Sample analyzer and method for determining a shortage of fluorescent reagent

Abstract

The application provides a method for determining insufficient amount of fluorescent reagent, comprising the following steps: continuously detecting a plurality of to-be-detected samples, obtaining at least scattering light signal intensity and fluorescent signal intensity of blood cells in each to-be-detected sample to form a scatter plot composed of at least scattering light signal and fluorescent signal, wherein each scatter plot corresponds to a to-be-detected sample; obtaining distribution information of blood cells of each to-be-detected sample in a preset position of the scatter plot in the fluorescent signal dimension to obtain to-be-detected sample fluorescent signal intensity distribution information; and determining insufficient amount of fluorescent reagent when the to-be-detected sample fluorescent signal intensity distribution information of the plurality of to-be-detected samples meets a preset condition of insufficient amount of fluorescent reagent. The application also provides a sample analyzer. The application can automatically identify insufficient amount of fluorescent reagent.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of sample analysis, in particular to a sample analyzer and a method for judging insufficient amount of fluorescent reagent. BACKGROUND

[0002] Blood cell analyzers count various cells in blood, and nucleic acid fluorescent staining is a commonly used method, and abnormal cells can be accurately identified. The implementation principle of this technology is to stain the nucleic acid substances in cells with fluorescent dyes, then irradiate with laser, collect the fluorescent signals generated by the cells, and combine other light signals to accurately detect various cells. When the fluorescent dye reagent required for measuring the sample is insufficient, the generated fluorescent signal is weak, and the fluorescent signal cannot be used to count the cells. At this time, the reported cell count result is inaccurate, and a method for detecting insufficient fluorescent dye reagent is needed. The industry detects whether the fluorescent dye reagent is present or not by detecting the fluorescent dye liquid level with a sensor to determine the amount of fluorescent dye. This method requires hardware support, and the hardware principle is complex, bulky, and because many components are required, once a component fails, the entire detection device will not work. The sensor detection is affected by many interference factors, such as the most common air bubble interference, which will misjudge the insufficient fluorescent reagent when there is an air bubble. Therefore, a simple, fast and effective method is needed to detect the amount of fluorescent dye in real time and to tell the detection personnel the status of the fluorescent reagent. SUMMARY

[0003] The embodiments of the present application disclose a method for judging insufficient amount of fluorescent reagent of a sample analyzer to solve the problem.

[0004] The method for judging insufficient amount of fluorescent reagent disclosed by the embodiments of the present application comprises the following steps:

[0005] A plurality of to-be-detected samples are continuously detected, and at least scattering light signal intensity and fluorescent signal intensity of blood cells in each to-be-detected sample are acquired to form a scatter plot composed of at least scattering light signal and fluorescent signal, wherein each scatter plot corresponds to a to-be-detected sample.

[0006] Distribution information of blood cells of each to-be-detected sample in the fluorescent signal dimension in a preset position of the scatter plot is acquired to obtain to-be-detected sample fluorescent signal intensity distribution information.

[0007] When the to-be-detected sample fluorescent signal intensity distribution information of the plurality of to-be-detected samples continuously meets a preset condition of insufficient amount of fluorescent reagent, it is determined that the amount of fluorescent reagent is insufficient.

[0008] The method for judging insufficient amount of fluorescent reagent disclosed by the embodiments of the present application comprises the following steps:

[0009] continuously detecting a plurality of samples, and obtaining at least fluorescence signal intensity of all blood cells in each of the samples;

[0010] obtaining fluorescence signal intensity distribution information of all blood cells in each of the samples to obtain sample fluorescence signal intensity distribution information;

[0011] when the sample fluorescence signal intensity distribution information of the plurality of samples continuously meets a preset condition of insufficient fluorescence reagent, determining that the fluorescence reagent is insufficient.

[0012] The embodiment of the present application further provides a sample analyzer which detects a plurality of samples in sequence, and comprises:

[0013] a sampling device configured to suck the samples and to inject each of the samples;

[0014] a reagent providing device configured to provide reaction reagents required by detection items of the samples, wherein the reaction reagents comprise fluorescence reagents;

[0015] a reaction container configured to receive the samples injected by the sampling device and to receive the reaction reagents provided by the reagent providing device, so that the samples and the reaction reagents are mixed to obtain mixed samples;

[0016] an optical detection device configured to irradiate the mixed samples to detect fluorescence signals and scattering signals of each blood cell in the samples;

[0017] a control device configured to:

[0018] continuously detecting a plurality of samples, and obtaining at least fluorescence signal intensity and scattering signal intensity of blood cells in each of the samples to form a scatter plot composed of at least the fluorescence signal and the scattering signal, wherein each of the scatter plots corresponds to one of the samples;

[0019] obtaining distribution information of blood cells in a preset position of the scatter plot in the fluorescence signal dimension to obtain sample fluorescence signal intensity distribution information;

[0020] when the sample fluorescence signal intensity distribution information of the plurality of samples continuously meets a preset condition of insufficient fluorescence reagent, determining that the fluorescence reagent is insufficient.

[0021] The embodiment of the present application further provides a sample analyzer which detects a plurality of samples in sequence, and comprises:

[0022] a sampling device configured to suck the samples and to inject each of the samples;

[0023] a reagent providing device configured to provide a reaction reagent required for the detection item of the sample to be tested, the reaction reagent including a fluorescent reagent;

[0024] a reaction container configured to receive the sample to be tested dispensed by the sampling device and receive the reaction reagent provided by the reagent providing device, so that the sample to be tested and the reaction reagent are mixed to obtain a mixed sample;

[0025] an optical detection device configured to irradiate the mixed sample to detect a fluorescent signal and a scattering signal of each blood cell in the sample to be tested;

[0026] a control device configured to:

[0027] continuously detect a plurality of samples to be tested, and obtain at least a fluorescent signal intensity of all blood cells in each sample to be tested;

[0028] obtain distribution information of the fluorescent signal intensity of all blood cells in each sample to be tested to obtain fluorescent signal intensity distribution information of the sample to be tested;

[0029] when the fluorescent signal intensity distribution information of the plurality of samples to be tested all satisfy a preset condition of insufficient fluorescent reagent, it is determined that the fluorescent reagent is insufficient.

[0030] The application also provides a computer readable storage medium applied to a sample analyzer, and the computer readable storage medium stores a computer program which, when executed by a processor, implements the steps of the method for judging insufficient fluorescent reagent.

[0031] The sample analyzer and the method for judging insufficient fluorescent reagent of the application continuously detect a plurality of samples to be tested, obtain a scattering light signal intensity and a fluorescent signal intensity of blood cells in each sample to be tested to form a scatter plot composed of at least a scattering light signal and a fluorescent signal, obtain distribution information of blood cells in a preset position of the scatter plot in the fluorescent signal dimension of each sample to be tested to obtain fluorescent signal intensity distribution information of the sample to be tested, and when the fluorescent signal intensity distribution information of the plurality of samples to be tested all satisfy a preset condition of insufficient fluorescent reagent, it is determined that the fluorescent reagent is insufficient. Thus, without increasing hardware, automatic detection of insufficient fluorescent reagent is realized in the form of software. BRIEF DESCRIPTION OF DRAWINGS

[0032] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following will briefly introduce the drawings needed to be used in the embodiments. Obviously, the drawings described in the following embodiments are only some embodiments of the present application, and for those skilled in the art, other drawings can be obtained from these drawings without creative labor.

[0033] Figure 1 The structure schematic diagram of the sample analyzer in an embodiment of the present application.

[0034] Figure 2 The module schematic diagram of the optical detection device in an embodiment of the present application.

[0035] Figure 3 The module schematic diagram of the control device in an embodiment of the present application.

[0036] Figures 4a-4e The schematic diagram of the change trend of the scatter plot when the fluorescent reagent is insufficient in an embodiment of the present application.

[0037] Figure 5 The schematic diagram of the change trend of the fluorescence signal intensity distribution characteristic value of the preset position of the scatter plot in an embodiment of the present application.

[0038] Figure 6 The schematic diagram of the preset threshold of the fluorescence signal intensity distribution characteristic value in an embodiment of the present application.

[0039] Figures 7a-7f The schematic diagram of the change trend of the scatter plot of the normal sample and the abnormal sample in an embodiment of the present application.

[0040] Figure 8 The flow schematic diagram of the judgment method of the fluorescent reagent being insufficient in an embodiment of the present application.

[0041] Figure 9 The flow schematic diagram of the judgment method of the fluorescent reagent being insufficient in another embodiment of the present application. DETAILED DESCRIPTION

[0042] The technical solutions in the embodiments of the present application will be described clearly and completely in the following with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only some embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all the other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present application.

[0043] Throughout the specification, unless otherwise specifically indicated otherwise, the terms used herein are to be understood in the manner as commonly used in the art. Thus, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. If there is a conflict between the present specification and the patent specification, the present specification takes precedence.

