White blood cell differential method, apparatus, medium, and device

Abstract

The application discloses a white blood cell classification method, device, medium and equipment, acquires the pulse signal set of the white blood cell sample to be classified under low-angle and medium-angle scattering angles, and constructs a signal intensity scatter diagram based on the signal intensity. Then, the overall particle distribution of the signal intensity scatter diagram under the medium-angle scattering angle is counted, and the signal intensity scatter diagram is divided into a first area scatter diagram and a second area scatter diagram. Next, based on the particle number change rate of the local particle distribution of the first area and the second area scatter diagram under the low-angle and medium-angle scattering angles, the coordinate center points of neutrophils, monocytes and lymphocytes are determined. Finally, the clustering operation is performed on each coordinate center point in the signal intensity scatter diagram, and the discrete points in each clustering cluster are respectively taken as neutrophil discrete points, monocyte discrete points and lymphocyte discrete points. It can be seen that the application is accurate in classification, and an operator does not need experimental experience and professional knowledge.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of leukocytes, and in particular to a leukocyte classification method, device, medium and equipment. BACKGROUND

[0002] A common method for leukocyte detection in a blood cell analyzer is laser scattering. After a sample to be tested is treated with a chemical reagent, the cells to be tested are arranged in a single row under the wrapping of a sheath fluid and flow into a flow chamber at a constant speed. The cells passing through the detection area are irradiated by light, and the scattered light signals of various types of particles are collected. Then, the light signals are processed and analyzed to classify and count the leukocytes. The detection principle is shown in FIG. 1. The collected light signals include low-angle scattering light signals, medium-angle scattering light signals, and high-angle scattering light signals. The low-angle scattering light signals can reflect the information of the cell volume size, the medium-angle scattering light signals can reflect the internal fine structure and particulate matter of the cell, and the high-angle scattering light signals can reflect the changes in the cell membrane, nuclear model, and cytoplasm. Finally, the three-dimensional scattering light signals are comprehensively utilized to classify the leukocytes. Figure 1

[0003] However, in the conventional leukocyte classification method, the data processing is generally based on manual judgment. However, this process requires certain experimental experience and professional knowledge. For people who do not have or do not fully have experimental experience and professional knowledge, it is difficult to operate, which leads to different accuracy of the classification results. SUMMARY

[0004] Therefore, it is necessary to provide a leukocyte classification method, device, medium and equipment to solve the problem that the leukocyte data processing has a high operation difficulty, which leads to different accuracy of the classification results.

[0005] A leukocyte classification method, the method comprising:

[0006] obtaining a pulse signal set of a leukocyte sample to be classified at a low-angle scattering angle and a medium-angle scattering angle, identifying the signal intensity of each pulse signal in the pulse signal set, and constructing a signal intensity scatter plot containing a plurality of discrete points based on the signal intensity; wherein the leukocyte sample to be classified contains neutrophils, monocytes and lymphocytes, and each discrete point indicates the signal intensity of a leukocyte at different scattering angles;

[0007] ​statistically analyze the overall particle distribution of the signal intensity scatter plot at the medium angle scattering angle, and divide the signal intensity scatter plot into a first region scatter plot and a second region scatter plot based on the particle number change rate of the overall particle distribution; wherein the particle distribution is used to indicate the particle number of blood cell particles of different signal intensities, the signal intensity of the first region scatter plot at the medium angle scattering angle is greater than the signal intensity of the second region scatter plot at the medium angle scattering angle;

[0008] statistically analyze the first local particle distribution of the first region scatter plot at the low angle scattering angle and the second local particle distribution at the medium angle scattering angle, and determine the first coordinate center point of the neutrophil based on the particle number change rate of the first local particle distribution and the second local particle distribution;

[0009] statistically analyze the third local particle distribution of the second region scatter plot at the low angle scattering angle and the fourth local particle distribution at the medium angle scattering angle, and determine the second coordinate center point of the monocyte and the third coordinate center point of the lymphocyte based on the particle number change rate of the third local particle distribution and the fourth local particle distribution; wherein the signal intensity of the second coordinate center point at the low angle scattering angle is greater than the signal intensity of the third coordinate center point at the low angle scattering angle;

[0010] perform clustering operations on the first coordinate center point, the second coordinate center point and the third coordinate center point in the signal intensity scatter plot respectively, and take the discrete points in the first clustering cluster to which the first coordinate center point belongs as neutrophil discrete points, take the discrete points in the second clustering cluster to which the second coordinate center point belongs as monocyte discrete points, and take the discrete points in the third clustering cluster to which the third coordinate center point belongs as lymphocyte discrete points.

[0011] In one embodiment, the signal intensity scatter plot is divided into a first region scatter plot and a second region scatter plot based on the particle number change rate of the overall particle distribution, which includes:

[0012] calculate the particle number change rate of each type of signal intensity in the overall particle distribution to obtain an overall change rate condition;

[0013] search for a rising zero point in the overall change rate condition, and determine a first critical signal intensity corresponding to a local minimum value of the particle number in the particle distribution based on the searched rising zero point;

[0014] In the signal intensity scatter plot, the region where the signal intensity at the medium-angle scattering angle is greater than or equal to the first critical signal intensity is divided into the first region scatter plot, and the region where the signal intensity at the medium-angle scattering angle is less than the first critical signal intensity is divided into the second region scatter plot.

[0015] In one embodiment, the first coordinate center point of the neutrophil is determined based on the particle number change rate of the first local particle distribution and the second local particle distribution, including:

[0016] The particle number change rate of each type of signal intensity in the first local particle distribution and the second local particle distribution is calculated respectively to obtain a first change rate condition at a low-angle scattering angle and a second change rate condition at a medium-angle scattering angle.

[0017] The falling zero points in the first change rate condition and the second change rate condition are searched respectively, and a second critical signal intensity corresponding to a local maximum of the particle number is determined in the first local particle distribution based on the searched falling zero points, and a third critical signal intensity corresponding to a local maximum of the particle number is determined in the second local particle distribution.

[0018] The second critical signal intensity and the third critical signal intensity are combined to obtain the first coordinate center point.

