CN113454453A - Whole blood sample analyzer, whole blood sample analyzing method, whole blood sample analyzing apparatus, and storage medium - Google Patents

Whole blood sample analyzer, whole blood sample analyzing method, whole blood sample analyzing apparatus, and storage medium Download PDF

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CN113454453A
CN113454453A CN201980092567.7A CN201980092567A CN113454453A CN 113454453 A CN113454453 A CN 113454453A CN 201980092567 A CN201980092567 A CN 201980092567A CN 113454453 A CN113454453 A CN 113454453A
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blood sample
particles
peripheral blood
whole blood
detected
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郑文波
陈鹏震
叶波
祁欢
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Shenzhen Mindray Bio Medical Electronics Co Ltd
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Shenzhen Mindray Bio Medical Electronics Co Ltd
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    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10Investigating individual particles
    • G01N15/14Optical investigation techniques, e.g. flow cytometry
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483Physical analysis of biological material
    • G01N33/487Physical analysis of biological material of liquid biological material
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Abstract

A whole blood sample analyzer, a whole blood sample analyzing method, and an apparatus and a storage medium therefor, wherein: a method of analyzing a whole blood sample that can be used to analyze a peripheral blood sample includes: acquiring optical signal information of the peripheral blood sample after the reagent treatment (S201), wherein the optical signal information comprises at least two of a forward scattered light signal, a side scattered light signal and a fluorescence signal; identifying foreign particles in the peripheral blood sample to be detected based on the optical signal information (S202); processing (S203) optical signal information of the identified impurity particles; classifying and counting the particles in the peripheral blood sample to be detected according to the optical signal information processed by the impurity particles (S204); the classification count result of the peripheral blood sample to be detected is output (S205).

Description

Whole blood sample analyzer, whole blood sample analyzing method, whole blood sample analyzing apparatus, and storage medium Technical Field
The present application relates to the field of medical testing, in particular to the field of blood cell testing, and relates to, but is not limited to, a whole blood sample analyzer, a whole blood sample analyzing method, a device thereof, and a storage medium.
Background
Blood routine tests are one of clinical diagnostic test items, and play an important role in diagnosis and treatment of diseases. The collection of blood samples is divided into venous blood collection and peripheral blood collection. In the routine detection of blood, the elbow vein is selected for collecting venous blood, the blood vessel has large crude flow rate, so that detection personnel can extract the blood easily, the influence of air temperature and peripheral circulation is small, and the actual physical condition of a patient can be accurately reflected. The collection of peripheral blood is mostly carried out scraping or suction through the finger tip, the operation is simple and convenient, and the pain of repeated puncture can be avoided. Peripheral blood collection is usually adopted for infants; some emergency patients need to be examined for many times a day, leukemia, tumor and the like need repeated routine blood examination during treatment, and venous blood is collected every time to easily cause injury and affect treatment, so peripheral blood collection methods are frequently used for the cases.
However, since the peripheral blood collection site is special, the peripheral blood flow rate is slow, and repeated squeezing is required if bleeding is not smooth. The outermost layer of the epidermis at the tip is the stratum corneum, which is composed of flat, dead, anucleated cells. When peripheral blood is collected, the cutin is easy to fall off when the skin is squeezed and scraped, and the cutin cell fragments with different sizes are brought into a peripheral blood sample collection sample, so that partial detection results of a blood cell analyzer are interfered. In the peripheral blood sample collected by the blood scraping method, the situation that keratinocyte fragments interfere cell counting is inevitable, and the fragment interference on a blood cell classification scatter diagram is very obvious, so that the accuracy of a detection result is seriously influenced.
Reliable detection results are the guideline for clinical diagnosis, so a method for reducing the influence of impurities on cell differential counting in the peripheral blood collection process is urgently needed to solve the problems.
Disclosure of Invention
In view of the above, embodiments of the present application are intended to provide a whole blood sample analyzer, a whole blood sample analyzing method, a device thereof, and a storage medium, which solve the problem of inaccurate detection results due to foreign particles brought by the external environment when peripheral blood is collected. In addition, the method and the device can be used for processing and analyzing the whole blood sample in a targeted manner according to the sample type of the whole blood sample, so that the accuracy of the detection result is improved.
The technical scheme of the embodiment of the application is realized as follows:
the present application provides in a first aspect a whole blood sample analyzer usable for analyzing a peripheral blood sample, the whole blood sample analyzer comprising:
a sampling device having a pipette with a pipette nozzle and having a driving device for driving the pipette to quantitatively aspirate a peripheral blood sample through the pipette nozzle;
the reaction device is provided with a reaction pool and a liquid supply part, wherein the reaction pool is used for receiving the peripheral blood sample sucked by the sampling device, and the liquid supply part is used for supplying a reagent to the reaction pool, so that the peripheral blood sample sucked by the sampling device and the reagent supplied by the liquid supply part react in the reaction pool to prepare a peripheral blood sample to be detected;
an optical detection device having a light source, a flow chamber, wherein particles of a reagent-treated peripheral blood sample can flow within the flow chamber, a light emitted by the light source illuminates the particles in the flow chamber to generate optical signal information, and a light collector for collecting the optical signal information, wherein the optical signal information includes at least two of a forward scattered light signal, a side scattered light signal, and a fluorescence signal;
the conveying device is used for conveying the peripheral blood sample treated by the reagent in the reaction pool to the optical detection device;
a processor configured to: acquiring the optical signal information from the optical detection device; identifying impurity particles in the to-be-detected peripheral blood sample according to the optical signal information; processing the optical signal information of the identified impurity particles; classifying and counting the particles in the peripheral blood sample to be detected according to the optical signal information processed by the impurity particles; and outputting the classification counting result of the peripheral blood sample to be detected.
In the above scheme, the impurity particles may be caused by external environment interference, especially caused by taking a peripheral blood sample by a blood scraping method.
In the above aspect, the impurity particles may be skin keratinocyte fragments.
In the above solution, the processor may be configured to, when the step of identifying the foreign particles in the peripheral blood sample to be detected according to the optical signal information is performed, perform the following steps:
generating a scatter diagram based on the forward scattered light signals and the side scattered light signals in the optical signal information;
judging whether the particles of the peripheral blood sample to be detected are in a preset interference area of the scatter diagram;
identifying particles in the preset interference region as impurity particles.
Preferably, the preset interference region may be a preset fixed region, in particular, a fixed region which may be determined according to a forward scattered light signal and a side scattered light signal scattergram of each particle of the normal whole blood sample and the interference peripheral blood sample; or the preset interference region can also be dynamically determined according to the distribution of forward scattered light signals and side scattered light signals of all particles in the peripheral blood sample to be detected.
In the above-described aspect, the predetermined interference region may be located between the lymphocyte population and the eosinophil population and/or on the upper right of the neutrophil population in the scattergram having the forward scattered light signal as the ordinate and the side scattered light signal as the abscissa.
In the above solution, the processor may be configured to, when the step of identifying the foreign particles in the peripheral blood sample to be detected according to the optical signal information is performed, perform the following steps:
judging whether the forward scattering light pulse width of the particles of the peripheral blood sample to be detected is larger than a preset pulse width threshold value or not;
particles with a forward scattered light pulse width greater than a preset pulse width threshold are identified as contaminant particles.
Preferably, the preset pulse width threshold may be a preset fixed threshold, in particular, a fixed threshold determined according to the pulse width distribution of forward scattered light of each particle of the normal whole blood sample and the interference peripheral blood sample; or the preset pulse width threshold value can be dynamically determined according to the average value of the pulse widths of the forward scattered light of all particles in the peripheral blood sample to be detected.
In the above solution, the processor may be configured to, when the step of identifying the foreign particles in the peripheral blood sample to be detected according to the optical signal information is performed, perform the following steps:
generating a scatter diagram based on the forward scattered light signals and the side scattered light signals in the optical signal information;
judging whether the particles of the to-be-detected peripheral blood sample are in a preset interference area of the scatter diagram and judging whether the forward scattering light pulse width of the particles of the to-be-detected peripheral blood sample is larger than a preset pulse width threshold value;
particles that are in the predetermined interference region and have a forward scattered light pulse width greater than a predetermined pulse width threshold are identified as contaminant particles.