[0044] It should be noted that, in the embodiments of the present application, the terms "comprising", "containing" or any other variants thereof are intended to cover non-exclusive inclusion, so that a method or device comprising a series of elements not only includes the elements explicitly listed, but also includes other elements not explicitly listed, or further includes elements inherent in the implementation of the method or device. Without more limitations, the element defined by the sentence "comprising a" does not exclude the presence of other related elements (such as steps in the method or units in the device, where the unit can be a part of circuit, a part of processor, a part of program or software, etc.) in the method or device comprising the element.

[0045] It should be noted that the terms "first", "second", "third" involved in the embodiments of the present application are only to distinguish similar objects, and do not represent a specific order of the objects. Understandably, "first", "second", "third" can be interchanged in a specific order or sequence as allowed. It should be understood that the objects distinguished by "first", "second", "third" can be interchanged under appropriate circumstances, so that the embodiments of the present application described herein can be implemented in an order other than those illustrated or described herein.

[0046] The embodiments of the present application first propose a sample analyzer. As shown in Figure 1 The sample analyzer 100 at least includes a sampling device 110, a reagent providing device 120, a reaction container (not shown in the figure), an optical detection device 130 and a control device 140.

[0047] The sampling device 110 is configured to aspirate the samples to be tested and to perform dispensing of each of the samples to be tested; in the embodiments, the samples to be tested are blood samples. It can be understood that in other embodiments, the samples to be tested can be other samples, which are not limited herein.

[0048] Specifically, the sampling device 110 has a pipette (e.g. a sampling needle) with a pipette nozzle and has a driving part for driving the pipette to quantitatively aspirate the samples to be tested through the pipette nozzle, for example, the sampling needle moves under the driving of the driving part to aspirate the samples to be tested from a sample container containing the samples to be tested.

[0049] The reagent providing device 120 is configured to provide the reaction reagents required for the detection items of the sample to be tested, which include fluorescent reagents. In some embodiments, the reagent providing device includes a first reagent supply part for supplying a white blood cell reagent, which includes, for example, a hemolytic agent capable of dissolving red blood cells in the sample to be tested and capable of distinguishing different types of white blood cells, and optionally includes a fluorescent reagent capable of staining white blood cells. In some embodiments, the reagent providing device includes a second reagent supply part for supplying a red blood cell reagent, which is, for example, a diluent. In other embodiments, the reagent providing device includes a third reagent supply part for supplying a hemoglobin reagent, which is, for example, a hemolytic agent capable of dissolving red blood cells in the sample to be tested, releasing hemoglobin in the red blood cells, and converting the hemoglobin into methemoglobin. In some embodiments, the white blood cell reagent and the hemoglobin reagent are the same hemolytic agent, i.e., the first reagent supply part and the third reagent supply part are the same reagent supply part.

[0050] The reaction container is configured to receive the sample to be tested dispensed by the sampling device and to receive the reaction reagents provided by the reagent providing device, so that the sample to be tested is mixed with the reaction reagents to obtain a mixed sample.

[0051] The optical detection device 140 is configured to illuminate the mixed sample to detect the fluorescence signal and the scattering light signal of each blood cell in the sample to be tested; it can be understood that the scattering light signal includes a forward scattering signal or a side scattering signal. The optical detection part 140 has a light source 1311, a beam shaping assembly 1312, a flow chamber 1313, and a forward scattering light detector 1314 arranged in sequence on a straight line. On one side of the flow chamber 1313, a dichroic mirror 1316 is arranged at an angle of 45° to the straight line. The side light emitted by the blood cells in the flow chamber 1313, a part of which transmits through the dichroic mirror 1316 and is captured by a fluorescence detector 1315 arranged behind the dichroic mirror 1316 at an angle of 45° to the dichroic mirror 1316, and the other part of the side light is reflected by the dichroic mirror 1316 and captured by a side scattering light detector 1317 arranged in front of the dichroic mirror 1316 at an angle of 45° to the dichroic mirror 1316. According to the forward scattering light signal captured by the forward scattering light detector 1314, the side scattering light signal captured by the side scattering light detector 1317, and the fluorescence signal captured by the fluorescence detector 1315, the white blood cells in the sample to be tested can be counted and classified, for example, the white blood cells can be classified into at least neutrophils, lymphocytes, and monocytes, and optionally further detect platelet parameters in the sample to be tested, for example, obtain the number of platelets.

[0052] In some embodiments, as Figure 3As shown, the control device 150 at least includes a processing component 151, a RAM 152, a ROM 153, a communication interface 154, a storage 156 and an I / O interface 155. The processing component 151, the RAM 152, the ROM 153, the communication interface 154, the storage 156 and the I / O interface 155 communicate through a bus 157. The processing component can be a CPU, a GPU or other chip with computing capability. The storage 156 stores various computer programs and data required for executing the computer programs, such as operating systems and application programs, for the processing component 151 to execute. In addition, data required to be stored locally during the analysis of the samples under test can also be stored in the storage 156. The I / O interface 155 is composed of serial interfaces such as USB, IEEE 1394 or RS-232C, parallel interfaces such as SCSI, IDE or IEEE 1284, and analog signal interfaces composed of D / A converters and A / D converters. The I / O interface 155 is connected with input devices composed of a keyboard, a mouse, a touch screen or other control buttons, and a user can input data directly to the control device 150 through the input devices. In addition, the I / O interface 155 can also be connected with display devices with display functions, such as liquid crystal screens, touch screens, LED display screens, etc. The control device 150 can output processed data in the form of image display data to the display devices for display, such as analysis data, instrument operating parameters, etc. The communication interface 154 can be an interface of any communication protocol known at present. The communication interface 154 communicates with the outside through a network. The control device 150 can transmit data between any device connected through the network through the communication interface 154 in a certain communication protocol.

[0053] The control device 150 is configured to:

[0054] continuously detect a plurality of samples under test, and obtain at least a scattering light signal intensity and a fluorescence signal intensity of blood cells of each sample under test to form a scatter plot composed of at least the scattering light signal and the fluorescence signal, wherein each scatter plot corresponds to a sample under test;

[0055] obtain distribution information of blood cells of each sample under test in a preset position of the scatter plot in the fluorescence signal dimension to obtain fluorescence signal intensity distribution information of the sample under test;

[0056] when the fluorescence signal intensity distribution information of a plurality of samples under test all satisfy a preset condition of insufficient amount of fluorescence reagent, it is determined that the amount of fluorescence reagent is insufficient.

[0057] Therefore, in the present application, a plurality of to-be-tested samples are continuously detected, the scattering light signal intensity and the fluorescence signal intensity of blood cells in each of the to-be-tested samples are acquired to form a scatter plot composed of at least the scattering light signal and the fluorescence signal, the distribution information of blood cells in each of the to-be-tested samples in the fluorescence signal dimension in a preset position of the scatter plot is acquired to obtain fluorescence signal intensity distribution information of the to-be-tested sample, and when the fluorescence signal intensity distribution information of the to-be-tested samples in the plurality of to-be-tested samples all meet the preset condition of insufficient fluorescence reagent amount, it is determined that the fluorescence reagent amount is insufficient. Therefore, without increasing hardware, automatic detection of insufficient fluorescence reagent amount is realized in the form of software, and detection cost is reduced.

[0058] Specifically, in one of the embodiments, the fluorescence signal intensity distribution information includes fluorescence signal intensity distribution characteristic values, and the fluorescence signal intensity distribution characteristic values include at least one of a mean value of the fluorescence signal intensity of blood cells in the to-be-tested sample in the preset position of the scatter plot, a median value of the fluorescence signal intensity, a mode value of the fluorescence signal intensity, a maximum value of the fluorescence signal intensity, and a minimum value of the fluorescence signal intensity.

[0059] The mean value of the fluorescence signal intensity of blood cells in the preset position of the scatter plot refers to the mean value of the fluorescence signal intensity of all particles in the preset position region of the scatter plot. The median value of the fluorescence signal intensity of blood cells in the preset position of the scatter plot refers to the value in the middle of the fluorescence signal intensity values of blood cells in the preset position of the scatter plot after the fluorescence signal intensity values are sorted in order from high to low. The mode value of the fluorescence signal intensity of blood cells in the preset position of the scatter plot refers to the value with the highest frequency among the fluorescence signal intensity values of blood cells in the preset position of the scatter plot. The maximum value of the fluorescence signal intensity of blood cells in the preset position of the scatter plot refers to the maximum value of the fluorescence signal intensity values of blood cells in the preset position of the scatter plot. The minimum value of the fluorescence signal intensity of blood cells in the preset position of the scatter plot refers to the minimum value of the fluorescence signal intensity values of blood cells in the preset position of the scatter plot.

[0060] It can be understood that the fluorescence signal intensity distribution information can also be a fluorescence signal intensity distribution graph, and the preset condition of insufficient fluorescence reagent amount is used to determine whether the fluorescence reagent amount is insufficient by image comparison.

