CN116256304A - Sample analyzer and method for analyzing blood sample - Google Patents

Sample analyzer and method for analyzing blood sample Download PDF

Info

Publication number
CN116256304A
CN116256304A CN202111508951.6A CN202111508951A CN116256304A CN 116256304 A CN116256304 A CN 116256304A CN 202111508951 A CN202111508951 A CN 202111508951A CN 116256304 A CN116256304 A CN 116256304A
Authority
CN
China
Prior art keywords
particles
compensation coefficient
compensation
sample
signal
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202111508951.6A
Other languages
Chinese (zh)
Inventor
杜贤算
刘斌
黄大欣
姚栋蓝
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shenzhen Mindray Bio Medical Electronics Co Ltd
Original Assignee
Shenzhen Mindray Bio Medical Electronics Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shenzhen Mindray Bio Medical Electronics Co Ltd filed Critical Shenzhen Mindray Bio Medical Electronics Co Ltd
Priority to CN202111508951.6A priority Critical patent/CN116256304A/en
Publication of CN116256304A publication Critical patent/CN116256304A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/10Investigating individual particles
    • G01N15/14Electro-optical investigation, e.g. flow cytometers
    • G01N15/1434Electro-optical investigation, e.g. flow cytometers using an analyser being characterised by its optical arrangement
    • G01N15/149
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/10Investigating individual particles
    • G01N15/14Electro-optical investigation, e.g. flow cytometers
    • G01N2015/1486Counting the particles
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The embodiment of the application provides a sample analyzer and an analysis method of a blood sample, wherein the sample analyzer comprises a sampling device, a sample preparation part, an optical measuring device and a signal processing device; the sample preparation part is used for preparing a sample liquid to be detected, wherein the sample liquid to be detected at least comprises first particles and second particles; the optical detector of the optical measuring device is used for detecting an optical output electric signal generated by particles passing through the detection area after the particles are irradiated by light; the signal processing device is used for obtaining a temperature value representing the temperature of the sample liquid to be detected, determining a first compensation coefficient and a second compensation coefficient according to the temperature value, carrying out compensation processing on the electric signal based on the first compensation coefficient and the second compensation coefficient, and obtaining an analysis result of at least the first particle and the second particle according to the electric signal after the compensation processing. And carrying out different temperature compensation on the electric signals corresponding to different particles in a distinguishing way based on the first compensation coefficient and the second compensation coefficient, and improving the accuracy of analysis results.

Description

Sample analyzer and method for analyzing blood sample
Technical Field
The application relates to the technical field of medical equipment, in particular to a sample analyzer and a blood sample analysis method
Background
The sample analyzer may be used to analyze cellular particles in a biological sample, such as to perform classification and counting of cellular particles. The sample analyzer may be a blood analyzer or a flow cytometer.
Sample analyzers typically have a sample collection device to quantitatively collect a sample from outside the instrument and send it to the inside of the instrument; and a reagent supply device for sucking a reagent from outside the instrument and supplying the reagent to the sample reaction device. The sample and the reagent are mixed and incubated in a sample reaction device to obtain a sample. The sample is conveyed to an optical measuring device by a sample conveying device, scattered light or fluorescence formed by cell particles in the sample irradiated by a light source is collected and converted into an electric signal, and then the electric signal is analyzed to realize cell classification and counting.
But the scattered light or fluorescence is related to the temperature in addition to the sample itself, e.g. the higher the temperature the weaker the fluorescence signal, exhibiting a negative correlation characteristic. At present, the temperature is controlled to be constant or the temperature compensation is carried out to reduce the influence of the temperature, but the compensation effect is not good enough, and the measurement accuracy is influenced.
Disclosure of Invention
The application provides a sample analyzer and an analysis method of a blood sample, which aim to reduce the influence of temperature on an analysis result and improve the accuracy of the analysis result of the sample analyzer.
