Chromatographic liquid delivery system and chromatographic liquid delivery method

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

[Technical Field]

[0001] The present invention relates to a chromatographic liquid delivery system and a chromatographic liquid delivery method. [Background technology]

[0002] A liquid chromatography delivery system may be provided with a function for detecting liquid delivery failures caused by the generation of bubbles in the solvent so that the solvent serving as the mobile phase can be delivered stably. For example, in the liquid chromatography delivery system described in Patent Document 1, the liquid is continuously delivered by a delivery mechanism including two plunger pumps. The system also reads fluctuations in the delivery pressure within one drive cycle of the delivery mechanism.

[0003] Here, the difference in liquid delivery pressure between the start and end points of the discharge operation of one plunger pump is calculated as a first fluctuation value, and the difference in liquid delivery pressure between the start and end points of the discharge operation of the other plunger pump is calculated as a second fluctuation value. If only one of the first fluctuation value and the second fluctuation value is positive, a fluctuation range of the liquid delivery pressure is calculated based on the first fluctuation value and the second fluctuation value. If the number of consecutive periods in which the calculated fluctuation range exceeds a predetermined reference value reaches a predetermined reference number, a liquid delivery failure due to air bubbles entering the plunger pump is detected.

[0004] [Patent Document 1] International Publication No. 2020 / 183774 Summary of the Invention [Problem to be solved by the invention]

[0005] The method described in Patent Document 1 can detect a liquid transfer failure when the amount of air bubbles mixed into the plunger pump is relatively large. However, it is difficult to detect a liquid transfer failure when the amount of air bubbles mixed into the plunger pump is small. Therefore, there is a need for a method to detect a liquid transfer failure more accurately.

[0006] An object of the present invention is to provide a chromatographic liquid delivery system and a chromatographic liquid delivery method that are capable of accurately detecting liquid delivery failures. [Means for solving the problem]

[0007] One aspect of the present invention includes a liquid delivery unit that includes one or more plunger pumps and delivers a mobile phase by periodically driving the pumps; a pressure acquisition unit that acquires pressures of the mobile phase at multiple points in each drive cycle of the liquid delivery unit; a maximum value identification unit that identifies a maximum pressure among the pressures acquired by the pressure acquisition unit for each drive cycle of the liquid delivery unit; a minimum value identification unit that identifies a minimum pressure among the pressures acquired by the pressure acquisition unit for each drive cycle of the liquid delivery unit; and a detection unit that detects a liquid delivery failure due to the intrusion of air bubbles into the one or more plunger pumps based on the maximum pressure identified by the maximum value identification unit and the minimum pressure identified by the minimum value identification unit. The one or more plunger pumps include a first plunger pump and a second plunger pump connected in series and driven complementarily, the second plunger pump is disposed downstream of the first plunger pump, a check valve is disposed between the first plunger pump and the second plunger pump, the first plunger pump compresses the mobile phase until a time point that is predetermined as a time point at which the check valve should be opened before discharging the mobile phase, and the maximum value specifying unit obtains a maximum pressure among pressures obtained by the pressure obtaining unit within a predetermined period including the predetermined time point. The present invention relates to a liquid delivery system for chromatography.

[0008] Another aspect of the present invention includes periodically driving a liquid delivery unit including one or more plunger pumps to deliver a mobile phase; acquiring pressures of the mobile phase at multiple points in each drive cycle of the liquid delivery unit; identifying a maximum pressure among the acquired pressures for each drive cycle of the liquid delivery unit; identifying a minimum pressure among the acquired pressures for each drive cycle of the liquid delivery unit; and detecting a liquid delivery 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 one or more plunger pumps include a first plunger pump and a second plunger pump connected in series and driven complementarily, the second plunger pump being disposed downstream of the first plunger pump, a check valve being disposed between the first plunger pump and the second plunger pump, the first plunger pump compressing the mobile phase until a predetermined time point at which the check valve should be opened before discharging the mobile phase, and identifying the maximum pressure includes obtaining a maximum pressure among pressures obtained within a predetermined period of time including the predetermined time point. The present invention relates to a method for delivering a liquid to a chromatograph. [Effects of the Invention]

[0009] According to the present invention, a liquid transfer failure can be accurately detected. [Brief explanation of the drawings]

[0010] [Figure 1] FIG. 1 is a diagram showing the configuration of a chromatograph including a liquid delivery system according to one embodiment of the present invention. [Figure 2] FIG. 2 is a diagram for explaining the shape characteristics of the cam. [Figure 3] FIG. 3 is a diagram showing changes in the pressure of the mobile phase within one drive cycle of the liquid delivery unit. [Figure 4] FIG. 4 is a diagram showing the configuration of the control unit in FIG. [Figure 5] FIG. 5 is a flowchart showing an example of a liquid transfer failure detection process performed by the control unit in FIG. [Figure 6] FIG. 6 is a diagram for explaining a method for detecting a liquid transfer failure in a reference example. DETAILED DESCRIPTION OF THE INVENTION

[0011] (1) Chromatography configuration A liquid delivery system for chromatography (hereinafter simply referred to as a liquid delivery system) and a liquid delivery method for chromatography according to an embodiment of the present invention will be described in detail below with reference to the drawings. Fig. 1 is a diagram showing the configuration of a chromatograph including a liquid delivery system according to one embodiment of the present invention. Note that the chromatograph 200 in this embodiment is a liquid chromatograph, but it may also be a supercritical fluid chromatograph.