[0061] Further, in one of the embodiments, the control device 150 is configured to: when the fluorescence signal intensity distribution characteristic values of blood cells in the preset position of the scatter plot in the plurality of to-be-tested samples are lower than a preset threshold value and the fluorescence signal intensity distribution characteristic values of blood cells in the preset position of the scatter plot in the plurality of to-be-tested samples present a downward trend in the detection order of the plurality of to-be-tested samples, it is determined that the fluorescence reagent amount is insufficient. For example, reference can be made to Figures 4a-4eThe scatter plot is obtained with the scattering light signal SS as the horizontal coordinate and the fluorescence signal FL as the vertical coordinate. It can be understood that in other embodiments, the scatter plot can be obtained with the fluorescence signal FL as the horizontal coordinate and the scattering light signal as the vertical coordinate, which is not limited herein. The preset position is a position of one or more particle groups in the scatter plot of the sample to be detected. Figure 4a In the embodiment, the fluorescence signal intensity distribution characteristic value of the particle group at the preset position of the scatter plot is greater than or equal to the preset threshold value, and it is determined that the fluorescence reagent amount is normal. However, in the embodiment, the fluorescence signal intensity distribution characteristic value of the particle group at the preset position of the scatter plot is less than the preset threshold value and shows a downward trend in the detection order of the plurality of samples to be detected, and it is determined that the fluorescence reagent amount is insufficient. Figures 4b-4e

[0062] Therefore, according to the comparison result of the fluorescence signal intensity distribution characteristic value of the blood cells at the preset position of the scatter plot in the continuous plurality of samples to be detected and the preset threshold value, and the fluctuation trend of the fluorescence signal intensity distribution characteristic value of the plurality of samples to be detected at the preset position of the scatter plot in the detection order of the continuous plurality of samples to be detected, it can be accurately determined whether the fluorescence reagent amount is sufficient, the judgment process is simple, and the detection cost can be reduced.

[0063] Further, in one of the embodiments, the preset threshold value is a preset empirical value or a fixed threshold value, for example, a threshold value range as shown in Figure 5

[0064] Further, in one of the embodiments, please refer to Figure 6 Considering the difference in circuit gain of different instruments, the detected signal has a deviation, in order to adapt to such difference, the preset threshold value is a dynamic threshold value, and the control device 150 is configured to determine the dynamic threshold value, including:

[0065] determining a preset number of samples to be detected before the current sample to be detected in the detection order, and obtaining the fluorescence signal intensity distribution characteristic value of the blood cells at the preset position of the scatter plot of the preset number of samples to be detected;

[0066] averaging the sum of the fluorescence signal intensity distribution characteristic values of the blood cells at the preset position of the scatter plot of the preset number of samples to be detected to obtain a threshold center value;

[0067] calculating the standard deviation of the fluorescence signal intensity distribution information of the blood cells at the preset position of the scatter plot of the preset number of samples to be detected before the current sample to be detected in the detection order;

[0068] The dynamic threshold value is calculated according to the threshold center value and the standard deviation.

[0069] ​​Further, in one embodiment, the dynamic threshold is calculated according to the threshold center value and the standard deviation, including the dynamic threshold = threshold center value - k*standard deviation, k is a preset value set according to a required confidence interval.

[0070] Specifically, in the embodiment, the control device 150 is configured to:

[0071] The current sample to be tested is denoted as the ith sample, the upper limit of the fluorescence signal intensity distribution information of the ith sample is denoted as SflMean_Up(i), and the lower limit of the fluorescence signal intensity distribution information of the ith sample is denoted as SflMean_Down(i).

[0072] If the following conditions are met simultaneously:

[0073] 1. SFL_Mean(i+2) < K1*SFL_Mean_Down(i)

[0074] 2. SFL_Mean(i+1) < K1*SFL_Mean_Down(i)

[0075] 3. SFL_Mean(i) < K1*SFL_Mean_Down(i)

[0076] then the ith+2 sample to be tested is determined to be insufficient in fluorescence reagent, wherein K1 is less than 1.

[0077] Therefore, when the preset threshold is a dynamic threshold, the difference in circuit gain of different instruments can be adapted, the detection result is more accurate, and the detection cost is reduced.

[0078] Further, in one embodiment, the preset position of the scatter plot corresponds to a position of all blood cells in the scatter plot of the sample to be tested, and the control device 150 is configured to:

[0079] Obtain fluorescence signal intensity distribution information of all blood cells in the scatter plot of each of the plurality of samples to be tested.

[0080] Therefore, by obtaining the fluorescence signal intensity distribution information of all blood cells in the scatter plot of the plurality of samples to be tested, it is determined that the fluorescence signal intensity distribution information of the plurality of samples to be tested satisfies the preset condition of insufficient fluorescence reagent, and then it is determined whether the fluorescence reagent is sufficient, thereby reducing the detection cost.

[0081] Further, in another embodiment, please refer to Figures 4a-4e In the embodiment, the preset position is a position of one or more particle groups in the scatter plot of the sample to be tested. The control device 150 is configured to:

[0082] acquire the fluorescence signal intensity distribution information of the blood cells in one, two or more particle groups in the scatter plot of each of the plurality of samples to be measured. Figure 1

[0083] Thus, by acquiring the fluorescence signal intensity distribution information of the blood cells in one, two or more particle groups in the scatter plot of each of the plurality of samples to be measured, and determining whether the fluorescence signal intensity distribution information of the plurality of samples to be measured satisfies the preset condition of insufficient amount of fluorescence reagent, the amount of fluorescence reagent is determined to be sufficient or insufficient, thereby reducing the detection cost. For example, please refer to Figures 4a-4e Figure 5 When the characteristic value of the fluorescence signal intensity distribution of the particle group at the preset position of the scatter plot is lower than the preset threshold value and shows a downward trend in the detection order of the plurality of samples to be measured, it is determined that the amount of fluorescence reagent is insufficient. When the fluorescence signal intensity distribution information of the plurality of samples to be measured at the preset position of the scatter plot satisfies the preset condition of insufficient amount of fluorescence reagent, it is further determined that the amount of fluorescence reagent is insufficient, thereby reducing the detection cost.

[0084] Alternatively, in other embodiments, the preset position is a region enclosed by the respective partial regions of two or more adjacent particle groups in the scatter plot of the sample to be measured, or a region between two or more adjacent particle groups in the scatter plot of the sample to be measured. The control device 150 is configured to:

[0085] acquire the fluorescence signal intensity distribution information in the region enclosed by the respective partial regions of two or more adjacent particle groups in the scatter plot of the sample to be measured; or

[0086] acquire the fluorescence signal intensity distribution information of the blood cells in the region between two or more adjacent particle groups in the scatter plot of the sample to be measured.

[0087] acquire the fluorescence signal intensity distribution information in the region enclosed by the respective partial regions of two or more adjacent particle groups in the scatter plot of each of the plurality of samples to be measured, or acquire the fluorescence signal intensity distribution information of the blood cells in the region between two or more adjacent particle groups in the scatter plot of each of the plurality of samples to be measured, and determine whether the fluorescence signal intensity distribution information of the plurality of samples to be measured at the preset position of the scatter plot satisfies the preset condition of insufficient amount of fluorescence reagent, thereby determining whether the amount of fluorescence reagent is sufficient or insufficient, thereby reducing the detection cost.

[0088] ​​Further, in an embodiment, the particle groups can be one or more of lymphocyte particle groups, monocyte particle groups, neutrophil particle groups, eosinophil particle groups, basophil particle groups, and red blood cell particle groups.

[0089] Further, in an embodiment, the control device 150 is configured to: Figures 7a-7f

[0090] When the fluorescence signal intensity distribution information of the plurality of test samples all satisfy the preset condition of insufficient fluorescence reagent, before determining that the fluorescence reagent is insufficient, it is determined whether each test sample is a normal sample.

[0091] When the test sample is a normal sample, the fluorescence signal intensity distribution information of each test sample is compared with the preset condition of insufficient fluorescence reagent. It can be understood that, in an embodiment, the control device 150 is configured to:

[0092] When it is determined that the test sample is an abnormal sample, the test sample cannot be used as a sample for determining whether the fluorescence reagent is insufficient, i.e., the fluorescence signal intensity distribution information of the test sample is not compared with the preset condition of insufficient fluorescence reagent; or,

[0093] When it is determined that the test sample is an abnormal sample, the fluorescence signal intensity distribution information of the test sample is compared with the preset condition of insufficient fluorescence reagent, but does not participate in the alarm of insufficient fluorescence reagent.

[0094] Thus, the detection result of the abnormal sample is avoided to misjudge the insufficient fluorescence reagent.

[0095] Further, in an embodiment, for example, as shown in FIG. 6, the control device 150 is configured to: Figures 7a-7f

[0096] According to the acquired scattering light signal and fluorescence signal of the blood sample, it is determined whether the blood sample is abnormal.

[0097] Further, in an embodiment, the abnormality includes at least one of cell classification abnormality, cell count abnormality, and identification of abnormal cells.

