Liquid chromatograph device and method for detecting abnormality thereof

Abstract

Provided is a liquid chromatograph device in which sudden stops due to a failure or the like of the device, economic damage due to opportunity loss, and a user injury are minimized. A liquid chromatograph device comprises a sipper 102 that suctions a specimen, a syringe 103 that generates a negative pressure in a first pipe 104 communicating with the sipper 102 to cause the specimen to be suctioned by the sipper 102, a pump 105 that pressure feeds a diluent for diluting the specimen, a mixing part 109 that houses and mixes the diluent pressure-fed by the pump 105 and the specimen suctioned by the sipper 102, a second pipe 106 that communicates the pump 105 with the mixing part, a first pressure sensor 107 which is disposed in the first pipe 104 and detects the pressure in the first pipe 104, a second pressure sensor 108 which is disposed in the second pipe 106 and detects the pressure in the second pipe 106, and a verification part 114 that verifies abnormality on the basis of the pressure detected by the second pressure sensor 108 when the first pressure sensor 107 detects an abnormality in the pressure.

Description

Liquid chromatograph device and method for detecting abnormality therein

[0001] The present invention relates to a liquid chromatograph and an abnormality detection method thereof.

[0002] In testing centers, university hospitals, and the like, liquid chromatography / mass spectrometry (HPLC / MS) systems are used to perform tests for immunosuppressants, anticancer drugs, neonatal metabolic disorder tests, therapeutic drug monitoring (TDM), and other tests. To minimize variability in test results, the reproducibility and accuracy of the sample injection process into the liquid chromatography / mass spectrometry system are important. Patent Document 1 (JP-A-2005-102626) discloses a technology for detecting pressure abnormalities, such as clogged flow paths and leaks, that includes a pump pressure sensor for monitoring the pressure within a flow path, an injection valve for switching between a liquid delivery path from the pump and a flow path from a syringe, a sample loop connected to the injection valve, a syringe for aspirating / discharging the sample, and a syringe pressure sensor for monitoring the aspirating / discharging state of the syringe.

[0003] WO2022 / 230282 publication

[0004] In Patent Document 1, when a pump pressure sensor that monitors the pressure in the flow path detects a pressure abnormality, the pump pressure sensor does not include a verification unit that verifies the abnormality based on the pressure value of a syringe pressure sensor that monitors the suction / discharge status of the syringe.

[0005] An object of the present invention is to provide a liquid chromatograph and a method for detecting anomalies in a liquid chromatograph that can minimize, through predictive diagnosis, sudden shutdowns due to breakdowns or malfunctions in the device or parts, economic losses due to lost opportunities, and health or other damage to workers or users of the product.

[0006] In order to achieve the above object, the present invention is configured as follows.

[0007] The liquid chromatograph apparatus comprises a sipper that aspirates a sample, a syringe that is a negative pressure generating source that generates negative pressure in a first pipe that is connected to the sipper in order to aspirate the sample into the sipper, a pump that pumps out a diluent that dilutes the sample, a mixing section that accommodates and mixes the diluent pumped by the pump and the sample aspirated by the sipper, a second pipe that connects the pump to the mixing section, a first pressure sensor that is disposed in the first pipe and detects the pressure within the first pipe, a second pressure sensor that is disposed in the second pipe and detects the pressure within the second pipe, and a verification section that, if the first pressure sensor detects an abnormality in pressure, verifies the abnormality based on the pressure detected by the second pressure sensor.

[0008] In addition, in a method for detecting an abnormality in a liquid chromatograph apparatus, negative pressure is generated in a first pipe connected to a sipper, a sample is sucked into the sipper, the diluent pumped by the pump and the sample sucked by the sipper are mixed in the mixing section via a second pipe connecting the pump and a mixing section, and the mixed diluent and sample are sent to a separation section, if a first pressure sensor that detects the pressure in the first pipe detects an abnormality in pressure, the abnormality is verified based on the pressure detected by a second pressure sensor that detects the pressure in the second pipe.

[0009] According to the present invention, it is possible to provide a liquid chromatograph and a method for detecting an anomaly in a liquid chromatograph that can minimize, through predictive diagnosis, sudden shutdowns due to breakdowns or malfunctions in the device or parts, economic losses due to lost opportunities, and health or other damage to workers or users of the product.

