. 6 is a diagram for explaining a method for detecting liquid feeding failure in a reference example.
　（１）クロマトグラフの構成
　以下、本発明の実施の形態に係るクロマトグラフ用送液システム（以下、単に送液システムと呼ぶ。）およびクロマトグラフ用送液方法について図面を参照しながら詳細に説明する。図１は、本発明の一実施の形態に係る送液システムを含むクロマトグラフの構成を示す図である。なお、本実施の形態におけるクロマトグラフ２００は液体クロマトグラフであるが、超臨界流体クロマトグラフであってもよい。 (1) Structure of chromatograph Hereinafter, a chromatograph liquid feeding system (hereinafter simply referred to as liquid feeding system) and a chromatograph liquid feeding method according to an embodiment of the present invention will be explained in detail with reference to the drawings. do. FIG. 1 is a diagram showing the configuration of a chromatograph including a liquid feeding system according to an embodiment of the present invention. Note that although the chromatograph 200 in this embodiment is a liquid chromatograph, it may be a supercritical fluid chromatograph.
　図１に示すように、クロマトグラフ２００は、送液システム１００、移動相容器１１０、試料供給部１２０、分離カラム１３０、検出器１４０および処理装置１５０を備える。移動相容器１１０は、水溶液または有機溶媒等の溶媒を移動相として貯留する。クロマトグラフ２００は、異なる複数の溶媒をそれぞれ貯留する複数の移動相容器１１０を備えてもよい。 As shown in FIG. 1, the chromatograph 200 includes a liquid delivery system 100, a mobile phase container 110, a sample supply section 120, a separation column 130, a detector 140, and a processing device 150. The mobile phase container 110 stores a solvent such as an aqueous solution or an organic solvent as a mobile phase. The chromatograph 200 may include a plurality of mobile phase containers 110 each storing a plurality of different solvents.
　送液システム１００は、送液部１０、圧力センサ２０および制御部３０を含む。本例では、送液部１０は、直列型ダブルプランジャ方式で構成され、２つのプランジャポンプ１１，１２、２つの逆止弁１３，１４、カム軸１５およびアクチュエータ１６を含む。逆止弁１３，１４は、プランジャポンプ１１の上流および下流にそれぞれ配置される。プランジャポンプ１２は、逆止弁１４の下流に配置される。 The liquid feeding system 100 includes a liquid feeding section 10, a pressure sensor 20, and a control section 30. In this example, the liquid feeding section 10 is configured by a serial double plunger system, and includes two plunger pumps 11 and 12, two check valves 13 and 14, a camshaft 15, and an actuator 16. The check valves 13 and 14 are arranged upstream and downstream of the plunger pump 11, respectively. Plunger pump 12 is arranged downstream of check valve 14 .
　カム軸１５には、２つのカム１５ａ，１５ｂが設けられる。カム１５ａ，１５ｂは、プランジャポンプ１１，１２のプランジャにそれぞれ接続され、アクチュエータ１６の回転駆動力をプランジャの往復運動に変換する。これにより、プランジャポンプ１１，１２が駆動する。アクチュエータ１６は、例えばステッピングモータである。本例では、プランジャポンプ１１，１２は共通のカム軸１５を介して１つのアクチュエータ１６により駆動されるが、別個のアクチュエータにより駆動されてもよい。 The cam shaft 15 is provided with two cams 15a and 15b. The cams 15a and 15b are connected to the plungers of the plunger pumps 11 and 12, respectively, and convert the rotational driving force of the actuator 16 into reciprocating motion of the plungers. This drives the plunger pumps 11 and 12. The actuator 16 is, for example, a stepping motor. In this example, the plunger pumps 11, 12 are driven by one actuator 16 via a common camshaft 15, but they may be driven by separate actuators.
　プランジャポンプ１１とプランジャポンプ１２とは、互いに相補的に駆動する。したがって、基本的に、プランジャポンプ１１が吐出動作を行う期間にプランジャポンプ１２が吸入動作を行い、プランジャポンプ１１が吸入動作を行う期間にプランジャポンプ１２が吐出動作を行う。これにより、移動相容器１１０に貯留された移動相が安定的に下流に送液される。送液部１０の詳細については後述する。 The plunger pump 11 and the plunger pump 12 are driven complementary to each other. Therefore, basically, the plunger pump 12 performs a suction operation during the period when the plunger pump 11 performs a discharge operation, and the plunger pump 12 performs a discharge operation during a period when the plunger pump 11 performs a suction operation. Thereby, the mobile phase stored in the mobile phase container 110 is stably sent downstream. Details of the liquid feeding section 10 will be described later.
　圧力センサ２０は、送液部１０の下流に配置され、送液部１０により送液された移動相の圧力を検出する。制御部３０は、例えばＣＰＵ（中央演算処理装置）およびメモリを含む。制御部３０は、圧力センサ２０により検出された移動相の圧力に基づいて、プランジャポンプ１１への気泡の混入に起因した送液不良が発生していることを検知する。制御部３０の詳細については後述する。 The pressure sensor 20 is arranged downstream of the liquid sending unit 10 and detects the pressure of the mobile phase sent by the liquid sending unit 10. The control unit 30 includes, for example, a CPU (central processing unit) and memory. The control unit 30 detects, based on the pressure of the mobile phase detected by the pressure sensor 20, that a liquid feeding failure has occurred due to the inclusion of air bubbles in the plunger pump 11. Details of the control unit 30 will be described later.
　試料供給部１２０は、例えばサンプルインジェクタであり、送液部１０により送液された移動相に分析対象の試料を供給する。試料供給部１２０により供給された試料は、移動相に混合され、分離カラム１３０に導入される。また、本例では、試料供給部１２０は、図示しない廃液部２０１に接続される。試料供給部１２０は、制御部３０により送液不良が検知された場合、送液部１０により送液された移動相を廃液部２０１に廃棄する。 The sample supply unit 120 is, for example, a sample injector, and supplies a sample to be analyzed to the mobile phase sent by the liquid delivery unit 10. The sample supplied by the sample supply section 120 is mixed with a mobile phase and introduced into the separation column 130. Further, in this example, the sample supply section 120 is connected to a waste liquid section 201 (not shown). When the control unit 30 detects a liquid feeding failure, the sample supply unit 120 discards the mobile phase fed by the liquid feeding unit 10 to the waste liquid unit 201.
　分離カラム１３０は、図示しないカラム恒温槽の内部に収容され、所定の一定温度に調整される。分離カラム１３０は、導入された試料を化学的性質または組成の違いにより成分ごとに分離する。検出器１４０は、例えばＵＶ（紫外可視分光）検出器、吸光度検出器またはＲＩ（示差屈折率）検出器である。検出器１４０は、分離カラム１３０により分離された試料の成分を検出し、検出強度を示す検出信号を処理装置１５０に与える。 The separation column 130 is housed inside a column constant temperature bath (not shown), and is adjusted to a predetermined constant temperature. The separation column 130 separates the introduced sample into components based on differences in chemical properties or composition. The detector 140 is, for example, a UV (ultraviolet-visible spectroscopy) detector, an absorbance detector, or an RI (differential refractive index) detector. The detector 140 detects the components of the sample separated by the separation column 130 and provides a detection signal indicating the detection intensity to the processing device 150.
　処理装置１５０は、例えばＣＰＵおよびメモリを含み、送液システム１００、試料供給部１２０、分離カラム１３０（カラム恒温槽）および検出器１４０の動作を制御する。また、処理装置１５０は、検出器１４０により与えられた検出信号を処理することにより、分離カラム１３０による試料の各成分の保持時間と検出強度との関係を示すクロマトグラムを生成する。 The processing device 150 includes, for example, a CPU and a memory, and controls the operations of the liquid feeding system 100, the sample supply section 120, the separation column 130 (column constant temperature bath), and the detector 140. Further, the processing device 150 generates a chromatogram showing the relationship between the retention time of each component of the sample by the separation column 130 and the detection intensity by processing the detection signal provided by the detector 140.
　（２）送液部の動作
　図２は、カム１５ａ，１５ｂの形状特性を説明するための図である。図２の横軸はカム軸１５の回転角度を示し、縦軸はプランジャの移動量を示す。また、図２では、上流のプランジャポンプ１１のプランジャの移動量が点線で示され、下流のプランジャポンプ１２のプランジャの移動量が一点鎖線で示され、合成されたプランジャの移動量が実線で示される。カム１５ａの形状は、図２の点線で示されるプランジャの移動量の変化が実現されるように形成される。カム１５ｂの形状は、図２の一点鎖線で示されるプランジャの移動量の変化が実現されるように形成される。プランジャの移動量が正のときに、当該移動量に対応する量の送液が行われる。以下、送液部１０の動作の詳細について説明する。 (2) Operation of liquid feeding section FIG. 2 is a diagram for explaining the shape characteristics of the cams 15a and 15b. The horizontal axis in FIG. 2 indicates the rotation angle of the camshaft 15, and the vertical axis indicates the amount of movement of the plunger. In addition, in FIG. 2, the amount of movement of the plunger of the upstream plunger pump 11 is shown by a dotted line, the amount of movement of the plunger of the downstream plunger pump 12 is shown by a dashed line, and the combined amount of movement of the plunger is shown by a solid line. It will be done. The shape of the cam 15a is formed so that the change in the amount of movement of the plunger shown by the dotted line in FIG. 2 is realized. The shape of the cam 15b is formed so that the change in the amount of movement of the plunger shown by the dashed line in FIG. 2 is realized. When the amount of movement of the plunger is positive, liquid is fed in an amount corresponding to the amount of movement. The details of the operation of the liquid feeding section 10 will be described below.