[0098] ​​Specifically, in the sample analyzer, the sample to be tested is mixed with a hemolytic agent, the red blood cells in the blood cells are connected through the hemolytic agent, and the white blood cells are differentially processed, so that different types of cells have a certain degree of difference in volume and complexity; and after the sample to be tested is mixed with the hemolytic agent, the sample is also dyed with a fluorescent reagent, and the nucleic acid substances in the white blood cells are labeled with a fluorescent substance. Because the nucleic acid content of cells of different types, different maturity stages or abnormal development states is different, the amount of fluorescent dye labeling is also different, the size difference of the cell volume can be represented in the low-angle scattered light signal, the complexity difference of the internal particles of the cell can be represented in the high-angle scattered light signal, and the fluorescence signal intensity reflects the degree of cell staining. The DIFF channel realizes the differentiation of main cell subgroups (lymphocytes, monocytes, neutrophils, and eosinophils) by identifying the signal difference of the three-dimensional space of the actually processed cells, and identifies and alarms abnormal cells such as immature granulocytes, abnormal lymphocytes, and blast cells.

[0099] It can be understood that the judgment of the abnormal sample can also be determined by counting each type of cell to determine whether the current sample is a normal sample or an abnormal sample.

[0100] Therefore, by analyzing the abnormality of the cells, the abnormality of the cell counting, or the identification of the abnormal cells, it is determined whether the current sample to be tested is an abnormal sample, so as to avoid the misjudgment caused by the insufficient amount of fluorescent reagent in the detection result of the abnormal sample.

[0101] Further, in one embodiment, the control device 150 is configured to issue a warning when it is confirmed that the fluorescent reagent is insufficient.

[0102] It can be understood that the warning can be at least one of a voice warning, a light warning, and a text warning.

[0103] Therefore, the user can be informed in time of the insufficient amount of fluorescent reagent, so as to avoid the error detection caused by the insufficient amount of fluorescent reagent.

[0104] Alternatively, in other embodiments, the control device 150 is configured to

[0105] continuously detect a plurality of samples to be tested, and obtain at least the fluorescence signal intensity of all blood cells in each of the samples to be tested;

[0106] obtain the fluorescence signal intensity distribution information of all blood cells in each of the samples to be tested to obtain the fluorescence signal intensity distribution information of the sample to be tested;

[0107] compare the fluorescence signal intensity distribution information of the plurality of samples to be tested with the preset condition of insufficient amount of fluorescent reagent, respectively;

[0108] When the fluorescence signal intensity distribution information of the plurality of continuous test samples all satisfy the preset condition of insufficient fluorescence reagent amount, it is determined that the fluorescence reagent amount is insufficient.

[0109] Therefore, in the present application, a plurality of test samples are continuously detected, and the fluorescence signal intensity of blood cells in each test sample is acquired to obtain fluorescence signal intensity distribution information of the test sample. When the fluorescence signal intensity distribution information of the plurality of continuous test samples all satisfy the preset condition of insufficient fluorescence reagent amount, it is determined that the fluorescence reagent amount is insufficient. Thus, without increasing hardware, automatic detection of insufficient fluorescence reagent amount is realized in the form of software.

[0110] Specifically, in one embodiment, the fluorescence signal intensity distribution information includes fluorescence signal intensity distribution characteristic values, and the fluorescence signal intensity distribution characteristic values include at least one of mean value, median value, mode value, maximum value and minimum value of the fluorescence signal intensity of all blood cells in the test sample.

[0111] The mean value of the fluorescence signal intensity of all blood cells in the test sample is the mean value of the fluorescence signal intensity of all particles in the test sample. The median value of the fluorescence signal intensity of all blood cells in the test sample refers to the middle value of the fluorescence signal intensity values of all blood cells in the test sample in the order of high and low. The mode value of the fluorescence signal intensity of all blood cells in the test sample refers to the value with the highest frequency among the fluorescence signal intensity values of all blood cells in the test sample. The maximum value of the fluorescence signal intensity of all blood cells in the test sample refers to the maximum value of the fluorescence signal intensity values of all blood cells in the test sample. The minimum value of the fluorescence signal intensity of all blood cells in the test sample refers to the minimum value of the fluorescence signal intensity values of all blood cells in the test sample.

[0112] It can be understood that the fluorescence signal intensity distribution information can also be a fluorescence signal intensity distribution graph, and the preset condition of insufficient fluorescence reagent amount is used to determine whether the fluorescence reagent amount is insufficient by image comparison.

[0113] Further, in one embodiment, when the fluorescence signal intensity distribution information of the plurality of continuous test samples all satisfy the preset condition of insufficient fluorescence reagent amount, it is determined that the fluorescence reagent amount is insufficient, including:

[0114] When the fluorescence signal intensity distribution characteristic values of all blood cells in each of the plurality of continuous test samples are lower than a preset threshold value, and the fluorescence signal intensity distribution characteristic values of the plurality of continuous test samples present a downward trend in the detection order of the plurality of test samples, it is determined that the fluorescence reagent amount is insufficient.

[0115] Therefore, according to the comparison result of the characteristic value of the fluorescence signal intensity distribution of all blood cells in each of the plurality of to-be-tested samples with the preset threshold value, and the fluctuation trend of the characteristic value of the fluorescence signal intensity distribution of all blood cells in each of the plurality of to-be-tested samples in the continuous detection order, it can be determined whether the fluorescence reagent is sufficient, the judgment process is simple, and the detection cost can be reduced.

[0116] Further, in one embodiment, the preset threshold value is a preset empirical value or a fixed threshold value, for example, a threshold value range as shown in Figure 5 .

[0117] Further, in one embodiment, please refer to Figure 6 , considering the difference in circuit gain of different instruments, the detected signal has deviation, in order to adapt to such difference, the preset threshold value is a dynamic threshold value, that is, each to-be-tested sample corresponds to a dynamic threshold value, and the control device 150 is configured to determine the dynamic threshold value, including the steps of:

[0118] The preset threshold value is a dynamic threshold value; the determination method of the dynamic threshold value includes the steps of:

[0119] Determining a preset number of to-be-tested samples before the current to-be-tested sample in the detection order, and obtaining the characteristic value of the fluorescence signal intensity distribution of all blood cells of the preset number of to-be-tested samples;

[0120] According to the sum of the characteristic values of the fluorescence signal intensity distribution of all blood cells of the preset number of to-be-tested samples, a threshold center value is obtained by averaging;

[0121] The standard deviation of the fluorescence signal intensity distribution characteristic value of the preset number of to-be-tested samples before the current to-be-tested sample in the detection order is calculated;

[0122] The dynamic threshold value is calculated according to the threshold center value and the standard deviation.

[0123] Further, in one embodiment, the dynamic threshold value is calculated according to the threshold center value and the standard deviation, including the dynamic threshold value = threshold center value - k*standard deviation, k is a preset value set according to the required confidence interval.

[0124] Specifically, in the embodiment, the control device 150 is configured to:

[0125] The current to-be-tested sample is recorded as the ith sample, the upper limit of the fluorescence signal intensity distribution information of the ith sample is recorded as SflMean_Up(i), and the lower limit of the fluorescence signal intensity distribution information of the ith sample is recorded as SflMean_Down(i).

[0126] If the following conditions are met simultaneously:

[0127] 1. SFL_Mean(i+2) < K1 * SFL_Mean_Down(i)

[0128] 2. SFL_Mean(i+1) < K1 * SFL_Mean_Down(i)

[0129] 3. SFL_Mean(i) < K1 * SFL_Mean_Down(i)

[0130] then the (i+2)th sample under test is determined to be insufficient in fluorescent reagent, wherein K1 is less than 1.

[0131] Therefore, when the preset threshold is a dynamic threshold, the difference in circuit gain of different instruments can be adapted, the detection result is more accurate, and the detection cost is reduced.

[0132] Further, in one embodiment, before the step of determining that the fluorescent reagent is insufficient, the method further comprises the steps of:

[0133] determining whether each sample under test is a normal sample;

[0134] when each sample under test is a normal sample, comparing the sample under test fluorescence signal intensity distribution information of each sample under test with the preset condition of insufficient fluorescent reagent.

[0135] When each sample under test is a normal sample, the sample under test fluorescence signal intensity distribution information of each sample under test is compared with the preset condition of insufficient fluorescent reagent. In short, a normal sample is a sample from a healthy person who has not been sick.

[0136] It can be understood that, in one embodiment, the control device 150 is configured to:

[0137] when it is determined that the sample under test is an abnormal sample, the sample under test fluorescence signal intensity distribution information of the sample under test is not compared with the preset condition of insufficient fluorescent reagent; or,

[0138] when it is determined that the sample under test is an abnormal sample, the sample under test fluorescence signal intensity distribution information of the sample under test is compared with the preset condition of insufficient fluorescent reagent, but does not participate in the alarm of insufficient fluorescent reagent.

[0139] Thus, the detection result of the abnormal sample is avoided to misjudge the insufficient fluorescent reagent.

