Blood cell analyzer and blood cell analysis method
Patent Information
- Application Number
- CN202380100055.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-12-29
- Publication Date
- 2026-02-13
- Estimated Expiration
- 2043-12-29
AI Technical Summary
The existing blood cell analyzer requires the preparation of three different assay samples and conducting three tests respectively, which leads to high reagent costs and large blood volume, making it difficult to obtain leukocyte detection results, reticulocyte detection results and hemoglobin concentration while reducing the cost and blood volume of reagents.
A blood cell analyzer is used to absorb the blood sample to be tested through a sample aspiration device, and mix it with the diluent and fluorescent stain in the first reaction cell to prepare the first measurement sample, and mix it with the hemolytic agent in the second reaction cell to prepare the second measurement sample. Combined with the optical detection device and the colorimetric detection device, the first optical information and colorimetric optical information are obtained respectively to realize the detection of the concentration of reticulocytes, platelets, red blood cells and hemoglobin.
Only two assay samples are required to obtain the detection results of white blood cells, reticulocytes, red blood cells and hemoglobin concentrations, reducing the cost of reagents and the amount of blood used.
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Figure CN121532634A_ABST
Abstract
Description
Blood cell analyzer and blood cell analysis method Technical Field
[0001] The present application relates to the field of blood analysis, and in particular to a blood cell analyzer and a blood cell analysis method. Background Art
[0002] A routine blood test is a basic clinical examination item. The test results generally include white blood cell count, red blood cell count, platelet count, hemoglobin concentration, reticulocyte count, etc. It also includes scatter plots or histograms of white blood cells, red blood cells, platelets and reticulocytes obtained during the test to assist doctors in making clinical diagnoses for patients.
[0003] Existing blood cell analyzers perform optical measurement of white blood cells based on flow laser technology and optical measurement of reticulocytes (or optical measurement of platelets) based on fluorescent staining technology, and measure hemoglobin concentration based on colorimetry. In the optical measurement of white blood cells, the count value and classification of white blood cells, including the count value and classification of neutrophils, lymphocytes, monocytes, eosinophils and basophils, are obtained, and in the optical measurement of reticulocytes, parameters such as the red blood cell count value, platelet count value, and reticulocyte count value are obtained.
[0004] The measurement principle of the colorimetric method is that the different solution concentrations of the test sample will result in different corresponding solution colors. Generally, the higher the solution concentration, that is, the higher the hemoglobin content, the darker the color of the solution. Conversely, the lower the solution concentration, that is, the lower the hemoglobin content, the lighter the solution color. Among them, the depth of the solution color of the test sample directly affects the degree of absorption of light by the test sample. That is, the darker the solution color of the test sample, the more light it absorbs and the less light it transmits. Conversely, the lighter the solution color, the less light it absorbs and the more light it transmits. Therefore, by measuring the intensity of the light that transmits the test sample, the solution concentration of the test sample can be measured, and then the hemoglobin concentration of the test sample can be determined.
[0005] However, in existing blood cell analyzers, it is usually necessary to prepare three different test samples and perform three tests respectively to obtain white blood cell test results, reticulocyte test results and hemoglobin concentration, resulting in high reagent costs and large blood consumption.
[0006] Summary of the Invention
[0007] In order to at least partially solve the above technical problems, the task of the present application is to provide a blood cell analyzer and a blood cell analysis method, which can simultaneously obtain white blood cell test results, reticulocyte test results and hemoglobin concentration while reducing reagent costs and blood usage.
[0008] In order to achieve the above-mentioned tasks of the present application, the first aspect of the present application provides a blood cell analyzer, comprising:
[0009] A sample suction device, used for sucking a blood sample to be tested;
[0010] a sample preparation device for mixing a portion of the blood sample to be tested, a diluent, and a fluorescent dye in a first reaction pool to prepare a first measurement sample, and mixing another portion of the blood sample to be tested and a hemolytic agent in a second reaction pool to prepare a second measurement sample;
[0011] an optical detection device comprising a liquid driving unit, a flow cell, a light source, and a light detector, wherein the liquid driving unit is configured to drive the first measurement sample from the first reaction cell through the flow cell, the light source is configured to irradiate the first measurement sample passing through the flow cell with light, and the light detector is configured to detect first optical information generated by the first measurement sample being irradiated with light while passing through the flow cell;
[0012] a colorimetric detection device, configured to detect the second measurement sample in the second reaction cell to obtain colorimetric optical information;
[0013] A data processing device configured to:
[0014] Obtaining a reticulocyte detection result, a platelet detection result, a red blood cell detection result, and a first white blood cell detection result of the blood sample to be tested based on the first optical information, wherein the first white blood cell detection result includes at least a lymphocyte percentage, a monocyte percentage, and a granulocyte percentage, and the granulocytes include neutrophils and eosinophils; and
[0015] The hemoglobin concentration of the blood sample to be tested is obtained based on the colorimetric optical information.