[0019] In one embodiment, the second coordinate center point of the monocyte and the third coordinate center point of the lymphocyte are determined based on the particle number change rate of the third local particle distribution and the fourth local particle distribution, including:

[0020] The particle number change rate of each type of signal intensity in the third local particle distribution and the fourth local particle distribution is calculated respectively to obtain a third change rate condition at a low-angle scattering angle and a fourth change rate condition at a medium-angle scattering angle.

[0021] The falling zero points in the third change rate condition and the fourth change rate condition are searched respectively, and a fourth critical signal intensity and a fifth critical signal intensity corresponding to a local maximum of the particle number are determined in the third local particle distribution based on the searched falling zero points, and a sixth critical signal intensity corresponding to a local maximum of the particle number is determined in the fourth local particle distribution; wherein the fourth critical signal intensity is greater than the fifth critical signal intensity.

[0022] combining the fourth critical signal intensity and the sixth critical signal intensity to obtain the second coordinate center point, and combining the fifth critical signal intensity and the sixth critical signal intensity to obtain the third coordinate center point.

[0023] In one embodiment, the formula for calculating the particle number change rate is:

[0024]

[0025] In the above formula, indicating the particle number change rate of the i-th signal intensity, indicating the particle number of blood cell particles of the i+1-th signal intensity, indicating the particle number of blood cell particles of the i-th signal intensity, and N indicating the total number of signal intensities.

[0026] In one embodiment, the clustering operation includes:

[0027] calculating the distance between the target coordinate center point and each discrete point in the signal intensity scatter plot, and determining the discrete points with a distance less than a preset distance threshold as candidate discrete points of the target coordinate center point; wherein the target coordinate center point is any one of the first coordinate center point, the second coordinate center point and the third coordinate center point;

[0028] If the number of determined candidate discrete points is greater than a preset number threshold, the target coordinate center point and the determined candidate discrete points are taken as a clustering cluster.

[0029] In one embodiment, the white blood cell sample to be classified further includes eosinophils, and the method further includes:

[0030] discrete points in the signal intensity scatter plot that satisfy the eosinophil condition are taken as the eosinophil discrete points; wherein the eosinophil condition is that the discrete points are not classified as the neutrophil discrete points, the monocyte discrete points and the lymphocyte discrete points, and the signal intensity at the medium angle scattering angle is within a preset distribution range.

[0031] A white blood cell classification device, the device comprising:

[0032] a scatter plot construction module configured to obtain a pulse signal set of a white blood cell sample to be classified at a low angle scattering angle and a medium angle scattering angle, identify the signal intensity of each pulse signal in the pulse signal set, and construct a signal intensity scatter plot containing a plurality of discrete points based on the signal intensity; wherein the white blood cell sample to be classified includes neutrophils, monocytes and lymphocytes, and each discrete point indicates the signal intensity of a white blood cell at different scattering angles.

[0033] a center point determination module configured to: count an overall particle distribution of the signal intensity scatter plot at a medium-angle scattering angle, and divide the signal intensity scatter plot into a first region scatter plot and a second region scatter plot based on a particle number change rate of the overall particle distribution, wherein the overall particle distribution is used to indicate a particle number of blood cell particles of different signal intensities, the signal intensity of the first region scatter plot at the medium-angle scattering angle is greater than the signal intensity of the second region scatter plot at the medium-angle scattering angle; count a first local particle distribution of the first region scatter plot at a low-angle scattering angle and a second local particle distribution of the first region scatter plot at the medium-angle scattering angle, and determine a first coordinate center point of the neutrophil based on a particle number change rate of the first local particle distribution and the second local particle distribution; and count a third local particle distribution of the second region scatter plot at the low-angle scattering angle and a fourth local particle distribution of the second region scatter plot at the medium-angle scattering angle, and determine a second coordinate center point of the monocyte and a third coordinate center point of the lymphocyte based on a particle number change rate of the third local particle distribution and the fourth local particle distribution, wherein the signal intensity of the second coordinate center point at the low-angle scattering angle is greater than the signal intensity of the third coordinate center point at the low-angle scattering angle;

[0034] a classification module configured to: respectively perform clustering operations on the first coordinate center point, the second coordinate center point and the third coordinate center point in the signal intensity scatter plot, and take discrete points in a first clustering cluster to which the first coordinate center point belongs as neutrophil discrete points, take discrete points in a second clustering cluster to which the second coordinate center point belongs as monocyte discrete points, and take discrete points in a third clustering cluster to which the third coordinate center point belongs as lymphocyte discrete points.

[0035] A computer readable storage medium storing a computer program, the computer program being executed by a processor to cause the processor to perform the steps of the white blood cell classification method.

[0036] A white blood cell classification device comprising a memory and a processor, the memory storing a computer program, the computer program being executed by the processor to cause the processor to perform the steps of the white blood cell classification method.

[0037] This invention provides a method, apparatus, medium, and device for classifying white blood cells. It acquires pulse signal sets from a white blood cell sample at low and medium scattering angles and constructs a signal intensity scatter plot based on the signal intensity. Then, it statistically analyzes the overall particle distribution of the signal intensity scatter plot at the medium scattering angle and divides it into a first region scatter plot and a second region scatter plot. Next, based on the rate of change of particle number in the local particle distribution of the first and second region scatter plots at low and medium scattering angles, it determines the coordinate center points of neutrophils, monocytes, and lymphocytes. Finally, it performs a clustering operation on each coordinate center point within the signal intensity scatter plot, using the discrete points within each cluster as discrete points for neutrophils, monocytes, and lymphocytes, respectively. Therefore, this invention provides accurate classification, and operators do not require experimental experience or specialized knowledge. Attached Figure Description

[0038] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0039] in:

[0040] Figure 1 This is a schematic diagram illustrating the principle of white blood cell monitoring.

[0041] Figure 2 This is a flowchart illustrating the white blood cell classification method.