[0010] 1 is a schematic diagram of a liquid chromatograph mass spectrometer; 2 is a schematic diagram of an anomaly detection process during sample aspiration; 3 is a diagram showing pressure profiles before and after smoothing; 4 is a schematic diagram of baseline correction; 5 is a flowchart of an anomaly detection process during sample injection; 6 is a schematic diagram of an anomaly detection process during sample injection;

[0011] Hereinafter, an embodiment of the present invention will be described with reference to the drawings.

[0012] FIG. 1 is a schematic diagram of a liquid chromatograph / mass spectrometer (HPLC / MS) 1000 .

[0013] The liquid chromatograph mass spectrometer 1000 includes an injection unit 100, a separation unit 111 that separates specimens, a detection unit 112, a verification unit 114, a control unit 601, and a display unit 116. The separation unit 111 includes a column.

[0014] The control unit 601 controls the operations of the display unit 116, the injection unit 100, the separation unit 111, and the detection unit 112. The verification unit 114 detects abnormalities in the components of the injection unit 100 based on pressures detected by a pressure sensor 107 (first pressure sensor) and a pressure sensor 108 (second pressure sensor) described below, and predicts the occurrence of a failure, etc.

[0015] The injection unit 100 is composed of a sipper 102, a syringe 103, a first pipe 104, a pump 105, a second pipe 106, a pressure sensor 107 provided in the first pipe 104 to detect the pressure in the first pipe 104, a pressure sensor 108 provided in the second pipe 106 to detect the pressure in the second pipe 106, a sample loop 109, and a valve 110. The syringe 103 is a negative pressure generating source that generates negative pressure in the first pipe 104. The sipper 102 is connected to the first pipe 104, and negative pressure is generated in the first pipe 104 to draw a sample into the sipper 102.

[0016] The specimen 101 is aspirated by a sipper nozzle 102. The sipper 102 is connected to a valve 110 via a third pipe 113. The valve 110 is also connected to a syringe 103 via a second pipe 104 and a pressure sensor 107. The tube 110 is also connected to a sample loop 109.

[0017] The valve 110 has two switching positions, position 1 and position 2. In position 1, the sipper 102 is connected to the sample loop 109 (mixing section) and the syringe 103.

[0018] At position 2, the flow path from the pump 105, the sample loop 109, and the separation section 111 are connected.

[0019] At position 1 , the syringe 103 is driven, and the specimen 101 is aspirated from the sipper 102 and introduced into the sample loop 109 .

[0020] At position 2, the flow path from the pump 105 and the sample loop 109 are connected, so that the specimen 101 introduced into the sample loop 109 at position 1 is introduced into the separation section 111. The pump 105 pumps a diluent that dilutes the sample.

[0021] The liquid chromatograph comprises an injection unit 100 , a control unit 601 , a verification unit 114 , a display unit 116 , and a separation unit 111 .

[0022] 2 and 3, abnormality detection during sample suction using the pressure sensor 107 provided in the first pipe 104 will be described. Fig. 2 is a schematic diagram of abnormality detection during sample suction (change over time in the pressure value detected by the pressure sensor 107 provided in the first pipe 104).

[0023] 2 is performed when the valve 110 is in position 1, as described above. The aspirating operation of the syringe 103 includes four steps. The first step is "air aspirating 202" to separate the specimen 101 from the solution in the piping to prevent dilution. The second step is "specimen aspirating 203" to introduce the specimen 101 into the piping. The third step is "loop aspirating 204" to aspirate air and transfer the specimen 101 introduced into the piping to the sample loop 109. The fourth step is "residual liquid ejection 205" to push any specimen 101 remaining in the piping out of the piping. Among these steps, the verification unit 114 detects clogging and dry aspirating based on pressure profiles at two timings. The first timing is a range α of 500 msec before the start of "air suction 202", and the second timing is a range β of 1000 msec to 1500 msec after the start of "loop suction 204".

[0024] Pressure data acquired at each timing v ｉ The analysis is carried out in four steps. The four steps are pressure value conversion, smoothing, baseline correction, and data processing for each detection. In the pressure value conversion process, the acquired pressure data vｉ The pressure value p in kPa ｅｉ Convert to.

[0025] In FIG. 2, the fine dotted line 206 indicates the pressure profile under normal conditions, the normal dotted line 207 indicates the pressure profile under dry suction, and the dashed-dotted line 208 indicates the profile under clogging.