In the above aspect, the processor may perform the following steps when performing processing on the optical signal information of the identified foreign particles:
removing optical signal information of the impurity particles; or setting the impurity particles as ghost particles; or displaying the impurity particles in a color different from other particles; or outputting prompt information of the impurity particles in the peripheral blood sample to be detected and/or outputting a prompt of whether the impurity particles are processed or not.
In the above solution, the processor is further configured to perform the following steps:
determining the number of real white blood cell particles and the number of impurity particles in the peripheral blood sample to be detected after identifying the impurity particles;
and when the number of the real white blood cell particles and the number of the impurity particles meet preset conditions, outputting prompt information of the impurity particles in the peripheral blood sample to be detected and/or outputting a prompt of whether the impurity particles are processed or not.
In the above aspect, the whole blood sample analyzer may further include a display device configured to receive and display the classification count result of the to-be-detected peripheral blood sample and/or a scattergram composed of at least two of the optical signal information from the processor.
A second aspect of the present application provides a whole blood sample analyzer that can analyze a venous blood sample and a peripheral blood sample, the whole blood sample analyzer comprising:
a sampling device having a pipette with a pipette nozzle and having a driving device for driving the pipette to quantitatively aspirate a whole blood sample through the pipette nozzle;
the reaction device is provided with a reaction pool and a liquid supply part, wherein the reaction pool is used for receiving the whole blood sample sucked by the sampling device, and the liquid supply part is used for supplying a reagent to the reaction pool, so that the whole blood sample sucked by the sampling device and the reagent supplied by the liquid supply part react in the reaction pool to prepare a whole blood sample to be detected;
an optical detection device having a light source, a flow chamber, wherein particles of a reagent-treated peripheral blood sample can flow within the flow chamber, a light emitted by the light source illuminates the particles in the flow chamber to generate optical signal information, and a light collector for collecting the optical signal information, wherein the optical signal information includes at least two of a forward scattered light signal, a side scattered light signal, and a fluorescence signal;
the conveying device is used for conveying the whole blood sample treated by the reagent in the reaction pool to the optical detection device;
a processor configured to: acquiring the optical signal information from the optical detection device; judging the sample type of the whole blood sample to be detected; when the sample type of the whole blood sample to be detected is a first sample type, classifying and counting the particles of the whole blood sample to be detected by using the optical signal information under a first classification counting algorithm, and when the sample type of the whole blood sample to be detected is a second sample type, classifying and counting the particles of the whole blood sample to be detected by using the optical signal information under a second classification counting algorithm different from the first classification counting algorithm; and outputting the classification counting result of the whole blood sample to be detected.
In the above scheme, the first and second class-counting algorithms may be related to a segmentation algorithm of a cell population in a whole blood sample.
In the above scheme, the first and second class-counting algorithms may be related to impurity particle interference in the whole blood sample.
In the above scheme, the foreign particle interference may be caused by external environment interference, especially caused by collecting a whole blood sample by a blood scraping method.
In the above scheme, the impurity particle interference may be interference caused by keratinocyte fragments.
In the above aspect, the processor may be configured to, when the sample type of the whole blood sample to be detected is a peripheral blood sample, identify impurity particles in the whole blood sample to be detected according to the optical signal information and process the optical signal information of the identified impurity particles.
In the above aspect, the whole blood sample analyzer may further include a mode selection portion configured to select a mode for detecting a peripheral blood sample or a venous blood sample and output mode information to the processor; the processor acquires mode information from the mode selection part to judge whether the whole blood sample to be detected is a peripheral blood sample collected by adopting a blood scraping method.
In a third aspect, the present application provides a method of analyzing a whole blood sample useful for analyzing a peripheral blood sample, the method comprising:
acquiring optical signal information of the peripheral blood sample after being processed by the reagent, wherein the optical signal information comprises at least two of forward scattered light signals, side scattered light signals and fluorescence signals;
identifying impurity particles in the to-be-detected peripheral blood sample according to the optical signal information;
processing the optical signal information of the identified impurity particles;
according to the optical signal information processed by the impurity particles, classifying and counting the particles in the peripheral blood sample to be detected; and
and outputting the classification counting result of the peripheral blood sample to be detected.
In the above scheme, the impurity particles may be caused by external environment interference, especially caused by collecting a whole blood sample by a blood scraping method.
In the above aspect, the impurity particles may be skin keratinocyte fragments.
In the above aspect, the step of identifying the impurity particles in the peripheral blood sample to be detected according to the optical signal information may include:
generating a scatter diagram based on the forward scattered light signals and the side scattered light signals in the optical signal information;
judging whether the particles of the peripheral blood sample to be detected are in a preset interference area of the scatter diagram;
identifying particles in the preset interference region as impurity particles.
Preferably, the preset interference region may be a preset fixed region, in particular a fixed region determined according to a forward scattered light signal and a side scattered light signal scattergram of each particle of the normal whole blood sample and the interference peripheral blood sample; or the preset interference region can also be dynamically determined according to the distribution of forward scattered light signals and side scattered light signals of all particles in the peripheral blood sample to be detected.
In the above-described aspect, the predetermined interference region may be located between the lymphocyte population and the eosinophil population and/or on the upper right of the neutrophil population in the scattergram having the forward scattered light signal as the ordinate and the side scattered light signal as the abscissa.
In the above aspect, the step of identifying the impurity particles in the peripheral blood sample to be detected according to the optical signal information may include:
judging whether the forward scattering light pulse width of the particles of the peripheral blood sample to be detected is larger than a preset pulse width threshold value or not;
particles with a forward scattered light pulse width greater than a preset pulse width threshold are identified as contaminant particles.
Preferably, the preset pulse width threshold may be a preset fixed threshold, in particular, a fixed threshold that may be determined according to the forward scattered light pulse width distributions of the respective particles of the normal whole blood sample and the interference peripheral blood sample; or the preset pulse width threshold value can be dynamically determined according to the average value of the pulse widths of the forward scattered light of all particles in the peripheral blood sample to be detected.
In the above aspect, the step of identifying the impurity particles in the peripheral blood sample to be detected according to the optical signal information may include:
generating a scatter diagram based on the forward scattered light signals and the side scattered light signals in the optical signal information;
judging whether the particles of the to-be-detected peripheral blood sample are in a preset interference area of the scatter diagram and judging whether the forward scattering light pulse width of the particles of the to-be-detected peripheral blood sample is larger than a preset pulse width threshold value;
particles that are in the predetermined interference region and have a forward scattered light pulse width greater than a predetermined pulse width threshold are identified as contaminant particles.
In the foregoing aspect, the processing the optical signal information of the identified impurity particles may include:
removing optical signal information of the impurity particles; or setting the impurity particles as ghost particles; or displaying the impurity particles in a color different from other particles; or outputting prompt information of the impurity particles in the peripheral blood sample to be detected and/or outputting a prompt of whether the impurity particles are processed or not.
In the above scheme, the method may further include:
determining the number of real white blood cell particles and the number of impurity particles in the peripheral blood sample to be detected after identifying the impurity particles;
and when the number of the real white blood cell particles and the number of the impurity particles meet preset conditions, outputting prompt information of the impurity particles in the peripheral blood sample to be detected and/or outputting a prompt of whether the impurity particles are processed or not.
A fourth aspect of the present application provides a method of analyzing a whole blood sample that can analyze a venous blood sample and a peripheral blood sample, the method comprising:
acquiring optical signal information of the whole blood sample after being processed by the reagent, wherein the optical signal information comprises at least two of a forward scattered light signal, a side scattered light signal and a fluorescence signal;
judging the sample type of the whole blood sample to be detected;
when the sample type of the whole blood sample to be detected is a first sample type, classifying and counting the particles of the whole blood sample to be detected by using the optical signal information under a first classification counting algorithm, and when the sample type of the whole blood sample to be detected is a second sample type, classifying and counting the particles of the whole blood sample to be detected by using the optical signal information under a second classification counting algorithm different from the first classification counting algorithm; and
and outputting the classification counting result of the whole blood sample to be detected.
In the above scheme, the step of determining whether the whole blood sample to be detected is a peripheral blood sample collected by a blood scraping method includes:
and judging whether the whole blood sample to be detected is a peripheral blood sample collected by adopting a blood scraping method or not according to mode selection information input by a user.
In the case of the protocol according to the fourth aspect of the present application, the method according to the third aspect of the present application is carried out when the type of sample of the whole blood sample to be tested is a peripheral blood sample.