　直列型ダブルプランジャ方式においては、上流のプランジャポンプ１１が吸引動作から吐出動作に切り替わる際、プランジャポンプ１１内の圧力が下流の流路内の圧力よりも高くなるまで逆止弁１４が開放されず、移動相の吐出が開始されない。そこで、下流のプランジャポンプ１２の吐出動作が終了する前に、図２に点線で示すように、プランジャポンプ１１により移動相を圧縮する予圧動作が行われる。 In the series double plunger system, when the upstream plunger pump 11 switches from suction operation to discharge operation, the check valve 14 is not opened until the pressure inside the plunger pump 11 becomes higher than the pressure inside the downstream flow path. , mobile phase dispensing does not start. Therefore, before the discharge operation of the downstream plunger pump 12 is completed, as shown by the dotted line in FIG. 2, the plunger pump 11 performs a pre-pressure operation to compress the mobile phase.
　予圧動作が行われることにより、プランジャポンプ１１内の圧力が下流の流路内の圧力よりも高くなり、逆止弁１４が開放される。これにより、プランジャポンプ１１の吐出動作が行われる。吐出動作の終了後、プランジャポンプ１１の吸引動作が行われる。その後、プランジャポンプ１１は、予圧動作に戻る。 By performing the prepressure operation, the pressure within the plunger pump 11 becomes higher than the pressure within the downstream flow path, and the check valve 14 is opened. Thereby, the discharge operation of the plunger pump 11 is performed. After the discharge operation is completed, the plunger pump 11 performs the suction operation. Thereafter, the plunger pump 11 returns to preload operation.
　また、図２に一点鎖線で示すように、プランジャポンプ１１の吸引動作および予圧動作が行われる間、プランジャポンプ１２の吐出動作が行われる。その後、プランジャポンプ１１の吐出動作が行われる間、プランジャポンプ１２の吸引動作が行われる。プランジャポンプ１１の吐出動作が行われる期間と、プランジャポンプ１２の吐出動作が行われる期間とは、部分的に重複してもよい。プランジャポンプ１２により最大の送液量で吸引動作が行われる期間を最大吸引期間と呼ぶ。 Furthermore, as shown by the dashed line in FIG. 2, while the suction operation and preload operation of the plunger pump 11 are performed, the discharge operation of the plunger pump 12 is performed. Thereafter, while the plunger pump 11 performs the discharge operation, the plunger pump 12 performs the suction operation. The period during which the plunger pump 11 performs the discharge operation and the period during which the plunger pump 12 performs the discharge operation may partially overlap. The period during which the plunger pump 12 performs the suction operation with the maximum amount of liquid sent is referred to as the maximum suction period.
　上記のプランジャポンプ１１，１２の動作により、図２に実線で示すように、プランジャポンプ１１の予圧動作が行われる期間を除き、一定量の移動相の送液が行われる。予圧動作においては、プランジャが高速で駆動される。これにより、圧縮が促進され、予圧動作が短時間で終了する。 Through the operations of the plunger pumps 11 and 12 described above, a fixed amount of mobile phase is delivered, as shown by the solid line in FIG. 2, except for the period in which the plunger pump 11 performs a pre-pressure operation. In the preload operation, the plunger is driven at high speed. This promotes compression and completes the preload operation in a short time.
　図３は、送液部１０の１つの駆動周期内における移動相の圧力の変化を示す図である。図３の横軸はアクチュエータ１６に与えられる駆動パルス数を示し、縦軸は移動相の圧力を示す。アクチュエータ１６に与えられる駆動パルス数は、カム軸１５の回転角度に対応する。図３には、プランジャポンプ１２の最大吸引期間が一点鎖線で示される。 FIG. 3 is a diagram showing changes in the pressure of the mobile phase within one drive cycle of the liquid feeding section 10. The horizontal axis in FIG. 3 indicates the number of drive pulses given to the actuator 16, and the vertical axis indicates the pressure of the mobile phase. The number of drive pulses given to the actuator 16 corresponds to the rotation angle of the camshaft 15. In FIG. 3, the maximum suction period of the plunger pump 12 is shown by a dashed line.
　図３に示すように、アクチュエータ１６に駆動パルスＰ１，Ｐ２が与えられる期間に、プランジャポンプ１１の予圧動作が行われることにより、移動相の圧力が上昇する。プランジャポンプ１１に気泡が混入していない理想的な状態においては、駆動パルスＰ２に対応する時点で移動相の圧縮が終了する。プランジャポンプ１１に気泡が混入していない理想的な状態における移動相の圧縮が終了する時点は既知であり、予め設定された移動相の情報およびカム１５ａの形状特性に基づいて算出可能である。 As shown in FIG. 3, the prepressure operation of the plunger pump 11 is performed during the period in which the drive pulses P1 and P2 are applied to the actuator 16, thereby increasing the pressure of the mobile phase. In an ideal state in which no bubbles are mixed in the plunger pump 11, compression of the mobile phase ends at the time corresponding to the drive pulse P2. The time point at which compression of the mobile phase ends in an ideal state where no air bubbles are mixed in the plunger pump 11 is known, and can be calculated based on preset mobile phase information and the shape characteristics of the cam 15a.
　予圧動作においては、移動相の圧縮が短時間で終了するように、プランジャが高速で駆動される。移動相の圧縮の終了後、すなわち駆動パルスＰ２に対応する時点の後、プランジャの駆動速度が低下される。この状態で、アクチュエータ１６に駆動パルスがさらに与えられることにより、移動相の圧力が低下することなく逆止弁１４が開放され、プランジャポンプ１１の吐出動作が行われる。 In the preload operation, the plunger is driven at high speed so that the compression of the mobile phase is completed in a short time. After the end of the compression of the mobile phase, ie after the time corresponding to the drive pulse P2, the drive speed of the plunger is reduced. In this state, by further applying a drive pulse to the actuator 16, the check valve 14 is opened without decreasing the pressure of the mobile phase, and the plunger pump 11 performs a discharge operation.
　しかしながら、実際には、プランジャポンプ１１に気泡が混入するため、プランジャポンプ１１の予圧動作において、移動相のみでなく気体の圧縮が行われる。この場合、駆動パルスＰ２に対応する時点では移動相の圧縮が終了しない。そのため、駆動パルスＰ２に対応する時点で、アクチュエータ１６に駆動パルスがさらに与えられても、逆止弁１４は開放されず、プランジャポンプ１１の吐出動作は行われない。 However, in reality, since air bubbles are mixed into the plunger pump 11, not only the mobile phase but also the gas is compressed in the prepressurization operation of the plunger pump 11. In this case, the compression of the mobile phase does not end at the time corresponding to the drive pulse P2. Therefore, even if a further drive pulse is applied to the actuator 16 at the time corresponding to the drive pulse P2, the check valve 14 is not opened and the discharge operation of the plunger pump 11 is not performed.
　プランジャポンプ１１に気泡が混入した状態においては、駆動パルスＰ２に対応する時点の近傍で移動相の圧力が最大になる。その後、アクチュエータ１６に駆動パルスがさらに与えられると、気体の容積分以上のプランジャの押し込みが行われるまで、移動相の圧力が低下する。また、プランジャポンプ１１の予圧動作の終了後、プランジャポンプ１２の吸引動作が開始されるので、気泡の混入量によっては、移動相の圧力は急激に低下する。 When air bubbles are mixed in the plunger pump 11, the pressure of the mobile phase reaches its maximum near the time corresponding to the drive pulse P2. Thereafter, when further driving pulses are applied to the actuator 16, the pressure of the mobile phase decreases until the plunger is pushed in by an amount equal to or more than the volume of the gas. Further, after the pre-pressure operation of the plunger pump 11 is completed, the suction operation of the plunger pump 12 is started, and therefore, depending on the amount of air bubbles mixed in, the pressure of the mobile phase decreases rapidly.
　その後、アクチュエータ１６に複数の駆動パルスが順次与えられる。この場合、駆動パルスＰ３に対応する時点で、逆止弁１４が開放される。この場合、プランジャポンプ１１の吐出動作が開始され、プランジャポンプ１２の最大吸引期間に移動相の圧力が最小になる。その後、移動相の圧力が駆動パルス数に比例して直線的に増加し、駆動パルスＰ４に対応する時点で、逆止弁１４が閉止される。これにより、プランジャポンプ１１の吐出動作が終了する。 After that, a plurality of drive pulses are sequentially applied to the actuator 16. In this case, the check valve 14 is opened at a time corresponding to the drive pulse P3. In this case, the discharge operation of the plunger pump 11 is started, and the pressure of the mobile phase becomes the minimum during the maximum suction period of the plunger pump 12. Thereafter, the pressure of the mobile phase increases linearly in proportion to the number of drive pulses, and at the time corresponding to drive pulse P4, the check valve 14 is closed. This completes the discharge operation of the plunger pump 11.