[0042] Figure 3 A schematic diagram illustrating the generation of scattered light at three different angles;

[0043] Figure 4 A scatter plot of the signal intensity of white blood cells under three-dimensional signal;

[0044] Figure 5 To be Figure 4 A schematic diagram of particle distribution mapped along the mid-angle scattering angle MS direction;

[0045] Figure 6 For the corresponding Figure 4 Scatter plot of the first region;

[0046] Figure 7 For the corresponding Figure 4 The second region scatter plot;

[0047] Figure 8 This is a schematic diagram of the local particle distribution in the first region under low-angle and medium-angle scattering angles;

[0048] Figure 9 This is a schematic diagram of the local particle distribution in the second region under low-angle and medium-angle scattering angles;

[0049] Figure 10 This is a schematic diagram of the results of white blood cell classification;

[0050] Figure 11 A schematic diagram of a white blood cell sorting device;

[0051] Figure 12 This is a structural block diagram of a white blood cell classification device. Detailed Implementation

[0052] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0053] The terms "first," "second," etc., in the specification, claims, and accompanying drawings of this application are used to distinguish different objects, not to describe a specific order. Furthermore, the terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion. For example, a process, method, system, product, or apparatus that includes a series of steps or units is not limited to the listed steps or units, but may optionally include steps or units not listed, or may optionally include other steps or units inherent to these processes, methods, products, or apparatuses.

[0054] In this document, the term "embodiment" means that a particular feature, structure, or characteristic described in connection with an embodiment may be included in at least one embodiment of this application. The appearance of this phrase in various places throughout the specification does not necessarily refer to the same embodiment, nor is it a separate or alternative embodiment mutually exclusive with other embodiments. It will be explicitly and implicitly understood by those skilled in the art that the embodiments described herein can be combined with other embodiments.

[0055] like Figure 2 As shown, Figure 2 This is a flowchart illustrating a white blood cell classification method in one embodiment. The steps provided by the white blood cell classification method in this embodiment include:

[0056] S201, Obtain the pulse signal set of the white blood cell sample to be classified at low-angle and medium-angle scattering angles, identify the signal intensity of each pulse signal in the pulse signal set, and construct a scatter plot of signal intensity containing multiple discrete points based on the signal intensity.

[0057] Wherein, the sample of white blood cells to be classified contains neutrophils, monocytes and lymphocytes, and the embodiment needs to further distinguish these categories of white blood cells.

[0058] Exemplarily, in one scenario, the sample of white blood cells to be classified is first treated with sufficient 5LDS hemolytic agent, and after the treatment, red blood cells are lysed, and white blood cells are dyed. Under the wrapping of sheath fluid, cells are arranged in a single row and flow into the flow chamber at a constant speed. Under the irradiation of the laser beam, three different angles of scattered light are generated. Figure 3 The generated scattered light includes low-angle scattered light, medium-angle scattered light and high-angle scattered light. The low-angle scattered light is the scattered light in the low-angle forward region, the medium-angle scattered light is the scattered light in the medium-angle forward region, and the high-angle scattered light is the scattered light in the high-angle lateral region. The low-angle scattered light can reflect the size of the cell, the medium-angle scattered light can reflect the internal fine structure and particulate matter of the cell, and the high-angle forward scattered light can also reflect the internal fine structure and particulate matter of the cell. The aperture of the receiving part is used to determine whether there is scattered light, and the first receiver receives the medium-angle scattered light emitted from the flow chamber and converts it into a medium-angle pulse signal, constituting a pulse signal set corresponding to the medium angle; the second receiver receives the high-angle scattered light emitted from the flow chamber and converts it into a high-angle pulse signal, constituting a pulse signal set corresponding to the high angle; and the third receiver receives the low-angle scattered light emitted from the flow chamber and converts it into a low-angle pulse signal, constituting a pulse signal set corresponding to the low angle. In the embodiment, only the pulse signal sets under the low-angle scattering angle and the medium-angle scattering angle are used.

[0059] Further, the signal intensity of each pulse signal in the pulse signal set is identified by using existing pulse identification algorithms, such as threshold detection algorithm or energy threshold algorithm. The signal intensity of each pulse signal in the pulse signal set is identified by using existing pulse identification algorithms, such as threshold detection algorithm or energy threshold algorithm. Further, based on these signal intensities, the signal intensity scatter plot of white blood cells under three-dimensional signals can be summarized. Exemplarily, as shown in , the Y-axis-LS represents the signal intensity of low-angle scattered light, and the X-axis-MS represents the signal intensity of medium-angle scattered light. It can be understood that each discrete point in the signal intensity scatter plot indicates the signal intensity of a white blood cell under different scattering angles.

[0060] Further, based on these signal intensities, the signal intensity scatter plot of white blood cells under three-dimensional signals can be summarized. Exemplarily, as shown in Figure 4 , the Y-axis-LS represents the signal intensity of low-angle scattered light, and the X-axis-MS represents the signal intensity of medium-angle scattered light. It can be understood that each discrete point in the signal intensity scatter plot indicates the signal intensity of a white blood cell under different scattering angles.

[0061] S202, Statistically analyze the overall particle distribution of the signal intensity scatter plot under the mid-angle scattering angle, and divide the signal intensity scatter plot into a first region scatter plot and a second region scatter plot based on the rate of change of the number of particles in the overall particle distribution.

[0062] The particle distribution is used to indicate the number of blood cell particles with different signal intensities. This is represented as... Instructions The number of particles of signal strength class, where N is the total number of signal strength classes. For example, corresponding to... Figure 4 ,Will Figure 4 The scatter plot in the image is mapped along the direction of the mid-angle scattering angle MS to obtain... Figure 5 The particle distribution is shown. The scatter plots for the first and second regions are respectively... Figure 5 A scatter plot of the two "peaks".

[0063] In one specific embodiment, the signal strength scatter plot is divided into a first region scatter plot and a second region scatter plot in the following manner:

[0064] (1) Calculate the rate of change of the number of particles of each type of signal intensity in the overall particle distribution to obtain the overall rate of change.

[0065] Based on this rate of change, we can understand the trend of particle number changes at each signal intensity in the particle distribution.