[0026] In the smoothing process, the pressure value p ｅｉ Moving average p ｓｉ An outline of the smoothing process is shown in FIG. 3. FIG. 3 shows a pressure profile 301 after the smoothing process and a pressure profile 302 before the smoothing process. The average value of the target point and 10 points before and after the target point (21 points in total) is calculated. When i=a, a≧11 and i ｍａｘ Smoothing processing is performed when -a≧10. However, if the pressure value p does not satisfy the condition ｅｉ Smoothing processing is not performed on the region, and the data in that region is excluded from the analysis.

[0027]

[0028] The baseline correction process corrects errors in pressure values ​​in the baseline section. The baseline correction process will be described with reference to Fig. 4. Fig. 4 shows a pressure profile 401 before the baseline correction process and a pressure profile 402 after the baseline correction process.

[0029] When the trigger point is set to i=b, baseline correction is performed. Specifically, the average pressure value in the baseline section (baseline section) shown in the following formula (2) is calculated, and each data p after smoothing is ｓｉ The pressure average value is subtracted from the pressure value and the pressure after correction is calculated. ｂｉ However, if the average pressure value in the baseline section is an abnormal value (10 kPa or more or less than −10 kPa), the data in that region is excluded from the analysis.

[0030]

[0031] The data processing for each detection will be described. The average pressure Z in the abnormality detection data region in the range β from 1000 msec to 1500 msec after the start of the loop suction 204 ＣＡ When the average pressure value of the baseline data area is set to 0 kPa, the average pressure value Z ＣＡ If the pressure average value is -50 kPa or less, it is determined to be clogged. ＣＡ If the pressure is less than or equal to -10 kPa, the suction is judged to be normal. ＣＡ If the pressure is greater than -10 kPa, it is determined that the air is being sucked dry. The threshold value can be changed as appropriate depending on environmental conditions such as temperature and air pressure.

[0032] The average pressure Z within the abnormality detection data range within 1000 msec from the start of residual liquid discharge Ｆ When the average pressure value of the baseline data area is set to 0 kPa, the average pressure value Z Ｆ If it is >100 kPa, it is judged as normal. Ｆ If the pressure is less than 100 kPa, it is determined that there is a malfunction in the electromagnetic valve of the gear pump 105. The threshold value can be changed as appropriate depending on environmental conditions such as temperature and air pressure.

[0033] In this way, by detecting an abnormality during sample suction using the pressure sensor 107 provided in the first pipe 104, it is possible to determine whether there is clogging, dry suction, or a malfunction of the electromagnetic valve of the pump 105. Among these, the threshold value of the pressure sensor 107 provided in the first pipe 104 in the case of a dry suction abnormality is Z ＣＡ > -10 kPa, and the normal threshold is -50 kPa < Z ＣＡ <-10 kPa. Typical pressure values ​​under normal conditions are -30 kPa < Z ＣＡ <-20 kPa, and about -20 kPa < Z ＣＡ If the calculated value is less than −10 kPa, this is not an abnormality in the case where the solution in the first pipe 104 is completely emptied, but there is a possibility that some air bubbles have been mixed in the first pipe 104.

[0034] Therefore, the accuracy of abnormality detection can be improved by performing abnormality detection by other methods in addition to detecting abnormalities during sample suction using pressure sensor 107 provided in first pipe 104. As another method, a method using pressure sensor 108 provided in second pipe 106 will be described.

[0035] Anomaly detection processing during sample injection (when a sample contained in the sample probe (mixing section) is supplied to the separation section 111) using the pressure sensor 108 provided in the second pipe 106 will be described with reference to FIGS. 5 and 6 . FIG. 5 is a flowchart of the anomaly detection processing during sample injection (pressure sensor 108 provided in the second pipe 106). FIG. 6 is a schematic diagram of anomaly detection during sample injection (pressure sensor 108 provided in the second pipe 106). In the flowchart of the anomaly detection processing during sample injection in FIG. 5 , the anomaly detection processing is performed based on the pressure value of the pressure sensor 108 provided in the second pipe 106. The pressure measurement section in which the pressure sensor 108 detects pressure starts when the sample contained in the sample loop 109, which is the mixing section, is supplied to the separation section 111.

[0036] 5, when sample measurement is started, in step S1, a pressure measurement command is issued from the control unit 601 to the injection unit 100 in step S2. Then, in step S7, pressure value information from the pressure sensor 108 is sent to the verification unit 114. Next, in step S3, a pressure value is calculated based on the pressure information from the pressure sensor 108.