[0012] 1, chromatograph 200 includes a liquid delivery system 100, a mobile phase container 110, a sample supply unit 120, a separation column 130, a detector 140, and a processing unit 150. Mobile phase container 110 stores a solvent such as an aqueous solution or an organic solvent as a mobile phase. Chromatograph 200 may include multiple mobile phase containers 110, each storing a different solvent.

[0013] The liquid delivery system 100 includes a liquid delivery unit 10, a pressure sensor 20, and a control unit 30. In this example, the liquid delivery unit 10 is configured as 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 disposed upstream and downstream of the plunger pump 11, respectively. The plunger pump 12 is disposed downstream of the check valve 14.

[0014] Two cams 15a and 15b are provided on the camshaft 15. 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, thereby driving the plunger pumps 11 and 12. The actuator 16 is, for example, a stepping motor. In this example, the plunger pumps 11 and 12 are driven by one actuator 16 via the common camshaft 15, but they may also be driven by separate actuators.

[0015] The plunger pump 11 and the plunger pump 12 are driven in a complementary manner. Therefore, basically, the plunger pump 12 performs a suction operation while the plunger pump 11 performs a discharge operation, and the plunger pump 12 performs a discharge operation while the plunger pump 11 performs a suction operation. This allows the mobile phase stored in the mobile phase container 110 to be stably delivered downstream. Details of the delivery unit 10 will be described later.

[0016] The pressure sensor 20 is disposed downstream of the liquid delivery unit 10 and detects the pressure of the mobile phase delivered by the liquid delivery unit 10. The control unit 30 includes, for example, a CPU (Central Processing Unit) and a memory. The control unit 30 detects the occurrence of a liquid delivery failure caused by the intrusion of air bubbles into the plunger pump 11 based on the pressure of the mobile phase detected by the pressure sensor 20. The control unit 30 will be described in detail later.

[0017] The sample supply unit 120 is, for example, a sample injector, and supplies a sample to be analyzed to the mobile phase delivered by the liquid delivery unit 10. The sample delivered by the sample supply unit 120 is mixed with the mobile phase and introduced into the separation column 130. In this example, the sample supply unit 120 is connected to a waste liquid unit 201 (not shown). If the control unit 30 detects a liquid delivery failure, the sample supply unit 120 discards the mobile phase delivered by the liquid delivery unit 10 into the waste liquid unit 201.

[0018] The separation column 130 is housed inside a column thermostatic bath (not shown) and is adjusted to a predetermined constant temperature. The separation column 130 separates the introduced sample into individual components based on differences in chemical properties or composition. The detector 140 is, for example, a UV (ultraviolet-visible) detector, an absorbance detector, or an RI (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.

[0019] The processing device 150 includes, for example, a CPU and a memory, and controls the operations of the liquid delivery system 100, the sample supply unit 120, the separation column 130 (column thermostatic bath), and the detector 140. The processing device 150 also processes the detection signal given by the detector 140 to generate a chromatogram showing the relationship between the retention time of each component of the sample by the separation column 130 and the detection intensity.

[0020] (2) Operation of the liquid delivery unit FIG. 2 is a diagram illustrating the shape characteristics of cams 15a and 15b. The horizontal axis of FIG. 2 indicates the rotation angle of camshaft 15, and the vertical axis indicates the movement amount of the plunger. Also, in FIG. 2, the movement amount of the plunger of upstream plunger pump 11 is indicated by a dotted line, the movement amount of the plunger of downstream plunger pump 12 is indicated by a dashed line, and the combined movement amount of the plunger is indicated by a solid line. Cam 15a is shaped to realize the change in the movement amount of the plunger shown by the dotted line in FIG. 2. Cam 15b is shaped to realize the change in the movement amount of the plunger shown by the dashed line in FIG. 2. When the movement amount of the plunger is positive, an amount of liquid corresponding to that movement amount is delivered. The operation of liquid delivery unit 10 will be described in detail below.

[0021] In the serial double plunger system, when the upstream plunger pump 11 switches from suction to discharge, the check valve 14 does not open and discharge of the mobile phase does not begin until the pressure in the plunger pump 11 becomes higher than the pressure in the downstream flow path. Therefore, before the discharge operation of the downstream plunger pump 12 ends, a pre-pressure operation is performed by the plunger pump 11 to compress the mobile phase, as shown by the dotted line in Figure 2.

