Blood cell analyzer and blood cell analysis method

Abstract

A blood cell analyzer (100) and a blood cell analysis method (300), the blood cell analysis method (300) comprising: sucking a blood sample to be detected; preparing a first determination sample and obtaining first optical information; preparing a second determination sample and obtaining second optical information; generating a first white blood cell differential scatter diagram and a second white blood cell differential scatter diagram; determining a first count result of neutrophil granulocytes of the blood sample to be detected based on the first white blood cell differential scatter diagram and the second white blood cell differential scatter diagram; determining an actual distribution area of the neutrophil granulocytes from the first white blood cell differential scatter diagram; determining a segmented granulocyte distribution area from the actual distribution area based on a reference distribution area of the neutrophil granulocytes of a reference white blood cell differential scatter diagram of a normal blood sample; determining a second count result of cells falling into the segmented granulocyte distribution area; and determining a count result of rod-shaped nucleus granulocytes in the blood sample to be detected based on the first count result and the second count result.

Description

Technical Field

[0001] This application relates to the field of blood analysis technology, and in particular to blood cell analyzers and blood cell analysis methods. Background Technology

[0002] A complete blood count (CBC) is a basic clinical examination. The results generally include white blood cell count, red blood cell count, platelet count, hemoglobin concentration, and reticulocyte count. The results are output as scatter plots or histograms of white blood cells, red blood cells, platelets, and reticulocytes to assist doctors in clinical diagnosis.

[0003] Existing blood cell analyzers use fluorescence staining technology to perform optical measurements of white blood cells and reticulocytes (or platelets). White blood cell optical measurements obtain the count and classification of white blood cells, including the counts and classification of neutrophils (Neu), lymphocytes (Lym), monocytes (Mon), eosinophils (Eos), and basophils (Baso). Reticulocyte optical measurements obtain parameters such as red blood cell count, optical platelet count, and reticulocyte count.

[0004] Neutrophils include segmented neutrophils and band neutrophils. Under normal circumstances, band neutrophils account for a small proportion of neutrophils, with segmented neutrophils being the majority. However, in cases of inflammation or other abnormalities, the number of band neutrophils in the blood will increase.

[0005] Therefore, determining whether there is an abnormal increase in band neutrophils in a blood sample and determining the band neutrophil count in the blood sample can help doctors diagnose abnormalities such as inflammation. Summary of the Invention

[0006] Against this background, this application aims to provide a blood cell analyzer and a blood cell analysis method that can determine whether there is an abnormal increase in band neutrophils in a blood sample and / or determine the count of band neutrophils in the blood sample.

[0007] According to a first aspect of the embodiments of this application, a blood cell analyzer is provided, comprising:

[0008] A sampling device is used to collect blood samples for testing.

[0009] A sample preparation apparatus for mixing a portion of the blood sample to be tested, a hemolysin, and a first fluorescent staining agent to prepare a first assay sample for white blood cell classification, and for mixing another portion of the blood sample to be tested, a diluent, and a second fluorescent staining agent to prepare a second assay sample for identifying platelets and / or reticulocytes.

[0010] An optical detection device includes a flow chamber, a light source, and a photodetector. The flow chamber allows a first test sample and a second test sample to pass through, respectively. The light source illuminates the first and second test samples as they pass through the flow chamber. The photodetector detects first and second optical information generated by the illumination of the first and second test samples as they pass through the flow chamber.

[0011] The data processing device is configured as follows:

[0012] A first scatter plot of white blood cell classification is generated based on the first optical information, and a second scatter plot of white blood cell classification is generated based on the second optical information.

[0013] Based on the first white blood cell differential scatter plot and the second white blood cell differential scatter plot, the first neutrophil count result of the blood sample to be tested is determined.

[0014] The actual distribution area of ​​neutrophils was determined from the first white blood cell classification scatter plot.

[0015] Based on the reference distribution region of neutrophils in a scatter plot of reference white blood cell classification from one or more normal blood samples, the distribution region of segmented neutrophils is determined from the actual distribution region. The reference white blood cell classification scatter plot is generated based on reference optical information generated after a reference assay sample prepared from normal blood samples for white blood cell classification is irradiated with light.

[0016] A second count of cells falling within the said segmented neutrophil distribution region, and

[0017] Based on the first counting result and the second counting result, determine whether to issue an alarm for an abnormal increase in band neutrophils in the blood sample to be tested, and / or determine and output the count result of band neutrophils in the blood sample to be tested.

[0018] According to a second aspect of the embodiments of this application, a blood cell analyzer is provided, comprising:

[0019] A sampling device is used to collect blood samples for testing.

[0020] A sample preparation apparatus for mixing a portion of the blood sample to be tested, a hemolysin, and a first fluorescent staining agent to prepare a first assay sample for white blood cell classification, and for mixing another portion of the blood sample to be tested, a diluent, and a second fluorescent staining agent to prepare a second assay sample for identifying platelets and / or reticulocytes.

[0021] An optical detection device includes a flow chamber, a light source, and a photodetector. The flow chamber allows a first test sample and a second test sample to pass through, respectively. The light source illuminates the first and second test samples as they pass through the flow chamber. The photodetector detects first and second optical information generated by the illumination of the first and second test samples as they pass through the flow chamber.

[0022] The data processing device is configured to: when it is determined that an abnormal increase in band neutrophils is present in the blood sample to be tested,

[0023] A first scatter plot of white blood cell classification is generated based on the first optical information, and a second scatter plot of white blood cell classification is generated based on the second optical information.

[0024] Based on the first white blood cell differential scatter plot and the second white blood cell differential scatter plot, the first neutrophil count result of the blood sample to be tested is determined.

[0025] The actual distribution area of ​​neutrophils was determined from the first white blood cell classification scatter plot.

[0026] Based on the reference distribution region of neutrophils in a scatter plot of reference white blood cell classification from one or more normal blood samples, the distribution region of segmented neutrophils is determined from the actual distribution region. The reference white blood cell classification scatter plot is generated based on reference optical information generated after a reference assay sample prepared from normal blood samples for white blood cell classification is irradiated with light.

[0027] A second count of cells falling within the said segmented neutrophil distribution region, and

[0028] Based on the first counting result and the second counting result, the count result of band neutrophils in the blood sample to be tested is determined and output.

[0029] According to a third aspect of the embodiments of this application, a blood cell analysis method is provided, comprising:

[0030] Collect the blood sample to be tested;

[0031] A portion of the blood sample to be tested, a hemolysin, and a first fluorescent staining agent are mixed to prepare a first test sample for white blood cell classification, and the particles in the first test sample are passed one by one through an optical detection area irradiated by light to obtain the first optical information generated by the particles in the first test sample after being irradiated by light.

[0032] Another portion of the blood sample to be tested, the diluent, and the second fluorescent staining agent are mixed to prepare a second assay sample for identifying platelets and / or reticulocytes. Particles in the second assay sample are then passed one by one through an optically illuminated detection area to obtain second optical information generated by the particles in the second assay sample after illumination.

[0033] When it is determined that there is an abnormal increase in band neutrophils in the blood sample to be tested:

[0034] A first scatter plot of white blood cell classification is generated based on the first optical information, and a second scatter plot of white blood cell classification is generated based on the second optical information.

[0035] Based on the first white blood cell differential scatter plot and the second white blood cell differential scatter plot, the first neutrophil count result of the blood sample to be tested is determined.

[0036] The actual distribution area of ​​neutrophils was determined from the first white blood cell classification scatter plot.

[0037] Based on the reference distribution region of neutrophils in a scatter plot of reference white blood cell classification from one or more normal blood samples, the distribution region of segmented neutrophils is determined from the actual distribution region. The reference white blood cell classification scatter plot is generated based on reference optical information generated after a reference assay sample prepared from normal blood samples for white blood cell classification is irradiated with light.

[0038] A second count of cells falling within the said segmented neutrophil distribution region, and

[0039] Based on the first counting result and the second counting result, the count result of band neutrophils in the blood sample to be tested is determined and output.

[0040] According to a fourth aspect of the embodiments of this application, a method for blood cell analysis is provided, comprising:

[0041] Collect the blood sample to be tested;

[0042] A portion of the blood sample to be tested, a hemolysin, and a first fluorescent staining agent are mixed to prepare a first test sample for white blood cell classification, and the particles in the first test sample are passed one by one through an optical detection area irradiated by light to obtain the first optical information generated by the particles in the first test sample after being irradiated by light.