In a first aspect, embodiments of the present application provide a sample analyzer, comprising:
a sampling device comprising a sampling needle for sucking a blood sample to be tested;
a sample preparation part having a reaction cell for receiving a portion of a blood sample to be measured sucked by the sampling device and a reagent supply part for supplying a reagent to the reaction cell so that the portion of the blood sample to be measured is mixed with the reagent in the reaction cell to prepare a sample liquid to be measured; the sample liquid to be detected at least comprises first particles and second particles; wherein the second particles and the first particles are different particles;
the optical measuring device comprises a flow chamber, a light source and a light detector, wherein the light source is used for emitting light beams to irradiate a detection area of the flow chamber, the flow chamber is communicated with the reaction tank, so that each particle in a sample liquid to be measured in the reaction tank can pass through the detection area of the flow chamber, and the light detector is used for detecting a light output electric signal generated by the particles passing through the detection area after the particles are irradiated by light;
the signal processing device is used for obtaining a temperature value representing the temperature of the sample liquid to be detected, determining a first compensation coefficient and a second compensation coefficient according to the temperature value, carrying out compensation processing on the electric signal based on the first compensation coefficient and the second compensation coefficient, and obtaining an analysis result of at least the first particle and the second particle according to the electric signal after the compensation processing.
In a second aspect, embodiments of the present application provide a sample analyzer, comprising:
a sampling device comprising a sampling needle for sucking a blood sample to be tested;
a sample preparation part having a reaction cell for receiving a portion of a blood sample to be measured sucked by the sampling device and a reagent supply part for supplying a reagent to the reaction cell so that the portion of the blood sample to be measured is mixed with the reagent in the reaction cell to prepare a sample liquid to be measured; the sample liquid to be detected at least comprises first particles and second particles; wherein the second particles and the first particles are different particles;
the optical measuring device comprises a flow chamber, a light source and a light detector, wherein the light source is used for emitting light beams to irradiate a detection area of the flow chamber, the flow chamber is communicated with the reaction tank, so that each particle in a sample liquid to be measured in the reaction tank can pass through the detection area of the flow chamber, and the light detector is used for detecting fluorescent output fluorescent electric signals generated by the particles passing through the detection area after the particles are irradiated by light;
the signal processing device is used for obtaining a temperature value representing the temperature of the sample liquid to be detected, determining a first compensation coefficient and a second compensation coefficient according to the temperature value, and carrying out compensation processing on the fluorescent electric signal based on the first compensation coefficient and the second compensation coefficient; and distinguishing the erythrocyte particle group particles from the platelet particle group particles in the particles passing through the detection zone according to the fluorescence electric signals after compensation treatment to obtain an analysis result of at least the erythrocyte particle group and the platelet particle group.
In a third aspect, embodiments of the present application provide a sample analyzer, comprising:
a sampling device comprising a sampling needle for sucking a blood sample to be tested;
a sample preparation part having a reaction cell for receiving a portion of a blood sample to be measured sucked by the sampling device and a reagent supply part for supplying a reagent to the reaction cell so that the portion of the blood sample to be measured is mixed with the reagent in the reaction cell to prepare a sample liquid to be measured; the sample liquid to be detected at least comprises first particles and second particles; wherein the second particles and the first particles are different particles;
the optical measuring device comprises a flow chamber, a light source and a light detector, wherein the light source is used for emitting light beams to irradiate a detection area of the flow chamber, the flow chamber is communicated with the reaction tank, so that each particle in a sample liquid to be measured in the reaction tank can pass through the detection area of the flow chamber, and the light detector is used for detecting a light output electric signal generated by the particles passing through the detection area after the particles are irradiated by light;
the signal processing device is used for obtaining a temperature value representing the temperature of the sample liquid to be detected, and determining a first compensation coefficient and a second compensation coefficient according to the temperature value; adjusting a first classification parameter based on the first compensation coefficient, and adjusting a second classification parameter based on the second compensation coefficient; and distinguishing at least two particles in the first particles according to the electric signal based on the adjusted first classification parameter to obtain an analysis result of the first particles; and distinguishing at least two particles in the second particles according to the electric signals based on the adjusted second classification parameters to obtain analysis results of the second particles.