[0140] Further, in one of the embodiments, referring to Figures 7a-7f , the control device 150 is configured to:

[0141] According to the acquired scattering light signal and fluorescence signal of the blood sample, it is determined whether the blood sample is abnormal.

[0142] Further, in one of the embodiments, the abnormality includes at least one of cell classification abnormality, cell count abnormality, and identification of abnormal cells.

[0143] Specifically, in the sample analyzer, the sample to be tested is mixed with a hemolytic agent, the red blood cells in the blood cells are dissolved by the hemolytic agent, and the white blood cells are differentially processed, so that different types of cells have a certain degree of difference in volume and complexity; and after the sample to be tested is mixed with the hemolytic agent, a fluorescent reagent is also used for staining, and nucleic acid substances in the white blood cells are labeled by a fluorescent substance. Because the nucleic acid content of cells of different types, different maturity stages, or abnormal development states is different, the amount of fluorescent dye labeling is also different, and the size difference of cell volume can be represented in low-angle scattering light signal, and the complexity difference of cell internal particles can be represented in high-angle scattering light signal, and the fluorescence signal intensity reflects the degree of cell staining. The DIFF channel realizes the differentiation of main cell subgroups (lymphocytes, monocytes, neutrophils, and eosinophils) by identifying the signal difference of the three-dimensional space of the actually processed cells, and identifies and alarms abnormal cells such as immature granulocytes, abnormal lymphocytes, and blast cells.

[0144] It can be understood that the judgment of the abnormal sample can also be made by counting each type of cell to determine whether the current sample is a normal sample or an abnormal sample.

[0145] Thus, by identifying cell analysis abnormality, cell count abnormality, or identification of abnormal cells, it is determined whether the sample to be tested is an abnormal sample, thereby avoiding misjudgment of the detection result of the abnormal sample due to insufficient fluorescent reagent.

[0146] Further, in one of the embodiments, the control device 150 is configured to: when it is confirmed that the fluorescent reagent is insufficient, an alarm is issued.

[0147] It can be understood that the alarm can be at least one of a voice alarm, a light alarm, and a text alarm.

[0148] Thus, it is convenient for the user to know in time that the fluorescent reagent is insufficient, thereby avoiding false detection caused by insufficient fluorescent reagent.

[0149] Please refer to Figure 8 , Figure 8A flowchart of the method for determining the insufficient amount of fluorescent reagent in an embodiment of the present application. The steps of the method for determining the insufficient amount of fluorescent reagent can be adjusted according to actual needs, which are not limited herein. The method for determining the insufficient amount of fluorescent reagent comprises:

[0150] Step 81: continuously detecting a plurality of to-be-tested samples, and obtaining at least the scattering light signal intensity and the fluorescent signal intensity of blood cells in each to-be-tested sample to form a scatter plot composed of at least the scattering light signal and the fluorescent signal, wherein each scatter plot corresponds to a to-be-tested sample.

[0151] Step 82: obtaining the distribution information of blood cells in each to-be-tested sample in the fluorescent signal dimension in a preset position of the scatter plot to obtain the to-be-tested sample fluorescent signal intensity distribution information.

[0152] Step 83: comparing the to-be-tested sample fluorescent signal intensity distribution information of the continuous plurality of to-be-tested samples with the preset condition of the insufficient amount of fluorescent reagent respectively, determining whether the to-be-tested sample fluorescent signal intensity distribution information of the continuous plurality of to-be-tested samples meets the preset condition of the insufficient amount of fluorescent reagent, if yes, proceeding to step 84, otherwise, proceeding to step 85.

[0153] Step 84: determining that the amount of fluorescent reagent is insufficient.

[0154] Step 85: determining that the amount of fluorescent reagent is sufficient.

[0155] Thus, in the present application, a plurality of to-be-tested samples are continuously detected, and the scattering light signal intensity and the fluorescent signal intensity of blood cells in each to-be-tested sample are obtained to form a scatter plot composed of at least the scattering light signal and the fluorescent signal; the distribution information of blood cells in each to-be-tested sample in the fluorescent signal dimension in a preset position of the scatter plot is obtained to obtain the to-be-tested sample fluorescent signal intensity distribution information; and when the to-be-tested sample fluorescent signal intensity distribution information of the continuous plurality of to-be-tested samples meets the preset condition of the insufficient amount of fluorescent reagent, it is determined that the amount of fluorescent reagent is insufficient. Thus, without increasing hardware, the automatic detection of the insufficient amount of fluorescent reagent is displayed in the form of software.

[0156] It can be understood that the preset position of the scatter plot can be a part of the area or the whole area of the scatter plot, and when the preset position of the scatter plot is a part of the area of the scatter plot, the preset positions of the scatter plots of the continuous plurality of to-be-tested samples are the same corresponding area, so that the comparison of the fluorescent signal intensity distribution information of the scatter plot preset position is meaningful.

[0157] Further, in one embodiment, step 83 specifically comprises:

[0158] determining whether the characteristic value of the fluorescence signal intensity distribution of the blood cells located at the preset position of the scatter plot in the plurality of samples is lower than the preset threshold value and whether the characteristic values of the fluorescence signal intensity distribution of the blood cells located at the preset position of the scatter plot in the plurality of samples are in a downward trend according to the detection order of the plurality of samples, if so, entering step 84, otherwise, entering step 85.

[0159] Further, in one embodiment, the preset threshold value is a preset empirical value or a fixed threshold value, for example, a threshold value range as shown in Figures 4a-4e and Figure 5 .

[0160] Further, in one embodiment, please refer to Figures 7a-7f , considering the difference in circuit gain of different instruments, the detected signal has deviation, in order to adapt to such difference, the preset threshold value is a dynamic threshold value, the step of determining the dynamic threshold value by the control device 150 includes:

[0161] determining a preset number of samples before the current sample in the detection order, and obtaining the characteristic value of the fluorescence signal intensity distribution of the blood cells located at the preset position of the scatter plot of the preset number of samples;

[0162] obtaining the sum of the characteristic values of the fluorescence signal intensity distribution of the blood cells located at the preset position of the scatter plot of the preset number of samples, and then averaging to obtain a threshold center value;

[0163] calculating the standard deviation of the fluorescence signal intensity distribution information of the blood cells located at the preset position of the scatter plot of the preset number of samples before the current sample in the detection order;

[0164] the dynamic threshold value is calculated according to the threshold center value and the standard deviation.

[0165] Further, in one embodiment, the dynamic threshold value is calculated according to the threshold center value and the standard deviation, including the dynamic threshold value = threshold center value-k*standard deviation, k is a preset value set according to the required confidence interval.

[0166] Specifically, in the embodiment, the control device 150 is configured to:

[0167] the current sample is recorded as the ith sample, the upper limit of the fluorescence signal intensity distribution information of the ith sample is recorded as SflMean_Up(i), and the lower limit of the fluorescence signal intensity distribution information of the ith sample is recorded as SflMean_Down(i).

[0168] if the following conditions are met simultaneously:

[0169] SFL_Mean(i+2) < K1 * SFL_Mean_Down(i)

[0170] SFL_Mean(i+1) < K1 * SFL_Mean_Down(i)

[0171] SFL_Mean(i) < K1 * SFL_Mean_Down(i)

[0172] then the i+2th sample is determined to be insufficient in fluorescent reagent, wherein K1 is less than 1.

[0173] Therefore, when the preset threshold is a dynamic threshold, the difference in circuit gain of different instruments can be adapted, the detection result is more accurate, and the detection cost is reduced.

[0174] Specifically, in one embodiment, the preset position is the position of all blood cells in the scatter plot of the plurality of samples. The distribution information of the blood cells in the fluorescent signal dimension of each sample in the scatter plot of the preset position is obtained to obtain the fluorescent signal intensity distribution information of the sample, including:

[0175] The fluorescent signal intensity distribution information of all blood cells in the scatter plot of each sample in the plurality of samples is obtained.

[0176] Therefore, by obtaining the fluorescent signal intensity distribution information of all blood cells in the scatter plot of the plurality of samples, it is determined that the fluorescent signal intensity distribution information of the plurality of samples satisfies the preset condition of insufficient fluorescent reagent, and then it is determined whether the fluorescent reagent is sufficient, thereby reducing the detection cost.

[0177] Further, in another embodiment, please refer to Figures 4a-4e The distribution information of the blood cells in the fluorescent signal dimension of each sample in the scatter plot of the preset position is obtained to obtain the fluorescent signal intensity distribution information of the sample, including:

[0178] The fluorescent signal intensity distribution information of the blood cells in the scatter plot of each sample in the plurality of samples is obtained. Figure 1 one or more particle groups.