[0043] Another portion of the blood sample to be tested, the diluent, and the second fluorescent staining agent are mixed to prepare a second assay sample for identifying platelets and / or reticulocytes. Particles in the second assay sample are then passed one by one through an optically illuminated detection area to obtain second optical information generated by the particles in the second assay sample after illumination.

[0044] When it is determined that there is an abnormal increase in band neutrophils in the blood sample to be tested:

[0045] A first scatter plot of white blood cell classification is generated based on the first optical information, and a second scatter plot of white blood cell classification is generated based on the second optical information.

[0046] Based on the first white blood cell differential scatter plot and the second white blood cell differential scatter plot, the first neutrophil count result of the blood sample to be tested is determined.

[0047] The actual distribution area of ​​neutrophils was determined from the first white blood cell classification scatter plot.

[0048] Based on the reference distribution region of neutrophils in a scatter plot of reference white blood cell classification from one or more normal blood samples, the distribution region of segmented neutrophils is determined from the actual distribution region. The reference white blood cell classification scatter plot is generated based on reference optical information generated after a reference assay sample prepared from normal blood samples for white blood cell classification is irradiated with light.

[0049] A second count of cells falling within the said segmented neutrophil distribution region, and

[0050] Based on the first counting result and the second counting result, the count result of band neutrophils in the blood sample to be tested is determined and output.

[0051] According to a fifth aspect of the present application, a blood cell analyzer is provided, comprising: a sample aspiration device for aspirating a blood sample to be tested; a sample preparation device for mixing a portion of the blood sample to be tested, a hemolysin, and a first fluorescent staining agent to prepare a first assay sample for white blood cell classification, and for mixing another portion of the blood sample to be tested, a diluent, and a second fluorescent staining agent to prepare a second assay sample for identifying platelets and / or reticulocytes; an optical detection device including a flow chamber, a light source, and a photodetector, wherein the flow chamber is for the first assay sample and the second assay sample to pass through respectively, the light source is for illuminating the first assay sample and the second assay sample passing through the flow chamber respectively, and the photodetector is for detecting first optical information and second optical information generated by the first assay sample and the second assay sample after being illuminated by light when passing through the flow chamber respectively; and a data processing device configured to: identify whether there is an abnormal increase in band neutrophils in the blood sample to be tested based on the first optical information and the second optical information, and / or provide a count result of band neutrophils in the blood sample to be tested.

[0052] According to a sixth aspect of the embodiments of this application, a blood cell analysis method is provided, comprising: aspirating a blood sample to be tested; mixing a portion of the blood sample to be tested, a hemolysin, and a first fluorescent staining agent to prepare a first assay sample for white blood cell classification, and allowing particles in the first assay sample to pass one by one through an optically irradiated area to obtain first optical information generated by the particles in the first assay sample after being irradiated by light; mixing another portion of the blood sample to be tested, a diluent, and a second fluorescent staining agent to prepare a second assay sample for identifying platelets and / or reticulocytes, and allowing particles in the second assay sample to pass one by one through an optically irradiated area to obtain second optical information generated by the particles in the second assay sample after being irradiated by light; and based on the first optical information and the second optical information, identifying whether there is an abnormal increase in band neutrophils in the blood sample to be tested, and / or providing a count result of band neutrophils in the blood sample to be tested. Attached Figure Description

[0053] The accompanying drawings, which form part of this specification, illustrate embodiments of this application and, together with the specification, serve to explain the principles of this application.

[0054] This application can be more clearly understood with reference to the accompanying drawings and the following detailed description, wherein:

[0055] Figure 1 This is a schematic diagram of the structure of a blood cell analyzer according to some embodiments of this application;

[0056] Figure 2A specific example of an optical detection device is shown;

[0057] Figure 3 A scatter plot of the first white blood cell classification of a blood sample from a dog without band neutrophil abnormality according to some embodiments of this application is shown.

[0058] Figure 4 A scatter plot showing the first white blood cell classification of a blood sample from a cat without band neutrophil abnormalities according to some embodiments of this application;

[0059] Figure 5 A scatter plot of the first white blood cell classification of a blood sample from a dog with an abnormal increase in band neutrophils, according to some embodiments of this application;

[0060] Figure 6 A scatter plot of the first white blood cell classification of a blood sample from a cat with an abnormal increase in band neutrophils, according to some embodiments of this application;

[0061] Figure 7 A scatter plot of second white blood cell classification of a blood sample according to some embodiments of this application is shown;

[0062] Figure 8 A scatter plot of reticulocyte channels in a blood sample according to some embodiments of this application is shown;

[0063] Figure 9 A schematic diagram of a reference distribution area according to some embodiments of the present disclosure is shown;

[0064] Figure 10 The diagram illustrates the distribution region of segmented neutrophils in an actual distribution region according to some embodiments of the present disclosure;

[0065] Figure 11 A schematic flowchart of a blood cell analysis method according to some embodiments of the present disclosure is shown;

[0066] Figure 12 A schematic flowchart of a blood cell analysis method according to other embodiments of the present disclosure is shown.

[0067] It should be understood that the dimensions of the various parts shown in the accompanying drawings are not necessarily drawn to actual scale. Furthermore, the same or similar reference numerals denote the same or similar components. Detailed Implementation

[0068] Various exemplary embodiments of this application will now be described in detail with reference to the accompanying drawings. The descriptions of the exemplary embodiments are merely illustrative and are in no way intended to limit the scope of this application or its application or use. This application may be implemented in many different forms and is not limited to the embodiments described herein. These embodiments are provided to make the application thorough and complete, and to fully express the scope of the application to those skilled in the art. It should be noted that, unless otherwise specifically stated, the relative arrangement of components and steps, the composition of materials, numerical expressions, and values ​​set forth in these embodiments should be interpreted as merely exemplary and not as limiting.

[0069] The terms "first," "second," and similar words used in this application do not indicate any order, quantity, or importance, but are merely used to distinguish different parts. Words such as "including" or "contains" mean that the element preceding the word encompasses the element listed after it, and do not exclude the possibility of encompassing other elements as well. Terms such as "above" and "below" are used only to indicate relative positional relationships; when the absolute position of the described object changes, this relative positional relationship may also change accordingly.

[0070] In this application, when a specific component is described as being located between a first component and a second component, an intermediary component may or may not be present between the specific component and the first or second component. When a specific component is described as connecting to other components, the specific component may be directly connected to the other components without an intermediary component, or it may not be directly connected to the other components but may have an intermediary component.

[0071] All terms used in this application (including technical or scientific terms) have the same meaning as understood by one of ordinary skill in the art to which this application pertains, unless otherwise specifically defined. It should also be understood that terms defined in general dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant art, and not as having an idealized or highly formalized meaning, unless expressly defined herein.

[0072] Techniques, methods, and equipment known to those skilled in the art may not be discussed in detail, but where appropriate, such techniques, methods, and equipment should be considered part of the specification.

[0073] To facilitate subsequent explanations, a brief explanation of some terms used below will be provided first:

[0074] 1) Scatter Plot: A two-dimensional or three-dimensional graph generated by a blood cell analyzer, displaying two-dimensional or three-dimensional feature information of multiple particles. The X, Y, and Z axes of a scatter plot each represent a characteristic of each particle. For example, in a scatter plot, the X axis represents the forward scatter (FS) signal intensity, the Y axis represents the fluorescence (FL) signal intensity, and the Z axis represents the side scatter (SS) signal intensity.

[0075] 2) Cell clusters: Clusters of particles with the same characteristics distributed in a certain area of ​​a scatter plot, such as white blood cell clusters, as well as neutrophil clusters, lymphocyte clusters, monocyte clusters, eosinophil clusters, or basophil clusters among white blood cells.

[0076] 3) Blood shadow: Fragment particles obtained by dissolving red blood cells and platelets in blood with a hemolytic reagent.

[0077] Currently, blood cell analyzers can test human blood and blood samples from other mammals (such as dogs, cats, and horses), birds, and fish. Typically, blood cell analyzers use the DIFF channel (white blood cell differential channel) to count and classify white blood cells, classifying them into five types: lymphocytes (Lym), monocytes (Mon), neutrophils (Neu), eosinophils (Eos), and basophils (Baso). In addition, blood cell analyzers use the RET channel (reticulocyte detection channel, or platelet optical detection channel) to obtain reticulocyte counts, red blood cell counts, and platelet counts.