In a fourth aspect, embodiments of the present application provide a sample analyzer, comprising:
a sampling device comprising a sampling needle for sucking a blood sample to be tested;
a sample preparation part having a reaction cell for receiving a portion of a blood sample to be measured sucked by the sampling device and a reagent supply part for supplying a reagent to the reaction cell so that the portion of the blood sample to be measured is mixed with the reagent in the reaction cell to prepare a sample liquid to be measured; the sample liquid to be detected at least comprises first particles and second particles; wherein the second particles and the first particles are different particles;
the optical measuring device comprises a flow chamber, a light source and a light detector, wherein the light source is used for emitting light beams to irradiate a detection area of the flow chamber, the flow chamber is communicated with the reaction tank, so that each particle in a sample liquid to be measured in the reaction tank can pass through the detection area of the flow chamber, and the light detector is used for detecting a light output electric signal generated by the particles passing through the detection area after the particles are irradiated by light;
the signal processing device is used for obtaining a temperature value representing the temperature of the sample liquid to be detected, and determining a first compensation coefficient and a second compensation coefficient according to the temperature value; carrying out compensation processing on particles passing through the detection area based on the first compensation coefficient, and distinguishing at least two particles in the first particles according to the electric signals subjected to the compensation processing based on the first compensation coefficient to obtain an analysis result of the first particles;
The signal processing device is further configured to adjust a second classification parameter based on the second compensation coefficient, and distinguish at least two particles in the second particles according to the compensated electrical signal corresponding to the second particles based on the adjusted second classification parameter, so as to obtain an analysis result of the second particles.
In a fifth aspect, embodiments of the present application provide a method for analyzing a blood sample, including:
acquiring an electric signal of light output generated by a light detector after detecting particles passing through a detection area by light irradiation, wherein a sample liquid to be detected passing through the detection area at least comprises first particles and second particles, and the second particles and the first particles are different particles;
acquiring a temperature value representing the temperature of a sample liquid to be measured;
determining a first compensation coefficient and a second compensation coefficient according to the temperature value;
performing compensation processing on the electric signal based on the first compensation coefficient and the second compensation coefficient;
and obtaining an analysis result of at least the first particles and the second particles according to the electric signals after the compensation treatment.
The embodiment of the application provides a sample analyzer and an analysis method of a blood sample, wherein a temperature value representing the temperature of a sample liquid to be measured is obtained, a first compensation coefficient and a second compensation coefficient are determined according to the temperature value, compensation processing is carried out on an electric signal based on the first compensation coefficient and the second compensation coefficient, and the electric signal is light output generated by a light detector after particles passing through a detection area are irradiated by light; because the electric signals corresponding to different particles in the sample liquid to be detected are differentially subjected to different temperature compensation based on the first compensation coefficient and the second compensation coefficient, the influence of different temperature drift characteristics of different particles on the sample analysis result can be eliminated, and the accuracy of the analysis result is improved.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the disclosure of embodiments of the present application.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings that are needed in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present application, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic block diagram of a sample analyzer provided in an embodiment of the present application;
FIG. 2 is a schematic diagram of an optical measurement device according to an embodiment;
FIG. 3 is a schematic diagram of a RET scatter plot in one embodiment;
FIG. 4 is a schematic diagram of a RET scattergram at 20℃in one embodiment;
FIG. 5 is a schematic diagram of a RET scatter plot at 40℃in one embodiment;
FIG. 6 is a schematic diagram showing the variation of optical signals generated by different particles with temperature according to one embodiment;
FIG. 7 is a schematic block diagram of a signal processing apparatus in one embodiment;
FIG. 8 is a schematic block diagram of a signal processing apparatus in another embodiment;
FIG. 9 is a schematic block diagram of a signal processing apparatus in yet another embodiment;
FIG. 10 is a schematic block diagram of a data processor of a signal processing apparatus in one embodiment;
FIG. 11 is a scatter plot of DIFF channels in one embodiment;
FIG. 12 is a scatter plot of WNB channels in one embodiment;
FIG. 13 is a schematic block diagram of a signal processing apparatus in yet another embodiment;
FIG. 14 is a schematic block diagram of a data processor of a signal processing apparatus in another embodiment;
FIG. 15 is a schematic block diagram of a signal processing apparatus in yet another embodiment;
FIG. 16 is a schematic block diagram of a data processor of a signal processing apparatus in yet another embodiment;
FIG. 17 is a schematic diagram of adjusting a boundary according to a compensation coefficient in one embodiment;
FIG. 18 is a schematic diagram of adjusting the demarcation line based on the compensation coefficient in another embodiment;
fig. 19 is a flow chart of a method for analyzing a blood sample according to an embodiment of the present application.