[0037] Next, in step S4, the verification unit 114 determines whether the calculated pressure value is within the threshold value. If it is not within the threshold value, the process proceeds to step S8, where the verification unit 114 transmits information that the pressure value is not within the threshold value to the control unit 601. In accordance with the information from the verification unit 114, the control unit 601 causes the display unit 116 to display an alarm notifying that an abnormality has occurred during sample injection. The process then proceeds to step S5.

[0038] In step S4, if the calculated pressure value is within the threshold value, the process proceeds to step S5, where the injection pressure value is output, and then to step S6, where the measurement of the sample is completed.

[0039] A specific operation will now be described.

[0040] When the valve 110 is in position 1, the syringe 103 is driven, and the sample 101 is introduced from the shipper 102 into the sample loop 109. Then, the valve 110 switches to position 2, and sample measurement begins. When the sample measurement begins, a pressure measurement command 603 is sent from the control unit 601 of this automated analyzer to the pump firmware 602, along with an arbitrarily set pressure measurement interval and pressure measurement time. After receiving the pressure measurement command 603, the pump firmware 602 calculates the maximum, minimum, and average pressure values ​​for each of the pressure measurement intervals (1) 606, pressure measurement interval (2) 607, pressure measurement interval (3) 608, pressure measurement interval (4) 609, and pressure measurement interval (5) 610, and after all intervals are completed, the five sets of values ​​are collected and returned to the control unit 601. Among the five sets of maximum, minimum, and average values ​​returned to the control unit 601, the data set corresponding to the measurement section (pmtime1) 606 is used as the calculation target, and the pressure value Z is calculated using the following equation (3). Ｇ Calculate.

[0041] Maximum value - minimum value = Z Ｇ ...(3) Calculated pressure value Z Ｇ If the pressure is greater than 15 MPa, it is determined to be an abnormality during specimen injection. This abnormality occurs when an empty suction abnormality occurs during sample aspiration, and the valve 110 is switched to position 2 with air bubbles remaining in the sample loop 109. The threshold value can be changed as appropriate depending on environmental conditions such as temperature and air pressure.

[0042] If the pressure sensor 108 provided in the second pipe 106 determines that there is an abnormality during sample injection, the abnormality is displayed on the GUI screen (display unit 116) of the control unit 601, and the user is notified of the abnormality during sample injection as a system alarm. At the same time, a data alarm is added to the test results for the corresponding sample on the GUI screen. The user will then recognize that there is an abnormality in the test data and will perform a retest or discard the data.

[0043] On the other hand, if the pressure sensor 107 installed in the first pipe 104 determines that an abnormality has been detected during sample suction, the abnormal condition is displayed on the GUI screen of the control unit 601, and the user is notified of the abnormality during sample suction as a system alarm.

[0044] The occurrence of dry suction can be determined by detecting an abnormality during sample suction using pressure sensor 107 provided in first pipe 104, and detecting an abnormality during specimen injection using pressure sensor 108 provided in second pipe 106. The calculated pressure value of pressure sensor 107 provided in first pipe 104 is 100 kPa or less, and the calculated pressure value of pressure sensor 108 provided in second pipe 106 is several MPa or less, which is a pressure difference of about 10 times, allowing for a clearer determination of the presence or absence of an abnormality.

[0045] The pressure information acquired by the pressure sensor 107 provided on the first pipe 104 and the pressure sensor 108 provided on the second pipe 106 is stored in a database of the control unit 601. By performing pressure trend analysis using information from the two different types of pressure sensors 107, 108 and performing long-term abnormality trend analysis, it is possible not only to detect temporary clogging and dry suction, but also to diagnose operational abnormalities and failure states at an early stage.

[0046] Specifically, by analyzing the following cases: 1) when there is only an abnormality due to pressure information obtained from the pressure sensor 107 provided in the first pipe 104, 2) when there is only an abnormality due to pressure information obtained from the pressure sensor 108 provided in the second pipe 106, and 3) when there are abnormalities due to both the pressure sensor 107 provided in the first pipe 104 and the pressure sensor 108 provided in the second pipe 106, it becomes easier to identify the defective part within the liquid chromatograph device 1000.

[0047] For example, in the case of an abnormality based on pressure information obtained from the two pressure sensors 107 and 108 in 3), it is found that the sample loop 109 or the valve 110, which is a common part of the first pipe 104 and the second pipe 106, is the defective part.