　その後、アクチュエータ１６に駆動パルスＰ５が与えられるまで、プランジャポンプ１２の吐出動作が行われる。アクチュエータ１６に駆動パルスＰ５が与えられることにより、送液部１０の１つの駆動周期が終了する。この送液部１０の動作が繰り返される。移動相の圧力が最大および最小になる時点は、プランジャポンプ１１に混入する気泡の混入量に応じて送液部１０の駆動周期ごとに変化する。また、移動相の最大の圧力および最小の圧力も、送液部１０の駆動周期ごとに変化する。 Thereafter, the discharge operation of the plunger pump 12 is performed until the drive pulse P5 is applied to the actuator 16. By applying the drive pulse P5 to the actuator 16, one drive cycle of the liquid feeding section 10 ends. This operation of the liquid feeding section 10 is repeated. The point in time when the pressure of the mobile phase reaches its maximum and minimum changes with each driving cycle of the liquid feeding section 10, depending on the amount of bubbles mixed into the plunger pump 11. Further, the maximum pressure and minimum pressure of the mobile phase also change every drive cycle of the liquid feeding section 10.
　（３）制御部の構成
　図４は、図１の制御部３０の構成を示す図である。図４に示すように、制御部３０は、機能部として、圧力取得部３１、最大値特定部３２、最小値特定部３３、変動幅取得部３４、判定部３５、計数部３６、検知部３７および出力部３８を含む。制御部３０のＣＰＵがメモリ等に記憶された送液不良検知プログラムを実行することにより、制御部３０の機能部が実現される。制御部３０の機能部の一部または全部が電子回路等のハードウエアにより実現されてもよい。あるいは、制御部３０の機能部の一部または全部が処理装置１５０により実現されてもよい。 (3) Configuration of control unit FIG. 4 is a diagram showing the configuration of the control unit 30 in FIG. 1. As shown in FIG. 4, the control unit 30 includes a pressure acquisition unit 31, a maximum value identification unit 32, a minimum value identification unit 33, a fluctuation range acquisition unit 34, a determination unit 35, a counting unit 36, and a detection unit 37 as functional units. and an output section 38. The functional units of the control unit 30 are realized by the CPU of the control unit 30 executing a liquid feeding failure detection program stored in a memory or the like. A part or all of the functional units of the control unit 30 may be realized by hardware such as an electronic circuit. Alternatively, some or all of the functional units of the control unit 30 may be realized by the processing device 150.
　圧力取得部３１は、圧力センサ２０により検出された移動相の圧力を所定の周期で取得する。圧力取得部３１による圧力取得の周期は、図１の送液部１０の駆動周期よりも十分に短い。したがって、送液部１０の各駆動周期内における複数時点の圧力が圧力取得部３１により取得される。圧力取得部３１による圧力取得の周期は、送液部１０の駆動周期の１／１０以下であってもよい。 The pressure acquisition unit 31 acquires the pressure of the mobile phase detected by the pressure sensor 20 at a predetermined period. The cycle of pressure acquisition by the pressure acquisition unit 31 is sufficiently shorter than the driving cycle of the liquid feeding unit 10 in FIG. 1 . Therefore, the pressure acquisition unit 31 acquires the pressure at multiple points in time within each driving cycle of the liquid feeding unit 10 . The cycle of pressure acquisition by the pressure acquisition unit 31 may be 1/10 or less of the drive cycle of the liquid feeding unit 10.
　最大値特定部３２は、圧力取得部３１により取得された各駆動周期内における複数の時点の圧力のうち、最大の圧力を特定する。図３には、最大値特定部３２により特定された最大の圧力が丸Ａにより示される。上記のように、図１のプランジャポンプ１１に気泡が混入していない理想的な状態における移動相の圧縮が終了する時点は既知である。そこで、最大値特定部３２は、各駆動周期において移動相の圧縮が終了する時点を含む予め定められた期間内の最大の圧力を特定してもよい。 The maximum value identifying unit 32 identifies the maximum pressure among the pressures at a plurality of times within each drive cycle acquired by the pressure acquiring unit 31. In FIG. 3, the maximum pressure specified by the maximum value specifying section 32 is indicated by a circle A. As described above, the point in time at which compression of the mobile phase ends in an ideal state in which no air bubbles are mixed in the plunger pump 11 of FIG. 1 is known. Therefore, the maximum value specifying unit 32 may specify the maximum pressure within a predetermined period including the time when compression of the mobile phase ends in each drive cycle.
　最小値特定部３３は、圧力取得部３１により取得された各駆動周期内における複数の時点の圧力のうち、最小の圧力を特定する。図３には、最小値特定部３３により特定された最小の圧力が丸Ｂにより示される。上記のように、移動相の圧力は、図１のプランジャポンプ１２の最大吸引期間に最小になる。そこで、最小値特定部３３は、各駆動周期においてプランジャポンプ１２の最大吸引期間内の最小の圧力を特定してもよい。 The minimum value identifying unit 33 identifies the minimum pressure among the pressures at a plurality of times within each drive cycle acquired by the pressure acquiring unit 31. In FIG. 3, the minimum pressure specified by the minimum value specifying section 33 is indicated by a circle B. As mentioned above, the pressure of the mobile phase is at a minimum during the period of maximum suction of plunger pump 12 of FIG. Therefore, the minimum value specifying unit 33 may specify the minimum pressure within the maximum suction period of the plunger pump 12 in each drive cycle.
　変動幅取得部３４は、各駆動周期内における圧力の変動幅を取得する。本例では、最大値特定部３２により特定された各駆動周期内の最大の圧力と、最小値特定部３３により特定された同駆動周期内の最小の圧力との差が算出されることにより、圧力の変動幅が取得される。図３には、変動幅取得部３４により取得された変動幅が点線により示される。 The fluctuation range acquisition unit 34 acquires the pressure fluctuation range within each drive cycle. In this example, by calculating the difference between the maximum pressure within each drive period specified by the maximum value specifying section 32 and the minimum pressure within the same drive period specified by the minimum value specifying section 33, The pressure fluctuation range is obtained. In FIG. 3, the fluctuation range acquired by the fluctuation range acquisition unit 34 is shown by a dotted line.
　判定部３５は、各駆動周期について、変動幅取得部３４により取得された圧力の変動幅が基準値よりも大きいか否かを判定する。基準値は、予め定められた値であってもよいし、使用者により指定された値であってもよい。計数部３６は、判定部３５により圧力の変動幅が基準値よりも大きいと判定された駆動周期の連続数を計数する。 The determination unit 35 determines whether the pressure fluctuation range acquired by the fluctuation range acquisition unit 34 is larger than the reference value for each drive cycle. The reference value may be a predetermined value or a value specified by the user. The counting unit 36 counts the number of consecutive driving cycles in which the determining unit 35 determines that the pressure fluctuation width is larger than the reference value.
　検知部３７は、計数部３６により計数された駆動周期の連続数が予め定められた基準回数よりも大きい場合、プランジャポンプ１１への気泡の混入に起因した送液不良が発生していることを検知する。基準回数は、予め定められた回数であってもよいし、使用者により指定された回数であってもよい。出力部３８は、検知部３７による送液不良の検知結果を処理装置１５０に出力する。 If the number of consecutive drive cycles counted by the counting unit 36 is greater than a predetermined reference number, the detection unit 37 detects that a liquid feeding failure has occurred due to air bubbles entering the plunger pump 11. Detect. The reference number of times may be a predetermined number of times, or may be a number of times specified by the user. The output unit 38 outputs the detection result of poor liquid feeding by the detection unit 37 to the processing device 150.
　処理装置１５０は、送液不良の検知結果が出力された場合、送液部１０により送液された移動相を図１の廃液部２０１に廃棄するように試料供給部１２０を制御してもよい。あるいは、処理装置１５０は、送液不良の検知結果が出力された場合、試料の分析を中断してもよい。また、処理装置１５０は、送液不良の検知結果が出力された場合、その旨を使用者に通知してもよい。 The processing device 150 may control the sample supply unit 120 to discard the mobile phase sent by the liquid delivery unit 10 to the waste liquid unit 201 in FIG. 1 when a detection result of poor liquid delivery is output. . Alternatively, the processing device 150 may interrupt the analysis of the sample when a detection result of poor liquid delivery is output. Furthermore, when a detection result of poor liquid feeding is output, the processing device 150 may notify the user to that effect.
　処理装置１５０による通知の例として、図１のクロマトグラフ２００が表示装置を含む場合には、送液不良が発生したことを示す文字列が表示されてもよい。クロマトグラフ２００が音声出力装置を含む場合には、同様の内容を示す音声が出力されてもよいし、ブザー等の警告音が出力されてもよい。クロマトグラフ２００がランプ等の表示灯を含む場合には、通知の内容に対応する態様で表示灯が点灯、消灯または点滅されてもよい。 As an example of the notification by the processing device 150, if the chromatograph 200 in FIG. 1 includes a display device, a character string indicating that a liquid feeding failure has occurred may be displayed. When the chromatograph 200 includes an audio output device, audio indicating the same content may be output, or a warning sound such as a buzzer may be output. When the chromatograph 200 includes an indicator light such as a lamp, the indicator light may be turned on, turned off, or blinked in a manner corresponding to the content of the notification.