The present application provides in a fifth aspect a whole blood sample analyzer for use in a whole blood sample analyzer, the whole blood sample analyzer comprising:
a memory configured to store executable instructions;
a processor configured to execute the memory stored executable instructions to perform the whole blood sample analysis method as described above.
A sixth aspect of the present application provides a computer-readable storage medium having stored thereon executable instructions, wherein the computer-readable storage medium is configured to cause a processor to execute the executable instructions to implement the method for analyzing a whole blood sample as described above.
The embodiment of the application provides a whole blood sample analyzer, whole blood sample analysis method and device and storage medium thereof, wherein, when carrying out whole blood sample analysis to ending blood sample, owing to adopt when scraping the blood method and gathering ending blood sample, need extrude repeatedly and scrape the skin, thereby lead to unavoidably having the foreign particle in ending blood sample, and then cause the interference to sample analyzer's partial testing result, consequently when carrying out whole blood sample analysis to ending blood sample, need discern and handle the foreign particle that brings because the external environment in the whole blood sample, thereby can avoid the foreign particle to produce the influence to whole blood sample classification count result, further guarantee the accuracy of analysis result.
Drawings
FIG. 1 is a schematic diagram of the overall structure of the whole blood sample analyzer of the present application;
FIG. 2 is a first schematic flow chart of a first embodiment of the method for analyzing a whole blood sample according to the present application;
FIG. 3A is a SS-FS scattergram of cell particles of a peripheral blood sample without being subjected to a spot treatment;
FIG. 3B is a SS-FS scatter plot of cell particles of a peripheral blood sample after removal of outlier interferences according to the methods of the present application;
FIG. 4 is a schematic flow chart II of the first embodiment of the whole blood sample analysis method according to the present application;
FIG. 5A is a two-dimensional scattergram of SS signal intensity and FS signal intensity of cell particles in a hemolyzed normal whole blood sample;
FIG. 5B is a two-dimensional scattergram of SS signal intensity and FS signal intensity of cell particles in a hemolyzed perturbed peripheral blood sample;
FIG. 6A is a schematic diagram of a two-dimensional scatter diagram of SS-FS with a rectangular region fixed as a particle region with a particle impurity point according to an embodiment of the present disclosure;
fig. 6B is a schematic diagram of fixedly setting a circular arc region as a particle region with a mixed point in a SS-FS two-dimensional scattergram according to the embodiment of the present application;
FIG. 7A is a schematic diagram of dynamically setting a rectangular region as a particle region with a particle impurity in a SS-FS two-dimensional scattergram according to an embodiment of the present application;
FIG. 7B is a schematic diagram of dynamically setting a circular region as a particle region with a particle impurity in a SS-FS two-dimensional scattergram according to an embodiment of the present application;
FIG. 8 is a schematic diagram of a FS-SS-FSW three-dimensional scattergram in which a rectangular parallelepiped region is fixedly set as a hetero-point particle region according to an embodiment of the present application;
FIG. 9 is a third schematic flow chart of the first embodiment of the method for analyzing a whole blood sample according to the present application;
FIG. 10A is a schematic diagram of the forward scattered light pulse signals of normal leukocyte particles;
FIG. 10B is a diagram showing the forward scattered light pulse signal of the impurity particles;
FIG. 11A is a FSW-FS scattergram of leukocyte particles in a hemolyzed normal whole blood sample;
FIG. 11B is a FSW-FS scattergram of leukocyte particles in a hemolyzed perturbed peripheral blood sample;
FIG. 12 is a diagram illustrating setting of a preset pulse width threshold in relation to a mean value of pulse widths of forward scattered light of all particles in a peripheral blood sample to be detected according to an embodiment of the present application;
FIG. 13 is a fourth schematic flow chart of the first embodiment of the method for analyzing a whole blood sample according to the present application;
FIG. 14 is a schematic diagram illustrating the method shown in FIG. 13 for determining the particles with the abnormal points in the peripheral blood sample to be detected;
FIG. 15 is a schematic flow chart of a second embodiment of the method for analyzing a whole blood sample according to the present application;
FIG. 16A is a FL-FS scattergram of red blood cells and platelets of venous blood;
FIG. 16B is a FL-FS scattergram of red blood cells and platelets of peripheral blood;
FIG. 17 is a schematic view of the structure of a whole blood sample analyzer according to an embodiment of the present application.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present application clearer, specific technical solutions of the present invention will be described in further detail below with reference to the accompanying drawings. The following examples are intended to illustrate the present application but are not intended to limit the scope of the present application.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing embodiments of the present application only and is not intended to be limiting of the application.
In the following description, reference is made to "some embodiments" which describe a subset of all possible embodiments, but it is understood that "some embodiments" may be the same subset or different subsets of all possible embodiments, and may be combined with each other without conflict.
It should be noted that the terms "first \ second \ third" referred to in the embodiments of the present application are only used for distinguishing similar objects, and do not represent a specific ordering for the objects.
For the convenience of the following description, some terms referred to hereinafter will first be briefly described as follows.
1) A scatter diagram: the two-dimensional or three-dimensional image is generated by a blood cell analyzer, and two-dimensional or three-dimensional characteristic information of a plurality of particles is distributed on the two-dimensional or three-dimensional image, wherein an X coordinate axis, a Y coordinate axis and a Z coordinate axis of the scattergram all represent one characteristic of each particle, for example, in the scattergram, the X coordinate axis represents the forward scattered light intensity, the Y coordinate axis represents the fluorescence intensity, and the Z coordinate axis represents the side scattered light intensity.
2) Cell population (b): the particle clusters distributed in a certain region of the scattergram and formed of a plurality of particles having the same characteristics, for example, a leukocyte population, and a neutrophil population, a lymphocyte population, a monocyte population, an eosinophil population, a basophil population, and the like in leukocytes.
3) And (3) ghosting: is a particle of debris obtained by lysing red blood cells and platelets in blood with a hemolytic agent.
Embodiments of the present application first provide a whole blood sample analyzer that can be used to analyze at least a peripheral blood sample. Fig. 1 is a schematic diagram showing a constitutional structure of a whole blood sample analyzer 100 according to an embodiment of the present application. As shown in FIG. 1, the whole blood sample analyzer 100 includes at least a sampling device (not shown), a reaction device 110, an optical detection device 120, a transport device 130, and a processor 140.
The sampling device, not shown, can have a pipette with a pipette nozzle and a drive device for driving the pipette to aspirate a whole blood sample, for example a peripheral blood sample collected by the apheresis method, quantitatively via the pipette nozzle. Further, the sampling device is driven by its driving means and moved to the reaction cell 111 of the reaction device 110 after sucking the whole blood sample, and the whole blood sample sucked is injected into the reaction cell 111.
The reaction device 110 has at least one reaction cell 111 and a liquid supply portion (not shown), wherein the reaction cell 111 is used for receiving the whole blood sample sucked by the sampling device, and the liquid supply portion supplies a reagent to the reaction cell 111, so that the whole blood sample sucked by the sampling device and the reagent supplied by the liquid supply portion react in the reaction cell to prepare a whole blood sample to be detected. For example, the liquid supply portion may be used to inject a suitable hemolytic agent and a fluorescent dye into the reaction cell to perform hemolytic treatment and fluorescent staining treatment on particles in the whole blood sample, thereby preparing the whole blood sample to be detected for detecting leukocytes therein.
Optical detection device 120 has a light source 121, a flow cell 122, and light collectors 123, 124, 125, wherein: flow chamber 122 has an orifice 1221, and particles of the reagent-processed whole blood sample in reaction device 110 may flow within flow chamber 122 and pass through orifice 1221 one by one. Light emitted by the light source 121 illuminates particles in the flow cell 122 to produce optical signal information. The collectors 123, 124, 125 are used for collecting the optical signal information, wherein the optical signal information includes at least two of the forward scattered light signal, the side scattered light signal and the fluorescence signal, i.e. the optical detection device 120 includes at least two of the forward scattered light collector 123, the side scattered light collector 124 and the fluorescence collector 125. The light collector is constructed as a photoelectric sensor, such as a photodiode or a photomultiplier tube. As shown in fig. 1, forward scattered light emitted from blood cells (e.g., white blood cells) flowing in the flow cell 122 is received by a photodiode (forward scattered light collector) 123 through a condenser lens 126 and a pinhole 127. The side scattered light is received by a photomultiplier tube (side scattered light collector) 124 through a condenser 126, a dichroic mirror 128, an optical film 129, and a pinhole 127. The fluorescence is received by a photomultiplier (fluorescence collector) 125 through a condenser 126 and a dichroic mirror 128. The optical signals output from the respective light collectors 123, 124, and 125 are subjected to analog signal processing such as amplification and waveform processing by an amplifier 150, and then are supplied to a processor 140.