[0022] As a result of the pre-pressure operation, the pressure inside plunger pump 11 becomes higher than the pressure inside the downstream flow path, and check valve 14 opens. This causes plunger pump 11 to perform a discharge operation. After the discharge operation is completed, plunger pump 11 performs a suction operation. Thereafter, plunger pump 11 returns to the pre-pressure operation.

[0023] 2, the discharge operation of plunger pump 12 is performed while the suction operation and pre-pressurization operation of plunger pump 11 are being performed. Thereafter, the suction operation of plunger pump 12 is performed while the discharge operation of plunger pump 11 is being performed. The period during which the discharge operation of plunger pump 11 is performed and the period during which the discharge operation of plunger pump 12 is performed may partially overlap. The period during which plunger pump 12 performs the suction operation at the maximum amount of liquid delivered is called the maximum suction period.

[0024] The above-described operation of plunger pumps 11 and 12 delivers a constant amount of mobile phase, as shown by the solid line in Figure 2, except for the period during which the plunger pump 11 performs pre-pressurization. During pre-pressurization, the plunger is driven at high speed, which promotes compression and allows the pre-pressurization to be completed in a short time.

[0025] 3 is a diagram showing changes in the pressure of the mobile phase within one drive cycle of the liquid delivery unit 10. The horizontal axis of FIG. 3 indicates the number of drive pulses applied to the actuator 16, and the vertical axis indicates the pressure of the mobile phase. The number of drive pulses applied to the actuator 16 corresponds to the rotation angle of the cam shaft 15. In FIG. 3, the maximum suction period of the plunger pump 12 is indicated by a dashed line.

[0026] 3, during the period when drive pulses P1 and P2 are applied to actuator 16, the pre-pressurization operation of plunger pump 11 is performed, thereby increasing the pressure of the mobile phase. In an ideal state where no air bubbles are mixed into plunger pump 11, compression of the mobile phase ends at the point corresponding to drive pulse P2. The point at which compression of the mobile phase ends in the ideal state where no air bubbles are mixed into plunger pump 11 is known and can be calculated based on preset mobile phase information and the shape characteristics of cam 15a.

[0027] 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 compression of the mobile phase is completed, i.e., after the time corresponding to drive pulse P2, the plunger drive speed is reduced. In this state, by applying another drive pulse to actuator 16, check valve 14 is opened without reducing the pressure of the mobile phase, and plunger pump 11 performs a discharge operation.

[0028] However, in reality, because air bubbles are mixed in plunger pump 11, not only the mobile phase but also the gas is compressed during the pre-pressurization operation of plunger pump 11. In this case, the compression of the mobile phase does not end at the time corresponding to drive pulse P2. Therefore, even if another drive pulse is applied to actuator 16 at the time corresponding to drive pulse P2, check valve 14 does not open, and plunger pump 11 does not perform a discharge operation.

[0029] When air bubbles are mixed in plunger pump 11, the pressure of the mobile phase reaches a maximum near the time corresponding to drive pulse P2. After that, when another drive pulse is applied to actuator 16, the pressure of the mobile phase decreases until the plunger is pushed in by a volume equal to or greater than the volume of the gas. Furthermore, after the pre-pressurization operation of plunger pump 11 ends, the suction operation of plunger pump 12 begins, so the pressure of the mobile phase may decrease rapidly depending on the amount of mixed air bubbles.

[0030] Thereafter, a plurality of drive pulses are sequentially applied to actuator 16. In this case, check valve 14 opens at the time corresponding to drive pulse P3. In this case, the discharge operation of plunger pump 11 starts, and the pressure of the mobile phase becomes minimum during the maximum suction period of 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, check valve 14 closes. This ends the discharge operation of plunger pump 11.

[0031] Thereafter, the plunger pump 12 performs a discharge operation until drive pulse P5 is applied to actuator 16. When drive pulse P5 is applied to actuator 16, one drive cycle of liquid delivery unit 10 ends. This operation of liquid delivery unit 10 is repeated. The points at which the pressure of the mobile phase reaches its maximum and minimum change with each drive cycle of liquid delivery unit 10 depending on the amount of air bubbles mixed into plunger pump 11. The maximum and minimum pressures of the mobile phase also change with each drive cycle of liquid delivery unit 10.

[0032] (3) Control Unit Configuration 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, as functional units, 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, a detection unit 37, and an output unit 38. The functional units of the control unit 30 are realized by the CPU of the control unit 30 executing a liquid transfer failure detection program stored in a memory or the like. Some or all of the functional units of the control unit 30 may be realized by hardware such as electronic circuits. Alternatively, some or all of the functional units of the control unit 30 may be realized by a processing device 150.