[0179] Therefore, by obtaining the fluorescent signal intensity distribution information of the plurality of samples, it is determined whether the fluorescent signal intensity distribution information of the plurality of samples satisfies the preset condition of insufficient fluorescent reagent, and then it is determined whether the fluorescent reagent is sufficient, thereby reducing the cost of detection of the fluorescent reagent. Please refer to Figure 5When the fluorescence signal intensity distribution information of the continuous multiple samples to be tested at the preset position of the scatter plot does not satisfy the preset condition of insufficient fluorescence reagent amount, it is further determined that the fluorescence reagent amount is sufficient; when the fluorescence signal intensity distribution information of the continuous multiple samples to be tested at the preset position of the scatter plot satisfies the preset condition of insufficient fluorescence reagent amount, it is further determined that the fluorescence reagent amount is insufficient, thereby reducing the detection cost.

[0180] Alternatively, in other embodiments, the preset position is a region enclosed by respective partial regions of the same two or more adjacent particle groups in the scatter plot of the multiple samples to be tested, or a region between the same two or more adjacent particle groups in the scatter plot of the multiple samples to be tested. The distribution information of blood cells in the fluorescence signal dimension of each sample to be tested at the preset position of the scatter plot is obtained to obtain the fluorescence signal intensity distribution information of the sample to be tested, including:

[0181] Obtaining the fluorescence signal intensity distribution information in the region enclosed by respective partial regions of the same two or more adjacent particle groups in the scatter plot of the multiple samples to be tested; or,

[0182] Obtaining the fluorescence signal intensity distribution information of blood cells in the region between the same two or more adjacent particle groups in the scatter plot of the multiple samples to be tested.

[0183] Therefore, by obtaining the fluorescence signal intensity distribution information in the region enclosed by respective partial regions of the same two or more adjacent particle groups in the scatter plot of the continuous multiple samples to be tested or the fluorescence signal intensity distribution information of blood cells in the region between the same two or more adjacent particle groups, it is determined whether the fluorescence signal intensity distribution information of the continuous multiple samples to be tested at the preset position of the scatter plot satisfies the preset condition of insufficient fluorescence reagent amount to determine whether the fluorescence reagent amount is sufficient, thereby reducing the detection cost.

[0184] Further, in one embodiment, the particle groups can be one or more of lymphocyte particle groups, monocyte particle groups, neutrophil particle groups, eosinophil particle groups, basophil particle groups, and red blood cell ion groups.

[0185] Further, in one embodiment, please refer to Figures 7a-7f Before comparing the fluorescence signal intensity distribution information of the continuous multiple samples to be tested with the preset condition of insufficient fluorescence reagent amount, the method further includes the step of:

[0186] Determining whether each sample to be tested is a normal sample;

[0187] When each of the to-be-tested samples is a normal sample, the to-be-tested sample fluorescence signal intensity distribution information of each to-be-tested sample is compared with the preset condition of insufficient fluorescence reagent respectively. The normal sample is briefly a sample from a healthy person without disease.

[0188] It can be understood that, in one embodiment, when it is determined that the to-be-tested sample is an abnormal sample, the to-be-tested sample fluorescence signal intensity distribution information of the continuous multiple to-be-tested samples is not compared with the preset condition of insufficient fluorescence reagent; or,

[0189] When it is determined that the to-be-tested sample is an abnormal sample, the to-be-tested sample fluorescence signal intensity distribution information of the continuous multiple to-be-tested samples is compared with the preset condition of insufficient fluorescence reagent respectively, but does not participate in the alarm of insufficient fluorescence reagent.

[0190] Thus, the detection result of the abnormal sample is avoided to cause a false judgment of insufficient fluorescence reagent.

[0191] Further, in one embodiment, whether each to-be-tested sample is a normal sample includes:

[0192] According to the acquired scattering light signal and fluorescence signal of the blood sample, whether the blood sample is abnormal is determined.

[0193] Further, in one embodiment, the abnormality includes at least one of cell classification abnormality, cell count abnormality, and identification of abnormal cells.

[0194] Specifically, in the sample analyzer, the to-be-tested sample is mixed with a hemolytic agent, the red blood cells in the blood cells are connected through the hemolytic agent, and the white blood cells are differentially processed, so that different types of cells have a certain degree of difference in volume and complexity; and after the to-be-tested sample is mixed with the hemolytic agent, the to-be-tested sample is also dyed with a fluorescence reagent, and nucleic acid substances in the white blood cells are labeled with a fluorescent substance. Because the nucleic acid content of cells of different types, different maturity stages, or abnormal development states is different, the amount of fluorescent dye labeling is also different, the size difference of cell volume can be represented in low-angle scattering light signal, the complexity difference of cell internal particles can be represented in high-angle scattering light signal, and the fluorescence signal intensity reflects the degree of cell dyeing. The DIFF channel realizes the differentiation of main cell subgroups (lymphocytes, monocytes, neutrophils, and eosinophils) by identifying the signal difference of the three-dimensional space of the actually processed cells, and identifies and alarms abnormal cells such as immature granulocytes, abnormal lymphocytes, and blast cells.

[0195] It can be understood that, the judgment of the abnormal sample can also be determined by counting each type of cell to determine whether the current sample is a normal sample or an abnormal sample.

[0196] Thus, by analyzing the cell, the cell count is abnormal, or the identification of abnormal cells is identified, it is determined whether the current sample to be tested is an abnormal sample, and the detection result of the abnormal sample is avoided to misjudge the insufficient amount of fluorescent reagent.

[0197] Further, in one embodiment, the method further comprises:

[0198] Step 86: When it is confirmed that the fluorescent reagent is insufficient, an alarm is issued.

[0199] It can be understood that the alarm can be at least one of a voice alarm, a light alarm, a text alarm, etc.

[0200] Thus, the user can be informed of the insufficient amount of fluorescent reagent in a timely manner, and the error detection caused by the insufficient amount of fluorescent reagent is avoided.

[0201] Please refer to Figure 9 , Figure 9 The flowchart of the method for judging the insufficient amount of fluorescent reagent in an embodiment of the present application. The steps of the method for judging the insufficient amount of fluorescent reagent can be adjusted according to actual needs, which are not limited herein. The method for judging the insufficient amount of fluorescent reagent comprises:

[0202] Step 91: Continuously detecting a plurality of samples to be tested, and obtaining at least the fluorescence signal intensity of all blood cells in each of the samples to be tested.

[0203] Step 92: Obtaining the fluorescence signal intensity distribution information of all blood cells in each of the samples to be tested to obtain the fluorescence signal intensity distribution information of the sample to be tested.

[0204] Step 93: Comparing the fluorescence signal intensity distribution information of the plurality of samples to be tested with the preset condition of the insufficient amount of fluorescent reagent, respectively, to determine whether the fluorescence signal intensity distribution information of the plurality of samples to be tested meets the preset condition of the insufficient amount of fluorescent reagent, if so, proceed to step 94, otherwise, proceed to step 95.

[0205] Step 94: Determine that the amount of fluorescent reagent is insufficient.

[0206] Step 95: Determine that the amount of fluorescent reagent is sufficient.

[0207] Thus, in the present application, a plurality of samples to be tested are continuously detected, and the fluorescence signal intensity of blood cells in each of the samples to be tested is obtained to obtain the fluorescence signal intensity distribution information of the sample to be tested; when the fluorescence signal intensity distribution information of the plurality of samples to be tested meets the preset condition of the insufficient amount of fluorescent reagent, it is determined that the amount of fluorescent reagent is insufficient. Thus, without increasing hardware, the automatic detection of the insufficient amount of fluorescent reagent is displayed in the form of software.

[0208] Further, in one embodiment, step 93 specifically comprises:

[0209] determining whether the characteristic value of the fluorescence signal intensity distribution of all blood cells in each of the plurality of samples is lower than a preset threshold value, and whether the characteristic value of the fluorescence signal intensity distribution of all blood cells in each of the plurality of samples is in a downward trend according to the detection order of the plurality of samples, if so, entering step 94, otherwise, entering step 95.

[0210] Further, in one embodiment, the preset threshold value is a preset empirical value or a fixed threshold value, for example, a threshold value range as shown in Figure 5 .

[0211] Further, in one embodiment, please refer to Figure 6 , considering the difference in circuit gain of different instruments, the detected signal has deviation, in order to adapt to such difference, the preset threshold value is a dynamic threshold value, the step of determining the dynamic threshold value by the control device 150 comprises:

[0212] determining a preset number of samples before the current sample in the detection order, and obtaining the fluorescence signal intensity distribution characteristic value of all blood cells in each of the preset number of samples;

[0213] averaging the sum of the fluorescence signal intensity distribution characteristic values of the preset number of samples to obtain a threshold center value;

[0214] calculating the standard deviation of the fluorescence signal intensity distribution information of all blood cells in the preset number of samples before the current sample in the detection order;

[0215] the dynamic threshold value is calculated according to the threshold center value and the standard deviation.

[0216] Further, in one embodiment, the dynamic threshold value is calculated according to the threshold center value and the standard deviation, including the dynamic threshold value = threshold center value-k*standard deviation, k is a preset value set according to the required confidence interval.