[0066] Optionally, the formula for calculating the particle number change rate of the i-th type of signal intensity is:

[0067]

[0068] In the above formula, The rate of change of the particle number indicating the intensity of the i-th type of signal. The number of blood cell particles indicating the intensity of the (i+1)th type of signal. N indicates the number of blood cell particles representing the intensity of signal i, and N indicates the total number of signal classes.

[0069] (2) Search for the rising zero-crossing point in the overall rate of change, and determine the first critical signal intensity corresponding to the local minimum of the number of particles in the particle distribution based on the searched rising zero-crossing point.

[0070] In the overall rate of change, a value less than 0 in the local region to the left of the zero-crossing point indicates that the number of particles with signal strength in the corresponding particle distribution is continuously decreasing; a value greater than 0 in the local region to the right of the zero-crossing point indicates that the number of particles with signal strength in the corresponding particle distribution is continuously increasing. Based on these conditions, the zero-crossing point can be found in the overall rate of change. Optionally, the zero-crossing point can be defined as the rate of change of the number of particles for a signal strength of type i. In general, if the following conditions are met, it is determined to be a point that rises above zero:

[0071]

[0072] Then, based on these zero-crossing points found, the local minimum of the particle number and the first critical signal intensity can be determined in the particle distribution. For example... Figure 5 As shown, the vertical coordinate of point p1 is the local minimum of the particle number, and the horizontal coordinate of point p1 is the first critical signal intensity.

[0073] (3) In the signal intensity scatter plot, the region with signal intensity greater than or equal to the first critical signal intensity at the mid-angle scattering angle is divided into the first region scatter plot, and the region with signal intensity less than the first critical signal intensity at the mid-angle scattering angle is divided into the second region scatter plot.

[0074] For example, such as Figure 6 As shown, Figure 6 For the corresponding Figure 4 The first region scatter plot; as shown Figure 7 As shown, Figure 7 For the corresponding Figure 4 The second scatter plot shows that the signal strength of the first scatter plot at the mid-angle scattering angle is greater than that of the second scatter plot at the mid-angle scattering angle.

[0075] S203, Statistically analyze the first local particle distribution in the first region scatter plot at the low scattering angle and the second local particle distribution at the medium scattering angle, and determine the first coordinate center point of the neutrophils based on the particle number change rate of the first local particle distribution and the second local particle distribution.

[0076] For example, such as Figure 8 As shown, Figure 8 (a) is the corresponding Figure 6 The scatter plot of the first region shows the local particle distribution at a low-angle scattering angle. Figure 8 (b) is the corresponding Figure 6 The first region scatter plot shows the second local particle distribution at the mid-angle scattering angle.

[0077] In one embodiment, the first coordinate center point of the neutrophil is determined by the following way:

[0078] (1) The particle number change rate of each signal intensity in the first local particle distribution and the second local particle distribution is calculated respectively, so as to obtain the first change rate condition under the low-angle scattering angle and the second change rate condition under the medium-angle scattering angle.

[0079] The calculation method of the change rate is the same as above, which will not be repeated here.

[0080] (2) The falling zero points in the first change rate condition and the second change rate condition are searched respectively, and the second critical signal intensity corresponding to the local maximum particle number in the first local particle distribution and the third critical signal intensity corresponding to the local maximum particle number in the second local particle distribution are determined based on the searched falling zero points.

[0081] In the change rate condition, the local range to the left of the falling zero point is greater than 0, indicating that the particle number of the signal intensity in the corresponding particle distribution is always increasing; the local range to the right of the falling zero point is less than 0, indicating that the particle number of the signal intensity in the corresponding particle distribution is always decreasing, and the falling zero point can be found in the change rate condition based on the above conditions. Optionally, the falling zero point is defined as the particle number change rate of a signal intensity of the i-th type , if the following conditions are met, it is determined as the falling zero point:

[0082]

[0083] Then, based on the searched falling zero points, the local maximum particle number, the first critical signal intensity and the second critical signal intensity in the particle distribution condition can be determined. As shown in Figure 8 (a), the ordinate of point p2 is the local maximum particle number, and the abscissa of point p2 is the second critical signal intensity, which is represented as . As shown in Figure 8 (b), the ordinate of point p3 is the local maximum particle number, and the abscissa of point p3 is the third critical signal intensity, which is represented as .

[0084] (3) The second critical signal intensity and the third critical signal intensity are combined to obtain the first coordinate center point of the neutrophil.

[0085] Correspondingly, the first coordinate center point of the neutrophil is represented as

[0086] S204, statistics the third local particle distribution of the second area scatter plot at low-angle scattering angle and the fourth local particle distribution at medium-angle scattering angle, and determines the second coordinate center point of monocytes and the third coordinate center point of lymphocytes based on the particle number change rate of the third local particle distribution and the fourth local particle distribution.

[0087] As shown in Figure 9 , Figure 9 (a) is the third local particle distribution of the second area scatter plot corresponding to the low-angle scattering angle, Figure 7 Figure 9 (b) is the fourth local particle distribution of the second area scatter plot corresponding to the medium-angle scattering angle. Figure 7

[0088] In one specific embodiment, the second coordinate center point of monocytes and the third coordinate center point of lymphocytes are determined by the following way:

[0089] (1) Calculate the particle number change rate of each type of signal intensity in the third local particle distribution and the fourth local particle distribution respectively, to obtain the third change rate condition at low-angle scattering angle and the fourth change rate condition at medium-angle scattering angle.

[0090] Wherein, the calculation method of the change rate is the same as above, which will not be repeated here.

[0091] (2) Search the falling zero points in the third change rate condition and the fourth change rate condition respectively, and based on the searched falling zero points, determine the fourth critical signal intensity and the fifth critical signal intensity corresponding to the local maximum of particle number in the third local particle distribution, and determine the sixth critical signal intensity corresponding to the local maximum of particle number in the fourth local particle distribution.