　また、送液部１０の各駆動周期において、変動幅取得部３４により変動幅が取得された後、移動相の圧力が正常に単調増加または単調減少しているか否かが判定されてもよい。例えば、図３において、プランジャポンプ１２の最大吸引期間の終了後、アクチュエータ１６に２駆動パルスが与えられた時点と、アクチュエータ１６に駆動パルスＰ５が与えられた時点との移動相の圧力の差が取得される。この圧力の差が一定の値よりも大きい場合には、移動相の圧力が正常に単調増加または単調減少していると判定されてもよい。 Furthermore, after the fluctuation range is acquired by the fluctuation range acquisition unit 34 in each driving cycle of the liquid feeding unit 10, it may be determined whether the pressure of the mobile phase is normally monotonically increasing or decreasing. For example, in FIG. 3, after the end of the maximum suction period of the plunger pump 12, the difference in mobile phase pressure between the time when two drive pulses are given to the actuator 16 and the time when the drive pulse P5 is given to the actuator 16 is be obtained. If this pressure difference is larger than a certain value, it may be determined that the mobile phase pressure is normally monotonically increasing or monotonically decreasing.
　（４）送液不良検知処理
　図５は、図４の制御部３０による送液不良検知処理の一例を示すフローチャートである。図５の送液不良検知処理は、制御部３０のＣＰＵがメモリ等に記憶された送液不良検知プログラムを実行することにより行われる。以下、図１のクロマトグラフ２００、図４の制御部３０および図５のフローチャートを用いて本実施の形態における送液不良検知処理の一例を説明する。 (4) Liquid feeding failure detection processing FIG. 5 is a flowchart showing an example of liquid feeding failure detection processing performed by the control unit 30 of FIG. 4. The liquid feeding failure detection process in FIG. 5 is performed by the CPU of the control unit 30 executing a liquid feeding failure detection program stored in a memory or the like. Hereinafter, an example of the liquid feeding failure detection process in this embodiment will be described using the chromatograph 200 in FIG. 1, the control unit 30 in FIG. 4, and the flowchart in FIG.
　まず、計数部３６は、変数ｎの値を０に設定する（ステップＳ１）。ここで、変数ｎは、移動相の圧力の変動幅が所定の基準回数を超えた送液部１０の駆動周期の数を示す。次に、圧力取得部３１は、圧力センサ２０により検出された移動相の圧力を送液部１０の駆動周期よりも十分に短い周期で取得する（ステップＳ２）。 First, the counting unit 36 sets the value of the variable n to 0 (step S1). Here, the variable n indicates the number of driving cycles of the liquid feeding unit 10 in which the range of fluctuation in the pressure of the mobile phase exceeds a predetermined reference number of times. Next, the pressure acquisition section 31 acquires the pressure of the mobile phase detected by the pressure sensor 20 at a cycle sufficiently shorter than the drive cycle of the liquid feeding section 10 (step S2).
　続いて、圧力取得部３１は、送液部１０の駆動周期が終了したか否かを判定する（ステップＳ３）。送液部１０の駆動周期が終了していない場合、圧力取得部３１はステップＳ２に戻る。送液部１０の駆動周期が終了するまでステップＳ２，Ｓ３が繰り返される。これにより、送液部１０の１つの駆動周期内における複数時点の圧力が取得される。 Subsequently, the pressure acquisition unit 31 determines whether the driving cycle of the liquid feeding unit 10 has ended (step S3). If the drive cycle of the liquid feeding section 10 has not ended, the pressure acquisition section 31 returns to step S2. Steps S2 and S3 are repeated until the driving cycle of the liquid feeding section 10 ends. Thereby, pressures at multiple points in time within one drive cycle of the liquid feeding section 10 are acquired.
　その後、最大値特定部３２は、ステップＳ２で取得された複数の時点の圧力のうち、最大の圧力を特定する（ステップＳ４）。また、最小値特定部３３は、ステップＳ２で取得された複数の時点の圧力のうち、最小の圧力を特定する（ステップＳ５）。ステップＳ４，Ｓ５は、いずれが先に実行されてもよいし、同時に実行されてもよい。 After that, the maximum value specifying unit 32 specifies the maximum pressure among the pressures at the plurality of times acquired in step S2 (step S4). Moreover, the minimum value specifying unit 33 specifies the minimum pressure among the pressures at the plurality of times acquired in step S2 (step S5). Steps S4 and S5 may be executed either first or at the same time.
　ステップＳ４で、最大値特定部３２は、移動相の圧縮が終了する時点を含む予め定められた期間内の最大の圧力を特定してもよい。また、ステップＳ５で、最小値特定部３３は、プランジャポンプ１２の最大吸引期間内の最小の圧力を特定してもよい。これらの場合、ステップＳ４，Ｓ５は、ステップＳ３の終了前に実行されてもよい。また、この場合においては、ステップＳ４は、ステップＳ５よりも先に実行されてもよい。 In step S4, the maximum value identifying unit 32 may identify the maximum pressure within a predetermined period including the time when compression of the mobile phase ends. Further, in step S5, the minimum value specifying unit 33 may specify the minimum pressure within the maximum suction period of the plunger pump 12. In these cases, steps S4 and S5 may be executed before the end of step S3. Further, in this case, step S4 may be executed before step S5.
　次に、変動幅取得部３４は、ステップＳ４で特定された最大の圧力と、ステップＳ５で特定された最小の圧力との差を算出することにより、圧力の変動幅を取得する（ステップＳ６）。続いて、判定部３５は、ステップＳ６で取得された圧力の変動幅が予め定められた基準値よりも大きいか否かを判定する（ステップＳ７）。 Next, the variation range acquisition unit 34 obtains the pressure variation range by calculating the difference between the maximum pressure identified in step S4 and the minimum pressure identified in step S5 (step S6). . Subsequently, the determining unit 35 determines whether the pressure fluctuation range acquired in step S6 is larger than a predetermined reference value (step S7).
　圧力の変動幅が基準値以下である場合、判定部３５はステップＳ１に戻る。これにより、ステップＳ１で変数ｎが０に設定され、ステップＳ２以降の処理が繰り返される。圧力の変動幅が基準値よりも大きい場合、計数部３６は、変数ｎの値を１だけ増加させる（ステップＳ８）。これにより、圧力の変動幅が基準値よりも大きいと判定された駆動周期の数（連続数）が計数される。その後、検知部３７は、ステップＳ８における変数ｎが基準回数よりも大きいか否かを判定する（ステップＳ９）。基準回数は、２以上の整数であり、本例では５である。 If the pressure fluctuation width is less than or equal to the reference value, the determination unit 35 returns to step S1. As a result, the variable n is set to 0 in step S1, and the processes from step S2 onwards are repeated. If the pressure fluctuation width is larger than the reference value, the counting unit 36 increases the value of the variable n by 1 (step S8). As a result, the number of drive cycles (consecutive number) in which the range of pressure fluctuation is determined to be larger than the reference value is counted. After that, the detection unit 37 determines whether the variable n in step S8 is larger than the reference number of times (step S9). The reference number of times is an integer greater than or equal to 2, and is 5 in this example.
　変数ｎが基準回数以下である場合、検知部３７はステップＳ２に戻る。これにより、変数ｎが維持されたまま、ステップＳ２以降の処理が繰り返される。変数ｎが基準回数よりも大きい場合、検知部３７は、プランジャポンプ１１への気泡の混入に起因した送液不良が発生していることを検知する（ステップＳ１０）。出力部３８は、ステップＳ１０における送液不良の検知結果を処理装置１５０に出力し（ステップＳ１１）、送液不良検知処理を終了する。 If the variable n is less than or equal to the reference number of times, the detection unit 37 returns to step S2. As a result, the process from step S2 onwards is repeated while the variable n is maintained. If the variable n is larger than the reference number of times, the detection unit 37 detects that a liquid feeding failure has occurred due to the inclusion of air bubbles in the plunger pump 11 (step S10). The output unit 38 outputs the detection result of the liquid feeding failure in step S10 to the processing device 150 (step S11), and ends the liquid feeding failure detection process.
　（５）効果
　本実施の形態に係る送液システム１００においては、プランジャポンプ１１，１２を含む直列型ダブルプランジャ方式の送液部１０が周期的に駆動することにより移動相が送液される。送液部１０の各駆動周期内における複数の時点の移動相の圧力が圧力取得部３１により取得される。 (5) Effect In the liquid feeding system 100 according to the present embodiment, the mobile phase is fed by periodically driving the serial double plunger type liquid feeding unit 10 including the plunger pumps 11 and 12. The pressure of the mobile phase at a plurality of times within each driving cycle of the liquid feeding section 10 is acquired by the pressure acquisition section 31 .
　送液部１０の各駆動周期について、圧力取得部３１により取得された圧力のうち、最大の圧力が最大値特定部３２により特定される。また、送液部１０の各駆動周期について、圧力取得部３１により取得された圧力のうち、最小の圧力が最小値特定部３３により特定される。最大値特定部３２により特定された最大の圧力および最小値特定部３３により特定された最小の圧力に基づいて、プランジャポンプ１１への気泡の混入に起因した送液不良が検知部３７により検知される。 For each driving period of the liquid feeding section 10, the maximum pressure among the pressures acquired by the pressure acquisition section 31 is specified by the maximum value specifying section 32. Further, for each drive cycle of the liquid feeding section 10, the minimum pressure among the pressures acquired by the pressure acquisition section 31 is specified by the minimum value specifying section 33. Based on the maximum pressure specified by the maximum value specification section 32 and the minimum pressure specified by the minimum value specification section 33, the detection section 37 detects a liquid feeding failure due to the inclusion of air bubbles in the plunger pump 11. Ru.
