Method for determining abnormality in particle analyzer and particle analyzer

• US 10,151,696 B2
• Filed: 09/29/2015
• Issued: 12/11/2018
• Est. Priority Date: 09/30/2014
• Status: Active Grant

• Current Assignee: Sysmex Corporation
• Original Assignee: Sysmex Corporation
• Inventors: Yokoyama, Koji, Morisaki, Hiromi
• Primary Examiner(s): Crow, Robert T.
• Application Number:
  US14/869,156
• Publication Number:
  US 20160091428A1
• Time in Patent Office: 1,169 Days
• Field of Search: None
• CPC Class Codes: G01N 15/1012 Calibrating particle analysers; References therefor
• CPC Class Codes: G01N 15/1425 using an analyser being characterised by its control arrangement
• CPC Class Codes: G01N 15/1429 Signal processing
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 2015/1014 Constitution of reference particles
• CPC Class Codes: G01N 2015/1026 Recognising analyser failures, e.g. bubbles; Quality control for particle analysers
• CPC Class Codes: G01N 2015/1402 Data analysis by thresholding or gating operations performed on the acquired signals or stored data
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 35/00623 of instruments

Abstract

Disclosed is a method for determining abnormality in a particle analyzer. The method includes: staining first control particles but not staining second control particles which emit fluorescence; irradiating with light the first control particles and the second control particles flowing in a flow cell, and detecting fluorescence from the first control particles and the second control particles; obtaining a first management value indicating a detection result of the fluorescence emitted from the first control particles and a second management value indicating a detection result of the fluorescence emitted from the second control particles; and determining abnormality in the staining step, based on a value calculated from the first management value and the second management value or a ratio between the first management value and the second management value.

Claims

1. A method performed by a particle analyzer for determining an abnormality in a particle analysis process carried out by the particle analyzer, the method comprising:

mixing first control particles and fluorescence emitting second control particles with a fluorescent stain in a specimen preparation unit,

wherein the first control particles react with the fluorescent stain and the second control particles do not react with the fluorescent stain;

irradiating the first control particles and the second control particles flowing in a flow cell with light, and detecting fluorescence from the first control particles and the second control particles;

obtaining a first management value indicating a detection result of the fluorescence emitted from the first control particles and a second management value indicating a detection result of the fluorescence emitted from the second control particles,

wherein the first management value is based on an intensity of detected fluorescence from the first control particles, and the detection result is related to an abnormality in the specimen preparation unit or detecting fluorescence from the first control particles, and

wherein the second management value is based on an intensity of detected fluorescence from the second control particles, and the detection result is related to an abnormality in detecting fluorescence from the second control particles;

calculating a third management value by dividing the first management value and the second management value, or a ratio of the first management value and the second management value by an analysis unit that determines an abnormality in specimen preparation of the first control particles and the second control particles when the third management value or the ratio of the first and second management values is outside of an upper threshold and a lower threshold; and

displaying, on an output unit, a screen showing a message to suggest replacement of the fluorescent stain when an abnormality is determined based on the third management value or the ratio.

2. The method for determining abnormality of claim 1, further comprising determining abnormality in the detecting fluorescence from the first control particles and the second control particles based on the second management value.

3. The method for determining abnormality of claim 1, further comprising prohibiting measurement on a clinical sample by the particle analyzer in a case where the second management value indicates abnormality and in a case where the ratio or the third management value is outside of the upper threshold and lower threshold.

4. The method for determining abnormality of claim 1, further comprising displaying a list including:

an abnormality determination result based on the second management value; and

an abnormality determination result based on one of the ratio or the third management value.

5. The method for determining abnormality of claim 1, wherein the first control particles are selected from the group consisting of cells, polyacrylamide particles, hydrophilic vinyl polymer particles, latex particles, and silica particles.

6. The method for determining abnormality of claim 1, wherein the first control particles are cells, and nuclei of the cells are stained with the fluorescent stain.

7. The method for determining abnormality of claim 6, further comprising contacting the first control particles with RNA remover.

8. The method for determining abnormality of claim 7, wherein,

in a case where the third management value is smaller than the lower threshold, it is determined that there is abnormality in the fluorescent stain, and

in a case where the third management value is greater than the upper threshold, it is determined that there is abnormality in the RNA remover.

9. The method for determining abnormality of claim 1, wherein the particle analyzer analyzes an amount of DNA of each of cells contained in a sample.

10. The method for determining abnormality of claim 1, wherein the particle analyzer analyzes an amount of DNA of each of cells contained in a sample to calculate a number of cells containing a predetermined amount or more of DNA.

11. The method for determining abnormality of claim 1, wherein the first management value is a value based on a representative value of a numerical value obtained from waveforms of fluorescence signals of the respective first control particles, and

the second management value is a value based on a representative value of a numerical value obtained from waveforms of fluorescence signals of the respective second control particles.

12. A method performed by a particle analyzer for determining abnormality in a particle analysis process carried out by the particle analyzer which analyzes, based on a signal waveform of fluorescence emitted from a fluorescence-stained cell nucleus, an amount of DNA contained in the cell nucleus, the method comprising:

mixing first control particles and fluorescence emitting second control particles with a fluorescent stain in a specimen preparation unit,

wherein the first control particles react with the fluorescent stain and the second control particles do not react with the fluorescent stain;

irradiating with light the first control particles and the second control particles flowing in a flow cell, and obtaining signal waveforms based on fluorescence from each first control particle and each second control particle;

obtaining a representative value of an area of a signal waveform of the fluorescence from each first control particle as a first fluorescence area, wherein the first fluorescence area is based on an intensity of detected fluorescence from the first control particles and is related to an abnormality in the specimen preparation unit or detecting fluorescence from the first control particles;

obtaining a representative value of an area of the signal waveform of the fluorescence from each second control particle as a second fluorescence area, wherein the second fluorescence area is based on an intensity of detected fluorescence from the second control particles and is related to an abnormality in detecting fluorescence from the second control particles;

calculating a ratio of the first and second fluorescence areas by an analysis unit that determines an abnormality in staining performed in the particle analyzer when the ratio is outside of an upper threshold and a lower threshold; and

displaying, on an output unit, a screen showing a message to suggest replacement of the fluorescent stain when an abnormality is determined based on the ratio.

13. The method for determining abnormality of claim 12, wherein the first control particles are cells.