[0033] The pressure acquisition unit 31 acquires the pressure of the mobile phase detected by the pressure sensor 20 at a predetermined cycle. The cycle of pressure acquisition by the pressure acquisition unit 31 is sufficiently shorter than the drive cycle of the liquid delivery unit 10 in FIG. 1. Therefore, the pressure acquisition unit 31 acquires pressure at multiple points in time within each drive cycle of the liquid delivery 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 delivery unit 10.

[0034] The maximum value specifying unit 32 specifies the maximum pressure among the pressures at multiple points in each drive cycle acquired by the pressure acquiring unit 31. In FIG. 3, the maximum pressure specified by the maximum value specifying unit 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 into the plunger pump 11 in FIG. 1 is known. Therefore, the maximum value specifying unit 32 may specify the maximum pressure within a predetermined period that includes the point in time at which compression of the mobile phase ends in each drive cycle.

[0035] The minimum value identifying unit 33 identifies the minimum pressure among the pressures at multiple points in time within each drive cycle acquired by the pressure acquiring unit 31. In FIG. 3, the minimum pressure identified by the minimum value identifying unit 33 is indicated by a circle B. As described above, the pressure of the mobile phase becomes minimum during the maximum suction period of the plunger pump 12 in FIG. 1. Therefore, the minimum value identifying unit 33 may identify the minimum pressure during the maximum suction period of the plunger pump 12 in each drive cycle.

[0036] The fluctuation range acquisition unit 34 acquires the fluctuation range of the pressure within each drive cycle. In this example, the fluctuation range of the pressure is acquired by calculating the difference between the maximum pressure within each drive cycle identified by the maximum value identification unit 32 and the minimum pressure within the same drive cycle identified by the minimum value identification unit 33. In Fig. 3, the fluctuation range acquired by the fluctuation range acquisition unit 34 is indicated by a dotted line.

[0037] The determination unit 35 determines whether the pressure fluctuation range acquired by the fluctuation range acquisition unit 34 for each drive cycle is greater than a reference value. The reference value may be a predetermined value or a value designated by the user. The counting unit 36 ​​counts the number of consecutive drive cycles in which the determination unit 35 determines that the pressure fluctuation range is greater than the reference value.

[0038] 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 delivery failure has occurred due to air bubbles entering the plunger pump 11. The reference number may be a predetermined number or a number designated by the user. The output unit 38 outputs the detection result of the liquid delivery failure by the detection unit 37 to the processing device 150.

[0039] When a detection result of a liquid delivery failure is output, the processing device 150 may control the sample supply unit 120 to discard the mobile phase delivered by the liquid delivery unit 10 into the waste liquid unit 201 in Figure 1. Alternatively, when a detection result of a liquid delivery failure is output, the processing device 150 may suspend the analysis of the sample. Furthermore, when a detection result of a liquid delivery failure is output, the processing device 150 may notify the user of this fact.

[0040] As an example of a notification by the processing device 150, if the chromatograph 200 in Fig. 1 includes a display device, a character string indicating that a liquid transfer failure has occurred may be displayed. If the chromatograph 200 includes an audio output device, a voice indicating the same content may be output, or an alarm sound such as a buzzer may be output. If the chromatograph 200 includes an indicator light such as a lamp, the indicator light may be turned on, off, or flashing in a manner corresponding to the content of the notification.

[0041] Furthermore, in each drive cycle of the liquid delivery unit 10, after the fluctuation range is acquired by the fluctuation range acquisition unit 34, it may be determined whether the pressure of the mobile phase is monotonically increasing or decreasing normally. For example, in FIG. 3, after the maximum suction period of the plunger pump 12 ends, the difference in the pressure of the mobile phase between the time when the second drive pulse is applied to the actuator 16 and the time when drive pulse P5 is applied to the actuator 16 is acquired. If this pressure difference is greater than a certain value, it may be determined that the pressure of the mobile phase is monotonically increasing or decreasing normally.

[0042] (4) Liquid transfer failure detection process Fig. 5 is a flowchart showing an example of a liquid transfer failure detection process by the control unit 30 of Fig. 4. The liquid transfer failure detection process of Fig. 5 is performed by the CPU of the control unit 30 executing a liquid transfer failure detection program stored in a memory or the like. An example of the liquid transfer failure detection process in this embodiment will be described below using the chromatograph 200 of Fig. 1, the control unit 30 of Fig. 4, and the flowchart of Fig. 5.

[0043] First, the counter 36 sets the value of the variable n to 0 (step S1). Here, the variable n indicates the number of drive cycles of the liquid delivery unit 10 in which the fluctuation range of the pressure of the mobile phase exceeds a predetermined reference number. Next, the pressure acquisition unit 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 delivery unit 10 (step S2).

[0044] Next, the pressure acquisition unit 31 determines whether the drive cycle of the liquid delivery unit 10 has ended (step S3). If the drive cycle of the liquid delivery unit 10 has not ended, the pressure acquisition unit 31 returns to step S2. Steps S2 and S3 are repeated until the drive cycle of the liquid delivery unit 10 ends. This allows pressures at multiple points in time within one drive cycle of the liquid delivery unit 10 to be acquired.