　この構成によれば、送液部１０の各駆動周期における移動相の最大の圧力および最小の圧力が特定される。そのため、プランジャポンプ１１への気泡の混入量が小さい場合でも、気泡の混入に起因する移動相の圧力の変化を容易に検知することが可能である。これにより、気泡の混入に起因した送液不良を正確に検知することができる。 According to this configuration, the maximum pressure and minimum pressure of the mobile phase in each driving cycle of the liquid feeding section 10 are specified. Therefore, even when the amount of air bubbles mixed into the plunger pump 11 is small, it is possible to easily detect a change in the pressure of the mobile phase caused by the air bubbles mixed in. This makes it possible to accurately detect liquid feeding failures caused by the inclusion of air bubbles.
　具体的には、変動幅取得部３４は、最大値特定部３２により特定された最大の圧力と、最小値特定部３３により特定された最小の圧力とに基づいて、送液部１０の各駆動周期内における圧力の変動幅を取得する。判定部３５は、送液部１０の各駆動周期について、変動幅取得部３４により取得された圧力の変動幅が基準値よりも大きいか否かを判定する。 Specifically, the fluctuation width acquisition unit 34 determines each drive of the liquid feeding unit 10 based on the maximum pressure specified by the maximum value specification unit 32 and the minimum pressure specified by the minimum value specification unit 33. Obtain the pressure fluctuation range within the period. The determination unit 35 determines whether or not the pressure fluctuation range acquired by the fluctuation range acquisition unit 34 is larger than a reference value for each driving cycle of the liquid feeding unit 10 .
　計数部３６は、判定部３５により圧力の変動幅が基準値よりも大きいと判定された駆動周期の連続数を計数する。検知部３７は、計数部３６により計数された駆動周期の連続数が所定回数よりも大きい場合に送液不良を検知する。これにより、気泡の混入に起因した送液不良をより正確に検知することができる。 The counting unit 36 counts the number of consecutive drive cycles in which the determining unit 35 determines that the pressure fluctuation width is larger than the reference value. The detection unit 37 detects a liquid feeding failure when the number of consecutive driving cycles counted by the counting unit 36 is greater than a predetermined number. This makes it possible to more accurately detect liquid feeding failures caused by the inclusion of air bubbles.
　ここで、最大値特定部３２は、逆止弁１４が開放されるべき時点として予め定められた時点を含む所定期間内に圧力取得部３１により取得された圧力のうち、最大の圧力を取得してもよい。この場合、所定期間外にノイズに起因する移動相の最大の圧力が圧力取得部３１により取得された場合でも、その最大の圧力は最大値特定部３２による特定対象から除外される。 Here, the maximum value identifying unit 32 acquires the maximum pressure among the pressures acquired by the pressure acquiring unit 31 within a predetermined period including a predetermined time point at which the check valve 14 should be opened. It's okay. In this case, even if the maximum pressure of the mobile phase due to noise is acquired by the pressure acquisition unit 31 outside the predetermined period, the maximum pressure is excluded from the identification target by the maximum value identification unit 32.
　また、最小値特定部３３は、プランジャポンプ１２の最大吸引期間内に圧力取得部３１により取得された圧力のうち、最小の圧力を取得してもよい。この場合、プランジャポンプ１２の最大吸引期間外に、ノイズに起因する移動相の最小の圧力が圧力取得部３１により取得された場合でも、その最小の圧力は最小値特定部３３による特定対象から除外される。これらの構成によれば、気泡の混入に起因した送液不良をより正確に検知することができる。 Furthermore, the minimum value identifying unit 33 may acquire the minimum pressure among the pressures acquired by the pressure acquiring unit 31 within the maximum suction period of the plunger pump 12. In this case, even if the minimum pressure of the mobile phase due to noise is acquired by the pressure acquisition unit 31 outside the maximum suction period of the plunger pump 12, the minimum pressure is excluded from the identification target by the minimum value identification unit 33. be done. According to these configurations, it is possible to more accurately detect liquid feeding failure caused by the inclusion of air bubbles.
　（６）参考例
　背景技術で説明されたように、特許文献１においては、一方のプランジャポンプの吐出動作の開始点および終了点における送液圧力の差が第１変動値として求められる。この送液不良の検知方法を図３の移動相の圧力の変化に適用する。図６は、参考例における送液不良の検知方法を説明するための図である。図６に示される移動相の圧力の変化は、図３の移動相の圧力の変化と同じである。 (6) Reference Example As explained in the background art, in Patent Document 1, the difference in liquid feeding pressure between the start point and end point of the discharge operation of one plunger pump is determined as the first fluctuation value. This method of detecting poor liquid feeding is applied to the change in mobile phase pressure shown in FIG. FIG. 6 is a diagram for explaining a method for detecting liquid feeding failure in a reference example. The change in mobile phase pressure shown in FIG. 6 is the same as the change in mobile phase pressure in FIG. 3.
　図６に示すように、プランジャポンプ１１の吐出動作の開始点は、駆動パルスＰ３に対応する時点である。このときの送液圧力が丸Ｃにより示される。また、プランジャポンプ１１の吐出動作の終了点は、駆動パルスＰ４に対応する時点である。このときの送液圧力が丸Ｄにより示される。すなわち、丸Ｃの送液圧力と丸Ｄの送液圧力との差が第１変動値として求められる。 As shown in FIG. 6, the discharge operation of the plunger pump 11 starts at a time corresponding to the drive pulse P3. The liquid feeding pressure at this time is indicated by circle C. Further, the end point of the discharge operation of the plunger pump 11 is a time point corresponding to the drive pulse P4. The liquid feeding pressure at this time is indicated by circle D. That is, the difference between the liquid feeding pressure of circle C and the liquid feeding pressure of circle D is determined as the first fluctuation value.
　この方法により求められた第１変動値の最大値は、図３に示された本実施の形態における圧力の最大値よりも小さい。また、第１変動値の最小値は、図３に示された本実施の形態における圧力の最小値よりも大きい。したがって、第１変動値は、図３に示された本実施の形態における圧力の変動幅よりも小さい。そのため、プランジャポンプ１１に混入する気泡量が小さい場合には、十分に大きい第１変動値は取得されず、送液不良を正確に検知することは困難である。 The maximum value of the first fluctuation value determined by this method is smaller than the maximum value of the pressure in this embodiment shown in FIG. Further, the minimum value of the first fluctuation value is larger than the minimum value of the pressure in the present embodiment shown in FIG. Therefore, the first fluctuation value is smaller than the pressure fluctuation width in this embodiment shown in FIG. Therefore, when the amount of bubbles mixed into the plunger pump 11 is small, a sufficiently large first fluctuation value is not obtained, and it is difficult to accurately detect a liquid feeding failure.
　（７）他の実施の形態
　（ａ）上記実施の形態において、送液部１０の各駆動周期内における圧力の変動幅に基づいて送液不良が検知されるが、実施の形態はこれに限定されない。各駆動周期内の最大の圧力と、最小の圧力とに基づいて決定された任意の評価値に基づいて送液不良が検知されてもよい。 (7) Other Embodiments (a) In the above embodiment, a liquid feeding failure is detected based on the range of pressure fluctuation within each drive cycle of the liquid feeding unit 10, but the embodiment is limited to this. Not done. A liquid feeding failure may be detected based on an arbitrary evaluation value determined based on the maximum pressure and minimum pressure within each drive cycle.
　（ｂ）上記実施の形態において、送液部１０の連続する複数の駆動周期で圧力の変動幅が基準値よりも大きいと判定された場合に送液不良が発生していることが検知されるが、実施の形態はこれに限定されない。送液部１０の１つの駆動周期で圧力の変動幅が基準値よりも大きいと判定された場合に送液不良が発生していることが検知されてもよい。 (b) In the above embodiment, it is detected that a liquid feeding failure has occurred when it is determined that the pressure fluctuation width is larger than the reference value in a plurality of consecutive drive cycles of the liquid feeding unit 10. However, the embodiment is not limited thereto. It may be detected that a liquid feeding failure has occurred when it is determined that the pressure fluctuation range is larger than a reference value in one driving cycle of the liquid feeding unit 10.
　（ｃ）上記実施の形態において、送液部１０は直列型ダブルプランジャ方式で構成されるが、実施の形態はこれに限定されない。送液部１０は、並列型ダブルプランジャ方式で構成されてもよい。 (c) In the above embodiment, the liquid feeding section 10 is configured with a serial double plunger system, but the embodiment is not limited to this. The liquid feeding section 10 may be configured with a parallel double plunger system.