The conveying device 130 is used for conveying the whole blood sample processed by the reagent in the reaction cell 111 to the optical detection device 120.
The processor 140 is arranged to acquire the optical signal information from the optical detection means 120 and to process the optical signal information. The processor 140 may have an a/D converter, not shown, for converting the analog signal provided by the optical detection device 120 into a digital signal. In particular, the processor 140 is configured to implement a method of analyzing a whole blood sample according to the present application, which is described in further detail below.
In the embodiment of the present invention, the Processor 140 may be at least one of an Application Specific Integrated Circuit (ASIC), a Digital Signal Processor (DSP), a Digital Signal Processing Device (DSPD), a ProgRAMmable Logic Device (PLD), a Field ProgRAMmable Gate Array (FPGA), a Central Processing Unit (CPU), a controller, a microcontroller, and a microprocessor. It is understood that the electronic devices for implementing the above processor functions may be other devices, and the embodiments of the present application are not limited in particular.
In addition, the whole blood sample analyzer 100 further includes a display device (not shown) configured to receive and display a whole blood sample analysis result and/or a scattergram made up of at least two of the optical signal information from the processor 140.
The whole blood sample analyzing method proposed in the present application will be described in detail below with reference to the whole blood sample analyzer 100 and the accompanying drawings. The whole blood sample analysis method may be performed by the processor 140 of the whole blood sample analyzer 100 described above according to the embodiments of the present application.
The present embodiment provides a whole blood sample analysis method 200, applied to a whole blood sample analyzer, which can be used to analyze a peripheral blood sample, wherein the whole blood sample analysis method can be implemented in a white blood cell detection channel of the whole blood sample analyzer 100. Fig. 2 is a schematic flow chart of a first embodiment of a method for analyzing a whole blood sample according to an embodiment of the present application, where as shown in fig. 2, the method 200 includes:
in step S201, optical signal information of the peripheral blood sample after the reagent treatment is acquired.
Here, the optical signal information includes at least two of a Forward Scattering (FS) signal, a Side Scattering (SS) signal, and a Fluorescence signal (FL), and particularly includes the forward Scattering signal and the Side Scattering signal. Wherein, the forward scattered light signal reflects the size of the cell particles, the side scattered light signal reflects the complexity of the internal structure of the cell particles, and the fluorescence signal reflects the content of substances, such as Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA), which can be stained by fluorescent dyes, in the cell particles. Further, the optical signal information may include, for example, a pulse width of the optical signal and/or a pulse peak of the optical signal, and the like.
Before step S201 is performed, in the leukocyte detection channel of the whole blood sample analyzer 100, the collected peripheral blood sample is first subjected to hemolysis processing and optionally fluorescence staining processing. For example, in the reaction device 110 of the whole blood sample analyzer 100, the peripheral blood sample collected by the sampling device is mixed with a reagent including a fluorescent dye and a hemolytic agent in a certain ratio, and the peripheral blood sample to be detected is obtained after the reaction. And after treatment, the red blood cells in the peripheral blood sample are broken, and the particles in the peripheral blood sample to be detected after treatment at least comprise ghost particles formed by the broken red blood cells and leukocyte particles. The optical detection device 120 in the whole blood analyzer 100 detects the peripheral blood sample to be detected after being processed by the reagent, so as to obtain optical signal information and transmit the optical signal information to the processor 140.
Step S202, identifying impurity particles in the peripheral blood sample to be detected according to the optical signal information.
In the present embodiment, when blood is collected from the finger of the subject by the scraping method, repeated squeezing is often required to collect a sufficient whole blood sample. The cuticle of the outermost layer of the epidermis at the finger tip is easy to fall off when the skin is squeezed and scraped during the collection of peripheral blood, so that the keratinocyte fragments are brought into a whole blood sample, and then the interference is caused on partial detection results of a sample analyzer. Therefore, in the embodiment of the present application, the foreign particles are caused by the external environment interference, especially caused by the whole blood sample collection by the blood scraping method. Further, the impurity particles may be skin keratinocyte fragments.
In order to avoid the interference of the keratinocyte fragments on the detection result of the peripheral blood sample, the peripheral blood sample to be detected needs to be identified by impurity particles so as to carry out subsequent processing on the identified impurity particles.
In step S203, the optical signal information of the identified impurity particles is processed.
Here, the step S203 may be performed by setting the impurity particles as the ghost particles or directly removing the information of the impurity particles; or the foreign particles may be displayed in a different color from the other particles at the same time.
Step S204, classifying and counting the particles in the peripheral blood sample to be detected according to the optical signal information processed by the impurity particles.
Here, for the peripheral blood sample, since the optical signal information after the impurity particle processing does not include the impurity particle information, it is possible to prevent the impurity particles from affecting the classification count result of the peripheral blood sample, and thus it is possible to ensure the accuracy of the analysis result.
And S205, outputting the classification counting result of the peripheral blood sample to be detected.
Here, white blood cells in several peripheral blood samples collected by the scrape blood method were counted according to the method shown in fig. 2, and the identified impurity particles were set as ghost particles or directly deleted, resulting in the results shown in table 1, in which the reference value was the white blood cell count result of a venous blood sample of the same subject.
TABLE 1 leukocyte count results before and after treatment of contaminating particles in peripheral blood samples
Figure PCTCN2019086075-APPB-000001
Furthermore, the result of classifying/counting leukocytes in a peripheral blood sample may be output as an SS-FS scattergram, as shown in fig. 3A and 3B, in which fig. 3A is an SS-FS scattergram of cell particles of the peripheral blood sample without being subjected to a spotting treatment, and fig. 3B is an SS-FS scattergram of cell particles of the peripheral blood sample after being subjected to a spotting removal according to the method 200 of the present application.
Therefore, according to the method, the interference of impurity particles brought by the external environment can be reduced when the peripheral blood sample collected by the blood scraping method is subjected to leukocyte classification counting, so that a more accurate analysis result can be obtained.
Fig. 4 is a schematic flow chart diagram two of the first implementation manner of the whole blood sample analysis method 200 according to the embodiment of the present application, and as shown in fig. 4, the step S202 of identifying the impurity particles in the to-be-detected distal blood sample according to the optical signal information may include:
step S202a is to generate a scattergram based on the forward scattered light signal and the side scattered light signal in the optical signal information.
Here, in the implementation of step S202a, a two-dimensional SS-FS scattergram may be generated based on the SS signal intensity and the FS signal intensity in the optical signal information; or generating a two-dimensional FSW-FS scattergram based on the pulse Width (FSW) of the forward scattered light and the FS signal intensity in the optical signal information; alternatively, a three-dimensional FS-SS-FSW scattergram is generated based on the forward scattered light pulse signal, the forward scattered light pulse width, and the side scattered light pulse signal in the particle detection information.
It should be noted that, in the embodiment of the present application, the scatter diagram is not limited by the form of graphical presentation, and may also be presented in the form of data.
Step S202b, determining whether the particles of the peripheral blood sample to be detected are in a preset interference area of the scattergram.
Since impurities in peripheral blood are horny substances and other unknown particles, and have large and complicated volumes, the front scattered light pulse width, the front scattered light intensity and the side scattered light intensity are all large, and impurity characteristic regions can be found through the characteristics.
Here, the preset interference region may be a predetermined fixed region, for example, a fixed region defined empirically or a fixed region determined from a forward scattered light signal and a side scattered light signal scattergram of each particle of the reagent-treated normal whole blood sample and the interference peripheral blood sample.
For a better understanding of the embodiments of the present application, the characteristics of a normal whole blood sample, such as a normal whole blood sample without noise interference of a certain subject, for example, a venous blood sample, and a peripheral blood sample collected by a scraping method of the same subject will be described first.