[0045] Thereafter, the maximum value identification unit 32 identifies the maximum pressure among the pressures at the multiple time points acquired in step S2 (step S4). The minimum value identification unit 33 identifies the minimum pressure among the pressures at the multiple time points acquired in step S2 (step S5). Steps S4 and S5 may be executed either first or simultaneously.

[0046] In step S4, the maximum value specifying unit 32 may specify the maximum pressure within a predetermined period including the time when the compression of the mobile phase ends. Also, 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. Also, in this case, step S4 may be executed before step S5.

[0047] Next, the fluctuation range acquisition unit 34 acquires the pressure fluctuation 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 determination unit 35 determines whether the pressure fluctuation range acquired in step S6 is greater than a predetermined reference value (step S7).

[0048] If the pressure fluctuation range is equal to or less than 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 range is greater than the reference value, the counting unit 36 ​​increases the value of the variable n by 1 (step S8). This counts the number of drive cycles (consecutive number) in which the pressure fluctuation range is determined to be greater than the reference value. Thereafter, the detection unit 37 determines whether the variable n in step S8 is greater than the reference number (step S9). The reference number is an integer equal to or greater than 2, and is 5 in this example.

[0049] If the variable n is equal to or less than the reference number of times, the detection unit 37 returns to step S2. As a result, the processing from step S2 onwards is repeated while maintaining the variable n. If the variable n is greater than the reference number of times, the detection unit 37 detects that a liquid transfer failure has occurred due to air bubbles entering the plunger pump 11 (step S10). The output unit 38 outputs the detection result of the liquid transfer failure in step S10 to the processing device 150 (step S11), and the liquid transfer failure detection processing ends.

[0050] (5) Effects In the liquid delivery system 100 according to this embodiment, the mobile phase is delivered by periodically driving the liquid delivery unit 10, which is a serial double plunger system including plunger pumps 11 and 12. The pressure of the mobile phase at multiple points in time within each drive cycle of the liquid delivery unit 10 is acquired by the pressure acquisition unit 31.

[0051] For each drive cycle of the liquid delivery unit 10, the maximum pressure among the pressures acquired by the pressure acquisition unit 31 is identified by the maximum value identification unit 32. Furthermore, for each drive cycle of the liquid delivery unit 10, the minimum pressure among the pressures acquired by the pressure acquisition unit 31 is identified by the minimum value identification unit 33. Based on the maximum pressure identified by the maximum value identification unit 32 and the minimum pressure identified by the minimum value identification unit 33, the detection unit 37 detects a liquid delivery failure caused by air bubbles entering the plunger pump 11.

[0052] This configuration identifies the maximum and minimum pressures of the mobile phase in each drive cycle of the liquid delivery unit 10. Therefore, even if the amount of air bubbles mixed into the plunger pump 11 is small, it is possible to easily detect changes in the pressure of the mobile phase caused by the mixed air bubbles. This makes it possible to accurately detect liquid delivery problems caused by the mixed air bubbles.

[0053] Specifically, the fluctuation range acquisition unit 34 acquires the fluctuation range of the pressure within each drive cycle of the liquid delivery unit 10 based on the maximum pressure identified by the maximum value identification unit 32 and the minimum pressure identified by the minimum value identification unit 33. The determination unit 35 determines whether the fluctuation range of the pressure acquired by the fluctuation range acquisition unit 34 is greater than a reference value for each drive cycle of the liquid delivery unit 10.

[0054] The counting unit 36 ​​counts the number of consecutive drive cycles in which the determining unit 35 determines that the pressure fluctuation range is greater than a reference value. The detecting unit 37 detects a liquid transfer failure when the number of consecutive drive cycles counted by the counting unit 36 ​​is greater than a predetermined number. This makes it possible to more accurately detect a liquid transfer failure caused by the inclusion of air bubbles.

[0055] Here, the maximum value identifying unit 32 may acquire the maximum pressure among the pressures acquired by the pressure acquiring unit 31 within a predetermined period including a time point that is predetermined as the time point at which the check valve 14 should be opened. In this case, even if the pressure acquiring unit 31 acquires a maximum pressure of the mobile phase caused by noise outside the predetermined period, the maximum pressure is excluded from the targets to be identified by the maximum value identifying unit 32.

[0056] Furthermore, the minimum value identifying unit 33 may acquire the minimum pressure among the pressures acquired by the pressure acquiring unit 31 during the maximum suction period of the plunger pump 12. In this case, even if the minimum pressure of the mobile phase caused by noise is acquired by the pressure acquiring unit 31 outside the maximum suction period of the plunger pump 12, the minimum pressure is excluded from the targets for identification by the minimum value identifying unit 33. These configurations enable more accurate detection of liquid transfer problems caused by the inclusion of air bubbles.