[0078] The blood cell analyzer used in this application uses flow cytometry technology combining laser scattering and fluorescent staining to classify and count particles in a sample. For example, the principle of white blood cell classification detection in the blood cell analyzer is as follows: First, a blood sample is drawn and treated with a hemolytic agent and fluorescent dye for white blood cell classification. Red blood cells are destroyed and dissolved by the hemolytic agent, while white blood cells are not dissolved. However, the fluorescent dye can enter the nucleus of white blood cells with the help of the hemolytic agent and bind to nucleic acid substances in the nucleus. Then, the particles in the blood sample pass one by one through a detection aperture irradiated by a laser beam. When the laser beam irradiates the particles, the characteristics of the particles themselves (such as volume, staining degree, size and content of cell contents, nucleus density, etc.) can block or change the direction of the laser beam, thereby generating scattered light at various angles corresponding to their characteristics. This scattered light is received by a photodetector to obtain relevant information about the particle structure and composition. Forward scattered light reflects the number and volume of particles, side scattered light reflects the complexity of the internal cell structure (such as intracellular particles or the cell nucleus), and fluorescence reflects the content of nucleic acid substances in the cell. Using this optical information, the particles in the sample can be classified and counted.

[0079] Figure 1 This is a schematic diagram of a blood cell analyzer according to some embodiments of this application. The blood cell analyzer 100 includes a sample aspiration device 110, a sample preparation device 120, an optical detection device 130, and a data processing device 140. The blood cell analyzer 100 also has a liquid path system (not shown) for connecting the sample aspiration device 110, the sample preparation device 120, and the optical detection device 130 to facilitate liquid transfer between these devices.

[0080] The sampling device 110 is used to collect the blood sample to be tested. The blood sample to be tested can be a human blood sample or an animal blood sample. Animal blood samples can be, but are not limited to, blood samples from mammals such as cats and dogs.

[0081] In some embodiments, the sampling device 110 has a sampling needle (not shown) for drawing up a blood sample to be tested. Furthermore, the sampling device 110 may also include, for example, a driving device for driving the sampling needle to quantitatively draw up the blood sample through the tip of the sampling needle. The sampling device 110 can deliver the collected blood sample to the sample preparation device 120.

[0082] The sample preparation apparatus 120 is used to mix a portion of the blood sample to be tested, a hemolysin, and a first fluorescent staining agent to prepare a first assay sample for white blood cell classification, and to mix another portion of the blood sample to be tested, a diluent (e.g., a low-osmotic diluent), and a second fluorescent staining agent to prepare a second assay sample for identifying platelets and / or reticulocytes. Furthermore, the second assay sample can also be used to identify platelets, mature red blood cells, reticulocytes, and white blood cells.

[0083] In the embodiments of this application, the hemolytic agent is used to dissolve red blood cells in the blood, breaking them into fragments, but maintaining the morphology of white blood cells essentially unchanged.

[0084] In this embodiment, the first fluorescent staining agent is a fluorescent dye used to stain the DNA in leukocytes for leukocyte classification. For example, it can be a fluorescent dye capable of classifying leukocytes in a blood sample into five leukocyte subsets (neutrophils, lymphocytes, monocytes, eosinophils, and basophils). The second fluorescent dye is different from the first fluorescent dye, and the second fluorescent dye is a fluorescent dye used to stain the DNA and RNA in reticulocytes to identify platelets and / or reticulocytes in the blood sample (capable of distinguishing reticulocytes, erythrocytes, platelets, and leukocytes).

[0085] In some embodiments, the sample preparation apparatus 120 may include at least one reaction cell and a reagent supply device (not shown). The at least one reaction cell receives the blood sample to be tested aspirated by the sampling device 110, and the reagent supply device provides processing reagents (including a hemolysin, a first fluorescent staining agent, a second fluorescent staining agent, etc.) to the at least one reaction cell, thereby mixing the blood sample to be tested aspirated by the sampling device 110 with the processing reagents provided by the reagent supply device in the reaction cell to prepare a test sample (including a first test sample and a second test sample).

[0086] For example, at least one reaction chamber may include a first reaction chamber (or a leukocyte reaction chamber) and a second reaction chamber (or a reticulocyte reaction chamber), and the reagent supply device may include a first reagent supply unit and a second reagent supply unit. The sampling device 110 is used to partially dispense the aspirated blood sample to be tested into the first reaction chamber and the second reaction chamber, respectively. The first reagent supply unit is used to provide a hemolysin and a first fluorescent staining agent to the first reaction chamber, thereby mixing and reacting the portion of the blood sample allocated to the first reaction chamber with the hemolysin and the first fluorescent staining agent to prepare a first assay sample. The second reagent supply unit is used to provide a second fluorescent staining agent and an optional diluent (e.g., for spheroidizing erythrocytes) to the second reaction chamber, thereby mixing and reacting the portion of the blood sample allocated to the second reaction chamber with the second fluorescent staining agent and the optional diluent to prepare a second assay sample.

[0087] The optical detection device 130 includes a flow chamber, a light source, and a photodetector. The flow chamber allows a first test sample and a second test sample to pass through, respectively. The light source illuminates the first and second test samples as they pass through the flow chamber. The photodetector detects the first and second optical information generated by the illumination of the first and second test samples as they pass through the flow chamber.

[0088] It can be understood here that the detection channel for white blood cell classification (also known as the DIFF channel) refers to the detection of the first assay sample prepared by the sample preparation device 120 by the optical detection device 130, while the detection channel for identifying platelets and / or reticulocytes (also known as the RET channel) refers to the detection of the second assay sample prepared by the sample preparation device 120 by the optical detection device 130.

[0089] In this document, a flow chamber refers to a chamber in which a focused liquid stream is used to detect light scattering and fluorescence signals. When a particle, such as a blood cell, passes through the detection aperture of the flow chamber, the particle scatters an incident light beam from a light source, directed through the aperture, in various directions. Photodetectors can be positioned at one or more different angles relative to the incident light beam to detect the light scattered by the particle, thereby obtaining a light scattering signal. Since different particles have different light scattering characteristics, the light scattering signal can be used to distinguish different groups of particles. Specifically, the light scattering signal detected near the incident light beam is generally referred to as a forward light scattering signal or a small-angle light scattering signal. In some embodiments, the forward light scattering signal can be detected from an angle of about 1° to about 10° relative to the incident light beam. In other embodiments, the forward light scattering signal can be detected from an angle of about 2° to about 6° relative to the incident light beam. The light scattering signal detected at about 90° relative to the incident light beam is generally referred to as a side-scattering light signal. In some embodiments, the side-scattering light signal can be detected from an angle of about 65° to about 115° relative to the incident light beam. Typically, the fluorescent signal emitted by blood cells stained with fluorescent dye is also detected in a direction at approximately 90° to the incident light beam.

[0090] In some embodiments, the photodetector may include a forward-scattering light detector for detecting forward-scattered light signals, a side-scattering light detector for detecting side-scattered light signals, and a fluorescence detector for detecting fluorescence signals. Accordingly, the first optical information may include the forward-scattered light signals, side-scattered light signals, and fluorescence signals of particles in the first measurement sample, and the second optical information may include the forward-scattered light signals, side-scattered light signals, and fluorescence signals of particles in the second measurement sample.

[0091] Figure 2 A specific example of an optical detection device 130 is shown. This optical detection device 130 has a light source 101, a beam shaping assembly 102, a flow chamber 103, and a forward scattering detector 104 arranged sequentially in a straight line. A dichroic mirror 106 is arranged at a 45° angle to the line on one side of the flow chamber 103. A portion of the side light emitted by particles in the flow chamber 103 passes through the dichroic mirror 106 and is captured by a fluorescence detector 105 arranged at a 45° angle to the dichroic mirror 106 behind it; the other portion of the side light is reflected by the dichroic mirror 106 and captured by a side scattering detector 107 arranged at a 45° angle to the dichroic mirror 106 in front of it.

[0092] The data processing device 140 is used to process and calculate data to obtain the required results. For example, it can generate two-dimensional or three-dimensional scatter plots based on various collected optical signals, and perform particle analysis on the scatter plots using a gating method. The data processing device 140 can also visualize intermediate or final calculation results and then display them through the display device 150. In this embodiment, the data processing device 140 is configured to implement the method steps, which will be described in further detail below.