　並列型ダブルプランジャ方式においては、最大値特定部３２は、送液部１０の各駆動周期について、プランジャポンプ１１による移動相の吐出動作に起因する第１の最大の圧力を特定する。また、最大値特定部３２は、送液部１０の各駆動周期について、プランジャポンプ１２による移動相の吐出動作に起因する第２の最大の圧力を特定する。 In the parallel double plunger method, the maximum value identifying unit 32 identifies the first maximum pressure resulting from the mobile phase discharge operation by the plunger pump 11 for each driving cycle of the liquid feeding unit 10. Further, the maximum value specifying unit 32 specifies the second maximum pressure caused by the discharge operation of the mobile phase by the plunger pump 12 for each drive cycle of the liquid feeding unit 10 .
　最小値特定部３３は、送液部１０の各駆動周期について、プランジャポンプ１１による移動相の吐出動作に起因する第１の最小の圧力を特定する。また、最小値特定部３３は、送液部１０の各駆動周期について、プランジャポンプ１２による移動相の吐出動作に起因する第２の最小の圧力を特定する。 The minimum value identifying unit 33 identifies the first minimum pressure resulting from the mobile phase discharge operation by the plunger pump 11 for each driving cycle of the liquid feeding unit 10. Further, the minimum value specifying unit 33 specifies the second minimum pressure caused by the discharge operation of the mobile phase by the plunger pump 12 for each driving cycle of the liquid feeding unit 10 .
　検知部３７は、送液部１０の各駆動周期について、最大値特定部３２により特定された第１の最大の圧力および最小値特定部３３により特定された第１の最小の圧力に基づいて、プランジャポンプ１１への気泡の混入に起因した送液不良を検知する。また、検知部３７は、送液部１０の各駆動周期について、最大値特定部３２により特定された第２の最大の圧力および最小値特定部３３により特定された第２の最小の圧力に基づいて、プランジャポンプ１２への気泡の混入に起因した送液不良を検知する。 The detection unit 37 detects the first maximum pressure specified by the maximum value specification unit 32 and the first minimum pressure specified by the minimum value specification unit 33 for each drive period of the liquid feeding unit 10, A liquid feeding failure caused by air bubbles entering the plunger pump 11 is detected. The detection unit 37 also detects the second maximum pressure specified by the maximum value specification unit 32 and the second minimum pressure specified by the minimum value specification unit 33 for each drive period of the liquid feeding unit 10. Then, a liquid feeding failure caused by air bubbles entering the plunger pump 12 is detected.
　（ｄ）上記実施の形態において、送液部１０は２つのプランジャポンプ１１，１２を含むが、実施の形態はこれに限定されない。送液部１０は、１つのプランジャポンプ１１を含むシングルプランジャ方式で構成されてもよい。 (d) In the above embodiment, the liquid feeding section 10 includes two plunger pumps 11 and 12, but the embodiment is not limited to this. The liquid feeding section 10 may be configured with a single plunger system including one plunger pump 11.
　シングルプランジャ方式においては、最大値特定部３２は、送液部１０の各駆動周期について、プランジャポンプ１１の吐出動作時の最大の圧力を特定する。最小値特定部３３は、送液部１０の各駆動周期について、プランジャポンプ１１の吐出動作時の最小の圧力を特定する。検知部３７は、送液部１０の各駆動周期について、最大値特定部３２により特定された最大の圧力および最小値特定部３３により特定された最小の圧力に基づいて送液不良を検知する。 In the single plunger method, the maximum value specifying unit 32 specifies the maximum pressure during the discharge operation of the plunger pump 11 for each driving cycle of the liquid feeding unit 10. The minimum value identifying unit 33 identifies the minimum pressure during the discharge operation of the plunger pump 11 for each drive cycle of the liquid feeding unit 10 . The detection unit 37 detects a liquid feeding failure based on the maximum pressure specified by the maximum value identification unit 32 and the minimum pressure specified by the minimum value identification unit 33 for each drive period of the liquid feeding unit 10.
　（８）態様
　上記の複数の例示的な実施の形態は、以下の態様の具体例であることが当業者により理解される。 (8) Aspects Those skilled in the art will understand that the multiple exemplary embodiments described above are specific examples of the following aspects.
　（第１項）一態様に係るクロマトグラフ用送液システムは、
　１以上のプランジャポンプを含み、周期的に駆動することにより移動相を送液する送液部と、
　前記送液部の各駆動周期内における複数の時点の移動相の圧力を取得する圧力取得部と、
　前記送液部の各駆動周期について、前記圧力取得部により取得された圧力のうち、最大の圧力を特定する最大値特定部と、
　前記送液部の各駆動周期について、前記圧力取得部により取得された圧力のうち、最小の圧力を特定する最小値特定部と、
　前記最大値特定部により特定された最大の圧力および前記最小値特定部により特定された最小の圧力に基づいて、前記１以上のプランジャポンプへの気泡の混入に起因した送液不良を検知する検知部とを備えてもよい。 (Section 1) The chromatographic liquid delivery system according to one embodiment includes:
a liquid sending section that includes one or more plunger pumps and that sends the mobile phase by being driven periodically;
a pressure acquisition unit that acquires the pressure of the mobile phase at a plurality of times within each driving cycle of the liquid feeding unit;
a maximum value identifying unit that identifies a maximum pressure among the pressures acquired by the pressure acquiring unit for each driving cycle of the liquid feeding unit;
a minimum value identifying unit that identifies a minimum pressure among the pressures acquired by the pressure acquiring unit for each driving cycle of the liquid feeding unit;
Detection of a liquid feeding failure caused by air bubbles being mixed into the one or more plunger pumps based on the maximum pressure specified by the maximum value specifying section and the minimum pressure specified by the minimum value specifying section. It may also include a section.
　このクロマトグラフ用送液システムにおいては、送液部の各駆動周期における移動相の最大の圧力および最小の圧力が特定される。そのため、プランジャポンプへの気泡の混入量が小さい場合でも、気泡の混入に起因する移動相の圧力の変化を容易に検知することが可能である。これにより、気泡の混入に起因した送液不良を正確に検知することができる。 In this liquid feeding system for chromatography, the maximum pressure and minimum pressure of the mobile phase in each driving cycle of the liquid feeding section are specified. Therefore, even if the amount of air bubbles mixed into the plunger pump is small, it is possible to easily detect a change in the pressure of the mobile phase caused by the air bubbles mixed in. This makes it possible to accurately detect liquid feeding failures caused by the inclusion of air bubbles.
　（第２項）第１項に記載のクロマトグラフ用送液システムは、
　前記最大値特定部により特定された最大の圧力と、前記最小値特定部により特定された最小の圧力とに基づいて、前記送液部の各駆動周期内における圧力の変動幅を取得する変動幅取得部をさらに備え、
　前記検知部は、前記変動幅取得部により取得された圧力の変動幅に基づいて送液不良を検知してもよい。 (Section 2) The chromatographic liquid delivery system described in Section 1,
a fluctuation range for obtaining a pressure fluctuation range within each drive cycle of the liquid feeding unit based on the maximum pressure identified by the maximum value identification unit and the minimum pressure identified by the minimum value identification unit; It further includes an acquisition section,
The detection unit may detect a liquid feeding failure based on the pressure fluctuation range acquired by the fluctuation range acquisition unit.
　この場合、気泡の混入に起因した送液不良を容易に検知することができる。 In this case, it is possible to easily detect a liquid feeding failure caused by the inclusion of air bubbles.
　（第３項）第２項に記載のクロマトグラフ用送液システムは、
　前記送液部の各駆動周期について、前記変動幅取得部により取得された圧力の変動幅が基準値よりも大きいか否かを判定する判定部をさらに備え、
　前記検知部は、前記判定部により圧力の変動幅が基準値よりも大きいと判定された場合に送液不良を検知してもよい。 (Section 3) The chromatographic liquid delivery system described in Section 2,
further comprising a determination unit that determines whether or not the pressure fluctuation range acquired by the fluctuation range acquisition unit is larger than a reference value for each drive cycle of the liquid feeding unit;
The detection unit may detect a liquid feeding failure when the determination unit determines that the pressure fluctuation range is larger than a reference value.
　この場合、気泡の混入に起因した送液不良をより容易に検知することができる。 In this case, it is possible to more easily detect a liquid feeding failure caused by the inclusion of air bubbles.
　（第４項）第３項に記載のクロマトグラフ用送液システムは、
　前記判定部により圧力の変動幅が基準値よりも大きいと判定された駆動周期の連続数を計数する計数部をさらに備え、
　前記検知部は、前記計数部により計数された駆動周期の連続数が所定回数よりも大きい場合に送液不良を検知してもよい。 (Section 4) The chromatographic liquid delivery system described in Section 3,
further comprising a counting unit that counts the number of consecutive driving cycles in which the pressure fluctuation width is determined to be larger than a reference value by the determining unit,
The detection unit may detect a liquid feeding failure when the number of consecutive driving cycles counted by the counting unit is greater than a predetermined number of times.
　この場合、気泡の混入に起因した送液不良をより正確に検知することができる。 In this case, it is possible to more accurately detect liquid feeding failures due to the inclusion of air bubbles.