[0092] Similarly, if the following conditions are met, it is determined as a falling zero point:

[0093]

[0094] Then, based on the searched falling zero points, the local maximum of particle number, the fourth critical signal intensity and the fifth critical signal intensity can be determined in the particle distribution condition. As shown in Figure 9 (a), the ordinate of point p4 is the local maximum of particle number, and the abscissa of point p4 is the fourth critical signal intensity, which is represented as . The ordinate of point p5 is the local maximum of particle number, and the abscissa of point p5 is the fifth critical signal intensity, which is represented as . It can be seen that the fourth critical signal intensity is greater than the fifth critical signal intensity. As shown in Figure 9 ​​(b) as shown, the ordinate of point p6 is the local maximum of the particle number, and the abscissa of point p6 is the sixth critical signal intensity, denoted as .

[0095] (3) combining the fourth critical signal intensity and the sixth critical signal intensity to obtain a second coordinate center point, and combining the fifth critical signal intensity and the sixth critical signal intensity to obtain a third coordinate center point.

[0096] Correspondingly, the second coordinate center point of the monocyte is denoted as , and the third coordinate center point of the lymphocyte is denoted as It can be seen that the signal intensity of the second coordinate center point at a low-angle scattering angle is greater than the signal intensity of the third coordinate center point at a low-angle scattering angle.

[0097] S205, respectively, the first coordinate center point, the second coordinate center point and the third coordinate center point in the signal intensity scatter plot are subjected to clustering operation, and the discrete points in the first clustering cluster to which the first coordinate center point belongs are taken as neutrophil discrete points, the discrete points in the second clustering cluster to which the second coordinate center point belongs are taken as monocyte discrete points, and the discrete points in the third clustering cluster to which the third coordinate center point belongs are taken as lymphocyte discrete points.

[0098] As shown in Figure 10 , after the first coordinate center point , the second coordinate center point , and the third coordinate center point are determined, the discrete points in the three elliptical regions can be determined as neutrophil discrete points, monocyte discrete points and lymphocyte discrete points through clustering operation. The clustering operation can be k-Modes, Squeezer and the like.

[0099] In one specific embodiment, the clustering operation comprises: calculating the distance between the target coordinate center point and each discrete point in the signal intensity scatter plot , and determining the discrete points with a distance less than a preset distance threshold as candidate discrete points of the target coordinate center point. Wherein, the target coordinate center point is any one of the first coordinate center point, the second coordinate center point and the third coordinate center point; the number of candidate discrete points is counted, and if the number of determined candidate discrete points is greater than a preset number threshold , the target coordinate center point and the determined candidate discrete points are taken as a clustering cluster.

[0100] Further, the white blood cell sample to be classified also contains eosinophils, and considering that the distribution of the discrete points corresponding to the eosinophils is relatively scattered, as Figure 10As shown, in one embodiment, the classification is also performed in the following way:

[0101] The discrete points in the signal intensity scatter plot that meet the eosinophil condition are taken as the eosinophil discrete points; wherein the eosinophil condition is that the discrete points are not classified as the neutrophil discrete points, the monocyte discrete points and the lymphocyte discrete points, and the signal intensity at the medium angle scattering angle is within the preset distribution range, which is represented as falling within the following distribution range:

[0102]

[0103] wherein , is an empirical threshold. In this way, the eosinophils can be further classified from the neutrophils, the monocytes and the lymphocytes.

[0104] The above white blood cell classification method obtains the pulse signal set of the white blood cell sample to be classified at the low angle scattering angle and the medium angle scattering angle, and constructs a signal intensity scatter plot based on the signal intensity. Then, the overall particle distribution of the signal intensity scatter plot at the medium angle scattering angle is counted, and the signal intensity scatter plot is divided into a first region scatter plot and a second region scatter plot. Next, based on the particle number change rate of the local particle distribution of the first region scatter plot and the second region scatter plot at the low angle scattering angle and the medium angle scattering angle, the coordinate center points of the neutrophils, the monocytes and the lymphocytes are determined. Finally, the clustering operation is performed on each coordinate center point in the signal intensity scatter plot, and the discrete points in each cluster are taken as the neutrophil discrete points, the monocyte discrete points and the lymphocyte discrete points respectively. It can be seen that the present application has high classification accuracy, and the operator does not need experimental experience and professional knowledge.

[0105] In one embodiment, as Figure 11 shown, a white blood cell classification device is proposed, which comprises:

[0106] The scatter plot construction module 1101 is configured to obtain the pulse signal set of the white blood cell sample to be classified at the low angle scattering angle and the medium angle scattering angle, identify the signal intensity of each pulse signal in the pulse signal set, and construct a signal intensity scatter plot containing a plurality of discrete points based on the signal intensity; wherein the white blood cell sample to be classified contains neutrophils, monocytes and lymphocytes, and each discrete point indicates the signal intensity of a white blood cell at different scattering angles.

[0107] The center point determination module 1102 is configured to: count an overall particle distribution of the signal intensity scatter plot at the medium-angle scattering angle, and divide the signal intensity scatter plot into a first region scatter plot and a second region scatter plot based on a particle number change rate of the overall particle distribution; the particle distribution is used to indicate the particle number of blood cell particles of different signal intensities, the signal intensity of the first region scatter plot at the medium-angle scattering angle is greater than the signal intensity of the second region scatter plot at the medium-angle scattering angle; and count a first local particle distribution of the first region scatter plot at the low-angle scattering angle and a second local particle distribution at the medium-angle scattering angle, and determine a first coordinate center point of the neutrophil based on a particle number change rate of the first local particle distribution and the second local particle distribution; and count a third local particle distribution of the second region scatter plot at the low-angle scattering angle and a fourth local particle distribution at the medium-angle scattering angle, and determine a second coordinate center point of the monocyte and a third coordinate center point of the lymphocyte based on a particle number change rate of the third local particle distribution and the fourth local particle distribution; the signal intensity of the second coordinate center point at the low-angle scattering angle is greater than the signal intensity of the third coordinate center point at the low-angle scattering angle.

[0108] The classification module 1103 is configured to: respectively perform clustering operations on the first coordinate center point, the second coordinate center point and the third coordinate center point in the signal intensity scatter plot, and take discrete points in a first clustering cluster to which the first coordinate center point belongs as neutrophil discrete points, take discrete points in a second clustering cluster to which the second coordinate center point belongs as monocyte discrete points, and take discrete points in a third clustering cluster to which the third coordinate center point belongs as lymphocyte discrete points.