[0217] Specifically, in the present embodiment, the control device 150 is configured to:

[0218] the current sample is recorded as the ith sample, the upper limit of the fluorescence signal intensity distribution information of the ith sample is recorded as SflMean_Up(i), and the lower limit of the fluorescence signal intensity distribution information of the ith sample is recorded as SflMean_Down(i).

[0219] if the following conditions are met simultaneously:

[0220] SFL_Mean(i+2) < K1 * SFL_Mean_Down(i)

[0221] SFL_Mean(i+1) < K1 * SFL_Mean_Down(i)

[0222] SFL_Mean(i) < K1 * SFL_Mean_Down(i)

[0223] then the i+2th sample to be tested is determined as insufficient fluorescent reagent, wherein K1 is less than 1.

[0224] Therefore, when the preset threshold is a dynamic threshold, the difference in circuit gain of different instruments can be adapted, the detection result is more accurate, and the detection cost is reduced.

[0225] Further, in one embodiment, referring to Figures 7a-7f Before determining that the fluorescent reagent is insufficient when the distribution information of the fluorescence signal intensity of the sample to be tested of the plurality of samples to be tested successively meets the preset condition of insufficient fluorescent reagent, the method further comprises the step of:

[0226] determining whether each sample to be tested is a normal sample;

[0227] When each sample to be tested is a normal sample, the distribution information of the fluorescence signal intensity of each sample to be tested is compared with the preset condition of insufficient fluorescent reagent, respectively. In short, a normal sample is a sample from a healthy person who has not been sick.

[0228] It can be understood that, in one embodiment, when the sample to be tested is determined to be an abnormal sample, the distribution information of the fluorescence signal intensity of the sample to be tested is not compared with the preset condition of insufficient fluorescent reagent; or,

[0229] When the sample to be tested is determined to be an abnormal sample, the distribution information of the fluorescence signal intensity of the sample to be tested is compared with the preset condition of insufficient fluorescent reagent, respectively, but does not participate in the alarm of insufficient fluorescent reagent.

[0230] Therefore, the detection result of the abnormal sample is avoided to misjudge the insufficient fluorescent reagent.

[0231] Further, in one embodiment, determining whether the sample to be tested is a normal sample comprises:

[0232] According to the acquired scattering light signal and fluorescence signal of the blood sample, it is determined whether the blood sample is abnormal.

[0233] Further, in one of the embodiments, the abnormality includes at least one of a cell classification abnormality, a cell count abnormality, and identification of an abnormal cell.

[0234] It can be understood that the determination of the abnormal sample can also be determined by counting each type of cell to determine whether the current sample is a normal sample or an abnormal sample.

[0235] Therefore, by analyzing the cell analysis abnormality, the cell count abnormality, or the identification of the abnormal cell, it is determined whether the current sample to be tested is an abnormal sample, thereby avoiding the detection result of the abnormal sample from being misjudged due to insufficient amount of fluorescent reagent.

[0236] Further, in one of the embodiments, the method further includes:

[0237] Step 96: When it is confirmed that the fluorescent reagent is insufficient, an alarm is issued.

[0238] It can be understood that the alarm can be at least one of a voice alarm, a light alarm, and a text alarm.

[0239] Therefore, the user can be informed in time of the insufficient amount of fluorescent reagent, thereby avoiding the error detection caused by the insufficient amount of fluorescent reagent.

[0240] The present application also provides a computer readable storage medium applied to a sample analyzer, the computer readable storage medium storing a computer program, and the computer program is executed by a processor to realize the steps of the method for determining the insufficient amount of fluorescent reagent.

[0241] In the above embodiments, the description of each embodiment has its own focus, and the parts not described in detail in a certain embodiment can be referred to the related description of other embodiments.

[0242] The above describes the embodiments of the present application in detail, and the principle and embodiments of the present application are described by applying specific examples; the above description of the embodiments is only used to help understand the method and its core idea of the present application; at the same time, for those skilled in the art, according to the idea of the present application, the specific embodiments and application range will be changed; in conclusion, the content of the specification should not be understood as the limitation of the present application.

Claims

1. A method for determining insufficient residual amount of a fluorescent reagent, characterized in that: Applied to a sample analyzer, the method comprises: Continuously detecting a plurality of samples to be tested, obtaining at least a scattered light signal intensity and a fluorescent signal intensity for blood cells in each of the samples to be tested, to form a scatter plot consisting of at least the scattered light signal and the fluorescent signal, wherein each scatter plot corresponds to one of the samples to be tested; Obtaining the distribution information of the blood cells located in the preset position of the scatter plot of each of the samples to be tested in the dimension of the fluorescence signal to obtain the distribution information of the fluorescence signal intensity of the samples to be tested; When the sample fluorescence signal intensity distribution information of a plurality of consecutive samples to be tested all meets the preset condition of insufficient residual amount of the fluorescent reagent, it is determined that the residual amount of the fluorescent reagent is insufficient.

2. The method for determining insufficient residual amount of fluorescent reagent according to claim 1, wherein: The fluorescence signal intensity distribution information includes a fluorescence signal intensity distribution characteristic value, and the fluorescence signal intensity distribution characteristic value includes at least one of the following: The mean value of the fluorescence signal intensity of the blood cells located at a preset position in the scatter plot in the sample to be tested; The median value of the fluorescence signal intensity of the blood cells located at a preset position of the scatter plot in the sample to be tested; The mode value of the fluorescence signal intensity of the blood cells located at a preset position in the scatter plot in the sample to be tested; the maximum value of the fluorescence signal intensity of the blood cells located at a preset position in the scatter plot in the sample to be tested; The minimum value of the fluorescence signal intensity of the blood cells located at the preset position of the scatter plot in the sample to be tested.

3. The method for determining insufficient residual amount of fluorescent reagent according to claim 2, wherein: When the fluorescent signal intensity distribution information of the consecutive samples to be tested all meets the preset condition of insufficient residual amount of the fluorescent reagent, determining that the residual amount of the fluorescent reagent is insufficient includes: When the fluorescence signal intensity distribution characteristic value of the blood cells located at the preset position of the scatter plot in a plurality of consecutive samples to be tested is lower than a preset threshold value, and the fluorescence signal intensity distribution characteristic values ​​of the blood cells located at the preset position of the scatter plot in a plurality of consecutive samples to be tested show a downward trend in the detection order of the plurality of consecutive samples to be tested, it is determined that the remaining amount of the fluorescent reagent is insufficient; Alternatively, the fluorescence signal intensity distribution characteristic value includes: the average value of the fluorescence signal intensity of blood cells located at a preset position in the scatter plot in the sample to be tested; when the fluorescence signal intensity distribution information of a plurality of consecutive samples to be tested all meet the preset condition of insufficient fluorescent reagent remaining amount, determining that the fluorescent reagent remaining amount is insufficient includes: When the average fluorescence signal intensity of blood cells of a plurality of consecutive samples to be tested located at preset positions in the scatter plot is lower than a preset threshold, and the average fluorescence signal intensity of blood cells of a plurality of consecutive samples to be tested located at preset positions in the scatter plot shows a downward trend in the detection order of the plurality of consecutive samples to be tested, it is determined that the remaining amount of fluorescent reagent is insufficient.

4. The method for determining insufficient residual amount of fluorescent reagent according to claim 3, characterized in that: The preset threshold is a preset empirical value or a fixed threshold.

5. The method for determining insufficient residual amount of fluorescent reagent according to claim 3, characterized in that: The preset threshold is a dynamic threshold; the method for determining the dynamic threshold comprises the steps of: Determining a preset number of samples to be tested that precede the current sample to be tested in a testing order, and obtaining blood cell fluorescence signal intensity distribution characteristic values ​​of the preset number of samples to be tested located at preset positions in the scatter plot; A threshold center value is obtained by averaging the sum of the fluorescence signal intensity distribution characteristic values ​​of the preset number of samples to be tested at the preset positions of the scatter plot; Calculating the standard deviation of the fluorescence signal intensity distribution characteristic values ​​at the preset positions of the scatter plot of a preset number of samples that precede the current sample in the detection order; The dynamic threshold is calculated based on the threshold center value and the standard deviation.

6. The method for determining insufficient residual amount of fluorescent reagent according to claim 5, characterized in that: The dynamic threshold is calculated based on the threshold center value and the standard deviation, including: the dynamic threshold = threshold center value - k * standard deviation, where k is a preset value set according to the required confidence interval.

7. The method for determining insufficient residual amount of a fluorescent reagent according to any one of claims 1 to 6, characterized in that: The preset position of the scatter plot corresponds to the position of all blood cells in the scatter plot of the sample to be tested, and the distribution information of the blood cells located in the preset position of the scatter plot of each sample to be tested in the dimension of the fluorescence signal is obtained to obtain the fluorescence signal intensity distribution information of the sample to be tested, including: The fluorescence signal intensity distribution information of all blood cells in the scattergram of each of the plurality of samples to be tested is obtained.