FIG. 5A is a two-dimensional scattergram of SS signal intensity and FS signal intensity of cellular particles in a normal whole blood sample after hemolysis treatment, and FIG. 5B is a two-dimensional scattergram of SS signal intensity and FS signal intensity of cellular particles in an interferential peripheral blood sample after hemolysis treatment. As can be seen by comparing fig. 5A and 5B, there is much interference of the hetero-dot particles in fig. 5B and the positions of the hetero-dot particles are relatively fixed, for example, the hetero-dot particles are fixedly present in the upper right of the real neutrophil population (refer to the normal whole blood sample) and between the real lymphocyte population (refer to the normal whole blood sample) and the real eosinophil population (refer to the normal whole blood sample). Therefore, in the embodiment of the present application, the preset interference region may be a preset fixed region, wherein the fixed region may be determined according to a scatter diagram consisting of SS signal intensity and FS signal intensity of the normal whole blood sample and the miscellaneous site interference sample after the hemolysis treatment.
For example, as shown in fig. 6A, a rectangular region at the upper right in the SS-FS two-dimensional scattergram, particularly at the upper right of the real neutrophil population, or a rectangular region between the real lymphocyte population and the real eosinophil population may be set in advance as a fixed region in which there is a noise interference. Of course, in addition to defining a rectangular region as the impurity interference region, a region having another shape may be defined as the impurity interference region, for example, an arc region shown in fig. 6B.
In addition, in other embodiments, the preset interference region may be dynamically determined according to the distribution of forward scattered light signals and side scattered light signals of all particles in the peripheral blood sample to be detected. As shown in fig. 7A, the center-of-gravity position coordinates of the leukocyte particle group in two directions of SS and FS are determined according to the forward scattered light signal and the side scattered light signal of the leukocyte particles in the peripheral blood sample to be detected, and then the reference point coordinates of the preset interference region are determined based on the center-of-gravity position coordinates of the leukocyte particle group, for example, when the preset interference region is a rectangular region, the length and width of the rectangular region are preset, the coordinates of the lower left vertex of the rectangular region can be determined according to the center-of-gravity position coordinates of the leukocyte particle group, and then the preset interference region is determined according to the length and width of the rectangular region and the coordinates of the lower left vertex. Of course, the preset interference region may be a circular region, as shown in fig. 7B, in this case, the radius of the circular region is preset, the coordinate of the center of circle of the circular region may be determined according to the coordinate of the center of gravity of the leukocyte particle group, and then the preset interference region is determined according to the radius and the coordinate of the center of circle of the circular region.
It should be noted that the shape of the preset interference area may be various, for example, it may be rectangular, circular, square and/or polygonal, and the like, and the present application is not limited in particular.
In other embodiments, the definition of the miscellaneous point region, such as a cuboid region, can also be directly performed in the FS-SS-FSW three-dimensional scatter diagram. As shown in fig. 8, a rectangular parallelepiped region shown by a dotted line may be set as the hetero particle region.
It should be noted that, if the scattergram is presented as a graph, the predetermined interference region may be regarded as a certain region in the graph, for example, the predetermined interference region may be located at the upper right of the neutrophil population and between the lymphocyte population and the eosinophil population in the scattergram with the forward scattered light signal as the ordinate and the side scattered light signal as the abscissa. If the scatter plot is presented in data form, the preset interference region may be considered as a numerical range interval.
In this step, it is possible to determine whether or not all particles in the peripheral blood sample to be detected are interfering particles. However, the inventors found that the impurity particles in the peripheral blood sample are often erroneously classified as eosinophils or neutrophils, and therefore it is also possible to pre-classify all the particles in the peripheral blood sample to be detected before identifying interfering particles, and then determine only whether the pre-classified eosinophils or neutrophils are in the preset interfering region.
Step S202c, identifying the particles in the preset interference region as impurity particles.
It should be noted that other steps in the embodiment shown in fig. 4 may refer to the description of the embodiment shown in fig. 2.
Fig. 9 is a third schematic flowchart of the first implementation manner of the method 200 for analyzing a whole blood sample according to the embodiment of the present application, and as shown in fig. 9, the step S202 of identifying impurity particles in the to-be-detected distal blood sample according to the optical signal information may include:
step S202d, determining whether the forward scattered light pulse width (FSW) of the particles of the peripheral blood sample to be detected is greater than a preset pulse width threshold.
As shown in fig. 10A and 10B, fig. 10A is the forward scattered light pulse signal of normal leukocyte granules, and fig. 10B is the forward scattered light pulse signal of impurity granules, and since the forward scattered light pulse signal FSW of impurity granules is larger than the FSW of normal leukocyte granules, it is possible to determine whether the granules of peripheral blood sample to be detected are the impurity granules by determining whether the FSW of the granules is larger than a preset pulse width threshold.
Preferably, the preset pulse width threshold may be a preset fixed threshold, which may be determined, for example, according to the pulse width distribution of forward scattered light of the normal whole blood sample after being treated with the reagent (e.g., after being hemolyzed) and the interference peripheral blood sample.
FIG. 11A is a FSW-FS scattergram of leukocyte particles in a hemolyzed normal whole blood sample, and FIG. 11B is a FSW-FS scattergram of leukocyte particles in a hemolyzed interference peripheral blood sample. As can be seen by comparing fig. 11A and 11B, the pulse width of the outlier particles is larger, and therefore the fixed threshold FSW _ BIG can be determined by the FSW distribution of the leukocyte particles in the normal whole blood sample.
In other embodiments, the preset pulse width threshold may be dynamically determined according to an average of the forward scattered light pulse widths of all particles in the peripheral blood sample to be detected. The predetermined pulse width threshold value FSW BIG, i.e. FSW BIG f (FSW aver), is determined, for example, by specifying a positive correlation function with the forward scattered light pulse width mean value FSW aver. For example, the preset pulse width threshold may be 1.5 times the average value of FSW of all particles, as shown in fig. 12.
In this step, it is possible to determine whether or not all particles in the peripheral blood sample to be detected are interfering particles. However, the inventors found that the impurity particle interference in the peripheral blood sample is usually wrongly classified as eosinophils or neutrophils, so that it is also possible to pre-classify all the particles in the peripheral blood sample to be detected before identifying the interfering particles, and then only determine whether the forward scattered light pulse width pre-classified as eosinophils or neutrophils is greater than the preset pulse width threshold.
And step 202e, identifying the particles with the forward scattering light pulse width larger than the preset pulse width threshold value as impurity particles.
It should be noted that other steps in the embodiment shown in fig. 9 may refer to the description of the embodiment shown in fig. 2.
In other embodiments, the determination of the impurity particles may also be performed by combining the embodiment shown in fig. 4 and the embodiment shown in fig. 9, as shown in fig. 13 and fig. 14, that is, it is determined whether the particles of the peripheral blood sample to be detected are in the preset interference region of the scattergram composed of the SS signal intensity and the FS signal intensity of the peripheral blood sample to be detected, and then it is determined whether the forward scattered light pulse width of the particles in the preset interference region is greater than the preset pulse width threshold. Or conversely, judging whether the forward scattering light pulse width of the particles of the peripheral blood sample to be detected is larger than a preset pulse width threshold value, and then judging whether the particles of which the forward scattering light pulse width is larger than the preset pulse width threshold value are in a preset interference area of a scatter diagram formed by SS signal intensity and FS signal intensity of the peripheral blood sample to be detected.
In addition, the method 200 for analyzing a whole blood sample may further include, before processing the optical signal information of the identified impurity particles:
determining the number of real white blood cell particles and the number of impurity particles in the peripheral blood sample to be detected after identifying the impurity particles;
and outputting prompt information of the impurity particles in the peripheral blood sample to be detected when the number of the real white blood cell particles and the number of the impurity particles meet preset conditions.
In the embodiment of the application, when the number of the impurity particles is large, the prompt information, namely the alarm, of the existence of the impurity particles in the peripheral blood sample to be detected can be output, and the prompt information can be output in various ways, for example, the text prompt information can be output on a display device of a whole blood sample analyzer, and the voice prompt information can also be output. When the prompt information is output, modes such as vibration and buzzing can be combined so that the detection personnel can obtain the prompt information in time.
Furthermore, when the prompt information of the impurity particles in the peripheral blood sample to be detected is output, a prompt of whether the impurity particles are processed or not can be output, and the user determines whether the impurity particles are processed or not. The prompt may be output, for example, on a display of the whole blood sample analyzer, and the content may be "the sample is a peripheral blood type sample, there may be impurities, whether impurity particle recognition and processing is performed", and a button control that can select "yes" or "no" is provided on the display of the whole blood sample analyzer.