[0016] A second aspect of the present application provides a blood cell analysis method, comprising:
[0017] Draw a blood sample to be tested;
[0018] Mixing a portion of the blood sample to be tested, a diluent, and a fluorescent dye in a first reaction well to prepare a first measurement sample, and allowing particles of the first measurement sample in the first reaction well to pass through an optical detection area irradiated with light one by one to obtain first optical information generated by the particles in the first measurement sample after being irradiated with light;
[0019] mixing another portion of the blood sample to be tested and a hemolytic agent in a second reaction pool to prepare a second measurement sample, and detecting the second measurement sample in the second reaction pool using a colorimetric method to obtain colorimetric optical information;
[0020] Obtaining a reticulocyte detection result, a platelet detection result, a red blood cell detection result, and a first white blood cell detection result of the blood sample to be tested based on the first optical information, wherein the first white blood cell detection result includes at least a lymphocyte percentage, a monocyte percentage, and a granulocyte percentage, and the granulocytes include neutrophils and eosinophils; and
[0021] The hemoglobin concentration of the blood sample to be tested is determined based on the colorimetric optical information.
[0022] In the technical solutions proposed in various aspects of the present application, it is only necessary to prepare a first measurement sample for identifying platelets, reticulocytes, and red blood cells and a second measurement sample for measuring the hemoglobin concentration, so as to obtain the reticulocyte test results, platelet test results, red blood cell test results, white blood cell test results and hemoglobin concentration of the blood sample to be tested, thereby reducing reagent costs and blood usage. BRIEF DESCRIPTION OF THE DRAWINGS
[0023] FIG1 is a schematic structural diagram of a blood cell analyzer according to some embodiments of the present application.
[0024] FIG2 is a schematic structural diagram of an optical detection device according to some embodiments of the present application.
[0025] FIG3 is a schematic structural diagram of a colorimetric detection device according to some embodiments of the present application.
[0026] FIG. 4 illustrates light signals generated after particles in a first measurement sample are irradiated with light according to some embodiments of the present application.
[0027] FIG5 is a first scattergram of FS-FL generated according to first optical information in some embodiments of the present application.
[0028] FIG6 is a second scattergram of FS-SS generated according to the first optical information in some embodiments of the present application.
[0029] FIG7 is a second scattergram of FS-SS generated according to the first optical information of some other embodiments of the present application.
[0030] Figure 8 is a third scatter plot of FS-SS generated according to the second optical information of some embodiments of the present application.
[0031] FIG9 is a schematic flow chart of a blood cell analysis method according to some embodiments of the present application. DETAILED DESCRIPTION
[0032] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments of this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.
[0033] It should be noted that the terms "first\second\third" involved in the embodiments of the present application are only used to distinguish similar objects and do not represent a specific order for the objects. It can be understood that "first\second\third" can be interchanged with a specific order or sequence when permitted.
[0034] Those skilled in the art will understand that, unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by those skilled in the art to which this application belongs.
[0035] To facilitate the subsequent explanation, here is a brief explanation of some of the terms involved below:
[0036] 1) Scatterplot: A 2D or 3D graph generated by a hematology analyzer that displays the 2D or 3D characteristic information of multiple particles. The X, Y, and Z axes of the scatterplot each represent a characteristic of each particle. For example, in a scatterplot, the X axis represents forward scattered light intensity, the Y axis represents fluorescence intensity, and the Z axis represents side scattered light intensity.
[0037] 2) Cell swarm: A particle cluster formed by multiple particles with the same characteristics distributed in a certain area of the scatter plot, such as a leukocyte swarm, and a neutrophil swarm, lymphocyte swarm, monocyte swarm, eosinophil swarm, or basophil swarm among the leukocytes.
[0038] 3) Blood ghosts: fragments obtained by dissolving red blood cells and platelets in the blood with hemolytic reagents.
[0039] Currently, hematology analyzers can test samples of human blood, blood from other mammals (such as dogs, cats, and horses), poultry, and fish. Typically, hematology analyzers use the DIFF channel (white blood cell classification channel) to count and classify white blood cells, for example, classifying white blood cells into five types: lymphocytes (Lym), monocytes (Mon), neutrophils (Neu), eosinophils (Eos), and eosinophils (Eos). In addition, hematology analyzers use the RET channel (reticulocyte detection channel or platelet optical detection channel) to obtain reticulocyte counts, red blood cell counts, platelet counts, and other values.
[0040] The blood cell analyzer used in the embodiments of the present application uses a flow cytometric technique that combines laser scattering and fluorescence staining to classify and count particles in a sample. For example, the blood cell analyzer's detection principle for reticulocytes, platelets, and red blood cells is as follows: first, a blood sample is drawn and treated with a diluent and a fluorescent dye. Then, particles in the blood sample pass through a detection aperture illuminated by a laser beam. When the laser beam illuminates the particles, their own characteristics (such as volume, staining level, size and content of cellular contents, and nuclear density) 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 signal detector, which can obtain information related to the particle structure and composition. Among them, forward scattered light (FS) reflects the number and volume of particles, side scattered light (SS) reflects the complexity of the cell's internal structure (such as intracellular granules or cell nuclei), and fluorescence (FL) reflects the content of nucleic acid substances in the cell. This optical information can be used to classify and count particles in the sample.
[0041] As mentioned in the background technology, in order to identify white blood cells and reticulocytes in the blood and measure the hemoglobin concentration while reducing reagent costs and blood usage, the embodiment of the present application proposes a technical solution that only requires the preparation of two test samples to simultaneously obtain white blood cell detection results, reticulocyte detection results and hemoglobin concentration.