[0057] (6) Reference example As explained in the background art, in Patent Document 1, the difference in liquid delivery pressure at the start and end points of the discharge operation of one plunger pump is calculated as the first fluctuation value. This liquid delivery failure detection method is applied to the change in mobile phase pressure in Figure 3. Figure 6 is a diagram for explaining the liquid delivery failure detection method in a reference example. The change in mobile phase pressure shown in Figure 6 is the same as the change in mobile phase pressure in Figure 3.

[0058] As shown in FIG. 6, the start point of the discharge operation of plunger pump 11 is the time corresponding to drive pulse P3. The liquid delivery pressure at this time is indicated by circle C. The end point of the discharge operation of plunger pump 11 is the time corresponding to drive pulse P4. The liquid delivery pressure at this time is indicated by circle D. That is, the difference between the liquid delivery pressure at circle C and the liquid delivery pressure at circle D is obtained as the first variation value.

[0059] The maximum value of the first fluctuation value obtained by this method is smaller than the maximum value of the pressure in the present embodiment shown in Fig. 3. Furthermore, the minimum value of the first fluctuation value is larger than the minimum value of the pressure in the present embodiment shown in Fig. 3. Therefore, the first fluctuation value is smaller than the fluctuation range of the pressure in the present embodiment shown in Fig. 3. Therefore, when the amount of air bubbles mixed into plunger pump 11 is small, a sufficiently large first fluctuation value is not obtained, making it difficult to accurately detect a liquid transfer failure.

[0060] (7) Other embodiments (a) In the above embodiment, a liquid delivery failure is detected based on the pressure fluctuation range within each drive cycle of the liquid delivery unit 10, but the embodiment is not limited to this. A liquid delivery failure may also be detected based on an arbitrary evaluation value determined based on the maximum and minimum pressures within each drive cycle.

[0061] (b) In the above embodiment, the occurrence of a liquid delivery failure is detected when it is determined that the pressure fluctuation range is larger than the reference value in multiple consecutive drive cycles of the liquid delivery unit 10, but the embodiment is not limited to this. The occurrence of a liquid delivery failure may also be detected when it is determined that the pressure fluctuation range is larger than the reference value in one drive cycle of the liquid delivery unit 10.

[0062] (c) In the above embodiment, the liquid delivery unit 10 is configured as a series double plunger system, but the embodiment is not limited to this. The liquid delivery unit 10 may be configured as a parallel double plunger system.

[0063] In the parallel double plunger system, the maximum value specifying unit 32 specifies a first maximum pressure resulting from the discharge operation of the mobile phase by the plunger pump 11 for each drive cycle of the liquid delivery unit 10. The maximum value specifying unit 32 also specifies a second maximum pressure resulting from the discharge operation of the mobile phase by the plunger pump 12 for each drive cycle of the liquid delivery unit 10.

[0064] The minimum value identifying unit 33 identifies a first minimum pressure resulting from the discharge operation of the mobile phase by the plunger pump 11 for each drive cycle of the liquid delivery unit 10. The minimum value identifying unit 33 also identifies a second minimum pressure resulting from the discharge operation of the mobile phase by the plunger pump 12 for each drive cycle of the liquid delivery unit 10.

[0065] The detection unit 37 detects a liquid delivery failure caused by the intrusion of air bubbles into the plunger pump 11 based on the first maximum pressure identified by the maximum value identification unit 32 and the first minimum pressure identified by the minimum value identification unit 33 for each drive cycle of the liquid delivery unit 10. The detection unit 37 also detects a liquid delivery failure caused by the intrusion of air bubbles into the plunger pump 12 based on the second maximum pressure identified by the maximum value identification unit 32 and the second minimum pressure identified by the minimum value identification unit 33 for each drive cycle of the liquid delivery unit 10.

[0066] (d) In the above embodiment, the liquid delivery unit 10 includes two plunger pumps 11 and 12, but the embodiment is not limited to this. The liquid delivery unit 10 may be configured as a single plunger system including one plunger pump 11.

[0067] 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 drive cycle of the liquid delivery unit 10. The minimum value specifying unit 33 specifies the minimum pressure during the discharge operation of the plunger pump 11 for each drive cycle of the liquid delivery unit 10. The detection unit 37 detects a liquid delivery failure based on the maximum pressure specified by the maximum value specifying unit 32 and the minimum pressure specified by the minimum value specifying unit 33 for each drive cycle of the liquid delivery unit 10.

[0068] (8) Mode It will be appreciated by those skilled in the art that the above exemplary embodiments are examples of the following aspects.