　（第５項）第１項～第４項のいずれか一項に記載のクロマトグラフ用送液システムにおいて、
　前記送液部は、前記１以上のプランジャポンプとして、直列に接続され、相補的に駆動する第１のプランジャポンプおよび第２のプランジャポンプを含み、
　前記第２のプランジャポンプは、前記第１のプランジャポンプの下流に配置され、前記第１のプランジャポンプと前記第２のプランジャポンプとの間に逆止弁が配置され、
　前記第１のプランジャポンプは、移動相の吐出動作の前に、前記逆止弁が開放されるべき時点として予め定められた時点まで移動相を圧縮し、
　前記最大値特定部は、前記予め定められた時点を含む所定期間内に前記圧力取得部により取得された圧力のうち、最大の圧力を取得してもよい。 (Section 5) In the chromatographic liquid delivery system according to any one of Items 1 to 4,
The liquid feeding unit includes a first plunger pump and a second plunger pump that are connected in series and driven complementary to each other as the one or more plunger pumps,
The second plunger pump is arranged downstream of the first plunger pump, and a check valve is arranged between the first plunger pump and the second plunger pump,
The first plunger pump compresses the mobile phase to a predetermined time point at which the check valve is to be opened, before discharging the mobile phase,
The maximum value identifying section may acquire the maximum pressure among the pressures acquired by the pressure acquiring section within a predetermined period including the predetermined time.
　この場合、送液部は、直列型ダブルプランジャ方式で構成される。ここで、上記の所定期間外に、ノイズに起因する移動相の最大の圧力が圧力取得部により取得された場合でも、その最大の圧力は最大値特定部による特定対象から除外される。これにより、気泡の混入に起因した送液不良をより正確に検知することができる。 In this case, the liquid feeding section is configured with an in-line double plunger system. Here, even if the maximum pressure of the mobile phase due to noise is acquired by the pressure acquisition unit outside the above-mentioned predetermined period, the maximum pressure is excluded from the identification target by the maximum value identification unit. This makes it possible to more accurately detect liquid feeding failures caused by the inclusion of air bubbles.
　（第６項）第１項～第４項のいずれか一項に記載のクロマトグラフ用送液システムにおいて、
　前記送液部は、前記１以上のプランジャポンプとして、直列に接続され、相補的に駆動する第１のプランジャポンプおよび第２のプランジャポンプを含み、
　前記第２のプランジャポンプは、前記第１のプランジャポンプの下流に配置され、
　前記最小値特定部は、前記第２のプランジャポンプにより吸引動作が行われている期間内に前記圧力取得部により取得された圧力のうち、最小の圧力を取得してもよい。 (Section 6) In the chromatographic liquid delivery system according to any one of Items 1 to 4,
The liquid feeding unit includes a first plunger pump and a second plunger pump that are connected in series and driven complementary to each other as the one or more plunger pumps,
the second plunger pump is located downstream of the first plunger pump,
The minimum value identifying section may acquire the minimum pressure among the pressures acquired by the pressure acquiring section within a period in which the second plunger pump is performing a suction operation.
　この場合、送液部は、直列型ダブルプランジャ方式で構成される。ここで、第２のプランジャポンプにより吸引動作が行われている期間外に、ノイズに起因する移動相の最小の圧力が圧力取得部により取得された場合でも、その最小の圧力は最小値特定部による特定対象から除外される。これにより、気泡の混入に起因した送液不良をより正確に検知することができる。 In this case, the liquid feeding section is configured with an in-line double plunger system. Here, even if the minimum pressure of the mobile phase due to noise is acquired by the pressure acquisition section outside the period when the suction operation is performed by the second plunger pump, the minimum pressure is determined by the minimum value identification section. excluded from specific targets. This makes it possible to more accurately detect liquid feeding failures caused by the inclusion of air bubbles.
　（第７項）第１項～第４項のいずれか一項に記載のクロマトグラフ用送液システムにおいて、
　前記送液部は、前記１以上のプランジャポンプとして、並列に接続され、相補的に駆動する第１のプランジャポンプおよび第２のプランジャポンプを含み、
　前記最大値特定部は、前記送液部の各駆動周期について、前記第１のプランジャポンプによる移動相の吐出動作に起因する第１の最大の圧力を特定するとともに、前記第２のプランジャポンプによる移動相の吐出動作に起因する第２の最大の圧力を特定し、
　前記最小値特定部は、前記送液部の各駆動周期について、前記第１のプランジャポンプによる移動相の吐出動作に起因する第１の最小の圧力を特定するとともに、前記第２のプランジャポンプによる移動相の吐出動作に起因する第２の最小の圧力を特定し、
　前記検知部は、前記最大値特定部により特定された第１の最大の圧力および前記最小値特定部により特定された第１の最小の圧力に基づいて、前記第１のプランジャポンプへの気泡の混入に起因した送液不良を検知し、前記最大値特定部により特定された第２の最大の圧力および前記最小値特定部により特定された第２の最小の圧力に基づいて、前記第２のプランジャポンプへの気泡の混入に起因した送液不良を検知してもよい。 (Section 7) In the chromatographic liquid delivery system according to any one of Items 1 to 4,
The liquid feeding unit includes a first plunger pump and a second plunger pump that are connected in parallel and driven complementary to each other as the one or more plunger pumps,
The maximum value specifying unit specifies, for each driving cycle of the liquid feeding unit, a first maximum pressure caused by the mobile phase discharging operation by the first plunger pump, and a first maximum pressure caused by the mobile phase discharging operation by the second plunger pump. identifying a second maximum pressure resulting from the dispensing operation of the mobile phase;
The minimum value specifying unit specifies, for each drive cycle of the liquid feeding unit, a first minimum pressure caused by the mobile phase discharging operation by the first plunger pump, and a first minimum pressure caused by the mobile phase discharging operation by the second plunger pump. identifying a second minimum pressure resulting from a dispensing operation of the mobile phase;
The detection unit detects air bubbles to the first plunger pump based on the first maximum pressure specified by the maximum value specification unit and the first minimum pressure specified by the minimum value specification unit. Detecting a liquid feeding failure due to contamination, the second maximum pressure specified by the maximum value specifying section and the second minimum pressure specified by the minimum value specifying section A liquid feeding failure caused by air bubbles entering the plunger pump may also be detected.
　この構成によれば、並列型ダブルプランジャ方式の送液部においても、気泡の混入に起因した送液不良を正確に検知することができる。 According to this configuration, it is possible to accurately detect a liquid feeding failure caused by the inclusion of air bubbles even in a parallel double plunger type liquid feeding section.
　（第８項）他の態様に係るクロマトグラフ用送液方法は、
　１以上のプランジャポンプを含む送液部が周期的に駆動することにより移動相を送液することと、
　前記送液部の各駆動周期内における複数の時点の移動相の圧力を取得することと、
　前記送液部の各駆動周期について、取得された圧力のうち、最大の圧力を特定することと、
　前記送液部の各駆動周期について、取得された圧力のうち、最小の圧力を特定することと、
　特定された最大の圧力および特定された最小の圧力に基づいて、前記１以上のプランジャポンプへの気泡の混入に起因した送液不良を検知することとを含んでもよい。 (Section 8) A chromatographic liquid feeding method according to another aspect includes:
Sending the mobile phase by periodically driving a liquid feeding section including one or more plunger pumps;
Obtaining the pressure of the mobile phase at a plurality of times within each driving cycle of the liquid feeding section;
Identifying the maximum pressure among the acquired pressures for each drive cycle of the liquid feeding section;
Identifying the minimum pressure among the acquired pressures for each drive cycle of the liquid feeding section;
The method may also include detecting a liquid feeding failure due to air bubbles being mixed into the one or more plunger pumps based on the specified maximum pressure and the specified minimum pressure.
　このクロマトグラフ用送液方法によれば、送液部の各駆動周期における移動相の最大の圧力および最小の圧力が特定される。そのため、プランジャポンプへの気泡の混入量が小さい場合でも、気泡の混入に起因する移動相の圧力の変化を容易に検知することが可能である。これにより、気泡の混入に起因した送液不良を正確に検知することができる。 According to this liquid feeding method for chromatography, the maximum pressure and minimum pressure of the mobile phase in each drive cycle of the liquid feeding section are specified. Therefore, even if the amount of air bubbles mixed into the plunger pump is small, it is possible to easily detect a change in the pressure of the mobile phase caused by the air bubbles mixed in. This makes it possible to accurately detect liquid feeding failures caused by the inclusion of air bubbles.