[0042] FIG1 is a schematic diagram of the structure of a hematology analyzer according to some embodiments of the present application. The hematology analyzer 100 includes a sample aspirator 110, a sample preparation device 120, an optical detection device 130, a data processing device 140, and a colorimetric detection device (not shown). The hematology analyzer 100 also includes a fluidic system (not shown) that connects the sample aspirator 110, the sample preparation device 120, the optical detection device 130, and the colorimetric detection device to facilitate liquid transfer between these devices.
[0043] The sample aspirating device 110 is used to aspirate a blood sample to be tested.
[0044] The sample preparation device 120 is used to mix a portion of the blood sample to be tested, a diluent, and a fluorescent dye in a first reaction pool to prepare a first measurement sample, and to mix another portion of the blood sample to be tested and a hemolytic agent in a second reaction pool to prepare a second measurement sample.
[0045] In the embodiments of the present application, the diluent may include, for example, a Tris buffer. By adjusting the amount of Tris buffer, the osmotic pressure of the diluent is adjusted to approximately 200 mOsm / kg (the osmotic pressure of mammalian blood cells is generally around 260-320). When blood cells are mixed with the diluent, red blood cells and white blood cells absorb water in the hypotonic fluid, causing their volume to increase, while the volume of platelets remains relatively unchanged.
[0046] In the embodiment of the present application, the fluorescent dye is a fluorescent dye used to distinguish reticulocytes, red blood cells, platelets and white blood cells. For example, the fluorescent dye is used to stain RNA and DNA in the cell nucleus.
[0047] Because mature red blood cells are anucleate and have minimal staining effects, while reticulocytes contain filaments, fluorescent staining can increase the intensity of reticulocyte fluorescence, distinguishing them from mature red blood cells. Furthermore, because the RNA and DNA content in white blood cell nuclei is significantly higher than that in reticulocytes, fluorescent staining results in the highest signal intensity in the fluorescence direction for white blood cells. Therefore, by controlling the staining time, platelets, mature red blood cells, reticulocytes, and white blood cells can be clearly distinguished.
[0048] In the embodiments of the present application, a hemolytic agent is used to lyse red blood cells in the blood, breaking them into fragments while preserving the morphology of white blood cells. For example, the hemolytic agent can be any one or a combination of a cationic surfactant, a nonionic surfactant, an anionic surfactant, or an amphiphilic surfactant. For another example, the hemolytic agent can include at least one of an alkyl glycoside, a triterpenoid saponin, or a steroidal saponin.
[0049] The optical detection device 130 includes a liquid driving unit, a flow chamber, a light source and a light detector. The liquid driving unit is used to drive the first measurement sample from the first reaction pool through the flow chamber, the light source is used to irradiate the first measurement sample passing through the flow chamber with light, and the light detector is used to detect the first optical information generated after the first measurement sample is irradiated with light when passing through the flow chamber.
[0050] It can be understood here that the detection channel for identifying reticulocytes, platelets, and red blood cells (also referred to as RET channel) refers to the detection of the first measurement sample prepared by the sample preparation device 120 by the optical detection device 130 .
[0051] The colorimetric detection device is used to detect the second measurement sample in the second reaction pool to obtain colorimetric optical information.
[0052] It is understood that red blood cells in the blood rupture under the action of a hemolytic agent and release hemoglobin, which can then be measured using a colorimetric method to determine the hemoglobin concentration (HGB). The detection channel for measuring hemoglobin concentration (also known as the HGB channel) refers to the detection of the second measurement sample prepared by the sample preparation device 120 by the colorimetric detection device.
[0053] The data processing device 140 is configured to:
[0054] Obtaining a reticulocyte detection result, a platelet detection result, a red blood cell detection result, and a first white blood cell detection result of the blood sample to be tested based on the first optical information, wherein the first white blood cell detection result includes at least a lymphocyte percentage, a monocyte percentage, and a granulocyte percentage, and the granulocytes include neutrophils and eosinophils; and
[0055] The hemoglobin concentration of the blood sample to be tested is obtained based on the colorimetric optical information.
[0056] In the above-mentioned blood cell analyzer 100, only a first measurement sample for identifying platelets, reticulocytes, and red blood cells and a second measurement sample for measuring hemoglobin concentration need to be prepared to obtain reticulocyte detection results, platelet detection results, red blood cell detection results, white blood cell detection results, and hemoglobin concentration of the blood sample to be tested, thereby reducing reagent costs and blood usage.
[0057] The blood cell analyzer 100 is further described below with reference to some embodiments.
[0058] In some embodiments, the sample aspirating device 110 includes a sampling needle (not shown) for aspirating a blood sample to be tested. Furthermore, the sample aspirating device 110 may further include a drive mechanism for driving the sampling needle to quantitatively aspirate the blood sample to be tested through the needle tip of the sampling needle. The sample aspirating device 110 may transport the collected blood sample to the sample preparation device 120.
[0059] In some embodiments, the sample preparation device 120 may include a first reaction cell, a second reaction cell, and a reagent supply device (not shown). Each reaction cell is used to receive the blood sample to be tested drawn by the sample aspirating device 110, and the reagent supply device provides processing reagents (including hemolytic agent, fluorescent dye, diluent, etc.) to the corresponding reaction cell, so that the blood sample to be tested drawn by the sample aspirating device 110 and the processing reagents provided by the reagent supply device are mixed in the corresponding reaction cell to prepare the measurement sample (including the first measurement sample and the second measurement sample).