[0093] In the embodiments of the application, the data processing device 140 includes, but is not limited to, devices such as a central processing unit (CPU), a microcontroller unit (MCU), a field-programmable gate array (FPGA), and a digital signal data processing device (DSP) used to interpret computer instructions and process data in computer software. For example, the data processing device 140 is used to execute various computer applications in a computer-readable storage medium, thereby enabling the blood cell analyzer 100 to perform corresponding detection procedures and analyze the optical information or optical signals detected by the optical detection device 130 in real time.

[0094] Furthermore, the blood cell analyzer 100 may also include a first housing 160 and a second housing 170. The display device 150 may be, for example, a user interface. An optical detection device 130 and a data processing device 140 are disposed inside the second housing 170. A sample preparation device 120 is disposed, for example, inside the first housing 160, and the display device 150 is disposed, for example, on the outer surface of the first housing 160 and is used to display the detection results of the blood cell analyzer 100.

[0095] This application proposes to combine first optical information obtained through the DIFF channel and second optical information obtained through the RET channel to identify whether there is an abnormal increase in band neutrophils in the blood sample to be tested, and / or to provide the count result of band neutrophils, so as to better assist doctors in making an assessment of inflammation.

[0096] According to the first embodiment of this application, the data processing device 140 is configured as follows:

[0097] A first white blood cell classification scatter plot is generated based on the first optical information, and a second white blood cell classification scatter plot is generated based on the second optical information.

[0098] Based on the first and second white blood cell differential scatter plots, the first count of neutrophils in the blood sample to be tested was determined.

[0099] Determine the actual distribution area of ​​neutrophils from the first white blood cell classification scatter plot;

[0100] The reference distribution area of ​​neutrophils is determined from the actual distribution area based on the reference white blood cell classification scatter plot of one or more normal blood samples. The reference white blood cell classification scatter plot is generated based on the reference optical information generated after the reference test sample for white blood cell classification prepared from normal blood samples is irradiated with light.

[0101] The second count of cells falling within the segmented neutrophil distribution region was determined; and

[0102] Based on the first and second count results, determine whether to issue an alarm for an abnormal increase in band neutrophils in the blood sample to be tested, and / or determine and output the count result of band neutrophils in the blood sample to be tested.

[0103] According to the first embodiment of this application, a first count result is obtained by combining the white blood cell differential scatter plot obtained through the DIFF channel and the white blood cell differential scatter plot obtained through the RET channel. Then, a second count result is obtained based on the actual distribution area of ​​neutrophils in the blood sample to be tested in the first white blood cell differential scatter plot and the reference distribution area of ​​neutrophils in a normal blood sample in a reference white blood cell differential scatter plot. Based on the first and second count results, the presence of an abnormal increase in band neutrophils in the blood sample to be tested can be identified, and an alarm is given when an abnormal increase in band neutrophils is present. Alternatively, the count result of band neutrophils in the blood sample to be tested can be determined and output based on the first and second count results. This can better assist doctors in diagnosis.

[0104] As one implementation of the first embodiment, the data processing device 140 is further configured to: output an alarm indicating an abnormal increase in rod neutrophils in the blood sample to be tested when the difference between the first counting result and the second counting result is greater than a preset threshold, and / or output the difference between the first counting result and the second counting result as the counting result of rod neutrophils in the blood sample to be tested.

[0105] According to the second embodiment of this application, the data processing device 140 is configured to, when it is determined that an abnormal increase in band neutrophils exists in the blood sample to be tested:

[0106] A first white blood cell classification scatter plot is generated based on the first optical information, and a second white blood cell classification scatter plot is generated based on the second optical information.

[0107] Based on the first white blood cell classification scatter plot and the second white blood cell classification scatter plot, the first count result of neutrophils in the blood sample to be tested is determined;

[0108] Determine the actual distribution area of ​​neutrophils from the first white blood cell classification scatter plot;

[0109] The reference distribution area of ​​neutrophils is determined from the actual distribution area based on the reference white blood cell classification scatter plot of one or more normal blood samples. The reference white blood cell classification scatter plot is generated based on the reference optical information generated after the reference test sample for white blood cell classification prepared from normal blood samples is irradiated with light.

[0110] The second count of cells falling within the segmented neutrophil distribution region was determined; and

[0111] Based on the first and second count results, the count results of band neutrophils in the blood sample to be tested are determined and output.

[0112] According to the second embodiment of this application, when an abnormal increase in band neutrophils is determined in the blood sample to be tested, a first count result is first obtained by combining the white blood cell classification scatter plot obtained through the DIFF channel and the white blood cell classification scatter plot obtained through the RET channel. Then, a second count result is obtained based on the actual distribution area of ​​neutrophils in the blood sample to be tested in the first white blood cell classification scatter plot and the reference distribution area of ​​neutrophils in a normal blood sample in a reference white blood cell classification scatter plot. Finally, the count result of band neutrophils in the blood sample to be tested is determined and output based on the first and second count results. This can better assist doctors in diagnosis.

[0113] It is understood that the difference between the first and second embodiments of this application lies in whether the data processing device 140 has already determined the presence of an abnormal increase in band neutrophils in the blood sample to be tested before performing the corresponding operation (e.g., the presence of an abnormal increase in band neutrophils in the blood sample to be tested has been determined through other detection procedures). If the presence of an abnormal increase in band neutrophils in the blood sample to be tested has been determined, the data processing device 140 only needs to determine and output the count result of the band neutrophils in the blood sample to be tested, without having to perform the operation of alarming for the presence of an abnormal increase in band neutrophils in the blood sample to be tested.

[0114] To facilitate understanding, we will use some scatter plots as an example below.

[0115] exist Figure 3 and Figure 4In the first white blood cell classification scatter plot shown, there are clear boundaries between the lymphocyte (DIFF_Lym) group, monocyte (DIFF_Mon) group, neutrophil (DIFF_Neu) group, eosinophil (DIFF_Eos) group, basophil (DIFF_Baso) group, and blood shadow particle group. At this time, the white blood cells in the blood sample can be accurately classified into five categories through the first white blood cell classification scatter plot of the DIFF channel, that is, the white blood cells are classified into neutrophils (DIFF_Neu), lymphocytes (DIFF_Lym), monocytes (DIFF_Mon), eosinophils (DIFF_Eos), and basophils (DIFF_Baso), and the white blood cell count value is equal to the total number of particles minus the blood shadow particles.

[0116] Understandable, Figure 3 and Figure 4 The first white blood cell differential scatter plot of a blood sample without abnormal band neutrophil increase can be used as a reference white blood cell differential scatter plot for normal blood samples.

[0117] And in Figure 5 and Figure 6 In the first white blood cell classification scatter plot shown, there are no clear boundaries between the lymphocyte (DIFF_Lym) group, the monocyte (DIFF_Mon) group, and the neutrophil (DIFF_Neu) group. In other words, when there is an abnormal increase in band neutrophils in a blood sample, it is difficult to accurately classify lymphocytes (DIFF_Lym), monocytes (DIFF_Mon), and neutrophils (DIFF_Neu) using the first white blood cell classification scatter plot.

[0118] Understandable, Figure 5 and Figure 6 In the case shown, the white blood cell count is still equal to the total number of particles minus the number of shadow particles, and the percentage of eosinophils (DIFF_Eos%) and basophils (DIFF_Baso%) can still be determined by the first white blood cell classification scatter plot.

[0119] It can also be understood that the first white blood cell differential scatter plot is the white blood cell differential scatter plot obtained through the DIFF channel.

[0120] As can be seen from the above explanation, when there is an abnormal increase in band neutrophils in the blood sample to be tested, it is difficult to directly and accurately obtain the neutrophil count (also known as the first count result) of the blood sample to be tested based on the first white blood cell classification scatter plot, and therefore it is also difficult to directly determine the band neutrophil count based on the first white blood cell classification scatter plot.

[0121] Based on this, the embodiments of this application can accurately determine the first count result of neutrophils in the blood sample to be tested based on the first white blood cell differential scatter plot and the second white blood cell differential scatter plot. It should be understood that the first count result may include the percentage of neutrophils and / or the neutrophil count value.

[0122] As one implementation, the data processing device 140 can be configured to first generate, based on the forward-scattered light signal and fluorescence signal in the second optical information, such as... Figure 8 The diagram shows a scatter plot of reticulocyte channels. Based on this scatter plot, leukocytes are identified. Then, based on the lateral and forward scattered light signals of the identified leukocytes, a data structure is generated as shown below. Figure 7 The second white blood cell differential scatter plot shown is, as can be understood, the white blood cell differential scatter plot obtained through the RET channel.