[0069] (Item 1) A chromatographic liquid delivery system according to one embodiment includes: a liquid delivery unit including one or more plunger pumps, which is periodically driven to deliver a mobile phase; a pressure acquisition unit that acquires pressures of the mobile phase at multiple points in time within each drive cycle of the liquid delivery unit; a maximum value specifying unit that specifies a maximum pressure among the pressures acquired by the pressure acquiring unit for each drive cycle of the liquid sending unit; a minimum value specifying unit that specifies a minimum pressure among the pressures acquired by the pressure acquiring unit for each drive cycle of the liquid sending unit; The pressure measuring device may further include a detection unit that detects poor liquid delivery caused by air bubbles entering the one or more plunger pumps based on the maximum pressure identified by the maximum value identification unit and the minimum pressure identified by the minimum value identification unit.

[0070] In this chromatographic liquid delivery system, the maximum and minimum pressures of the mobile phase are identified for each drive cycle of the liquid delivery unit. Therefore, even if the amount of air bubbles mixed into the plunger pump is small, it is possible to easily detect changes in the mobile phase pressure caused by the mixed air bubbles. This allows for accurate detection of liquid delivery problems caused by the mixed air bubbles.

[0071] (Item 2) The chromatographic liquid delivery system according to item 1, a fluctuation range acquisition unit that acquires a fluctuation range of the pressure within each drive cycle of the liquid delivery unit based on the maximum pressure identified by the maximum value identification unit and the minimum pressure identified by the minimum value identification unit; The detection unit may detect a liquid transfer failure based on the pressure fluctuation range acquired by the fluctuation range acquisition unit.

[0072] In this case, a liquid transfer failure caused by the inclusion of air bubbles can be easily detected.

[0073] (Item 3) The chromatographic liquid delivery system according to item 2, a determination unit that determines whether the pressure fluctuation range acquired by the fluctuation range acquisition unit is greater than a reference value for each drive cycle of the liquid delivery unit; The detection unit may detect a liquid transfer failure when the determination unit determines that the fluctuation range of the pressure is larger than a reference value.

[0074] In this case, it is possible to more easily detect a liquid transfer failure caused by the inclusion of air bubbles.

[0075] (Item 4) The chromatographic liquid delivery system according to item 3, a counting unit that counts the number of consecutive drive cycles in which the determining unit determines that the pressure fluctuation range is greater than a reference value, The detection unit may detect a liquid transfer failure when the number of consecutive drive cycles counted by the counting unit is greater than a predetermined number.

[0076] In this case, a liquid transfer failure caused by the inclusion of air bubbles can be detected more accurately.

[0077] (Item 5) In the chromatographic liquid delivery system according to any one of items 1 to 4, the liquid delivery unit includes, as the one or more plunger pumps, a first plunger pump and a second plunger pump that are connected in series and driven complementarily; the second plunger pump is disposed downstream of the first plunger pump, and a check valve is disposed between the first plunger pump and the second plunger pump; the first plunger pump compresses the mobile phase until a predetermined time when the check valve should be opened before discharging the mobile phase; The maximum value specifying unit may obtain a maximum pressure from among pressures obtained by the pressure obtaining unit within a predetermined period including the predetermined time point.

[0078] In this case, the liquid delivery unit is configured with a serial double plunger system. Even if the pressure acquisition unit acquires a maximum mobile phase pressure due to noise outside the predetermined period, the maximum pressure is excluded from the maximum value identification unit. This allows for more accurate detection of liquid delivery problems due to the inclusion of air bubbles.

[0079] (Item 6) In the chromatographic liquid delivery system according to any one of items 1 to 4, the liquid delivery unit includes, as the one or more plunger pumps, a first plunger pump and a second plunger pump that are connected in series and driven complementarily; the second plunger pump is disposed downstream of the first plunger pump; The minimum value specifying unit may obtain a minimum pressure from among the pressures obtained by the pressure obtaining unit during a period in which the second plunger pump is performing a suction operation.

[0080] In this case, the liquid delivery unit is configured with a serial double plunger system. Here, even if the minimum pressure of the mobile phase caused by noise is acquired by the pressure acquisition unit outside the period when the second plunger pump is performing a suction operation, the minimum pressure is excluded from the identification target by the minimum value identification unit. This allows for more accurate detection of liquid delivery problems caused by the inclusion of air bubbles.

[0081] (Item 7) In the chromatographic liquid delivery system according to any one of items 1 to 4, the liquid delivery unit includes, as the one or more plunger pumps, a first plunger pump and a second plunger pump that are connected in parallel and driven complementarily; the maximum value specifying unit specifies, for each drive cycle of the liquid delivery unit, a first maximum pressure caused by the first plunger pump discharging the mobile phase, and a second maximum pressure caused by the second plunger pump discharging the mobile phase; the minimum value identifying unit identifies, for each drive cycle of the liquid delivery unit, a first minimum pressure resulting from a discharging operation of the mobile phase by the first plunger pump, and identifies a second minimum pressure resulting from a discharging operation of the mobile phase by the second plunger pump; The detection unit may detect poor liquid delivery due to air bubbles entering the first plunger pump based on the first maximum pressure identified by the maximum value identification unit and the first minimum pressure identified by the minimum value identification unit, and may detect poor liquid delivery due to air bubbles entering the second plunger pump based on the second maximum pressure identified by the maximum value identification unit and the second minimum pressure identified by the minimum value identification unit.