[0060] For example, the reagent supply device may include a first reagent supply unit and a second reagent supply unit. The sample suction device 110 is used to partially distribute the collected blood sample to be tested to the first reaction pool and the second reaction pool, respectively. The first reagent supply unit is used to provide a diluent and a fluorescent dye to the first reaction pool, so that the portion of the blood sample to be tested distributed to the first reaction pool is mixed with the diluent and the fluorescent dye and reacts to prepare a first measurement sample. The second reagent supply unit is used to provide a hemolytic agent to the second reaction pool, so that the portion of the blood sample to be tested distributed to the second reaction pool is mixed with the hemolytic agent and reacts to prepare a second measurement sample.
[0061] In some embodiments, a flow chamber is a chamber containing a focused fluid flow suitable for detecting light scattering and fluorescence signals. When a particle, such as a blood cell, passes through a detection aperture of the flow chamber, the particle scatters an incident light beam directed from a light source into the detection aperture in various directions. A light detector can be positioned at one or more different angles relative to the incident light beam to detect light scattered by the particle, thereby generating a light scattering signal. Because different particles have different light scattering properties, the light scattering signal can be used to distinguish between different particle populations.
[0062] 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 at an angle of about 1° to about 10° from the incident light beam. In other embodiments, the forward light scattering signal can be detected at an angle of about 2° to about 6° from the incident light beam. The light scattering signal detected at a direction of about 90° to the incident light beam is generally referred to as a side light scattering signal. In some embodiments, the side light scattering signal can be detected at an angle of about 65° to about 115° from the incident light beam. Typically, the fluorescent signal emitted by blood cells stained with a fluorescent dye is also generally detected at a direction of about 90° to the incident light beam.
[0063] In some embodiments, the light detector may include a forward scattered light detector for detecting forward scattered light signals, a side scattered 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 signal, the side scattered light signal, and the fluorescence signal of particles in the first measurement sample after being irradiated with light.
[0064] FIG2 illustrates a specific example of an optical detection device 130. This optical detection device 130 comprises a light source 101, a beam shaping assembly 102, a flow cell 103, and a forward scattered light detector 104, arranged sequentially in a straight line. A dichroic mirror 106 is positioned on one side of the flow cell 103 at a 45° angle to the straight line. Sidelight emitted by particles in the flow cell 103 partially passes through the dichroic mirror 106 and is captured by a fluorescence detector 105 positioned behind the dichroic mirror 106 at a 45° angle. Another portion of the sidelight is reflected by the dichroic mirror 106 and captured by a side scattered light detector 107 positioned in front of the dichroic mirror 106 at a 45° angle.
[0065] In some embodiments, as shown in Figure 3, the colorimetric detection device may include a light source for irradiating the second measurement sample in the second reaction cell with light and a photometer for detecting information of light transmitted through the second measurement sample in the second reaction cell.
[0066] In some embodiments, the data processing device 140 is used to process and calculate data to obtain the required results. For example, it can generate a two-dimensional scatter plot or a three-dimensional scatter plot based on the various collected optical signals, and perform particle analysis on the scatter plot based on the gating method. The data processing device 140 can also visualize the intermediate or final calculation results and then display them through the display device 150. In the embodiment of the present application, the data processing device 140 is configured to implement the method steps described in detail below.
[0067] In some embodiments, the data processing device 140 includes, but is not limited to, a central processing unit (CPU), a microcontroller unit (MCU), a field-programmable gate array (FPGA), a digital signal processing device (DSP), and other devices for interpreting computer instructions and processing data in computer software. For example, the data processing device is used to execute various computer applications stored in a computer-readable storage medium, thereby enabling the hematology analyzer 100 to perform corresponding detection processes and analyze the optical information or optical signals detected by the optical detection device 130 in real time.
[0068] The hematology analyzer 100 may further include a first housing 160 and a second housing 170. The display device 150 may be, for example, a user interface. The optical detection device 130 and the data processing device 140 are disposed within the second housing 170. The sample preparation device 120 is, for example, disposed within the first housing 160. The display device 150 is, for example, disposed on the exterior of the first housing 160 and is used to display the test results of the hematology analyzer.
[0069] The following further describes the steps that the processor 140 needs to perform to obtain the white blood cell test results, the reticulocyte test results, and the hemoglobin concentration in conjunction with some embodiments.
[0070] In some embodiments, the data processing device 140 may be configured to, when acquiring the reticulocyte test result, platelet test result, red blood cell test result, and first white blood cell test result of the blood sample to be tested based on the first optical information:
[0071] generating a first scattergram based on at least the forward scattered light signal FS and the fluorescence signal FL in the first optical information, and acquiring the reticulocyte detection result, the platelet detection result, and the red blood cell detection result based on the first scattergram; and
[0072] A second scattergram is generated based on at least the forward scattered light signal FS and the side scattered light signal SS in the first optical information, and the first white blood cell detection result is acquired based on the second scattergram.
[0073] As shown in Figure 4, the first measurement sample in the first reaction cell passes through the flow cell. When the particles in the first measurement sample are illuminated by the light source (e.g., a laser beam) while passing through the flow cell, they generate a forward scattered light signal FS (at a low angle) and a side scattered light signal SS (at a high angle, 90 degrees). After the fluorescent dye stains red blood cells, platelets, reticulocytes, and white blood cells, the particles in the first measurement sample, upon exposure to the laser beam, also generate an excitation light signal of a higher wavelength. This excitation light signal and the side scattered light signal SS are received at the same angle (90 degrees). A spectroscope is used to separate the side scattered light signal SS from the excitation light signal, and the separated excitation light signal is referred to as the fluorescence signal FL. The forward scattered light signal FS can reflect cell volume, the side scattered light signal SS can reflect the complexity of the cell's internal structure (e.g., intracellular granules or nuclei), and the fluorescence signal FL can reflect the nucleic acid content (e.g., RNA / DNA) in the cell.