[0048] Furthermore, an internal standard substance is dispensed in a pretreatment step in the liquid chromatograph that constitutes the liquid chromatograph mass spectrometer 1000. The internal standard substance to be dispensed is prepared for each substance to be measured contained in the sample 101, and a specified amount of the internal standard substance of a known concentration is dispensed into the sample 101. For quality control during testing, QC measurements are periodically performed using a QC sample containing a substance to be measured of a known concentration.

[0049] For this reason, detection of dry-pumping abnormalities can also be determined from the peak intensities of the chromatograms of the analyte and internal standard output during QC measurement. If a dry-pumping abnormality occurs during sample aspiration and valve 110 is switched to position 2 with air bubbles remaining in sample loop 109, the peak intensities of the chromatograms of both the analyte and internal standard will be lower than normal. If normal chromatogram intensities are obtained for either the analyte or the internal standard, it can be determined that an abnormality occurred during dispensing in the pretreatment process.

[0050] As configured as described above, this embodiment can provide a liquid chromatograph and an anomaly detection method for a liquid chromatograph that can minimize, through predictive diagnosis, sudden shutdowns due to breakdowns or malfunctions in the device or parts, economic losses due to lost opportunities, and health or damage to workers or users of the product.

[0051] Such predictive diagnosis can minimize sudden shutdowns due to breakdowns or malfunctions of equipment or parts, economic losses due to lost opportunities, and health or other damage to workers or product users.

[0052] Furthermore, a feature of the syringe suction algorithm using pressure sensor 107 is that it can detect suction abnormalities such as clogs and dry suction by comparing the difference between the pressure information during loop suction and the baseline pressure information before suction. At the same time, it can detect injection abnormalities by comparing the difference between the maximum and minimum values ​​obtained during injection by pressure sensor 108 of pump 105 with normal pressure information.

[0053] In addition, by storing the pressure information obtained from the two pressure sensors 107 and 108 in a database and performing long-term abnormality trend analysis, it is possible not only to detect temporary blockages and dry suction, but also to diagnose operational abnormalities and failure states at an early stage.

[0054] Furthermore, using these functions contributes to reducing the cost of liquid chromatograph equipment, and also makes it possible to estimate the cause of any abnormality that may occur.

[0055] The present invention is not limited to the above-described embodiment, but includes various modifications and combinations within the scope of the gist of the present invention.

[0056] Furthermore, the present invention is not limited to an embodiment having all of the configurations described in the above embodiments, and includes an embodiment in which some of the configurations are omitted.

[0057] Furthermore, the above-described configurations, functions, etc. may be realized, in part or in whole, by designing them as an integrated circuit, for example.

[0058] Furthermore, each of the above configurations, functions, etc. may be realized by software, in which a processor interprets and executes a program that realizes each function.

[0059] 100: Injection unit, 101: Sample, 102: Sipper, 103: Syringe, 104: First pipe, 105: Pump, 106: Second pipe, 107: Pressure sensor provided in first pipe, 108: Pressure sensor provided in second pipe, 109: Sample loop (mixing unit), 110: Valve, 111: Separation unit, 112: Detection unit, 113: Third pipe, 114: Verification unit, 116: Display unit, 201: Syringe suction, 202: At the time of air suction, 203: At the time of sample suction, 204: At the time of loop suction, 205: At the time of residual liquid discharge, 206: Pressure profile under normal conditions, 207: At the time of empty suction Pressure profile, 208...pressure profile when clogged, 301...pressure profile before smoothing, 302...pressure profile after smoothing, 401...pressure profile before baseline correction, 402...pressure profile before and after baseline correction, 601...control unit, 602...pump firmware, 603...pressure measurement command, 604...pressure result command, 605...pressure profile, 606...pressure measurement section 1, 607...pressure measurement section 2, 608...pressure measurement section 3, 609...pressure measurement section 4, 610...pressure measurement section 5, 1000...liquid chromatograph mass spectrometer

Claims

1. A liquid chromatograph apparatus comprising: a sipper for aspirating a specimen; a syringe as a negative pressure generating source for generating negative pressure in a first pipe connected to the sipper in order to aspirate the specimen into the sipper; a pump for pumping a diluent for diluting the specimen; a mixing section in which the diluent pumped by the pump and the specimen aspirated by the sipper are stored and mixed; a second pipe connecting the pump and the mixing section; a first pressure sensor disposed in the first pipe for detecting pressure within the first pipe; a second pressure sensor disposed in the second pipe for detecting pressure within the second pipe; and a verification section for verifying the abnormality based on the pressure detected by the second pressure sensor if the first pressure sensor detects an abnormality in pressure.