Reference numerals illustrate: 10. a sampling device; 20. a sample preparation component; 21. a reaction tank; 22. a reagent supply unit; 30. an optical measurement device; 31. a flow chamber; 32. a light source; 33. a photodetector; 331. a fluorescence detector; 332. forward scatter detectors; 333. a side scatter detector;
40. A signal processing device; 41. an amplifying circuit; 411. a first amplifying circuit; 412. a second amplifying circuit; 42. an analog-to-digital conversion circuit; 43. a gain setting circuit; 44. a processor; 50. and a temperature detecting device.
Detailed Description
The following description of the embodiments of the present application will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are some, but not all, of the embodiments of the present application. All other embodiments, which can be made by one of ordinary skill in the art without undue burden from the present disclosure, are within the scope of the present disclosure.
The flow diagrams depicted in the figures are merely illustrative and not necessarily all of the elements and operations/steps are included or performed in the order described. For example, some operations/steps may be further divided, combined, or partially combined, so that the order of actual execution may be changed according to actual situations.
Some embodiments of the present application are described in detail below with reference to the accompanying drawings. The following embodiments and features of the embodiments may be combined with each other without conflict.
An embodiment of the present application provides a sample analyzer, such as shown in fig. 1, which is a schematic block diagram of the sample analyzer. The sample analyzer is, for example, a blood cell analyzer, which is an instrument that can detect cells in blood, and for example, can classify and count white blood cells, red blood cells, platelets, nucleated red blood cells, reticulocytes, and the like in blood. The sample analyzer is not limited to an analyzer that analyzes a blood sample, and may be an analyzer that analyzes other biological samples.
Example 1
Referring to fig. 1, the sample analyzer includes a sampling device 10, a sample preparation member 20, an optical measurement device 30, and a signal processing device 40.
Wherein the sampling device 10 comprises a sampling needle for aspirating a blood sample to be tested.
The sample preparation member 20 may also be referred to as a sample reaction device having a reaction cell 21 for receiving a portion of the blood sample to be measured sucked by the sampling device 10, and a reagent supply section 22 for supplying a reagent to the reaction cell 21 so that the portion of the blood sample to be measured is mixed with the reagent in the reaction cell 21 to prepare a sample liquid to be measured. For example, the sampling device 10 may also be referred to as a sample collection device for quantitatively collecting and transporting a sample to be measured, such as a blood sample to be measured, into the reaction cell 21 of the sample preparation member 20, and the reagent supply portion 22 for collecting a quantitative reagent from a reagent bottle and transporting the quantitative reagent to the reaction cell 21. The reaction cell 21 is used for providing a reaction place for a sample to be tested and a reagent to prepare a sample liquid to be tested.
Illustratively, the reagent includes a diluent for spherically treating the blood sample and a dye for staining the blood sample. For example, in RET (reticulocyte) channels of an analyzer of a sample analyzer, RBCs (red blood cells) are spheroidized by RET dilution, and nucleic acids of RBCs and PLTs (platelets) are stained by fluorescent dyes. In particular, RET channels are channels used to sort and/or count reticulocytes.