[0109] In one of the embodiments, the center point determination module 1102 is specifically configured to: calculate a particle number change rate of each type of signal intensity in the overall particle distribution to obtain an overall change rate condition; search for an upward zero-crossing point in the overall change rate condition, and determine a first critical signal intensity corresponding to a local minimum value of the particle number in the particle distribution based on the searched upward zero-crossing point; in the signal intensity scatter plot, divide a region with a signal intensity greater than or equal to the first critical signal intensity at the medium-angle scattering angle into the first region scatter plot, and divide a region with a signal intensity less than the first critical signal intensity at the medium-angle scattering angle into the second region scatter plot.

[0110] In one of the embodiments, the center point determination module 1102 is specifically configured to: calculate the particle number change rate of each type of signal intensity in the first local particle distribution and the second local particle distribution respectively, to obtain the first change rate condition at the low-angle scattering angle and the second change rate condition at the medium-angle scattering angle; search for the falling zero points in the first change rate condition and the second change rate condition respectively, and determine the second critical signal intensity corresponding to the local maximum of the particle number in the first local particle distribution and the third critical signal intensity corresponding to the local maximum of the particle number in the second local particle distribution based on the searched falling zero points; and combine the second critical signal intensity and the third critical signal intensity to obtain the first coordinate center point.

[0111] In one of the embodiments, the center point determination module 1102 is specifically configured to: calculate the particle number change rate of each type of signal intensity in the third local particle distribution and the fourth local particle distribution respectively, to obtain the third change rate condition at the low-angle scattering angle and the fourth change rate condition at the medium-angle scattering angle; search for the falling zero points in the third change rate condition and the fourth change rate condition respectively, and determine the fourth critical signal intensity and the fifth critical signal intensity corresponding to the local maximum of the particle number in the third local particle distribution and the sixth critical signal intensity corresponding to the local maximum of the particle number in the fourth local particle distribution based on the searched falling zero points; wherein the fourth critical signal intensity is greater than the fifth critical signal intensity; combine the fourth critical signal intensity and the sixth critical signal intensity to obtain the second coordinate center point, and combine the fifth critical signal intensity and the sixth critical signal intensity to obtain the third coordinate center point.

[0112] In one of the embodiments, the calculation formula of the particle number change rate is:

[0113]

[0114] In the above formula, denotes the particle number change rate of the i-th type of signal intensity, denotes the particle number of the blood cell particles of the i+1-th type of signal intensity, denotes the particle number of the blood cell particles of the i-th type of signal intensity, and N denotes the total number of types of signal intensity.

[0115] In one embodiment, the classification module 1103 is specifically used to: calculate the distance between the target coordinate center point and each discrete point in the signal strength scatter plot, and determine the discrete points whose distance is less than a preset distance threshold as candidate discrete points of the target coordinate center point; wherein, the target coordinate center point is any one of the first coordinate center point, the second coordinate center point and the third coordinate center point; if the number of determined candidate discrete points is greater than a preset number threshold, then the target coordinate center point and the determined candidate discrete points are treated as a cluster.

[0116] In one embodiment, the white blood cell sample to be classified further includes eosinophils, and the white blood cell classification device is further configured to: use discrete points in the signal intensity scatter plot that meet the eosinophil criteria as eosinophil discrete points; wherein, the eosinophil criteria are discrete points that are not classified as neutrophil discrete points, monocyte discrete points, or lymphocyte discrete points, and the signal intensity at the mid-angle scattering angle is within a preset distribution range.

[0117] Figure 12 An internal structural diagram of a white blood cell sorting device in one embodiment is shown. Figure 12 As shown, the white blood cell classification device includes a processor, a memory, and a network interface connected via a system bus. The memory includes a non-volatile storage medium and internal memory. The non-volatile storage medium stores an operating system and may also store a computer program. When executed by the processor, this computer program enables the processor to implement the white blood cell classification method. The internal memory may also store a computer program, which, when executed by the processor, enables the processor to perform the white blood cell classification method. Those skilled in the art will understand that… Figure 12 The structure shown is merely a block diagram of a portion of the structure related to the present application and does not constitute a limitation on the white blood cell classification device to which the present application is applied. A specific white blood cell classification device may include more or fewer components than those shown in the figure, or combine certain components, or have different component arrangements.

[0118] A computer readable storage medium stores a computer program, the computer program is executed by a processor to implement the following steps: obtaining a pulse signal set of a white blood cell sample to be classified under low-angle scattering angle and medium-angle scattering angle, identifying the signal intensity of each pulse signal in the pulse signal set, and constructing a signal intensity scatter plot containing a plurality of discrete points based on the signal intensity; wherein the white blood cell sample to be classified contains neutrophils, monocytes and lymphocytes, and each discrete point indicates the signal intensity of a white blood cell under different scattering angles; statistics of the overall particle distribution of the signal intensity scatter plot under the medium-angle scattering angle, and dividing the signal intensity scatter plot into a first region scatter plot and a second region scatter plot based on the particle number change rate of the overall particle distribution; statistics of the first local particle distribution of the first region scatter plot under the low-angle scattering angle and the second local particle distribution under the medium-angle scattering angle, and determining the first coordinate center point of the neutrophil based on the particle number change rate of the first local particle distribution and the second local particle distribution; statistics of the third local particle distribution of the second region scatter plot under the low-angle scattering angle and the fourth local particle distribution under the medium-angle scattering angle, and determining the second coordinate center point of the monocyte and the third coordinate center point of the lymphocyte based on the particle number change rate of the third local particle distribution and the fourth local particle distribution; respectively clustering the first coordinate center point, the second coordinate center point and the third coordinate center point in the signal intensity scatter plot, and taking the discrete points in the first clustering cluster to which the first coordinate center point belongs as neutrophil discrete points, the discrete points in the second clustering cluster to which the second coordinate center point belongs as monocyte discrete points, and the discrete points in the third clustering cluster to which the third coordinate center point belongs as lymphocyte discrete points.