2. A liquid chromatograph apparatus as described in claim 1, characterized in that the verification section verifies an abnormality based on the differential pressure between the average pressure value of the baseline section of the first pressure sensor and the average pressure value when the sample is introduced into the mixing section.

3. A liquid chromatograph apparatus as described in claim 1 or 2, characterized in that the verification unit verifies an abnormality based on the differential pressure between the maximum pressure value and the minimum pressure value in the pressure measurement section of the second pressure sensor.

4. A liquid chromatograph apparatus as described in claim 1, characterized in that the verification section has a pressure difference of approximately 10 times the pressure difference between the average pressure value in the baseline section of the first pressure sensor and the average pressure value when the sample is introduced into the mixing section, and the pressure difference between the maximum pressure value and the minimum pressure value in the pressure measurement section of the second pressure sensor.

5. A liquid chromatograph apparatus as described in claim 3, characterized in that the verification section has a pressure difference of approximately 10 times between the differential pressure between the average pressure value in the baseline section of the first pressure sensor and the average pressure value when the sample is introduced into the mixing section and the differential pressure between the maximum pressure value and the minimum pressure value in the pressure measurement section of the second pressure sensor.

6. A liquid chromatograph apparatus as claimed in claim 1, further comprising a separation section for separating a specimen, and wherein the pressure measurement by the second pressure sensor to detect pressure is initiated when the specimen contained in the mixing section is supplied to the separation section.

7. A liquid chromatograph apparatus as described in claim 1, characterized in that the verification unit detects dry suction of the sample or a blockage in the first pipe from the pressure value detected by the first pressure sensor, and detects dry suction of the sample from the pressure detected by the second pressure sensor.

8. A liquid chromatograph as claimed in claim 1, further comprising a display unit which displays an alarm notifying the occurrence of an abnormality in accordance with information from said verification unit.

9. A method for detecting an abnormality in a liquid chromatograph which generates negative pressure in a first pipe connected to a sipper, draws a specimen into the sipper, mixes in the mixing section a diluent pumped by the pump and the specimen drawn by the sipper via a second pipe connecting the pump and a mixing section, and sends the mixed diluent and specimen to a separation section, characterized in that if a first pressure sensor which detects the pressure in the first pipe detects an abnormality in pressure, the abnormality is verified based on the pressure detected by a second pressure sensor which detects the pressure in the second pipe.

10. A method for detecting an abnormality in a liquid chromatograph apparatus as described in claim 9, characterized in that an abnormality is verified based on the differential pressure between the average pressure value in the baseline section of the first pressure sensor and the average pressure value when the sample is introduced into the mixing section.

11. A method for detecting an abnormality in a liquid chromatograph apparatus as described in claim 9 or 10, characterized in that an abnormality is verified based on the differential pressure between the maximum pressure value and the minimum pressure value in the pressure measurement section of the second pressure sensor.

12. A method for detecting an abnormality in a liquid chromatograph apparatus as described in claim 9, characterized in that there is a pressure difference of approximately 10 times between the differential pressure between the average pressure value in the baseline section of the first pressure sensor and the average pressure value when the sample is introduced into the mixing section and the differential pressure between the maximum pressure value and the minimum pressure value in the pressure measurement section of the second pressure sensor.

13. A method for detecting an abnormality in a liquid chromatograph apparatus as described in claim 11, characterized in that there is a pressure difference of approximately 10 times between the differential pressure between the average pressure value in the baseline section of the first pressure sensor and the average pressure value when the sample is introduced into the mixing section and the differential pressure between the maximum pressure value and the minimum pressure value in the pressure measurement section of the second pressure sensor.

14. A method for detecting an abnormality in a liquid chromatograph apparatus as described in claim 9, characterized in that the pressure measurement by the second pressure sensor to detect the pressure is initiated when the sample contained in the mixing section is supplied to a separation section which separates the sample.

15. A method for detecting an abnormality in a liquid chromatograph apparatus as described in claim 9, characterized in that dry suction of a sample or a blockage in the first pipe is detected from the pressure value detected by the first pressure sensor, and dry suction of a sample is detected from the pressure detected by the second pressure sensor.

16. The method for detecting an abnormality in a liquid chromatograph as claimed in claim 9, further comprising displaying an alarm to inform the user that an abnormality has occurred.

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