[0123] In such Figure 7 In the second scatter plot of white blood cell differential shown, regardless of whether the blood sample tested has an abnormal increase in band neutrophils, there are clear boundaries between the lymphocyte (RET_Lym) population, monocyte (RET_Mon) population, and granulocyte (RET_Gran) population. Here, granulocytes include neutrophils and eosinophils.

[0124] In this case, the percentages of white blood cell groups can be calculated using a second white blood cell differential scatter plot, namely lymphocyte percentage (RET_Lym%), monocyte percentage (RET_Mon%), and granulocyte percentage (RET_Gran%).

[0125] exist Figure 8 The scatter plot of the reticulocyte channel shown indicates that, from left to right along the FL direction, the cells are mature erythrocytes, low-fluorescence reticulocytes, medium-fluorescence reticulocytes, high-fluorescence reticulocytes, and leukocytes. Based on the scatter plot of the reticulocyte channel, parameters such as optical erythrocyte count, optical platelet count, reticulocyte count, low-fluorescence reticulocytes, medium-fluorescence reticulocytes, and high-fluorescence reticulocytes can be determined.

[0126] As can be seen from the above description, regardless of whether there is an abnormal increase in band neutrophils in the blood sample to be tested, the data processing device 140 can accurately determine the first count result of neutrophils in the blood sample to be tested based on the first white blood cell classification scatter plot and the second white blood cell classification scatter plot.

[0127] The following describes some implementation methods for determining the first count of neutrophils in a blood sample based on the first and second white blood cell classification scatter plots.

[0128] As one implementation, the data processing device 140 can be configured to determine the eosinophil count and white blood cell count of the blood sample based on a first white blood cell classification scatter plot, and to determine the granulocyte percentage (i.e., RET_Gran%) of the blood sample based on a second white blood cell classification scatter plot. Granulocytes include neutrophils and eosinophils. Then, a first neutrophil count result of the blood sample can be determined based on the eosinophil count, white blood cell count, and granulocyte percentage.

[0129] The preceding text has already explained how the data processing device 140 accurately obtains the first count of neutrophils in the blood sample to be tested.

[0130] In order to detect the count of band neutrophils in a blood sample, the data processing device 140 of each embodiment of the present application is further configured to determine the actual distribution area of ​​neutrophils from a first white blood cell classification scatter plot, and to determine the distribution area of ​​segmented neutrophils from the actual distribution area based on the reference distribution area of ​​neutrophils in a reference white blood cell classification scatter plot of one or more normal blood samples.

[0131] Here, the reference leukocyte differential scatter plot is generated based on reference optical information produced when a reference assay sample for leukocyte differential preparation, obtained from a normal blood sample, is illuminated. A normal blood sample is one without an abnormal increase in band neutrophils. In other words, the reference leukocyte differential scatter plot is a leukocyte differential scatter plot of a normal blood sample obtained through the DIFF channel.

[0132] After determining the segmented neutrophil distribution area from the actual distribution area of ​​neutrophils in the first white blood cell classification scatter plot, the data processing device 140 is further configured to determine the count result (also referred to as the second count result) of cells falling within the segmented neutrophil distribution area. The second count result may include the percentage of cells falling within the segmented neutrophil distribution area relative to the cells in the actual distribution area and / or the count value of cells falling within the segmented neutrophil distribution area.

[0133] Since the majority of neutrophils in normal blood samples are segmented neutrophils, and the distribution of segmented neutrophils in the bleaching scatter plot under the DIFF channel is approximately the same across different blood samples, a segmented neutrophil distribution area that can approximate the distribution of segmented neutrophils can be determined from the actual distribution area based on the reference distribution area of ​​neutrophils in the reference bleaching scatter plot of a normal blood sample. In this case, the second count result of cells falling within the segmented neutrophil distribution area can be approximated as the segmented neutrophil count result of the blood sample being tested.

[0134] Therefore, the data processing device 140 can determine the count of band neutrophils in the blood sample to be tested based on the first count of neutrophils and the second count of cells falling into the distribution area of ​​segmented neutrophils, and determine whether there is an abnormal increase in band neutrophils in the blood sample to be tested based on the count of band neutrophils.

[0135] In some embodiments, the data processing device 140 may be configured to use the difference between the first counting result and the second counting result as the count result of band neutrophils in the blood sample to be tested, and to determine whether there is an abnormal increase in band neutrophils in the blood sample to be tested based on whether the determined count result of band neutrophils is greater than a preset threshold, thereby determining whether to issue an alarm for the presence of an abnormal increase in band neutrophils in the blood sample to be tested, and / or whether to output the count result of band neutrophils in the blood sample to be tested.

[0136] For example, the data processing device 140 is configured to output an alarm indicating an abnormal increase in band neutrophils in the blood sample being tested and / or output the count result of band neutrophils in the blood sample being tested when the difference between the first count result and the second count result is greater than a preset threshold. Alternatively, the data processing device 140 is configured not to output an alarm indicating an abnormal increase in band neutrophils in the blood sample being tested and / or not to output the count result of band neutrophils in the blood sample being tested when the difference between the first count result and the second count result is not greater than a preset threshold.

[0137] The following describes some embodiments of how the data processing device 140 determines the distribution area of ​​segmented nucleogranulocytes from the actual distribution area based on the reference distribution area of ​​neutrophils in a reference scatter plot of reference white blood cell classification of one or more normal blood samples.

[0138] In some embodiments, one or more normal blood samples and the blood sample to be tested are from the same species. For example, if the blood sample to be tested is from a cat, one or more normal blood samples are also from cats.

[0139] Because the distribution of segmented neutrophils in different blood samples from the same species is more approximate in the leukocyte classification scatter plot obtained from the DIFF channel, a more approximate segmented neutrophil distribution area can be determined from the actual distribution area based on a reference leukocyte classification scatter plot of a normal blood sample from the same species as the blood sample being tested. In this case, the second count of cells falling within the segmented neutrophil distribution area can more accurately represent the segmented neutrophil count, thus allowing for a more accurate determination of the band neutrophil count in the blood sample being tested based on both the first and second counts.

[0140] As one implementation, the blood cell analyzer 100 is configured to pre-store reference leukocyte classification scatter plots of multiple normal blood samples from different species. For example, these reference leukocyte classification scatter plots can be stored in... Figure 1 It may be stored in a data storage device not shown, or it may be directly stored in the data processing device 140.

[0141] In these implementations, the data processing device 140 can be configured to select from a pre-stored reference leukocyte classification scatter plot a reference leukocyte classification scatter plot of multiple normal blood samples from the same species as the blood sample to be tested, so as to determine the distribution area of ​​segmented neutrophils from the actual distribution area based on the selected reference leukocyte classification scatter plot.

[0142] In some embodiments, the data processing device 140 is configured to perform shape matching with the actual distribution region for each reference distribution region of a plurality of normal blood samples, so as to select the reference distribution region with the highest shape similarity to the actual distribution region from the plurality of reference distribution regions of the plurality of normal blood samples as the final reference distribution region, and to determine the segmented neutrophil distribution region from the actual distribution region based on the final reference distribution region.

[0143] It is understandable that there are certain differences in the reference distribution area of ​​neutrophils in the reference white blood cell classification scatter plot among different normal blood samples.

[0144] In the above embodiments, the reference distribution region with the highest shape similarity to the actual distribution region is selected from multiple reference distribution regions of multiple normal blood samples as the final reference distribution region. Based on the final reference distribution region, the segmented neutrophil distribution region is determined from the actual distribution region. In this way, a segmented neutrophil distribution region that more approximately represents the distribution of segmented neutrophils can be determined from the actual distribution region. Thus, the second count result of cells falling within the segmented neutrophil distribution region can more accurately represent the count result of segmented neutrophils, thereby allowing for a more accurate determination of the band neutrophil count result in the blood sample to be tested based on the first and second count results.

[0145] In some implementations, both the first white blood cell classification scatter plot and the reference white blood cell classification scatter plot consist of at least fluorescence signal intensity and scattered light signal intensity (e.g., side-scattered light signal intensity). In these implementations, the data processing device 140 is further configured to perform shape matching between the reference distribution region and the actual distribution region for each of the plurality of normal blood samples in a manner that...

[0146] First, each reference distribution region is divided into a first part and a second part. Here, the fluorescence signal intensity of any cell in the first part is not less than a preset fluorescence signal intensity, and the fluorescence signal intensity of any cell in the second part is not greater than a preset fluorescence signal intensity.