Illustratively, the reagent includes a hemolyzing agent for hemolyzing the blood sample and a staining solution for staining the blood sample. For example, in the DIFF channel and WNB (basophilic and nucleated red blood cell) channels of the analyzer of the sample analyzer, on one hand, red blood cells in blood cells are lysed by the action of specific reagent components in a hemolyzing agent, and then differential treatment is performed on white blood cells, so that different kinds of cells are different in volume and complexity to some extent; on the other hand, the leucocyte inner core acid substances are marked by the asymmetric cyanine fluorescent substances in the dye solution while the reagent acts. The amount of fluorescent dye labels varies depending on the nucleic acid content of the cells of different species, different maturation stages or abnormal development states. Specifically, DIFF channels are channels for classifying and/or counting leukocytes, while WNB channels are channels for classifying basophils and nucleated erythrocytes.
It will be appreciated that the channels described in the embodiments herein refer to detection channels that identify and/or count and/or classify a certain type of cells, and are not limited to the RET channels, DIFF channels and WNB channels described above, but may also include, for example, NRBC (nucleated red blood cells) channels for counting nucleated red blood cells, BASO (basophilic granulocyte) channels for counting basophilic granulocytes. It should be noted that the sample analyzer according to the embodiment of the present application may be applied to at least one of these channels.
The optical measuring device 30 comprises a flow cell 31, a light source 32, and a light detector 33, the light source 32 is used for emitting a light beam to irradiate a detection area of the flow cell 31, the flow cell 31 is communicated with the reaction cell 21, so that each particle in the sample liquid to be measured in the reaction cell 21 can pass through the detection area of the flow cell 31, and the light detector 33 is used for detecting a light output electric signal generated by the particle passing through the detection area after being irradiated by light.
The sample analyzer also includes, for example, a sample delivery device that delivers the sufficiently reacted sample fluid to be measured in the reaction cell 21, together with a diluent, to the optical measurement device 30.
Illustratively, the light source 32 in the optical measurement device 30 is configured to irradiate the sample liquid wrapped by the diluent flowing through the flow chamber 31 with light, and generate pulse-shaped optical signals reflecting different cell characteristics, such as scattered light and/or fluorescence, at different angles when the cell particles in the sample liquid pass through the detection region, where the scattered light and the fluorescence enter the light detector 33, and the light detector 33 outputs an electrical signal, such as an electrical pulse signal, corresponding to the intensity of the scattered light or the fluorescence of each particle.
In some embodiments, referring to FIG. 2, light detector 33 includes at least two of a fluorescence detector 331, a forward scatter detector 332, and a side scatter detector 333. The electrical signals include at least two of fluorescent electrical signals, forward scattered photoelectric signals, and side scattered photoelectric signals.
Illustratively, as shown in FIG. 2, after the cell particles pass through the detection region of the optical measurement device 30, they are excited to generate forward scattered light (or referred to as low-angle scattered light), side scattered light (or referred to as high-angle scattered light), and fluorescence, which are received and collected by the forward scattered light detector 332, the side scattered light detector 333, and the fluorescence detector 331, respectively, and converted into electrical signals. The electrical signal output by the forward scatter detector 332 may be referred to as a forward scatter photo-electric signal, the electrical signal output by the side scatter detector 333 may be referred to as a side scatter photo-electric signal, and the electrical signal output by the fluorescence detector 331 may be referred to as a fluorescence electrical signal. It will be appreciated that an electrical signal may be used to indicate the intensity of the optical signal, e.g. a fluorescent electrical signal may indicate the intensity of the fluorescent signal.
Illustratively, the forward scatter light detector 332, the side scatter light detector 333 may employ a Photodiode (PD), and the fluorescence light detector 331 may employ a vacuum photomultiplier tube (PMT) or a silicon photomultiplier tube (SiPMT). In some embodiments, the photoelectric conversion sensitivity of the vacuum photomultiplier or the silicon photomultiplier may be adjusted by the gain setting circuit 43.
In general, forward scattered light may reflect size information of the cell particles, side scattered light may reflect the complexity of the internal structure of the cell particles, and fluorescent signals may reflect the content of substances such as DNA, RNA, etc. within the cell particles that may be stained with fluorescent dyes. The optical signals can be used for classifying particles such as red blood cells, platelets and the like in the sample liquid to be detected, and meanwhile, the count value of various particles can be obtained.
