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EP-4741819-A1 - LIQUID CHROMATOGRAPH DEVICE AND METHOD FOR DETECTING ABNORMALITY THEREOF

EP4741819A1EP 4741819 A1EP4741819 A1EP 4741819A1EP-4741819-A1

Abstract

The present invention provides a liquid chromatograph device capable of minimizing sudden stop due to failure of the device, economic damage due to opportunity loss, and damage to a user. The liquid chromatograph device includes: a sipper 102 configured to aspirate a sample; a syringe 103 configured to generate a negative pressure in a first pipe 104 communicated with the sipper 102 to aspirate the sample into the sipper 102; a pump 105 configured to pump a diluent for diluting the sample; a mixing portion 109 configured to accommodate and mix the diluent pumped by the pump 105 and the sample aspirated by the sipper 102; a second pipe 106 communicating the pump 105 with the mixing portion; a first pressure sensor 107 disposed in the first pipe 104 and configured to detect a pressure in the first pipe 104; a second pressure sensor 108 disposed in the second pipe 106 and configured to detect a pressure in the second pipe 106; and a verification unit 114 configured to verify, when the first pressure sensor 107 detects an abnormality in the pressure, the abnormality based on the pressure detected by the second pressure sensor 108.

Inventors

  • NOGAMI, MAKOTO
  • TOBITA, Midori
  • HARADA, YUSHI

Assignees

  • HITACHI HIGH-TECH CORPORATION

Dates

Publication Date
20260513
Application Date
20240603

Claims (16)

  1. A liquid chromatograph device comprising: a sipper configured to aspirate a sample; a syringe which is a negative pressure generation source that generates a negative pressure in a first pipe communicating with the sipper to aspirate the sample into the sipper; a pump configured to pump a diluent for diluting the sample; a mixing portion configured to accommodate and mix the diluent pumped by the pump and the sample aspirated by the sipper; a second pipe communicating the pump with the mixing portion; a first pressure sensor disposed in the first pipe and configured to detect a pressure in the first pipe; a second pressure sensor disposed in the second pipe and configured to detect a pressure in the second pipe; and a verification unit configured to verify, when the first pressure sensor detects an abnormality in the pressure, the abnormality based on the pressure detected by the second pressure sensor.
  2. The liquid chromatograph device according to claim 1, wherein the verification unit verifies the abnormality based on a differential pressure between a pressure average value of the first pressure sensor in a baseline interval and a pressure average value during introduction of the sample into the mixing portion.
  3. The liquid chromatograph device according to claim 1 or 2, wherein the verification unit verifies the abnormality based on a differential pressure between a maximum value of a pressure value of the second pressure sensor in a pressure measurement time and a minimum value of the pressure value.
  4. The liquid chromatograph device according to claim 1, wherein by the verification unit, a pressure difference of about 10 times is present between a differential pressure between a pressure average value of the first pressure sensor in a baseline interval and a pressure average value during introduction of the sample into the mixing portion, and a differential pressure between a maximum value of a pressure value of the second pressure sensor in a pressure measurement time and a minimum value of the pressure value.
  5. The liquid chromatograph device according to claim 3, wherein by the verification unit, a pressure difference of about 10 times is present between the differential pressure between the pressure average value of the first pressure sensor in the baseline interval and the pressure average value during introduction of the sample into the mixing portion, and the differential pressure between the maximum value of the pressure value of the second pressure sensor in the pressure measurement time and the minimum value of the pressure value.
  6. The liquid chromatograph device according to claim 1, further comprising: a separation portion configured to separate the sample, wherein pressure measurement in which the second pressure sensor detects the pressure is started when the sample accommodated in the mixing portion is supplied to the separation portion.
  7. The liquid chromatograph device according to claim 1, wherein the verification unit detects air aspiration of the sample or clogging in the first pipe based on a pressure value detected by the first pressure sensor, and detects the air aspiration of the sample based on the pressure detected by the second pressure sensor.
  8. The liquid chromatograph device according to claim 1, further comprising: a display unit configured to display, in accordance with information from the verification unit, an alarm notifying that the abnormality occurred.
  9. An abnormality detection method for a liquid chromatograph device, comprising: generating a negative pressure in a first pipe communicating with a sipper and aspirating a sample into the sipper; mixing, by the mixing portion, a diluent pumped by a pump via a second pipe communicating the pump with the mixing portion and the sample aspirated by the sipper; and supplying the diluent and the sample that are mixed to a separation portion, wherein when a first pressure sensor for detecting a pressure in the first pipe detects an abnormality in the pressure, the abnormality is verified based on a pressure detected by a second pressure sensor for detecting the pressure in the second pipe.
  10. The abnormality detection method for a liquid chromatograph device according to claim 9, wherein the abnormality is verified based on a differential pressure between a pressure average value of the first pressure sensor in a baseline interval and a pressure average value during introduction of the sample into the mixing portion.
  11. The abnormality detection method for a liquid chromatograph device according to claim 9 or 10, wherein the abnormality is verified based on a differential pressure between a maximum value of a pressure value of the second pressure sensor in a pressure measurement time and a minimum value of the pressure value.
  12. The abnormality detection method for a liquid chromatograph device according to claim 9, wherein a pressure difference of about 10 times is present between a differential pressure between a pressure average value of the first pressure sensor in a baseline interval and a pressure average value during introduction of the sample into the mixing portion, and a differential pressure between a maximum value of a pressure value of the second pressure sensor in a pressure measurement time and a minimum value of the pressure value.
  13. The abnormality detection method for a liquid chromatograph device according to claim 11, wherein a pressure difference of about 10 times is present between the differential pressure between the pressure average value of the first pressure sensor in the baseline interval and the pressure average value during introduction of the sample into the mixing portion, and the differential pressure between the maximum value of the pressure value of the second pressure sensor in the pressure measurement time and the minimum value of the pressure value.
  14. The abnormality detection method for a liquid chromatograph device according to claim 9, wherein pressure measurement in which the second pressure sensor detects the pressure is started when the sample accommodated in the mixing portion is supplied to the separation portion that separates the sample.
  15. The abnormality detection method for a liquid chromatograph device according to claim 9, wherein air aspiration of the sample or clogging in the first pipe is detected based on a pressure value detected by the first pressure sensor, and the air aspiration of the sample is detected based on the pressure detected by the second pressure sensor.
  16. The abnormality detection method for a liquid chromatograph device according to claim 9, further comprising: displaying an alarm notifying that the abnormality occurred.