Claims (8)

  1. １以上のプランジャポンプを含み、周期的に駆動することにより移動相を送液する送液部と、
    　前記送液部の各駆動周期内における複数の時点の移動相の圧力を取得する圧力取得部と、
    　前記送液部の各駆動周期について、前記圧力取得部により取得された圧力のうち、最大の圧力を特定する最大値特定部と、
    　前記送液部の各駆動周期について、前記圧力取得部により取得された圧力のうち、最小の圧力を特定する最小値特定部と、
    　前記最大値特定部により特定された最大の圧力および前記最小値特定部により特定された最小の圧力に基づいて、前記１以上のプランジャポンプへの気泡の混入に起因した送液不良を検知する検知部とを備える、クロマトグラフ用送液システム。     a liquid sending section that includes one or more plunger pumps and that sends the mobile phase by being driven periodically;
    a pressure acquisition unit that acquires the pressure of the mobile phase at a plurality of times within each driving cycle of the liquid feeding unit;
    a maximum value identifying unit that identifies a maximum pressure among the pressures acquired by the pressure acquiring unit for each driving cycle of the liquid feeding unit;
    a minimum value identifying unit that identifies a minimum pressure among the pressures acquired by the pressure acquiring unit for each driving cycle of the liquid feeding unit;
    Detection of a liquid feeding failure caused by air bubbles being mixed into the one or more plunger pumps based on the maximum pressure specified by the maximum value specifying section and the minimum pressure specified by the minimum value specifying section. A liquid delivery system for chromatography, comprising:
  2. 前記最大値特定部により特定された最大の圧力と、前記最小値特定部により特定された最小の圧力とに基づいて、前記送液部の各駆動周期内における圧力の変動幅を取得する変動幅取得部をさらに備え、
    　前記検知部は、前記変動幅取得部により取得された圧力の変動幅に基づいて送液不良を検知する、請求項１記載のクロマトグラフ用送液システム。     a fluctuation range for obtaining a pressure fluctuation range within each drive cycle of the liquid feeding unit based on the maximum pressure identified by the maximum value identification unit and the minimum pressure identified by the minimum value identification unit; It further includes an acquisition section,
    The liquid feeding system for chromatography according to claim 1, wherein the detection unit detects a liquid feeding failure based on the pressure fluctuation range acquired by the fluctuation range acquisition unit.
  3. 前記送液部の各駆動周期について、前記変動幅取得部により取得された圧力の変動幅が基準値よりも大きいか否かを判定する判定部をさらに備え、
    　前記検知部は、前記判定部により圧力の変動幅が基準値よりも大きいと判定された場合に送液不良を検知する、請求項２記載のクロマトグラフ用送液システム。     further comprising a determination unit that determines whether or not the pressure fluctuation range acquired by the fluctuation range acquisition unit is larger than a reference value for each drive cycle of the liquid feeding unit;
    3. The liquid feeding system for chromatography according to claim 2, wherein the detection unit detects a liquid feeding failure when the determination unit determines that the range of pressure fluctuation is larger than a reference value.
  4. 前記判定部により圧力の変動幅が基準値よりも大きいと判定された駆動周期の連続数を計数する計数部をさらに備え、
    　前記検知部は、前記計数部により計数された駆動周期の連続数が所定回数よりも大きい場合に送液不良を検知する、請求項３記載のクロマトグラフ用送液システム。     further comprising a counting unit that counts the number of consecutive driving cycles in which the pressure fluctuation width is determined to be larger than a reference value by the determining unit,
    4. The liquid feeding system for chromatography according to claim 3, wherein the detection unit detects a liquid feeding failure when the number of consecutive driving cycles counted by the counting unit is greater than a predetermined number of times.
  5. 前記送液部は、前記１以上のプランジャポンプとして、直列に接続され、相補的に駆動する第１のプランジャポンプおよび第２のプランジャポンプを含み、
    　前記第２のプランジャポンプは、前記第１のプランジャポンプの下流に配置され、前記第１のプランジャポンプと前記第２のプランジャポンプとの間に逆止弁が配置され、
    　前記第１のプランジャポンプは、移動相の吐出動作の前に、前記逆止弁が開放されるべき時点として予め定められた時点まで移動相を圧縮し、
    　前記最大値特定部は、前記予め定められた時点を含む所定期間内に前記圧力取得部により取得された圧力のうち、最大の圧力を取得する、請求項１記載のクロマトグラフ用送液システム。     The liquid feeding unit includes a first plunger pump and a second plunger pump that are connected in series and driven complementary to each other as the one or more plunger pumps,
    The second plunger pump is arranged downstream of the first plunger pump, and a check valve is arranged between the first plunger pump and the second plunger pump,
    The first plunger pump compresses the mobile phase to a predetermined time point at which the check valve is to be opened, before discharging the mobile phase,
    2. The liquid feeding system for chromatography according to claim 1, wherein the maximum value specifying section obtains the maximum pressure among the pressures obtained by the pressure obtaining section within a predetermined period including the predetermined time.
  6. 前記送液部は、前記１以上のプランジャポンプとして、直列に接続され、相補的に駆動する第１のプランジャポンプおよび第２のプランジャポンプを含み、
    　前記第２のプランジャポンプは、前記第１のプランジャポンプの下流に配置され、
    　前記最小値特定部は、前記第２のプランジャポンプにより吸引動作が行われている期間内に前記圧力取得部により取得された圧力のうち、最小の圧力を取得する、請求項１記載のクロマトグラフ用送液システム。     The liquid feeding unit includes a first plunger pump and a second plunger pump that are connected in series and driven complementary to each other as the one or more plunger pumps,
    the second plunger pump is located downstream of the first plunger pump,
    The chromatograph according to claim 1, wherein the minimum value identifying unit acquires the minimum pressure among the pressures acquired by the pressure acquiring unit during a period in which the second plunger pump performs a suction operation. liquid delivery system.
  7. 前記送液部は、前記１以上のプランジャポンプとして、並列に接続され、相補的に駆動する第１のプランジャポンプおよび第２のプランジャポンプを含み、
    　前記最大値特定部は、前記送液部の各駆動周期について、前記第１のプランジャポンプによる移動相の吐出動作に起因する第１の最大の圧力を特定するとともに、前記第２のプランジャポンプによる移動相の吐出動作に起因する第２の最大の圧力を特定し、
    　前記最小値特定部は、前記送液部の各駆動周期について、前記第１のプランジャポンプによる移動相の吐出動作に起因する第１の最小の圧力を特定するとともに、前記第２のプランジャポンプによる移動相の吐出動作に起因する第２の最小の圧力を特定し、
    　前記検知部は、前記最大値特定部により特定された第１の最大の圧力および前記最小値特定部により特定された第１の最小の圧力に基づいて、前記第１のプランジャポンプへの気泡の混入に起因した送液不良を検知し、前記最大値特定部により特定された第２の最大の圧力および前記最小値特定部により特定された第２の最小の圧力に基づいて、前記第２のプランジャポンプへの気泡の混入に起因した送液不良を検知する、請求項１記載のクロマトグラフ用送液システム。     The liquid feeding unit includes a first plunger pump and a second plunger pump that are connected in parallel and driven complementary to each other as the one or more plunger pumps,
    The maximum value specifying unit specifies, for each driving cycle of the liquid feeding unit, a first maximum pressure caused by the mobile phase discharging operation by the first plunger pump, and a first maximum pressure caused by the mobile phase discharging operation by the second plunger pump. identifying a second maximum pressure resulting from the dispensing operation of the mobile phase;
    The minimum value specifying unit specifies, for each drive cycle of the liquid feeding unit, a first minimum pressure caused by the mobile phase discharging operation by the first plunger pump, and a first minimum pressure caused by the mobile phase discharging operation by the second plunger pump. identifying a second minimum pressure resulting from a dispensing operation of the mobile phase;
    The detection unit detects air bubbles to the first plunger pump based on the first maximum pressure specified by the maximum value specification unit and the first minimum pressure specified by the minimum value specification unit. Detecting a liquid feeding failure due to contamination, the second maximum pressure specified by the maximum value specifying section and the second minimum pressure specified by the minimum value specifying section 2. The liquid feeding system for chromatography according to claim 1, wherein a liquid feeding failure caused by air bubbles being mixed into the plunger pump is detected.
  8. １以上のプランジャポンプを含む送液部が周期的に駆動することにより移動相を送液することと、
    　前記送液部の各駆動周期内における複数の時点の移動相の圧力を取得することと、
    　前記送液部の各駆動周期について、取得された圧力のうち、最大の圧力を特定することと、
    　前記送液部の各駆動周期について、取得された圧力のうち、最小の圧力を特定することと、
    　特定された最大の圧力および特定された最小の圧力に基づいて、前記１以上のプランジャポンプへの気泡の混入に起因した送液不良を検知することとを含む、クロマトグラフ用送液方法。     Sending the mobile phase by periodically driving a liquid feeding section including one or more plunger pumps;
    Obtaining the pressure of the mobile phase at a plurality of times within each driving cycle of the liquid feeding section;
    Identifying the maximum pressure among the acquired pressures for each drive cycle of the liquid feeding section;
    Identifying the minimum pressure among the acquired pressures for each drive cycle of the liquid feeding section;
    A liquid feeding method for a chromatography, the method comprising: detecting a liquid feeding failure due to air bubbles being mixed into the one or more plunger pumps based on the specified maximum pressure and the specified minimum pressure.
PCT/JP2023/010443 2022-05-12 2023-03-16 Chromatograph liquid delivery system, and chromatograph liquid delivery method WO2023218758A1 (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000130353A (en) * 1998-10-30 2000-05-12 Shimadzu Corp Liquid feeding pump
WO2020183684A1 (en) * 2019-03-13 2020-09-17 株式会社島津製作所 Liquid chromatograph
WO2020183774A1 (en) * 2019-03-13 2020-09-17 株式会社島津製作所 Liquid feeding system for liquid chromatography

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000130353A (en) * 1998-10-30 2000-05-12 Shimadzu Corp Liquid feeding pump
WO2020183684A1 (en) * 2019-03-13 2020-09-17 株式会社島津製作所 Liquid chromatograph
WO2020183774A1 (en) * 2019-03-13 2020-09-17 株式会社島津製作所 Liquid feeding system for liquid chromatography

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