Therefore, in the embodiment, the prompt information of the existence of the impurity particles is output and the impurity particles are further processed only when the number of the impurity particles is large, and the processing is not performed when the number of the impurity particles is small, so that the detection efficiency can be improved while the accuracy of the detection result is ensured.
In other embodiments, prior to performing contaminant identification on the peripheral blood sample, the method may further include determining whether contaminant identification is required. For example, a switching device is provided on the whole blood sample analyzer 100 for turning on or off the identification and processing functions for foreign particles. The switch means may be, for example, physical buttons on the whole blood sample analyzer 100 or may be virtual buttons on its display means. The switching device may be turned on or off by default or may be manually set by an operator. Of course, the switching device may also be switched on or off depending on the sample type of the whole blood sample, e.g. only in a peripheral blood mode and switched off in other collection modes.
Since blood routine tests are one of clinical diagnostic test items, they play an important role in the diagnosis and treatment of diseases. The indexes of the number, the form and the distribution of the cells of the patient are obtained by detecting the blood cells, so that the physical health state and the disease deterioration degree of the patient can be known, various blood diseases can be effectively judged, and the treatment scheme formulated for the patient is more accurate and effective, so that the accuracy of the blood analysis result is very important for the patient and a doctor. The method provided by the embodiment of the application can effectively remove the influence of the miscellaneous point particles on the classification and counting of the white blood cells of the blood cell analyzer in the peripheral blood collection process, thereby improving the accuracy of the blood analysis result.
The embodiment of the application further provides a whole blood sample analysis method, which is applied to a whole blood sample analyzer and can analyze a venous blood sample and a peripheral blood sample. FIG. 15 is a schematic flow diagram of a second embodiment of a method 300 of whole blood analysis according to an embodiment of the present application, as shown in FIG. 15, the method 300 comprising:
step S301, acquiring optical signal information of the whole blood sample after the reagent treatment, wherein the optical signal information comprises at least two of a forward scattered light signal, a side scattered light signal and a fluorescence signal.
The method of reagent treatment is described above with reference to the first embodiment of the method of analyzing a whole blood sample according to the examples of the present application.
Step S302, obtaining the sample type of the whole blood sample to be detected.
Here, in the step S302, the sample type of the whole blood sample to be detected may be obtained by scanning the identifier on the container containing the whole blood sample to be detected.
In this embodiment, the identification portion of the container may be, for example, a bar code attached to the container. When the sample analysis detection is carried out, some related information of the whole blood sample, such as the name, age, sex, detection items of the detector, the sample type of the whole blood sample to be detected and the like, can be obtained by scanning the bar code.
Of course, it is also conceivable to determine whether the whole blood sample to be tested is a peripheral blood sample collected by the blood scraping method according to the mode selection information input by the user when step S302 is implemented. For example, the whole blood sample analyzer may include a mode selection portion configured to select a mode for detecting a peripheral blood sample or a venous blood sample and output mode information to the processor. The processor acquires mode information from the mode selection part to judge the sample type of the whole blood sample to be detected.
In an embodiment of the present application, the sample types of the whole blood sample to be tested comprise at least a first sample type and a second sample type, wherein the first sample type may be a peripheral blood type, in particular a peripheral blood type collected by a apheresis method, and the second sample type may be a venous blood type.
Step S303, judging whether the sample type of the whole blood sample to be detected is a first sample type.
Here, when the type of the whole blood sample to be detected is the first sample type, the process proceeds to step S304, and when the type of the whole blood sample to be detected is not the first sample type, i.e., the second sample type, the process proceeds to step S305.
Step S304, when the sample type of the whole blood sample to be detected is a first sample type, classifying and counting the particles of the whole blood sample to be detected by using the optical signal information under a first classification counting method.
Step S305, when the sample type of the whole blood sample to be detected is a second sample type, classifying and counting the particles of the whole blood sample to be detected by using the optical signal information under a second classification counting method.
The first sort count algorithm is different from the second sort count algorithm.
In the above scheme, the first and second class-counting algorithms may be related to impurity particle interference in the whole blood sample. In the embodiment of the present application, the first sample type may be a peripheral blood type, and in a peripheral blood type whole blood sample, since the fingertip of the subject is repeatedly squeezed and scraped during the blood collection process, skin keratinocyte fragments are easily mixed in the collected whole blood sample, and the skin keratinocyte fragments may affect the sample analysis result. Therefore, when the sample type of the whole blood sample to be tested is determined to be the peripheral blood type in step S303, the peripheral blood sample may be subjected to the identification processing of the impurity particles according to the whole blood sample analysis method 200 of the embodiment of the present application described above. In contrast, in the case of a non-peripheral blood sample, for example, in the case of a venous blood sample, since the blood collection needle is directly inserted into the vein at the time of collecting venous blood and there is no contamination with skin impurity particles, there is no need to identify and process impurity particles at the time of classifying and counting particles in the venous blood type whole blood sample. It should be noted here that this embodiment is implemented in the leukocyte detection channel of a whole blood sample analyzer.
In other embodiments, such as for the RET (reticulocyte) detection channel of a whole blood sample analyzer, the first and second class count algorithms may also be related to a cell population segmentation algorithm for red blood cells and Platelets (PLTs) in a whole blood sample.
Fig. 16A and 16B are FL-FS scattergrams of red blood cells and platelets of venous blood and peripheral blood, respectively, and as is clear from fig. 16A and 16B, since the morphology and distribution of red blood cells and the distribution of platelets, and particularly the distribution of platelets in the fluorescence direction, are different for venous blood and peripheral blood, different algorithms need to be used for the classification and counting of reticulocytes (low fluorescence, medium fluorescence, high fluorescence reticulocytes) in the red blood cells of venous blood and peripheral blood, and different algorithms need to be used for the classification and counting of IPF (immature platelets) in the platelets PLT of venous blood and peripheral blood, respectively, to ensure accuracy.
And S306, outputting the classification counting result of the whole blood sample to be detected.
In the whole blood sample analysis method provided by the embodiment of the application, before the particles of the whole blood sample are classified and counted, the sample type of the whole blood sample to be detected is firstly determined, and then the particles of the whole blood sample are classified and counted under different counting methods according to different whole blood sample types, so that the classified and counted result of the whole blood sample to be detected is obtained. In this way, different processing can be performed according to the characteristics of the whole blood samples of different sample types, so that the accuracy of the detection result can be ensured.
Fig. 17 is a schematic structural diagram of a whole blood sample analyzer 1000 according to an embodiment of the present invention, where the analyzer 1000 includes at least one processor 1001 and a memory 1002, and the memory 1002 stores instructions executable by the at least one processor 1001, where the instructions are executed by the at least one processor 1001 to perform the whole blood sample analyzing method.
Furthermore, the analysis apparatus 1000 may further comprise at least one network interface 1004 and a user interface 1003. The various components in the whole blood sample analysis device 1000 are coupled together by a bus system 1005. It is understood that bus system 1005 is used to enable communications among the components connected. The bus system 1005 includes a power bus, a control bus, and a status signal bus in addition to a data bus. But for clarity of illustration the various busses are labeled in fig. 17 as the bus system 1005.
The user interface 1003 may include a display, a keyboard, a mouse, a trackball, a click wheel, a key, a button, a touch pad, a touch screen, or the like, among others.
It will be appreciated that the memory 1002 can be either volatile memory or nonvolatile memory, and can include both volatile and nonvolatile memory. Among them, the nonvolatile Memory may be a Read Only Memory (ROM), a Programmable Read Only Memory (PROM), an Erasable Programmable Read-Only Memory (EPROM), an Electrically Erasable Programmable Read-Only Memory (EEPROM), a magnetic random access Memory (FRAM), a Flash Memory (Flash Memory), a magnetic surface Memory, an optical disk, or a Compact Disc Read-Only Memory (CD-ROM); the magnetic surface storage may be disk storage or tape storage. Volatile Memory can be Random Access Memory (RAM), which acts as external cache Memory. By way of illustration and not limitation, many forms of RAM are available, such as Static Random Access Memory (SRAM), Synchronous Static Random Access Memory (SSRAM), Dynamic Random Access Memory (DRAM), Synchronous Dynamic Random Access Memory (SDRAM), Double Data Rate Synchronous Dynamic Random Access Memory (DDRSDRAM), Enhanced Synchronous Dynamic Random Access Memory (ESDRAM), Enhanced Synchronous Dynamic Random Access Memory (Enhanced DRAM), Synchronous Dynamic Random Access Memory (SLDRAM), Direct Memory (DRmb Access), and Random Access Memory (DRAM). The memory 602 described in embodiments herein is intended to comprise these and any other suitable types of memory.