[0147] Taking a scatter plot of white blood cell differential counts with fluorescence signal intensity on the vertical axis and lateral scattered light signal intensity on the horizontal axis as an example, each reference distribution region can be along... Figure 9 The horizontal dashed line shown is divided into two parts. The fluorescence signal intensity corresponding to the dashed line is the preset fluorescence signal intensity. The part above the dashed line belongs to the first part, and the part below the dashed line belongs to the second part.

[0148] Then, the second part of each reference distribution area is shape-matched with the actual distribution area to select the final reference distribution area.

[0149] In other words, in these embodiments, instead of matching the entire reference distribution area to the actual distribution area, only the second portion of the reference distribution area with a lower fluorescence signal intensity is matched to the actual distribution area.

[0150] Since the fluorescence signal intensity of band neutrophils is generally greater than that of segmented neutrophils, shape matching is performed only on the second portion of the reference distribution region with the lower fluorescence signal intensity against the actual distribution region. This facilitates the accurate selection of the reference distribution region from multiple reference distribution regions whose distribution of segmented neutrophils most closely approximates the distribution of segmented neutrophils in the actual distribution region as the final reference distribution region. Thus, based on the first and second counting results, the count of band neutrophils in the blood sample being tested can be determined more accurately.

[0151] As one implementation, the data processing device 140 is further configured to perform shape matching between the second part of each reference distribution area and the actual distribution area in such a way as follows.

[0152] First, the actual distribution area is divided into a third part and a fourth part. Here, the fluorescence signal intensity of any cell in the third part is not less than the preset fluorescence signal intensity, and the fluorescence signal intensity of any cell in the fourth part is not greater than the preset fluorescence signal intensity.

[0153] For example, taking the scatter plot of the first white blood cell differential as an example, with the vertical axis representing fluorescence signal intensity and the horizontal axis representing lateral scattered light signal intensity, the actual distribution area can be along a similar... Figure 9 The dashed line divides the signal into two parts, with the fluorescence signal intensity corresponding to the dashed line being the preset fluorescence signal intensity. Similarly, the part above the dashed line belongs to the third part, and the part below the dashed line belongs to the fourth part.

[0154] Then, the second part of each reference distribution area is shape-matched with the fourth part of the actual distribution area to select the final reference distribution area.

[0155] In other words, in these implementations, instead of matching the second part of the reference distribution region with the entire actual distribution region, only the second part of the reference distribution region with the lower fluorescence signal intensity is matched with the fourth part of the actual distribution region. This allows for a more accurate selection of the final reference distribution region from multiple reference distribution regions whose distribution of segmented neutrophils most closely approximates the distribution of segmented neutrophils in the actual distribution region. Thus, based on the first and second counting results, the count of band neutrophils in the blood sample can be determined more accurately. Furthermore, this improves the efficiency of shape matching, enabling faster determination of the segmented neutrophil distribution region.

[0156] In some embodiments, the preset fluorescence signal intensity is between 90% and 110% of the average of the maximum and minimum fluorescence signal intensities in the reference distribution area. This ensures that the fluorescence signal intensity ranges corresponding to the first and second portions are substantially equivalent, thereby facilitating the more accurate selection of the reference distribution area from multiple reference distribution areas that most closely approximates the distribution of segmented neutrophils in the actual distribution area as the final reference distribution area. Furthermore, based on the first and second counting results, the count of band neutrophils in the blood sample to be tested can be determined more accurately.

[0157] In some preferred embodiments, the preset fluorescence signal intensity is the average of the maximum and minimum fluorescence signal intensities in the reference distribution area.

[0158] It is understood that the preset fluorescence signal intensities of multiple reference distribution regions can be the same or different. As a preferred implementation, the preset fluorescence signal intensities of the multiple reference distribution regions are the same. This eliminates the need to set a corresponding preset fluorescence signal intensity for each reference distribution region separately, thereby simplifying the processing.

[0159] In some embodiments, the data processing device 140 is further configured to, after selecting a final reference distribution region, map the final reference distribution region onto the actual distribution region of the first white blood cell classification scatter plot, thereby determining the mapped region of the final reference distribution region as the segmented neutrophil distribution region (see [link to documentation]). Figure 10 For example, the final reference distribution area can be mapped to the actual distribution area of ​​the first white blood cell classification scatter plot according to its position in the corresponding reference white blood cell classification scatter plot.

[0160] like Figure 11As shown in the embodiments of this application, a blood cell analysis method 200 is also provided, comprising:

[0161] S210, collect the blood sample to be tested;

[0162] S220, a portion of the blood sample to be tested, a hemolysin and a first fluorescent staining agent are mixed to prepare a first test sample for white blood cell classification, and the particles in the first test sample are passed one by one through an optical detection area irradiated by light to obtain the first optical information generated by the particles in the first test sample after being irradiated by light.

[0163] S230, another part of the blood sample to be tested, the diluent, and the second fluorescent staining agent are mixed to prepare a second assay sample for identifying platelets and / or reticulocytes, and the particles in the second assay sample are passed one by one through the optical detection area irradiated by light to obtain the second optical information generated by the particles in the second assay sample after being irradiated by light.

[0164] S240, based on the first optical information and the second optical information, identify whether there is an abnormal increase in band neutrophils in the blood sample to be tested, and / or provide the count result of band neutrophils in the blood sample to be tested.

[0165] As some implementation schemes, step S240 includes Figure 11 Shown:

[0166] S241, Generate a first white blood cell classification scatter plot based on the first optical information, and generate a second white blood cell classification scatter plot based on the second optical information;

[0167] S242, Based on the first white blood cell classification scatter plot and the second white blood cell classification scatter plot, determine the first count result of neutrophils in the blood sample to be tested;

[0168] S243, determine the actual distribution area of ​​neutrophils from the first white blood cell classification scatter plot;

[0169] S244, based on the reference distribution area of ​​neutrophils in a reference leukocyte classification scatter plot of one or more normal blood samples, the distribution area of ​​segmented nucleoid granulocytes is determined from the actual distribution area. The reference leukocyte classification scatter plot is generated based on the reference optical information generated after the reference test sample for leukocyte classification prepared from normal blood samples is irradiated with light.

[0170] S245, determining the second count of cells falling within the segmented neutrophil distribution area; and

[0171] S246, based on the first and second count results, determine whether to issue an alarm for an abnormal increase in band neutrophils in the blood sample to be tested, and / or determine and output the count result of band neutrophils in the blood sample to be tested.

[0172] In some embodiments, in step S246, when the difference between the first count result and the second count result is greater than a preset threshold, an alarm is output indicating an abnormal increase in band neutrophils in the blood sample to be tested. In other embodiments, in step S246, when the difference between the first count result and the second count result is greater than a preset threshold, the difference between the first count result and the second count result is output as the count result of band neutrophils in the blood sample to be tested.

[0173] In some other implementations, step S240 is performed when an abnormal increase in band neutrophils is determined in the blood sample to be tested. In this case, see [link to relevant documentation]. Figure 12 The blood cell analysis method 300 shown includes step S240, which includes:

[0174] S241, Generate a first white blood cell classification scatter plot based on the first optical information, and generate a second white blood cell classification scatter plot based on the second optical information;

[0175] S242, Based on the first white blood cell classification scatter plot and the second white blood cell classification scatter plot, determine the first count result of neutrophils in the blood sample to be tested;

[0176] S243, determine the actual distribution area of ​​neutrophils from the first white blood cell classification scatter plot;

[0177] S244, based on the reference distribution area of ​​neutrophils in a reference leukocyte classification scatter plot of one or more normal blood samples, the distribution area of ​​segmented nucleoid granulocytes is determined from the actual distribution area. The reference leukocyte classification scatter plot is generated based on the reference optical information generated after the reference test sample for leukocyte classification prepared from normal blood samples is irradiated with light.

[0178] S245, determining the second count of cells falling within the segmented neutrophil distribution area; and

[0179] S247, based on the first and second counting results, determine and output the count results of band neutrophils in the blood sample to be tested.

[0180] In some embodiments, one or more normal blood samples and the blood sample to be tested are from the same species.

[0181] In some embodiments, in step S241, based on a first white blood cell differential scatter plot, the eosinophil count and white blood cell count of the blood sample to be tested are determined, and based on a second white blood cell differential scatter plot, the granulocyte percentage of the blood sample to be tested is determined. Granulocytes include neutrophils and eosinophils. Then, based on the eosinophil count, white blood cell count, and granulocyte percentage, a first counting result is determined.