[0082] According to this configuration, even in a parallel double plunger type liquid delivery section, it is possible to accurately detect liquid delivery failure caused by the inclusion of air bubbles.

[0083] (Item 8) A chromatographic liquid delivery method according to another aspect includes: a liquid delivery unit including one or more plunger pumps is periodically driven to deliver a mobile phase; acquiring pressures of the mobile phase at a plurality of time points within each drive cycle of the liquid delivery unit; Identifying a maximum pressure among the acquired pressures for each drive cycle of the liquid delivery unit; Identifying a minimum pressure among the acquired pressures for each drive cycle of the liquid delivery unit; The method may further include detecting a liquid transfer failure caused by air bubbles entering the one or more plunger pumps based on the identified maximum pressure and the identified minimum pressure.

[0084] According to this chromatographic liquid delivery method, the maximum and minimum pressures of the mobile phase are identified for each drive cycle of the liquid delivery unit. Therefore, even if the amount of air bubbles mixed into the plunger pump is small, it is possible to easily detect changes in the mobile phase pressure caused by the mixed air bubbles. This allows for accurate detection of liquid delivery problems caused by the mixed air bubbles.

Claims

1. a liquid delivery unit including one or more plunger pumps, which is periodically driven to deliver a mobile phase; a pressure acquisition unit that acquires pressures of the mobile phase at multiple points in time within each drive cycle of the liquid delivery unit; a maximum value specifying unit that specifies a maximum pressure among the pressures acquired by the pressure acquiring unit for each drive cycle of the liquid sending unit; a minimum value specifying unit that specifies a minimum pressure among the pressures acquired by the pressure acquiring unit for each drive cycle of the liquid sending unit; a detection unit that detects a liquid transfer failure caused by air bubbles entering the one or more plunger pumps based on the maximum pressure identified by the maximum value identification unit and the minimum pressure identified by the minimum value identification unit, the one or more plunger pumps include a first plunger pump and a second plunger pump connected in series and driven in a complementary manner; the second plunger pump is disposed downstream of the first plunger pump, and a check valve is disposed between the first plunger pump and the second plunger pump; the first plunger pump compresses the mobile phase until a predetermined time when the check valve should be opened before discharging the mobile phase; The maximum value specifying unit obtains the maximum pressure among the pressures obtained by the pressure obtaining unit within a predetermined period including the predetermined time point.

2. a fluctuation range acquisition unit that acquires a fluctuation range of the pressure within each drive cycle of the liquid delivery unit based on the maximum pressure identified by the maximum value identification unit and the minimum pressure identified by the minimum value identification unit; 2. The chromatographic liquid delivery system according to claim 1, wherein the detection unit detects a liquid delivery failure based on the pressure fluctuation range acquired by the fluctuation range acquisition unit.

3. a determination unit that determines whether the pressure fluctuation range acquired by the fluctuation range acquisition unit is greater than a reference value for each drive cycle of the liquid delivery unit; 3. The chromatographic liquid delivery system according to claim 2, wherein the detection unit detects a liquid delivery failure when the determination unit determines that the pressure fluctuation range is greater than a reference value.

4. a counting unit that counts the number of consecutive drive cycles in which the determining unit determines that the pressure fluctuation range is greater than a reference value, 4. The chromatographic liquid delivery system according to claim 3, wherein the detection unit detects a liquid delivery failure when the number of consecutive drive cycles counted by the counter unit is greater than a predetermined number.

5. A liquid delivery system for chromatography as described in claim 1, wherein the minimum value identification unit acquires the minimum pressure among the pressures acquired by the pressure acquisition unit during the period in which the suction operation is being performed by the second plunger pump.

6. a liquid delivery unit including one or more plunger pumps is periodically driven to deliver a mobile phase; acquiring pressures of the mobile phase at a plurality of time points within each drive cycle of the liquid delivery unit; Identifying a maximum pressure among the acquired pressures for each drive cycle of the liquid delivery unit; Identifying a minimum pressure among the acquired pressures for each drive cycle of the liquid delivery unit; detecting a liquid delivery failure caused by air bubbles entering the one or more plunger pumps based on the identified maximum pressure and the identified minimum pressure; the one or more plunger pumps include a first plunger pump and a second plunger pump connected in series and driven in a complementary manner; the second plunger pump is disposed downstream of the first plunger pump, and a check valve is disposed between the first plunger pump and the second plunger pump; the first plunger pump compresses the mobile phase until a predetermined time when the check valve should be opened before discharging the mobile phase; A chromatographic liquid delivery method, wherein identifying the maximum pressure includes obtaining the maximum pressure from among pressures obtained within a predetermined period including the predetermined time point.

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