8. The method for determining insufficient residual amount of a fluorescent reagent according to any one of claims 1 to 6, wherein: The preset position is the position of one, two or more particle clusters in the scatter plot of the sample to be tested, or the area enclosed by the respective partial areas of two or more adjacent particle clusters in the scatter plot of the sample to be tested, or the area between two or more adjacent particle clusters in the scatter plot of the sample to be tested; Obtaining the distribution information of the blood cells located in the preset position of the scatter plot of each of the samples to be tested in the dimension of the fluorescence signal to obtain the distribution information of the fluorescence signal intensity of the sample to be tested, including: Obtaining fluorescence signal intensity distribution information of blood cells in one, two or more particle clusters in the scatter plot of each sample to be tested; or Obtaining the fluorescence signal intensity distribution information of the blood cells in the area enclosed by the respective partial areas of two or more adjacent particle clusters in the scatter plot of each of the samples to be tested; or The fluorescence signal intensity distribution information of the blood cells in the region between two or more adjacent particle clusters in the scatter plot of each of the samples to be tested is obtained.

9. The method for determining insufficient residual amount of fluorescent reagent according to claim 8, characterized in that: The particle clusters include at least one of lymphocyte particle clusters, monocyte particle clusters, neutrophil particle clusters, eosinophil particle clusters, basophil particle clusters and red blood cell particle clusters.

10. The method for determining insufficient residual amount of a fluorescent reagent according to any one of claims 1 to 6, characterized in that: When the fluorescent signal intensity distribution information of a plurality of consecutive samples to be tested all meets the preset condition of insufficient residual amount of the fluorescent reagent, before determining that the residual amount of the fluorescent reagent is insufficient, the method further includes: Determining whether each of the samples to be tested is a normal sample; When each of the samples to be tested is a normal sample, the sample fluorescence signal intensity distribution information of each of the samples to be tested is compared with the preset condition of insufficient residual amount of the fluorescent reagent.

11. The method for determining insufficient residual amount of fluorescent reagent according to claim 10, characterized in that: Determine whether the sample to be tested is a normal sample, including: Based on the obtained scattered light signal and fluorescent signal of the blood sample, it is determined whether the blood sample has abnormality.

12. The method for determining insufficient residual amount of fluorescent reagent according to claim 11, characterized in that: The abnormality includes at least one of abnormal cell classification, abnormal cell counting, and identification of abnormal cells.

13. The method for determining insufficient residual amount of a fluorescent reagent according to any one of claims 1 to 6, characterized in that: The method further comprises the steps of: When it is confirmed that the fluorescent reagent is insufficient, an alarm is issued.

14. A method for determining insufficient residual amount of a fluorescent reagent, characterized in that: Applied to a sample analyzer, the method: Continuously detecting a plurality of samples to be tested, and obtaining at least the fluorescence signal intensity of all blood cells in each of the samples to be tested; Obtaining the fluorescence signal intensity distribution information of all blood cells in each of the samples to be tested to obtain the fluorescence signal intensity distribution information of the samples to be tested; When the sample fluorescence signal intensity distribution information of a plurality of consecutive samples to be tested all meets the preset condition of insufficient residual amount of the fluorescent reagent, it is determined that the residual amount of the fluorescent reagent is insufficient.

15. The method for determining insufficient residual amount of fluorescent reagent according to claim 14, characterized in that: The fluorescence signal intensity distribution information includes a fluorescence signal intensity distribution characteristic value, and the fluorescence signal intensity distribution characteristic value includes at least one of the following: The mean value of the fluorescence signal intensity of all blood cells in the sample to be tested; The median value of the fluorescence signal intensity of all blood cells in the sample to be tested; The mode value of the fluorescence signal intensity of all blood cells in the sample to be tested; The maximum value of the fluorescence signal intensity of all blood cells in the sample to be tested; The minimum value of the fluorescence signal intensity of all blood cells in the sample to be tested.

16. The method for determining insufficient residual amount of fluorescent reagent according to claim 15, characterized in that: When the fluorescent signal intensity distribution information of the consecutive samples to be tested all meets the preset condition of insufficient residual amount of the fluorescent reagent, determining that the residual amount of the fluorescent reagent is insufficient includes: When the fluorescence signal intensity distribution characteristic values ​​of a plurality of consecutive samples to be tested are lower than a preset threshold, and the fluorescence signal intensity distribution characteristic values ​​of a plurality of consecutive samples to be tested show a downward trend in the detection order of the plurality of consecutive samples to be tested, it is determined that the remaining amount of the fluorescent reagent is insufficient.

17. The method for determining insufficient residual amount of a fluorescent reagent according to any one of claims 14 to 16, characterized in that: When the fluorescent signal intensity distribution information of a plurality of consecutive samples to be tested all meets the preset condition of insufficient residual amount of the fluorescent reagent, before determining that the residual amount of the fluorescent reagent is insufficient, the method further includes: Determining whether each of the samples to be tested is a normal sample; When each of the samples to be tested is a normal sample, the sample fluorescence signal intensity distribution information of each of the samples to be tested is compared with the preset condition of insufficient residual amount of the fluorescent reagent.

18. The method for determining insufficient residual amount of fluorescent reagent according to claim 16, characterized in that: The preset threshold is a dynamic threshold; the method for determining the dynamic threshold comprises the steps of: Determining a preset number of samples to be tested that precede the current sample to be tested in a testing order, and obtaining fluorescence signal intensity distribution characteristic values ​​of all blood cells in the preset number of samples to be tested; A threshold center value is obtained by averaging the sum of the fluorescence signal intensity distribution characteristic values ​​of all blood cells in the preset number of samples to be tested; Calculate the standard deviation of the fluorescence signal intensity distribution characteristic values ​​of a preset number of samples that precede the current sample to be tested in the testing order; The dynamic threshold is calculated based on the threshold center value and the standard deviation.

19. The method for determining insufficient residual amount of fluorescent reagent according to claim 18, wherein: The dynamic threshold is calculated based on the threshold center value and the standard deviation, including: the dynamic threshold = threshold center value - k * standard deviation, where k is a preset value set according to the required confidence interval.

20. A sample analyzer, characterized in that: According to the detection order, multiple samples to be tested are tested, and the sample analyzer includes: A sampling device configured to draw samples to be tested and dispense each of the samples to be tested; A reagent providing device configured to provide the reaction reagents required for the detection item of the sample to be tested, wherein the reaction reagents include fluorescent reagents; a reaction container configured to receive the sample to be tested dispensed by the sampling device and the reaction reagent provided by the reagent providing device, so that the sample to be tested and the reaction reagent are mixed to obtain a mixed sample; an optical detection device for illuminating the mixed sample to detect the fluorescence signal and scattering signal of each blood cell in the sample to be tested; A control device configured to: Continuously detecting a plurality of samples to be tested, obtaining at least a scattered light signal intensity and a fluorescent signal intensity for blood cells in each of the samples to be tested, to form a scatter plot consisting of at least the scattered light signal and the fluorescent signal, wherein each scatter plot corresponds to one of the samples to be tested; Obtaining the distribution information of the blood cells located in the preset position of the scatter plot of each of the samples to be tested in the dimension of the fluorescence signal to obtain the distribution information of the fluorescence signal intensity of the samples to be tested; When the sample fluorescence signal intensity distribution information of a plurality of consecutive samples to be tested all meets the preset condition of insufficient residual amount of the fluorescent reagent, it is determined that the residual amount of the fluorescent reagent is insufficient.

21. A sample analyzer, characterized in that: According to the detection order, multiple samples to be tested are tested, and the sample analyzer includes: A sampling device configured to draw samples to be tested and dispense each of the samples to be tested; A reagent providing device configured to provide the reaction reagents required for the detection item of the sample to be tested, wherein the reaction reagents include fluorescent reagents; a reaction container configured to receive the sample to be tested dispensed by the sampling device and the reaction reagent provided by the reagent providing device, so that the sample to be tested and the reaction reagent are mixed to obtain a mixed sample; an optical detection device for illuminating the mixed sample to detect the fluorescence signal and scattering signal of each blood cell in the sample to be tested; A control device configured to: Continuously detecting a plurality of samples to be tested, and obtaining at least the fluorescence signal intensity of all blood cells in each of the samples to be tested; Obtaining the fluorescence signal intensity distribution information of all blood cells in each of the samples to be tested to obtain the fluorescence signal intensity distribution information of the samples to be tested; When the sample fluorescence signal intensity distribution information of a plurality of consecutive samples to be tested all meets the preset condition of insufficient residual amount of the fluorescent reagent, it is determined that the residual amount of the fluorescent reagent is insufficient.

22. The sample analyzer according to any one of claims 20 or 21, characterized in that: The control device is provided in the optical detection device.

23. A computer-readable storage medium for a sample analyzer, wherein a computer program is stored on the computer-readable storage medium, characterized in that: When the computer program is executed by a processor, the steps of the method for determining insufficient residual amount of the fluorescent reagent according to any one of claims 1 to 19 are implemented.

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