The memory 1002 includes, but is not limited to: the ternary content addressable memory, static random access memory, and the like are capable of storing a wide variety of data such as received sensor signals to support the operation of the whole blood sample analysis device 1000.
The Processor 1001 may be a Central Processing Unit (CPU, or other general purpose Processor), a Digital Signal Processor (DSP), an Application Specific Integrated Circuit (ASIC), a Field-Programmable Gate Array (FPGA) or other Programmable logic device, discrete Gate or transistor logic, discrete hardware components, etc.
Furthermore, the present invention further provides a computer-readable storage medium. The computer readable storage medium has stored thereon executable instructions that when executed by the processor 1001 implement the various steps of the whole blood sample analysis method described previously. The computer readable storage medium may be the aforementioned memory or a component thereof, in which the computer program is stored and executed by the processor 1001 to perform the aforementioned method steps. The computer readable storage medium may be FRAM, ROM, PROM, EPROM, EEPROM, Flash Memory, magnetic surface Memory, optical disk or CD-ROM, etc., or may be various devices including one or any combination of the above storage media.
It is to be understood that the features, structures and advantages mentioned in the description, the claims and the drawings may be combined in any desired manner within the scope of the application. The features, structures and advantages described for the method according to the present application apply in a corresponding manner to the whole blood sample analyzer and to the whole blood sample analysis device according to the present invention and vice versa. It should be understood that, in the various embodiments of the present application, the sequence numbers of the above-mentioned processes do not mean the execution sequence, and the execution sequence of each process should be determined by its function and inherent logic, and should not constitute any limitation to the implementation process of the embodiments of the present application. The above-mentioned serial numbers of the embodiments of the present application are merely for description and do not represent the merits of the embodiments.
It should be noted that, in this document, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising an … …" does not exclude the presence of other like elements in a process, method, article, or apparatus that comprises the element.
In the several embodiments provided in the present application, it should be understood that the disclosed apparatus and method may be implemented in other ways. The above-described device embodiments are merely illustrative, for example, the division of the unit is only a logical functional division, and there may be other division ways in actual implementation, such as: multiple units or components may be combined, or may be integrated into another system, or some features may be omitted, or not implemented. In addition, the coupling, direct coupling or communication connection between the components shown or discussed may be through some interfaces, and the indirect coupling or communication connection between the devices or units may be electrical, mechanical or other forms.
The units described as separate parts may or may not be physically separate, and parts displayed as units may or may not be physical units; can be located in one place or distributed on a plurality of network units; some or all of the units can be selected according to actual needs to achieve the purpose of the solution of the embodiment.
In addition, all functional units in the embodiments of the present application may be integrated into one processing unit, or each unit may be separately regarded as one unit, or two or more units may be integrated into one unit; the integrated unit can be realized in a form of hardware, or in a form of hardware plus a software functional unit.
The above description is only for the embodiments of the present application, but the scope of the present application is not limited thereto, and any person skilled in the art can easily conceive of changes or substitutions within the technical scope of the present application, and shall be covered by the scope of the present application. Therefore, the protection scope of the present application shall be subject to the protection scope of the claims.

Claims (26)

  1. A whole blood sample analyzer operable to analyze a peripheral blood sample, the whole blood sample analyzer comprising:
    a sampling device having a pipette with a pipette nozzle and having a driving device for driving the pipette to quantitatively suck a peripheral blood sample collected by a blood scraping method through the pipette nozzle;
    the reaction device is provided with a reaction pool and a liquid supply part, wherein the reaction pool is used for receiving the peripheral blood sample sucked by the sampling device, and the liquid supply part is used for supplying a reagent to the reaction pool, so that the peripheral blood sample sucked by the sampling device and the reagent supplied by the liquid supply part react in the reaction pool to prepare a peripheral blood sample to be detected;
    an optical detection device having a light source, a flow chamber, wherein particles of a reagent-treated peripheral blood sample can flow within the flow chamber, a light emitted by the light source illuminates the particles in the flow chamber to generate optical signal information, and a light collector for collecting the optical signal information, wherein the optical signal information includes at least two of a forward scattered light signal, a side scattered light signal, and a fluorescence signal;
    the conveying device is used for conveying the peripheral blood sample to be detected after being treated by the reagent in the reaction tank to the optical detection device;
    a processor configured to: acquiring the optical signal information from the optical detection device; identifying impurity particles in the to-be-detected peripheral blood sample, which are caused by collecting the peripheral blood sample by a blood scraping method, according to the optical signal information; processing the optical signal information of the identified impurity particles; classifying and counting the particles in the peripheral blood sample to be detected according to the optical signal information processed by the impurity particles; and outputting the classification counting result of the peripheral blood sample to be detected.
  2. The whole blood sample analyzer of claim 1, wherein the foreign particles are skin keratinocyte fragments resulting from the collection of a peripheral blood sample by a scraping method.
  3. The whole blood sample analyzer according to claim 1 or 2, wherein the processor is configured to perform the following steps when performing the step of identifying the foreign particles in the to-be-detected distal blood sample based on the optical signal information:
    generating a scatter diagram based on the forward scattered light signals and the side scattered light signals in the optical signal information;
    judging whether the particles of the peripheral blood sample to be detected are in a preset interference area of the scatter diagram;
    identifying particles in the preset interference region as impurity particles.
  4. The whole blood sample analyzer according to claim 3, wherein the predetermined interference area is a predetermined fixed area, particularly a fixed area determined from a forward scattered light signal and a side scattered light signal scattergram of respective particles of the normal whole blood sample and the interference peripheral blood sample; or the preset interference region is dynamically determined according to the distribution of forward scattered light signals and side scattered light signals of all particles in the peripheral blood sample to be detected.
  5. The whole blood sample analyzer according to claim 3 or 4, wherein the predetermined interference area is located between the lymphocyte population and the eosinophil population and/or on the upper right of the neutrophil population in the scattergram with the forward scattered light signal as the ordinate and the side scattered light signal as the abscissa.
  6. The whole blood sample analyzer of claim 1, wherein the processor is configured to perform the following steps when performing the step of identifying foreign particles in the to-be-detected distal blood sample based on the optical signal information:
    judging whether the forward scattering light pulse width of the particles of the peripheral blood sample to be detected is larger than a preset pulse width threshold value or not;
    particles with a forward scattered light pulse width greater than a preset pulse width threshold are identified as contaminant particles.
  7. The whole blood sample analyzer according to claim 6, wherein the preset pulse width threshold is a preset fixed threshold, in particular a fixed threshold determined according to the pulse width distribution of forward scattered light of each particle of the normal whole blood sample and the disturbing peripheral blood sample; or the preset pulse width threshold value is dynamically determined according to the average value of the pulse widths of the forward scattered light of all particles in the peripheral blood sample to be detected.
  8. The whole blood sample analyzer of claim 1, wherein the processor is configured to perform the following steps when performing the step of identifying foreign particles in the to-be-detected distal blood sample based on the optical signal information:
    generating a scatter diagram based on the forward scattered light signals and the side scattered light signals in the optical signal information;
    judging whether the particles of the to-be-detected peripheral blood sample are in a preset interference area of the scatter diagram and judging whether the forward scattering light pulse width of the particles of the to-be-detected peripheral blood sample is larger than a preset pulse width threshold value;
    particles that are in the predetermined interference region and have a forward scattered light pulse width greater than a predetermined pulse width threshold are identified as contaminant particles.
  9. The whole blood sample analyzer according to any one of claims 1 to 8, wherein the processor, when performing the processing of the optical signal information of the identified impurity particles, performs the steps of:
    removing optical signal information of the impurity particles; or setting the impurity particles as ghost particles; or displaying the impurity particles in a color different from other particles; or outputting prompt information of the existence of the impurity particles in the whole blood sample to be detected and/or outputting a prompt of whether the impurity particles are processed or not.