[0074] The first optical information may include a forward scattered light signal FS, a side scattered light signal SS, and a fluorescence signal FL of particles in the first measurement sample after being irradiated with light.
[0075] For example, Figure 5 shows a first scatter plot generated based on at least the forward scattered light signal FS and the fluorescence signal FL in the first optical information. The direction of the forward scattered light signal FS corresponds to cell size, and the direction of the fluorescence signal FL corresponds to the intensity of the fluorescent dye staining. In this first scatter plot, from left to right in the direction of the fluorescence signal FL are mature red blood cells, low-fluorescent reticulocytes, medium-fluorescent reticulocytes, high-fluorescent reticulocytes, and white blood cells.
[0076] Based on the first scatter plot, reticulocyte test results, platelet test results, and red blood cell test results can be obtained. The reticulocyte test results may include reticulocyte count and reticulocyte classification, with reticulocyte classification including low-fluorescence reticulocytes, medium-fluorescence reticulocytes, and high-fluorescence reticulocytes. The platelet test results may include platelet count. The red blood cell test results may include red blood cell count.
[0077] In some embodiments, the parameter results shown in Table 1 can be obtained by combining the first scatter plot and the hemoglobin concentration of the test sample.
[0078] Table 1
[0079] For example, FIG6 shows a second scatter plot generated based on at least the forward scattered light signal FS and the side scattered light signal SS in the first optical information. The first white blood cell detection result obtained based on this second scatter plot includes at least the lymphocyte RET_Lym percentage, the monocyte RET_Mon percentage, and the granulocyte RET_Gran percentage. It should be understood that the granulocytes include neutrophils and eosinophils.
[0080] Furthermore, the first white blood cell detection result obtained based on the second scatter plot may also include a lymphocyte RET_Lym count, a monocyte RET_Mon count, and a granulocyte RET_Gran count.
[0081] In some embodiments, the sample preparation device 120 can be further used to additionally add a chemical dye when preparing the first measurement sample, so that the data processing device 140 can distinguish eosinophils from the granulocytes based on the first optical information, so that the first white blood cell detection result includes at least the lymphocyte RET_Lym percentage, the monocyte RET_Mon percentage, the eosinophil RET_Eos percentage and the neutrophil RET_Neu percentage, as shown in Figure 7.
[0082] Table 2 shows at least part of the parameter results of the first white blood cell detection result obtained based on the first optical information after adding the chemical stain.
[0083] Table 2
[0084] In this way, only a chemical stain needs to be added during the preparation of the first test sample for platelet, reticulocyte, and red blood cell (RBC) determination. This allows for classification of white blood cells into four categories: lymphocytes (Lym), monocytes (Mon), neutrophils (Neu), and eosinophils (Eos). This eliminates the need for additional test samples for counting and classifying white blood cells. In other words, the RET channel enables simultaneous acquisition of platelet, reticulocyte, RBC, and four-category RBC classification results, reducing reagent costs and blood usage.
[0085] Optionally, as shown in FIG7 , the data processing device 140 can be further configured to identify basophils RET_Baso in the first measurement sample based on the first optical information, so that the first white blood cell detection result also includes the basophil RET_Baso percentage. That is, the first white blood cell detection result includes the lymphocyte RET_Lym percentage, the monocyte RET_Mon percentage, the eosinophil RET_Eos percentage, the neutrophil RET_Neu percentage, and the basophil RET_Baso percentage.
[0086] Table 3 shows the results of various parameters obtained after the basophils in the first measurement sample were also identified based on the first optical information.
[0087] Table 3
[0088] In this way, only a chemical stain needs to be added during the preparation of the first platelet assay sample to classify white blood cells into the five types of white blood cells: lymphocytes (Lym), monocytes (Mon), neutrophils (Neu), eosinophils (Eos), and basophils (Baso). This eliminates the need for preparing additional test samples for counting and classifying white blood cells. In other words, the RET channel can simultaneously obtain platelet, reticulocyte, and red blood cell (RBC) test results, along with the five-type white blood cell classification results, reducing reagent costs and blood usage.
[0089] In some embodiments, the sample preparation device 120 may be further configured to add the chemical stain in a manner of mixing with the diluent and / or the fluorescent stain or add the chemical stain separately when preparing the first assay sample.
[0090] For example, the sample preparation device 120 can be further configured to add the chemical stain by mixing it in the diluent when preparing the first measurement sample. For another example, the sample preparation device 120 can be further configured to add the chemical stain by mixing it in the fluorescent stain when preparing the first measurement sample. For another example, the sample preparation device 120 can be further configured to add the chemical stain by mixing it simultaneously in the diluent and the fluorescent stain when preparing the first measurement sample. For another example, the sample preparation device 120 can be further configured to add the chemical stain separately to the first reaction cell when preparing the first measurement sample.
[0091] In some embodiments, the chemical coloring agent may be selected from acidic organic pigments.