Specifically, the sample liquid to be tested at least comprises first particles and second particles; wherein the second particles and the first particles are different particles. For example, the reagent includes a diluent and a dye solution, and the first particles and the second particles are selected from the group consisting of erythrocyte particle group particles and platelet particle group particles, but not limited thereto. For example, the first particle is a particle of a population of red blood cell particles, which may include red blood cells and reticulocytes; the second particles are platelet particle population particles, which may include platelets and immature platelets.
The electrical signal output by the photodetector 33 is amplified, conditioned, analog-to-digital converted by the signal processing device 40 to obtain a digital signal, and the digital signal is subjected to algorithm processing and calculation to obtain a sample analysis result. For convenience of description, the electrical signal output by the photodetector 33, the analog signal amplified by the signal processing device 40, conditioned, and analog-to-digital converted, the digital signal obtained by the analog-to-digital conversion, and the digital signal processed by the signal processing device 40 through the algorithm are collectively referred to as the electrical signal corresponding to the detector, such as the fluorescent electrical signal corresponding to the fluorescent detector 331, the forward scattered light detector 332, and the side scattered light detector 333. It is understood that the electrical signals include analog signals and digital signals.
In some embodiments, in fluorescent nucleic acid stained blood cell analyzers, there is typically a RET channel (reticulocyte channel) that enables measurement of Reticulocytes (RET), and the RET channel can also measure Platelets (PLT) and Immature Platelet Fraction (IPF) simultaneously. As shown in fig. 3, which is a schematic diagram of the RET scattergram, the abscissa (FL) represents information of the fluorescence electric signal, such as fluorescence intensity indicated by the fluorescence electric signal of the particle (such as pulse peak height of the fluorescence electric signal of the particle); the ordinate (FSC) represents information of the forward scattered photoelectric signal, such as the forward scattered light intensity indicated by the forward scattered photoelectric signal of the particle. As shown in fig. 3, the larger particles in circle No. 2 are platelets, and the area of circle No. 2 may be referred to as the platelet area; the smaller particles in circle 1 are immature platelets, and the area of circle 1 may be referred to as the platelet area; the particles in circle 3 are erythrocytes and reticulocytes, and the particles in circle 4 are reticulocytes. For example, the Immature Platelet Fraction (IPF) can be determined from the ratio of the number of particles in the immature platelet region in the RET channel to the number of particles in the platelet region in the RET channel. Typically the immature platelet region in the RET channel is of a fixed extent. It will be appreciated that the signal processing device 40 can distinguish between the erythrocyte particle group particles and the platelet particle group particles in the sample fluid to be tested, and also between the platelets and the immature platelets in the platelet particle group particles, based on the fluorescence electrical signal and the forward scattered photoelectric signal. Illustratively, platelets and IPF are detected mainly by means of fluorescence signal characteristics of RET channels, the stronger the fluorescence signal in the RET scattergram, the larger the development of PLT particle clusters in the fluorescence direction, the higher the IPF of the sample, so that the detected intensity of the fluorescence signal directly determines the detected IPF from the measurement result.
The intensity of the scattered light signal and the fluorescence signal is related to the temperature of the reaction and the measuring link thereof as well as the particle itself; for example, the higher the temperature, the weaker the fluorescent signal, exhibiting negative correlation properties. Referring to fig. 4 and 5, fig. 4 is a schematic diagram of the RET scattergram when the ambient temperature is 20 ℃, and fig. 5 is a schematic diagram of the RET scattergram when the ambient temperature is 40 ℃. Generally, for the instrument classification effect and the machine-to-machine consistency, the temperature control device is needed to control the temperature of each link of reaction and measurement so as to ensure the fluorescence energy excitation and detection machine-to-machine consistency and the classification effect.