  10. The whole blood sample analyzer as claimed in any one of claims 1 to 9, wherein the processor is further configured to perform the steps of:
    determining the number of real white blood cell particles and the number of impurity particles in the peripheral blood sample to be detected after identifying the impurity particles;
    and when the number of the real white blood cell particles and the number of the impurity particles meet preset conditions, outputting prompt information of the existence of the impurity particles in the whole blood sample to be detected and/or outputting a prompt of whether the impurity particles are processed or not.
  11. The whole blood sample analyzer according to any one of claims 1 to 10, further comprising a display device configured to receive and display the result of the differential counting of the peripheral blood sample to be detected and/or a scatter plot consisting of at least two of the optical signal information from the processor.
  12. A whole blood sample analyzer that can analyze a venous blood sample and a peripheral blood sample, the whole blood sample analyzer comprising:
    a sampling device having a pipette with a pipette nozzle and having a driving device for driving the pipette to quantitatively aspirate a whole blood sample through the pipette nozzle;
    the reaction device is provided with a reaction pool and a liquid supply part, wherein the reaction pool is used for receiving the whole blood sample sucked by the sampling device, and the liquid supply part is used for supplying a reagent to the reaction pool, so that the whole blood sample sucked by the sampling device and the reagent supplied by the liquid supply part react in the reaction pool to prepare a whole blood sample to be detected;
    an optical detection device having a light source, a flow chamber, wherein particles of a reagent-processed whole blood sample can flow within the flow chamber, a light emitted by the light source illuminates the particles in the flow chamber to generate optical signal information, and a light collector for collecting the optical signal information, wherein the optical signal information includes at least two of a forward scattered light signal, a side scattered light signal, and a fluorescence signal;
    the conveying device is used for conveying the whole blood sample to be detected after being treated by the reagent in the reaction pool to the optical detection device;
    a processor configured to: acquiring the optical signal information from the optical detection device; judging whether the whole blood sample to be detected is a peripheral blood sample collected by a blood scraping method; when the whole blood sample to be detected is a peripheral blood sample collected by adopting a blood scraping method, identifying impurity particles in the whole blood sample to be detected, which are brought by collecting the peripheral blood sample by adopting the blood scraping method, according to the optical signal information; processing the optical signal information of the identified impurity particles; classifying and counting the particles in the whole blood sample to be detected according to the optical signal information processed by the impurity particles; and outputting the classification counting result of the whole blood sample to be detected.
  13. The whole blood sample analyzer of claim 12, wherein the foreign particles are skin keratinocyte fragments resulting from the collection of a peripheral blood sample by a scraping method.
  14. The whole blood sample analyzer according to claim 12 or 13, comprising a mode selecting portion provided to select a mode for detecting a peripheral blood sample or a venous blood sample and output mode information to the processor;
    the processor acquires mode information from the mode selection part to judge whether the whole blood sample to be detected is a peripheral blood sample collected by adopting a blood scraping method.
  15. A method of analyzing a whole blood sample useful for analyzing a peripheral blood sample, the method comprising:
    acquiring optical signal information of a to-be-detected peripheral blood sample after being processed by a reagent, wherein the optical signal information comprises at least two of a forward scattered light signal, a side scattered light signal and a fluorescence signal, and the peripheral blood sample is collected by a blood scraping method;
    identifying impurity particles brought by collecting the peripheral blood sample by adopting a blood scraping method in the peripheral blood sample to be detected according to the optical signal information;
    processing the optical signal information of the identified impurity particles;
    according to the optical signal information processed by the impurity particles, classifying and counting the particles in the peripheral blood sample to be detected; and
    and outputting the classification counting result of the peripheral blood sample to be detected.
  16. The method of claim 15, wherein the contaminant particles are skin keratinocyte debris resulting from the collection of a peripheral blood sample by a scraping procedure.
  17. The method according to claim 15 or 16, wherein the step of identifying foreign particles in the peripheral blood sample to be detected based on the optical signal information comprises:
    generating a scatter diagram based on the forward scattered light signals and the side scattered light signals in the optical signal information;
    judging whether the particles of the peripheral blood sample to be detected are in a preset interference area of the scatter diagram;
    identifying particles in the preset interference region as impurity particles;
    preferably, the preset interference area is a preset fixed area, in particular a fixed area determined according to a forward scattered light signal and a side scattered light signal scattergram of each particle of the normal whole blood sample and the interference peripheral blood sample after being processed by the reagent; or the preset interference region is dynamically determined according to the distribution of forward scattered light signals and side scattered light signals of all particles in the peripheral blood sample to be detected.
  18. The method according to claim 17, wherein the predetermined interference area is between the lymphocyte population and the eosinophil population and/or to the upper right of the neutrophil population in the scatter plot of the forward scatter light signals and the side scatter light signals.
  19. The method of claim 15, wherein the step of identifying foreign particles in the peripheral blood sample to be detected based on the optical signal information comprises:
    judging whether the forward scattering light pulse width of the particles of the peripheral blood sample to be detected is larger than a preset pulse width threshold value or not;
    identifying particles with the forward scattering light pulse width larger than a preset pulse width threshold value as impurity particles;
    preferably, the preset pulse width threshold is a preset fixed threshold, in particular a fixed threshold determined according to the pulse width distribution of forward scattered light of each particle of the normal whole blood sample and the interference peripheral blood sample; or the preset pulse width threshold value is dynamically determined according to the average value of the pulse widths of the forward scattered light of all particles in the peripheral blood sample to be detected.
  20. The method of claim 15, wherein the step of identifying foreign particles in the peripheral blood sample to be detected based on the optical signal information comprises:
    generating a scatter diagram based on the forward scattered light signals and the side scattered light signals in the optical signal information;
    judging whether the particles of the to-be-detected peripheral blood sample are in a preset interference area of the scatter diagram and judging whether the forward scattering light pulse width of the particles of the to-be-detected peripheral blood sample is larger than a preset pulse width threshold value;
    particles that are in the predetermined interference region and have a forward scattered light pulse width greater than a predetermined pulse width threshold are identified as contaminant particles.
  21. The method of any one of claims 15 to 20, wherein the step of processing the optical signal information of the identified foreign particles comprises:
    removing optical signal information of the impurity particles; or setting the impurity particles as ghost particles; or displaying the impurity particles in a color different from other particles; or outputting prompt information of the existence of the impurity particles in the whole blood sample to be detected and/or outputting a prompt of whether the impurity particles are processed or not.
  22. The method according to any one of claims 15 to 21, further comprising:
    determining the number of real white blood cell particles and the number of impurity particles in the peripheral blood sample to be detected after identifying the impurity particles;
    and when the number of the real white blood cell particles and the number of the impurity particles meet preset conditions, outputting prompt information of the existence of the impurity particles in the whole blood sample to be detected and/or outputting a prompt of whether the impurity particles are processed or not.
  23. A method of analyzing a whole blood sample that analyzes a venous blood sample and a peripheral blood sample, the method comprising:
    acquiring optical signal information of a whole blood sample to be detected after being processed by a reagent, wherein the optical signal information comprises at least two of a forward scattered light signal, a side scattered light signal and a fluorescence signal;
    judging whether the whole blood sample to be detected is a peripheral blood sample collected by a blood scraping method;
    the method of any one of claims 15 to 22, when the whole blood sample to be tested is a peripheral blood sample collected by the apheresis method.
  24. The method according to claim 23, wherein the step of determining whether the whole blood sample to be tested is a peripheral blood sample collected by a scraping method comprises:
    and judging whether the whole blood sample to be detected is a peripheral blood sample collected by adopting a blood scraping method or not according to mode selection information input by a user.
  25. A whole blood sample analyzer applied to a whole blood sample analyzer, comprising:
    a memory configured to store executable instructions;
    a processor configured to execute the memory stored executable instructions to perform the whole blood sample analysis method of any one of claims 15 to 24.
  26. A computer readable storage medium storing executable instructions, wherein the computer readable storage medium is configured to cause a processor to implement the method of analyzing a whole blood sample according to any one of claims 15 to 24 when the executable instructions are executed.
CN201980092567.7A 2019-05-08 2019-05-08 Whole blood sample analyzer, whole blood sample analyzing method, whole blood sample analyzing apparatus, and storage medium Pending CN113454453A (en)

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