WO2023218758A1 - Système de distribution de liquide de chromatographe et procédé de distribution de liquide de chromatographe - Google Patents

Système de distribution de liquide de chromatographe et procédé de distribution de liquide de chromatographe 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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English (en)
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/fr

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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.

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  • Immunology (AREA)
  • Pathology (AREA)
  • Control Of Positive-Displacement Pumps (AREA)

Abstract

L'invention concerne un système de distribution de liquide de chromatographe qui comprend une unité de distribution de liquide, une unité d'acquisition de pression, une unité d'identification de valeur maximale, une unité d'identification de valeur minimale et une unité de détection. L'unité de distribution de liquide comprend une ou plusieurs pompes à piston, et est périodiquement entraînée pour distribuer une phase mobile. L'unité d'acquisition de pression acquiert une pression de la phase mobile à une pluralité d'instants pendant chaque cycle d'entraînement de l'unité de distribution de liquide. L'unité d'identification de valeur maximale identifie une pression maximale, parmi les pressions acquises par l'unité d'acquisition de pression, pour chaque cycle d'entraînement de l'unité de distribution de liquide. L'unité d'identification de valeur minimale identifie une pression minimale, parmi les pressions acquises par l'unité d'acquisition de pression, pour chaque cycle d'entraînement de l'unité de distribution de liquide. L'unité de détection détecte une défaillance d'apport de liquide résultant d'une contamination par des bulles dans les une ou plusieurs pompes à piston, sur la base de la pression maximale et de la pression minimale identifiées.
PCT/JP2023/010443 2022-05-12 2023-03-16 Système de distribution de liquide de chromatographe et procédé de distribution de liquide de chromatographe WO2023218758A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000130353A (ja) * 1998-10-30 2000-05-12 Shimadzu Corp 送液ポンプ
WO2020183774A1 (fr) * 2019-03-13 2020-09-17 株式会社島津製作所 Système d'alimentation en liquide pour chromatographie en phase liquide
WO2020183684A1 (fr) * 2019-03-13 2020-09-17 株式会社島津製作所 Chromatographe en phase liquide

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000130353A (ja) * 1998-10-30 2000-05-12 Shimadzu Corp 送液ポンプ
WO2020183774A1 (fr) * 2019-03-13 2020-09-17 株式会社島津製作所 Système d'alimentation en liquide pour chromatographie en phase liquide
WO2020183684A1 (fr) * 2019-03-13 2020-09-17 株式会社島津製作所 Chromatographe en phase liquide

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