[0119] A white blood cell classification device includes a memory, a processor, and a computer program stored in the memory and executable on the processor, the processor implementing the following steps when executing the computer program: obtaining a pulse signal set of a white blood cell sample to be classified at a low-angle scattering angle and a medium-angle scattering angle, identifying a signal intensity of each pulse signal in the pulse signal set, and constructing a signal intensity scatter plot including a plurality of discrete points based on the signal intensity; wherein the white blood cell sample to be classified includes neutrophils, monocytes, and lymphocytes, and each discrete point indicates a signal intensity of a white blood cell at different scattering angles; statistically analyzing an overall particle distribution of the signal intensity scatter plot at the medium-angle scattering angle, and dividing the signal intensity scatter plot into a first region scatter plot and a second region scatter plot based on a particle number change rate of the overall particle distribution; statistically analyzing a first local particle distribution of the first region scatter plot at the low-angle scattering angle and a second local particle distribution at the medium-angle scattering angle, and determining a first coordinate center point of the neutrophils based on a particle number change rate of the first local particle distribution and the second local particle distribution; statistically analyzing a third local particle distribution of the second region scatter plot at the low-angle scattering angle and a fourth local particle distribution at the medium-angle scattering angle, and determining a second coordinate center point of the monocytes and a third coordinate center point of the lymphocytes based on a particle number change rate of the third local particle distribution and the fourth local particle distribution; respectively performing clustering operations on the first coordinate center point, the second coordinate center point, and the third coordinate center point in the signal intensity scatter plot, and taking discrete points in a first cluster to which the first coordinate center point belongs as neutrophil discrete points, taking discrete points in a second cluster to which the second coordinate center point belongs as monocyte discrete points, and taking discrete points in a third cluster to which the third coordinate center point belongs as lymphocyte discrete points.

[0120] It should be noted that the above white blood cell classification method, device, equipment, and computer readable storage medium belong to one overall inventive concept, and the content in the white blood cell classification method, device, equipment, and computer readable storage medium embodiments can be mutually applicable.

[0121] Those skilled in the art can understand that all or part of the processes in the above-mentioned embodiment methods can be completed by instructing the relevant hardware through a computer program, and the program can be stored in a non-volatile computer readable storage medium. When the program is executed, it can include the processes of the above-mentioned embodiment methods. Any reference to memory, storage, database or other medium used in the embodiments provided in the present application can include non-volatile and / or volatile memory. Non-volatile memory can include read-only memory (ROM), programmable ROM (PROM), electrically programmable ROM (EPROM), electrically erasable programmable ROM (EEPROM) or flash memory. Volatile memory can include random access memory (RAM) or external cache memory. As an illustration but not limitation, RAM is available in various forms, such as static RAM (SRAM), dynamic RAM (DRAM), synchronous DRAM (SDRAM), double data rate SDRAM (DDR SDRAM), enhanced SDRAM (ESDRAM), synchronous link (Synchlink) DRAM (SLDRAM), memory bus (Rambus) direct RAM (RDRAM), direct memory bus dynamic RAM (DRDRAM), and memory bus dynamic RAM (RDRAM), etc.

[0122] The technical features of the above embodiments can be combined in any way. In order to make the description simple, not all possible combinations of the technical features in the above embodiments are described, but as long as the combinations of the technical features do not exist, they should be considered as the scope of the present application.

[0123] The above embodiments only express several implementation manners of the present application, and the description is specific and detailed, but it should not be understood as a limitation on the scope of the patent of the present application. It should be pointed out that for ordinary skilled in the art, without departing from the concept of the present application, a number of modifications and improvements can be made, which are all within the protection scope of the present application. Therefore, the protection scope of the patent of the present application should be subject to the appended claims.

Claims

1. A method for classifying white blood cells, characterized in that, The method includes: The pulse signal sets of the white blood cell sample to be classified are obtained at low-angle and medium-angle scattering angles. The signal intensity of each pulse signal in the pulse signal set is identified, and a scatter plot of signal intensity containing multiple discrete points is constructed based on the signal intensity. The white blood cell sample to be classified includes neutrophils, monocytes and lymphocytes, and each discrete point indicates the signal intensity of a white blood cell at different scattering angles. The overall particle distribution of the signal intensity scatter plot at the mid-angle scattering angle is statistically analyzed, and the signal intensity scatter plot is divided into a first region scatter plot and a second region scatter plot based on the rate of change of the number of particles in the overall particle distribution; wherein, the particle distribution is used to indicate the number of blood cell particles with different signal intensities, and the signal intensity of the first region scatter plot at the mid-angle scattering angle is greater than that of the second region scatter plot at the mid-angle scattering angle; The distribution of particles in the first local area at a low scattering angle and the distribution of particles in the second local area at a medium scattering angle are statistically analyzed, and the first coordinate center point of the neutrophil is determined based on the rate of change of the number of particles in the first local particle distribution and the second local particle distribution. The distribution of particles in the second region is statistically analyzed at the third local scattering angle and the fourth local scattering angle. Based on the particle number change rates of the third and fourth local particle distributions, the second coordinate center point of the monocyte and the third coordinate center point of the lymphocyte are determined. The signal intensity of the second coordinate center point at the low scattering angle is greater than that of the third coordinate center point at the low scattering angle. Clustering operations are performed on the first coordinate center point, the second coordinate center point, and the third coordinate center point in the signal intensity scatter plot. The discrete points in the first cluster to which the first coordinate center point belongs are taken as neutrophil discrete points, the discrete points in the second cluster to which the second coordinate center point belongs are taken as monocyte discrete points, and the discrete points in the third cluster to which the third coordinate center point belongs are taken as lymphocyte discrete points.