[0092] Optionally, the chemical dye is selected from the acid blue series;
[0093] Optionally, the chemical dye is selected from the group consisting of direct blue, acid green, acid yellow, acid orange, methyl red, methyl orange, aniline blue, alizarin yellow, reactive black, Sudan black B, and azo black E.
[0094] In some embodiments, the liquid driving unit in the optical detection device 130 can be further used to drive at least a portion of the second measurement sample from the second reaction pool through the flow chamber, and the light source is further used to irradiate the at least a portion of the second measurement sample passing through the flow chamber with light, and the light detector is further used to detect the second optical information generated after the at least a portion of the second measurement sample is irradiated with light when passing through the flow chamber.
[0095] Here, the data processing device 140 is further configured to obtain a second white blood cell test result of the blood sample to be tested based on the second optical information, wherein the second white blood cell test result at least includes white blood cell count, basophil count and basophil percentage.
[0096] It can be understood that the detection channel for detecting basophils (also referred to as the basophil detection channel) refers to the detection of at least a portion of the second measurement sample prepared by the sample preparation device 120 by the optical detection device 130 .
[0097] Table 4 shows at least part of the parameter results of the second white blood cell detection result obtained based on the second optical information.
[0098] Table 4
[0099] In this way, at least a portion of the prepared second assay sample can be directly used to count and classify basophils to obtain an accurate white blood cell count, basophil count, and basophil percentage, thereby eliminating the need to prepare additional test samples for identifying basophils. This reduces reagent costs and blood usage while also obtaining accurate white blood cell detection results.
[0100] In some embodiments, when the data processing device 140 obtains the second white blood cell detection result of the blood sample to be tested based on the second optical information: generates a third scatter plot based on the forward scattered light signal FS and the side scattered light signal SS in the second optical information, and obtains the second white blood cell detection result based on the third scatter plot.
[0101] For example, FIG8 shows a third scattergram generated based on the forward scattered light signal FS and the side scattered light signal SS in the second optical information. Basophils (Baso) in the second measurement sample can be identified based on this third scattergram.
[0102] In some embodiments, a first white blood cell detection result obtained through the RET channel and a second white blood cell detection result obtained by testing at least a portion of a second measurement sample can be combined to obtain more accurate five-part white blood cell differential detection results. Specifically, by simply preparing a first measurement sample for identifying platelets, reticulocytes, and red blood cells and a second measurement sample for measuring hemoglobin concentration, accurate reticulocyte detection results, platelet detection results, red blood cell detection results, white blood cell detection results, and hemoglobin concentration can be obtained.
[0103] In some embodiments, the liquid driving unit is configured to drive at least a portion of the second measurement sample from the second reaction well through the flow chamber after the colorimetric detection device detects the second measurement sample in the second reaction well to obtain the colorimetric optical information, so that the light detector can detect and obtain the second optical information. In other words, basophil counting and classification can be performed after hemoglobin concentration measurement.
[0104] In this way, the second measurement sample in the second reaction pool can be reused for counting and classifying basophils, thereby further reducing the reagent cost and blood volume required for the test.
[0105] In other embodiments, the liquid driving unit is configured to drive at least a portion of the second measurement sample from the second reaction well through the flow cell before the colorimetric detection device detects the second measurement sample in the second reaction well to obtain the colorimetric optical information, so that the light detector detects the second optical information generated by the at least a portion of the second measurement sample being irradiated with light while passing through the flow cell. In other words, basophil counting and classification can be performed before hemoglobin concentration measurement.
[0106] In this way, since the hemoglobin concentration of the second measurement sample retained in the second reaction pool is measured after the basophils are counted and classified, there is sufficient time for the blood sample and reagent in the second reaction pool to fully react before the hemoglobin concentration is measured, thereby improving the accuracy of the subsequent hemoglobin concentration measurement, thereby improving the accuracy of the obtained hemoglobin concentration.
[0107] Accordingly, as shown in FIG9 , the embodiment of the present application further provides a blood cell analysis method 200 , comprising:
[0108] S210, drawing a blood sample to be tested;
[0109] S220, mixing a portion of the blood sample to be tested, a diluent, and a fluorescent dye in a first reaction cell to prepare a first measurement sample, and allowing particles of the first measurement sample in the first reaction cell to pass through an optical detection area irradiated with light one by one to obtain first optical information generated by the particles in the first measurement sample after being irradiated with light;
[0110] S230, mixing another portion of the blood sample to be tested and a hemolytic agent in a second reaction pool to prepare a second measurement sample, and detecting the second measurement sample in the second reaction pool using a colorimetric method to obtain colorimetric optical information;
[0111] S240, acquiring a reticulocyte detection result, a platelet detection result, a red blood cell detection result, and a first white blood cell detection result of the blood sample to be tested based on the first optical information, wherein the first white blood cell detection result includes at least a lymphocyte percentage, a monocyte percentage, and a granulocyte percentage, and the granulocytes include neutrophils and eosinophils; and
[0112] S250: Determine the hemoglobin concentration of the blood sample to be tested based on the second optical information.
[0113] In some embodiments, in step S220, a chemical dye is additionally added when preparing the first measurement sample, so that in step S240, eosinophils among the granulocytes can be distinguished based on the first optical information, so that the first white blood cell detection result includes at least the percentage of lymphocytes, the percentage of monocytes, the percentage of eosinophils and the percentage of neutrophils.