[0182] In some embodiments, in step S244, for each reference distribution region of a plurality of normal blood samples, shape matching with the actual distribution region is performed to select the reference distribution region with the highest shape similarity to the actual distribution region from the plurality of reference distribution regions of the plurality of normal blood samples as the final reference distribution region. Then, based on the final reference distribution region, the segmented neutrophil distribution region is determined from the actual distribution region.

[0183] In some implementations, both the first leukocyte classification scatter plot and the reference leukocyte classification scatter plot consist of at least fluorescence signal intensity and scattered light signal intensity. In these implementations, each reference distribution region can be divided into a first part and a second part, and the second part of each reference distribution region can be shape-matched with the actual distribution region to select the final reference distribution region. Here, the fluorescence signal intensity of any cell in the first part is not less than a preset fluorescence signal intensity, and the fluorescence signal intensity of any cell in the second part is not greater than a preset fluorescence signal intensity.

[0184] As some preferred implementations, the actual distribution area can be divided into a third part and a fourth part, and the second part of each reference distribution area can be shape-matched with the fourth part of the actual distribution area to select the final reference distribution area. Here, the fluorescence signal intensity of any cell in the third part is not less than a preset fluorescence signal intensity, and the fluorescence signal intensity of any cell in the fourth part is not greater than a preset fluorescence signal intensity.

[0185] In some embodiments, the preset fluorescence signal intensity is between 90% and 110% of the average of the maximum and minimum fluorescence signal intensities in the reference distribution area, preferably the average value.

[0186] In some embodiments, the preset fluorescence signal intensity is the same in multiple reference distribution regions.

[0187] Further embodiments and advantages of the blood cell analysis method 200 / 300 proposed in this application can be found in the above description of the blood cell analyzer 100, and will not be repeated here.

[0188] All features or combinations of features mentioned above in the specification, drawings, and claims may be used in any combination or individually, provided they are meaningful within the scope of this application and do not contradict each other. The advantages and features described in the blood cell analyzer provided in the embodiments of this application are applicable in a corresponding manner to the blood cell analysis method provided in the embodiments of this application, and vice versa.

[0189] The above description is merely a preferred embodiment of this application and does not limit the patent scope of this application. All equivalent modifications made based on the inventive concept of this application and the contents of the specification and drawings of this application, or direct / indirect applications in other related technical fields, are included within the patent protection scope of this application.

Claims

1. A blood cell analyzer, comprising: A sampling device is used to collect blood samples for testing. A sample preparation apparatus for mixing a portion of the blood sample to be tested, a hemolysin, and a first fluorescent staining agent to prepare a first assay sample for white blood cell classification, and for mixing another portion of the blood sample to be tested, a diluent, and a second fluorescent staining agent to prepare a second assay sample for identifying platelets and / or reticulocytes. An optical detection device includes a flow chamber, a light source, and a photodetector. The flow chamber is used for the first test sample and the second test sample to pass through, respectively. The light source is used to illuminate the first test sample and the second test sample that have passed through the flow chamber. The photodetector is used to detect the first optical information and the second optical information generated by the first test sample and the second test sample after being illuminated by light when passing through the flow chamber. as well as The data processing device is configured as follows: A first scatter plot of white blood cell classification is generated based on the first optical information, and a second scatter plot of white blood cell classification is generated based on the second optical information. Based on the first white blood cell differential scatter plot and the second white blood cell differential scatter plot, the first neutrophil count result of the blood sample to be tested is determined. The actual distribution area of ​​neutrophils was determined from the first white blood cell classification scatter plot. Based on the reference distribution region of neutrophils in a scatter plot of reference white blood cell classification from one or more normal blood samples, the distribution region of segmented neutrophils is determined from the actual distribution region. The reference white blood cell classification scatter plot is generated based on reference optical information generated after a reference assay sample prepared from normal blood samples for white blood cell classification is irradiated with light. A second count of cells falling within the said segmented neutrophil distribution region, and Based on the first counting result and the second counting result, determine whether to issue an alarm for an abnormal increase in band neutrophils in the blood sample to be tested, and / or determine and output the count result of band neutrophils in the blood sample to be tested.

2. The blood cell analyzer according to claim 1, characterized in that, The data processing device is further configured to: When the difference between the first count result and the second count result is greater than a preset threshold, an alarm is outputting indicating an abnormal increase in band neutrophils in the blood sample to be tested, and / or The difference between the first counting result and the second counting result is output as the count result of the band neutrophils in the blood sample to be tested.

3. A blood cell analyzer, comprising: A sampling device is used to collect blood samples for testing. A sample preparation apparatus for mixing a portion of the blood sample to be tested, a hemolysin, and a first fluorescent staining agent to prepare a first assay sample for white blood cell classification, and for mixing another portion of the blood sample to be tested, a diluent, and a second fluorescent staining agent to prepare a second assay sample for identifying platelets and / or reticulocytes. An optical detection device includes a flow chamber, a light source, and a photodetector. The flow chamber is used for the first test sample and the second test sample to pass through, respectively. The light source is used to illuminate the first test sample and the second test sample that have passed through the flow chamber. The photodetector is used to detect the first optical information and the second optical information generated by the first test sample and the second test sample after being illuminated by light when passing through the flow chamber. as well as The data processing device is configured to: when it is determined that an abnormal increase in band neutrophils is present in the blood sample to be tested, A first scatter plot of white blood cell classification is generated based on the first optical information, and a second scatter plot of white blood cell classification is generated based on the second optical information. Based on the first white blood cell differential scatter plot and the second white blood cell differential scatter plot, the first neutrophil count result of the blood sample to be tested is determined. The actual distribution area of ​​neutrophils was determined from the first white blood cell classification scatter plot. Based on the reference distribution region of neutrophils in a scatter plot of reference white blood cell classification from one or more normal blood samples, the distribution region of segmented neutrophils is determined from the actual distribution region. The reference white blood cell classification scatter plot is generated based on reference optical information generated after a reference assay sample prepared from normal blood samples for white blood cell classification is irradiated with light. A second count of cells falling within the said segmented neutrophil distribution region, and Based on the first counting result and the second counting result, the count result of band neutrophils in the blood sample to be tested is determined and output.

4. The blood cell analyzer according to any one of claims 1-3, characterized in that, The data processing device is further configured to: For each of the multiple normal blood samples, shape matching with the actual distribution region is performed on the reference distribution region of each normal blood sample, so as to select the reference distribution region with the highest shape similarity with the actual distribution region from the multiple reference distribution regions of the multiple normal blood samples as the final reference distribution region. as well as Based on the final reference distribution region, the segmented neutrophil distribution region is determined from the actual distribution region.

5. The blood cell analyzer according to claim 4, characterized in that, Both the first leukocyte classification scatter plot and the reference leukocyte classification scatter plot consist of at least fluorescence signal intensity and scattered light signal intensity; The data processing device is further configured to: Each reference distribution area is divided into a first part and a second part. The fluorescence signal intensity of any cell in the first part is not less than the preset fluorescence signal intensity, and the fluorescence signal intensity of any cell in the second part is not greater than the preset fluorescence signal intensity. as well as The second portion of each reference distribution region is shape-matched with the actual distribution region to select the final reference distribution region.

6. The blood cell analyzer according to claim 5, characterized in that, The data processing device is further configured to: The actual distribution area is divided into a third part and a fourth part. The fluorescence signal intensity of any cell in the third part is not less than the preset fluorescence signal intensity, and the fluorescence signal intensity of any cell in the fourth part is not greater than the preset fluorescence signal intensity. as well as The second portion of each reference distribution region is shape-matched with the fourth portion of the actual distribution region to select the final reference distribution region.

7. The blood cell analyzer according to claim 5 or 6, characterized in that, The preset fluorescence signal intensity is between 90% and 110% of the average of the maximum and minimum fluorescence signal intensities in the reference distribution area, or is the average value.

8. The blood cell analyzer according to any one of claims 5-7, characterized in that, The preset fluorescence signal intensities are the same in the multiple reference distribution regions.

9. The blood cell analyzer according to any one of claims 1-8, characterized in that, The data processing device is further configured to: Based on the first white blood cell classification scatter plot, the eosinophil count and white blood cell count of the blood sample to be tested are determined. Based on the second white blood cell classification scatter plot, the percentage of granulocytes in the blood sample to be tested is determined, wherein the granulocytes include neutrophils and eosinophils; as well as The first count result is determined based on the eosinophil count, the white blood cell count, and the granulocyte percentage.