2. The method according to claim 1, characterized in that, The rate of change of the number of particles based on the overall particle distribution divides the signal intensity scatter plot into a first region scatter plot and a second region scatter plot, including: Calculate the rate of change of the number of particles for each type of signal intensity in the overall particle distribution to obtain the overall rate of change. Search for rising zero-crossing points in the overall rate of change, and determine the first critical signal intensity corresponding to the local minimum of the particle number in the particle distribution based on the searched rising zero-crossing points. In the signal strength scatter plot, the region with signal strength greater than or equal to the first critical signal strength at the mid-angle scattering angle is divided into the first region scatter plot, and the region with signal strength less than the first critical signal strength at the mid-angle scattering angle is divided into the second region scatter plot.

3. The method according to claim 1, characterized in that, The determination of the first coordinate center point of the neutrophil based on the rate of change of the particle number according to the first local particle distribution and the second local particle distribution includes: The rate of change of the number of particles for each type of signal intensity is calculated in the first local particle distribution and the second local particle distribution respectively, so as to obtain the first rate of change at the low angle scattering angle and the second rate of change at the medium angle scattering angle. The zero-crossing point of the drop is searched in the first change rate case and the second change rate case respectively. Based on the searched zero-crossing point of the drop, the second critical signal intensity corresponding to the local maximum of the particle number is determined in the first local particle distribution case, and the third critical signal intensity corresponding to the local maximum of the particle number is determined in the second local particle distribution case. The second critical signal intensity and the third critical signal intensity are combined to obtain the first coordinate center point.

4. The method according to claim 1, characterized in that, The determination of the second coordinate center point of the monocyte and the third coordinate center point of the lymphocyte based on the particle number change rate of the third local particle distribution and the fourth local particle distribution includes: The rate of change of the number of particles for each type of signal intensity is calculated in the third local particle distribution and the fourth local particle distribution respectively, so as to obtain the third rate of change at the low angle scattering angle and the fourth rate of change at the medium angle scattering angle. The zero-crossing points of descent are searched in the third and fourth rate-of-change scenarios, respectively. Based on the searched zero-crossing points, the fourth and fifth critical signal intensities corresponding to the local maxima of the particle number in the third local particle distribution scenario are determined, and the sixth critical signal intensity corresponding to the local maxima of the particle number in the fourth local particle distribution scenario is determined; wherein the fourth critical signal intensity is greater than the fifth critical signal intensity. The fourth critical signal intensity and the sixth critical signal intensity are combined to obtain the second coordinate center point, and the fifth critical signal intensity and the sixth critical signal intensity are combined to obtain the third coordinate center point.

5. The method according to any one of claims 2-4, characterized in that, The formula for calculating the rate of change of the particle number is: In the above formula, The rate of change of the particle number indicating the intensity of the i-th type of signal. The number of blood cell particles indicating the intensity of the (i+1)th type of signal. N indicates the number of blood cell particles representing the intensity of signal i, and N indicates the total number of signal classes.

6. The method according to claim 1, characterized in that, The clustering operation includes: Calculate the distance between the target coordinate center point and each discrete point in the signal strength scatter plot, and determine the discrete points whose distance is less than a preset distance threshold as candidate discrete points of the target coordinate center point; wherein, the target coordinate center point is any one of the first coordinate center point, the second coordinate center point, and the third coordinate center point; If the number of determined candidate discrete points is greater than a preset threshold, then the target coordinate center point and the determined candidate discrete points are treated as a cluster.

7. The method according to claim 1, characterized in that, The white blood cell sample to be classified also contains eosinophils, and the method further includes: Within the signal intensity scatter plot, discrete points that satisfy the eosinophil condition are designated as eosinophil discrete points; wherein, the eosinophil condition is that the discrete points are not classified as neutrophil discrete points, monocyte discrete points, or lymphocyte discrete points, and the signal intensity at the mid-angle scattering angle is within a preset distribution range.

8. A white blood cell classification device, characterized in that, The device includes: The scatter plot construction module is used to obtain the pulse signal set of the white blood cell sample to be classified at low-angle and medium-angle scattering angles, identify the signal intensity of each pulse signal in the pulse signal set, and construct a signal intensity scatter plot containing multiple discrete points based on the signal intensity; wherein, the white blood cell sample to be classified includes neutrophils, monocytes and lymphocytes, and each discrete point indicates the signal intensity of a white blood cell at different scattering angles; The center point determination module is used to statistically analyze the overall particle distribution of the signal intensity scatter plot at the mid-angle scattering angle, and divide the signal intensity scatter plot into a first region scatter plot and a second region scatter plot based on the rate of change of the number of particles in the overall particle distribution; wherein, the particle distribution is used to indicate the number of blood cell particles with different signal intensities, and the signal intensity of the first region scatter plot at the mid-angle scattering angle is greater than that of the second region scatter plot at the mid-angle scattering angle; and to statistically analyze the first local particle distribution of the first region scatter plot at the low-angle scattering angle and the second local particle distribution at the mid-angle scattering angle, and based on the... The first coordinate center point of the neutrophils is determined by the rate of change of the particle number in the first local particle distribution and the second local particle distribution; and the third local particle distribution in the second region is statistically analyzed at the low-angle scattering angle and the fourth local particle distribution at the medium-angle scattering angle, and the second coordinate center point of the monocytes and the third coordinate center point of the lymphocytes are determined based on the rate of change of the particle number in the third local particle distribution and the fourth local particle distribution; wherein the signal intensity of the second coordinate center point at the low-angle scattering angle is greater than the signal intensity of the third coordinate center point at the low-angle scattering angle; The classification module is used to perform clustering operations on the first coordinate center point, the second coordinate center point, and the third coordinate center point respectively in the signal intensity scatter plot, and to take the discrete points in the first cluster to which the first coordinate center point belongs as neutrophil discrete points, the discrete points in the second cluster to which the second coordinate center point belongs as monocyte discrete points, and the discrete points in the third cluster to which the third coordinate center point belongs as lymphocyte discrete points.

9. A computer-readable storage medium, characterized in that, The device stores a computer program that, when executed by a processor, causes the processor to perform the steps of the method as described in any one of claims 1 to 7.

10. A white blood cell classification device, characterized in that, It includes a memory and a processor, the memory storing a computer program that, when executed by the processor, causes the processor to perform the steps of the method as described in any one of claims 1 to 7.

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