[0114] Optionally, in step S240 , basophils in the first measurement sample are further identified based on the first optical information, so that the first white blood cell detection result further includes a basophil percentage.
[0115] In some embodiments, in step S220, the chemical dye is added in a manner of being mixed with the diluent and / or the fluorescent dye or is added separately when preparing the first measurement sample.
[0116] In some embodiments, the chemical coloring agent is selected from acidic organic pigments.
[0117] Optionally, the chemical dye is selected from the acid blue series;
[0118] Optionally, the chemical dye is selected from the group consisting of direct blue, acid green, acid yellow, acid orange, methyl red, methyl orange, aniline blue, alizarin yellow, reactive black, Sudan black B, and azo black E.
[0119] In some embodiments, step S240 may include: generating a first scatter plot based on at least the forward scattered light signal and the fluorescence signal in the first optical information, and obtaining the reticulocyte detection result, the platelet detection result, and the red blood cell detection result based on the first scatter plot; and generating a second scatter plot based on at least the forward scattered light signal and the side scattered light signal in the first optical information, and obtaining the first white blood cell detection result based on the second scatter plot.
[0120] In some embodiments, the blood cell analysis method 200 may further include the following steps:
[0121] allowing particles in at least a portion of the second assay sample in the second reaction pool to pass through an optical detection area irradiated with light one by one, so as to obtain second optical information generated by the particles in at least a portion of the second assay sample after being irradiated with light; and
[0122] A second white blood cell test result of the blood sample to be tested is obtained based on the second optical information, where the second white blood cell test result at least includes a white blood cell count, a basophil count, and a basophil percentage.
[0123] In some embodiments, obtaining a second white blood cell detection result of the blood sample to be tested based on the second optical information may include: generating a third scatter plot based on the forward scattered light signal and the side scattered light signal in the second optical information, and obtaining the second white blood cell detection result based on the third scatter plot.
[0124] In some embodiments, before or after the second measurement sample in the second reaction pool is detected by colorimetry to obtain the colorimetric optical information, particles in at least a portion of the second measurement sample in the second reaction pool are passed one by one through an optical detection area irradiated with light to obtain the second optical information.
[0125] More embodiments and advantages of the blood cell analysis method 200 proposed in the embodiment of the present application can be found in the above description of the blood cell analyzer 100 and will not be repeated here.
[0126] The features or feature combinations mentioned above in the specification, drawings, and claims may be used in any combination or individually, as long as they are meaningful and not mutually inconsistent within the scope of this application. The advantages and features described with reference to the blood cell analyzer provided in the embodiments of this application apply in a corresponding manner to the blood cell analysis method provided in the embodiments of this application, and vice versa.
[0127] The above description is only a preferred embodiment of the present application and does not limit the patent scope of the present application. All equivalent transformation schemes made by using the contents of the present application description and drawings under the inventive concept of the present application, or directly / indirectly applied in other related technical fields are included in the patent protection scope of the present application.
Claims
1. A blood cell analyzer, comprising: A sampling device for aspirating a blood sample to be tested; A sample preparation device for mixing a part of the blood sample to be tested, a diluent, and a fluorescent stain in a first reaction cell to prepare a first measurement sample, and mixing another part of the blood sample to be tested and a hemolytic agent in a second reaction cell to prepare a second measurement sample; An optical detection device, including a liquid driving part, a flow cell, a light source, and a light detector, wherein the liquid driving part is used to drive the first measurement sample from the first reaction cell through the flow cell, the light source is used to irradiate the first measurement sample passing through the flow cell with light, and the light detector is used to detect the first optical information generated after the first measurement sample is irradiated by light when passing through the flow cell; A colorimetric detection device for detecting the second measurement sample in the second reaction cell to obtain colorimetric optical information; A data processing device configured to: Obtain a reticulocyte detection result, a platelet detection result, an erythrocyte detection result, and a first white blood cell detection result of the blood sample to be tested based on the first optical information, wherein the first white blood cell detection result at least includes lymphocyte percentage, monocyte percentage, and granulocyte percentage, and the granulocytes include neutrophils and eosinophils; And Obtain the hemoglobin concentration of the blood sample to be tested based on the colorimetric optical information.
2. The blood cell analyzer according to claim 1, wherein The sample preparation device is further used to additionally add a chemical stain when preparing the first measurement sample, so that the data processing device can distinguish eosinophils in the granulocytes based on the first optical information, and the first white blood cell detection result at least includes lymphocyte percentage, monocyte percentage, eosinophil percentage, and neutrophil percentage; Optionally, the data processing device is further configured to identify basophils in the first measurement sample based on the first optical information, so that the first white blood cell detection result further includes basophil percentage.
3. The blood cell analyzer according to claim 2, characterized in that, The sample preparation device is further used to add the chemical stain in a manner of being mixed in the diluent and / or the fluorescent stain or separately when preparing the first measurement sample.
4. The blood cell analyzer according to claim 2 or 3, characterized in that, The chemical stain is selected from acidic organic dyes; Optionally, the chemical stain is selected from the acidic blue series; Optionally, the chemical stain is selected from the group consisting of direct blue, acidic green, acidic yellow, acidic orange, methyl red, methyl orange, aniline blue, alizarin yellow, reactive black, sudan black B, and azo black E.