10. The blood cell analyzer according to any one of claims 1-9, characterized in that, The one or more normal blood samples and the blood sample to be tested are from the same species.

11. A method for blood cell analysis, comprising: Collect the blood sample to be tested; A portion of the blood sample to be tested, a hemolysin, and a first fluorescent staining agent are mixed to prepare a first test sample for white blood cell classification, and the particles in the first test sample are passed one by one through an optical detection area irradiated by light to obtain the first optical information generated by the particles in the first test sample after being irradiated by light. Another portion of the blood sample to be tested, the diluent, and the second fluorescent staining agent are mixed to prepare a second assay sample for identifying platelets and / or reticulocytes, and the particles in the second assay sample are passed one by one through an optically irradiated detection area to obtain the second optical information generated by the particles in the second assay sample after being irradiated by light. A first white blood cell classification scatter plot is generated based on the first optical information, and a second white blood cell classification scatter plot is generated based on the second optical information. Based on the first white blood cell classification scatter plot and the second white blood cell classification scatter plot, the first count result of neutrophils in the blood sample to be tested is determined; The actual distribution area of ​​neutrophils was determined from the first white blood cell classification scatter plot; Based on a reference scatter plot of leukocyte classification from one or more normal blood samples, a reference distribution area of ​​neutrophils is determined from the actual distribution area, and the reference leukocyte classification scatter plot is generated based on reference optical information generated after a reference assay sample for leukocyte classification prepared from normal blood samples is irradiated with light. A second count of cells falling within the distribution region of the segmented neutrophils was determined; as well as Based on the first counting result and the second counting result, determine whether to issue an alarm for an abnormal increase in band neutrophils in the blood sample to be tested, and / or determine and output the count result of band neutrophils in the blood sample to be tested.

12. The method according to claim 11, characterized in that, Based on the first and second counting results, determine whether to issue an alarm for an abnormal increase in band neutrophils in the blood sample to be tested, and / or determine and output the count result of band neutrophils in the blood sample to be tested, including: When the difference between the first count result and the second count result is greater than a preset threshold, an alarm is outputting indicating an abnormal increase in band neutrophils in the blood sample to be tested, and / or The difference between the first counting result and the second counting result is output as the count result of the band neutrophils in the blood sample to be tested.

13. A method for analyzing blood cells, comprising: Collect the blood sample to be tested; A portion of the blood sample to be tested, a hemolysin, and a first fluorescent staining agent are mixed to prepare a first test sample for white blood cell classification, and the particles in the first test sample are passed one by one through an optical detection area irradiated by light to obtain the first optical information generated by the particles in the first test sample after being irradiated by light. Another portion of the blood sample to be tested, the diluent, and the second fluorescent staining agent are mixed to prepare a second assay sample for identifying platelets and / or reticulocytes, and the particles in the second assay sample are passed one by one through an optically irradiated detection area to obtain the second optical information generated by the particles in the second assay sample after being irradiated by light. as well as When it is determined that there is an abnormal increase in band neutrophils in the blood sample to be tested: A first scatter plot of white blood cell classification is generated based on the first optical information, and a second scatter plot of white blood cell classification is generated based on the second optical information. Based on the first white blood cell differential scatter plot and the second white blood cell differential scatter plot, the first neutrophil count result of the blood sample to be tested is determined. The actual distribution area of ​​neutrophils was determined from the first white blood cell classification scatter plot. Based on the reference distribution region of neutrophils in a scatter plot of reference white blood cell classification from one or more normal blood samples, the distribution region of segmented neutrophils is determined from the actual distribution region. The reference white blood cell classification scatter plot is generated based on reference optical information generated after a reference assay sample prepared from normal blood samples for white blood cell classification is irradiated with light. A second count of cells falling within the said segmented neutrophil distribution region, and Based on the first counting result and the second counting result, the count result of band neutrophils in the blood sample to be tested is determined and output.

14. The method according to any one of claims 11-13, characterized in that, Based on a reference distribution region of neutrophils from a reference leukocyte classification scatter plot of one or more normal blood samples, the distribution region of segmented neutrophils is determined from the actual distribution region, including: For each of the multiple normal blood samples, shape matching with the actual distribution region is performed on the reference distribution region of each normal blood sample to select the reference distribution region with the highest shape similarity to the actual distribution region from the multiple reference distribution regions of the multiple normal blood samples as the final reference distribution region; and Based on the final reference distribution region, the segmented neutrophil distribution region is determined from the actual distribution region.

15. The method according to claim 14, characterized in that, Both the first leukocyte classification scatter plot and the reference leukocyte classification scatter plot consist of at least fluorescence signal intensity and scattered light signal intensity; For the reference distribution region of each of multiple normal blood samples, shape matching with the actual distribution region is performed, including: Each reference distribution area is divided into a first part and a second part. The fluorescence signal intensity of any cell in the first part is not less than the preset fluorescence signal intensity, and the fluorescence signal intensity of any cell in the second part is not greater than the preset fluorescence signal intensity. as well as The second portion of each reference distribution region is shape-matched with the actual distribution region to select the final reference distribution region.

16. The method according to claim 15, characterized in that, The second portion of each reference distribution region is shape-matched with the actual distribution region to select the final reference distribution region, including: The actual distribution area is divided into a third part and a fourth part. The fluorescence signal intensity of any cell in the third part is not less than the preset fluorescence signal intensity, and the fluorescence signal intensity of any cell in the fourth part is not greater than the preset fluorescence signal intensity. The second portion of each reference distribution region is shape-matched with the fourth portion of the actual distribution region to select the final reference distribution region.

17. The method according to claim 15 or 16, characterized in that, The preset fluorescence signal intensity is between 90% and 110% of the average of the maximum and minimum fluorescence signal intensities in the reference distribution area, or is the average value.

18. The method according to any one of claims 15-17, characterized in that, The preset fluorescence signal intensities are the same in the multiple reference distribution regions.

19. The method according to any one of claims 11-18, characterized in that, Based on the first white blood cell differential scatter plot and the second white blood cell differential scatter plot, the first count result of neutrophils in the blood sample to be tested is determined, including: Based on the first white blood cell classification scatter plot, the eosinophil count and white blood cell count of the blood sample to be tested are determined. Based on the second white blood cell differential scatter plot, the percentage of granulocytes in the blood sample to be tested is determined, wherein the granulocytes include neutrophils and eosinophils; and The first count result is determined based on the eosinophil count, the white blood cell count, and the granulocyte percentage.

20. The method according to any one of claims 11-19, characterized in that, The one or more normal blood samples and the blood sample to be tested are from the same species.

21. A blood cell analyzer, comprising: A sampling device is used to collect blood samples for testing. A sample preparation apparatus for mixing a portion of the blood sample to be tested, a hemolysin, and a first fluorescent staining agent to prepare a first assay sample for white blood cell classification, and for mixing another portion of the blood sample to be tested, a diluent, and a second fluorescent staining agent to prepare a second assay sample for identifying platelets and / or reticulocytes. An optical detection device includes a flow chamber, a light source, and a photodetector. The flow chamber is used for the first test sample and the second test sample to pass through, respectively. The light source is used to illuminate the first test sample and the second test sample that have passed through the flow chamber. The photodetector is used to detect the first optical information and the second optical information generated by the first test sample and the second test sample after being illuminated by light when passing through the flow chamber. as well as The data processing device is configured to: identify, based on the first optical information and the second optical information, whether there is an abnormal increase in band neutrophils in the blood sample to be tested, and / or provide the count result of band neutrophils in the blood sample to be tested.

22. A method for analyzing blood cells, comprising: Collect the blood sample to be tested; A portion of the blood sample to be tested, a hemolysin, and a first fluorescent staining agent are mixed to prepare a first test sample for white blood cell classification, and the particles in the first test sample are passed one by one through an optical detection area irradiated by light to obtain the first optical information generated by the particles in the first test sample after being irradiated by light. Another portion of the blood sample to be tested, the diluent, and the second fluorescent staining agent are mixed to prepare a second assay sample for identifying platelets and / or reticulocytes, and the particles in the second assay sample are passed one by one through an optically irradiated detection area to obtain the second optical information generated by the particles in the second assay sample after being irradiated by light. as well as Based on the first optical information and the second optical information, identify whether there is an abnormal increase in band neutrophils in the blood sample to be tested, and / or provide the count result of band neutrophils in the blood sample to be tested.

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