Description

Technical Field The present invention relates to a liquid chromatograph device and an abnormality detection method therefor. Background Art In inspection centers, university hospitals, or the like, inspections such as immunosuppressive agents, anticancer agents, neonatal metabolic abnormality inspections, and therapeutic drug monitoring (TDM) are performed using a liquid chromatograph mass spectrometer (HPLC/MS). In order to prevent variation in an inspection result, reproducibility and accuracy of a sample introduction (injection) step of introducing a sample into the liquid chromatograph mass spectrometer are important. Here, PTL 1 discloses a technique for detecting a pressure abnormality such as clogging or leakage of a flow path, the technique including a pump pressure sensor that monitors a pressure in the flow path, an injection valve that switches between a liquid feed flow path from a pump and a flow path from a syringe, a sample loop coupled to the injection valve, the syringe that aspirates or discharges a sample, and a syringe pressure sensor that monitors an aspiration or discharge state of the syringe. Citation List Patent Literature PTL 1: WO2022/230282A Summary of Invention Technical Problem In PTL 1, a verification unit that verifies an abnormality based on a pressure value of the syringe pressure sensor for monitoring the aspiration or discharge state of the syringe when the pump pressure sensor for monitoring the pressure in the flow path detects a pressure abnormality is not provided. An object of the invention is to provide a liquid chromatograph device and an abnormality detection method for the liquid chromatograph device capable of minimizing, by a predictive diagnosis, sudden stop due to a failure or a defect of a device or a component, economic damage due to opportunity loss, or health and damage to a worker or a user of a product. Solution to Problem In order to achieve the above object, the invention is formed as follows. A liquid chromatograph device includes: a sipper configured to aspirate a sample; a syringe which is a negative pressure generation source that generates a negative pressure in a first pipe communicating with the sipper to aspirate the sample into the sipper; a pump configured to pump a diluent for diluting the sample; a mixing portion configured to accommodate and mix the diluent pumped by the pump and the sample aspirated by the sipper; a second pipe communicating the pump with the mixing portion; a first pressure sensor disposed in the first pipe and configured to detect a pressure in the first pipe; a second pressure sensor disposed in the second pipe and configured to detect a pressure in the second pipe; and a verification unit configured to verify, when the first pressure sensor detects an abnormality in the pressure, the abnormality based on the pressure detected by the second pressure sensor. An abnormality detection method for a liquid chromatograph device includes: generating a negative pressure in a first pipe communicating with a sipper and aspirating a sample into the sipper; mixing, by the mixing portion, a diluent pumped by the pump via a second pipe communicating the pump with the mixing portion and the sample aspirated by the sipper; and supplying the diluent and the sample that are mixed to a separation portion, in which when a first pressure sensor for detecting a pressure in the first pipe detects an abnormality in the pressure, the abnormality is verified based on a pressure detected by a second pressure sensor for detecting the pressure in the second pipe. Advantageous Effects of Invention According to the invention, it is possible to provide a liquid chromatograph device and an abnormality detection method for the liquid chromatograph device capable of minimizing, by a predictive diagnosis, sudden stop due to a failure or a defect of a device or a component, economic damage due to opportunity loss, or health and damage to a worker or a user of a product. Brief Description of Drawings FIG. 1 is a schematic diagram of a liquid chromatograph mass spectrometer.FIG. 2 is a schematic diagram of an abnormality detection process during sample aspiration.FIG. 3 is a diagram showing pressure profiles before and after a smoothing process.FIG. 4 is a schematic diagram of baseline correction.FIG. 5 is a flowchart of an abnormality detection process during sample injection.FIG. 6 is a schematic view of abnormality detection during the sample injection. Description of Embodiments Hereinafter, embodiments of the invention will be described with reference to the drawings. [Examples] FIG. 1 is a schematic diagram of a liquid chromatograph mass spectrometer (HPLC/MS) 1000. The liquid chromatograph mass spectrometer 1000 includes an injection portion 100, a separation portion 111 that separates a sample, a detection unit 112, a verification unit 114, a control unit 601, and a display unit 116. The separation portion 111 includes a column. The control unit 60