5. The blood cell analyzer according to any one of claims 1 to 4, characterized in that The data processing device obtains the reticulocyte detection result, the platelet detection result, the erythrocyte detection result, and the first white blood cell detection result of the blood sample to be tested based on the first optical information, including: the data processing device Generates a first scatter plot based on at least the forward scatter light signal and the fluorescence signal in the first optical information, and obtains the reticulocyte detection result, the platelet detection result, and the erythrocyte detection result based on the first scatter plot; and Generate a second scatter plot based on at least the forward scattered light signal and the lateral scattered light signal in the first optical information, and obtain the first white blood cell detection result based on the second scatter plot.
6. The blood cell analyzer according to any one of claims 1 to 5, characterized in that, The liquid driving unit is further configured to drive at least a part of the second measurement sample from the second reaction cell through the flow cell, the light source is further configured to irradiate the at least a part of the second measurement sample passing through the flow cell with light, and the light detector is further configured to detect second optical information generated after the at least a part of the second measurement sample is irradiated with light when passing through the flow cell. The data processing device is further configured to obtain a second white blood cell detection result of the blood sample to be tested based on the second optical information, and the second white blood cell detection result includes at least white blood cell count, basophil count, and basophil percentage.
7. The blood cell analyzer according to claim 6, characterized in that, The data processing device obtains the second white blood cell detection result of the blood sample to be tested based on the second optical information, including: the data processing device Generates a third scatter plot based on the forward scattered light signal and the lateral scattered light signal in the second optical information, and obtains the second white blood cell detection result based on the third scatter plot.
8. The blood cell analyzer according to claim 6 or 7, characterized in that, The liquid driving unit is arranged to drive at least a part of the second measurement sample from the second reaction cell through the flow cell before or after the colorimetric detection device detects the second measurement sample in the second reaction cell to obtain the colorimetric optical information, so that the light detector can detect the second optical information.
9. A blood cell analysis method, comprising: Aspirate a blood sample to be tested. Mix a part of the blood sample to be tested, a diluent, and a fluorescent stain in a first reaction cell to prepare a first measurement sample, and make the particles in the first measurement sample in the first reaction cell pass through the optically detected area irradiated with light one by one, so as to obtain first optical information generated after the particles in the first measurement sample are irradiated with light. Mix another part of the blood sample to be tested and a hemolytic agent in a second reaction cell to prepare a second measurement sample, and perform colorimetric detection on the second measurement sample in the second reaction cell to obtain colorimetric optical information. Obtain the reticulocyte detection result, platelet detection result, red blood cell detection result, and first white blood cell detection result of the blood sample to be tested based on the first optical information, wherein the first white blood cell detection result includes at least lymphocyte percentage, monocyte percentage, and granulocyte percentage, and the granulocytes include neutrophils and eosinophils. And Determine the hemoglobin concentration of the blood sample to be tested based on the colorimetric optical information.
10. The blood cell analysis method according to claim 9, wherein When preparing the first measurement sample, a chemical stain is additionally added, so that eosinophils in the granulocytes can be distinguished based on the first optical information, and the first white blood cell detection result includes at least lymphocyte percentage, monocyte percentage, eosinophil percentage, and neutrophil percentage. Optionally, based on the first optical information, basophils in the first measurement sample are also identified, such that the first white blood cell test result further includes the percentage of basophils.
11. The blood cell analysis method according to claim 10, wherein When preparing the first measurement sample, the chemical stain is added in a manner of being mixed in the diluent and / or the fluorescent stain, or added separately.
12. The blood cell analysis method according to claim 10 or 11, characterized in that, The chemical stain is selected from acidic organic dyes; Optionally, the chemical stain is selected from the acidic blue series; Optionally, the chemical stain is selected from the group consisting of direct blue, acidic green, acidic yellow, acidic orange, methyl red, methyl orange, aniline blue, alizarin yellow, reactive black, sudan black B, and azo black E.
13. The blood cell analysis method according to any one of claims 9 to 12, characterized in that, Based on the first optical information, reticulocyte test results, platelet test results, red blood cell test results, and first white blood cell test results of the blood sample to be tested are obtained, including: generating a first scatter plot based on at least the forward scatter light signal and the fluorescence signal in the first optical information, and obtaining the reticulocyte test results, platelet test results, and red blood cell test results based on the first scatter plot; and generating a second scatter plot based on at least the forward scatter light signal and the side scatter light signal in the first optical information, and obtaining the first white blood cell test result based on the second scatter plot.
14. The blood cell analysis method according to any one of claims 9 to 13 further includes: causing at least a part of the particles in the second measurement sample in the second reaction cell to pass one by one through an optically detected area irradiated with light, so as to obtain second optical information generated by the at least a part of the particles in the second measurement sample after being irradiated with light; and obtaining a second white blood cell test result of the blood sample to be tested based on the second optical information, where the second white blood cell test result at least includes white blood cell count, basophil count, and basophil percentage.
15. The blood cell analysis method according to claim 14, wherein Obtaining the second white blood cell test result of the blood sample to be tested based on the second optical information includes: generating a third scatter plot based on the forward scatter light signal and the side scatter light signal in the second optical information, and obtaining the second white blood cell test result based on the third scatter plot.
16. The blood cell analysis method according to claim 14 or 15, characterized in that, Before or after detecting the second measurement sample in the second reaction cell by a colorimetric method to obtain the colorimetric method optical information, causing at least a part of the particles in the second measurement sample in the second reaction cell to pass one by one through an optically detected area irradiated with light, so as to obtain the second optical information.
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