In the low-cost fluorescent nucleic acid staining blood cell analyzer without temperature control, the temperature control device is omitted, so that the sample liquid to be measured and the cell particles therein, which are irradiated by light, and the optical measurement device 30, etc. are all affected by the ambient temperature, and the intensity of the excited scattered light, the fluorescence and the electrical signal output by the light detector 33 are all changed with the ambient temperature. The analysis results corresponding to fig. 4 and 5 obviously have a large difference, that is, the analysis result of the sample analyzer varies with different environmental temperatures, and is not accurate enough.
At present, the influence of temperature reduction is also caused by temperature compensation, for example, fluorescent signals generated by all cells/particles are amplified according to the same amplification factor according to the temperature of the current sample liquid, and then analog-digital conversion is carried out to obtain digital signals, and algorithm identification, classification and counting are carried out on the digital signals; but the compensation effect is not good enough and the measurement accuracy is still affected.
The inventors of the present application found that, after the removal of the thermostatic control of the temperature control device, the optical signals generated by the cells/particles of different subpopulations in the same channel are different with respect to the temperature, for example, the intensity of the fluorescent signals is different with respect to the temperature (hereinafter referred to as fluorescent temperature drift). For example, in RET channels, there is a large difference in fluorescence temperature drift between red blood cells (RBC, including reticulocyte RET) and platelets (including immature platelets), as shown in FIG. 6, the temperature drift of red blood cells is about-2.5%/DEG C, and the temperature drift of platelets (including immature platelets) is about-3.5%/DEG C. If the temperature compensation is performed on the whole RET channel according to the same temperature drift, such as the uniform temperature drift of red blood cells, the analysis result, such as the detection result of IPF, is inevitably caused to have larger error, and the measurement accuracy is affected.
Based on this finding, the inventors of the present application improved the sample analyzer, at least improved the compensation processing of the electrical signal, and reduced the influence of temperature on the analysis result to increase the accuracy of the analysis result of the sample analyzer.
Specifically, the signal processing device 40 is configured to obtain a temperature value representing a temperature of the sample liquid to be measured, determine a first compensation coefficient and a second compensation coefficient according to the temperature value, perform compensation processing on the electrical signal based on the first compensation coefficient and the second compensation coefficient, and obtain an analysis result of at least the first particle and the second particle according to the electrical signal after the compensation processing.
The sample analyzer further comprises a temperature detecting device 50, and the signal processing device 40 is configured to obtain a temperature value detected by the temperature detecting device 50. For example, a temperature value (for example, referred to as an in-machine temperature) detected by the temperature detecting device 50 inside the sample analyzer may be taken as a temperature value representing the temperature of the sample liquid to be measured; for example, the temperature detecting device 50 inside the sample analyzer needs to be placed at a position far away from the heat source such as the reaction tank 21 and the power source.
Illustratively, the signal processing device 40 is configured to obtain the temperature value from a temperature detection device 50 external to the sample analyzer, such as the temperature detection device 50 within a clinical laboratory. For example, the temperature of the environment detected by the temperature detecting device 50 outside the sample analyzer may be used as a temperature value representing the temperature of the sample liquid to be measured, for example, the temperature inside the instrument has a substantially stable temperature difference from the ambient temperature, so that the temperature compensation calculation is performed by using the temperature inside the instrument or the ambient temperature, and the result is not affected. For example, the temperature in the machine may be determined according to a temperature difference between the temperature in the machine and the ambient temperature, and the temperature in the machine may be used as a temperature value representing the temperature of the sample liquid to be measured.
The signal processing device 40 is for determining the corresponding first compensation coefficient and the corresponding second compensation coefficient according to the preset temperature value based on the corresponding relation between the temperature value and the first compensation coefficient and the second compensation coefficient.
In some embodiments, the first light intensity and the second light intensity corresponding to the temperature value may be determined according to a correspondence between a preset temperature value and a first light intensity of the light signal corresponding to the first particle and a second light intensity of the light signal corresponding to the second particle; and determining a first compensation coefficient and a second compensation coefficient corresponding to the temperature value detected by the temperature detection device 50 according to the first light intensity and the second light intensity corresponding to the temperature value and the first light intensity and the second light intensity corresponding to the preset reference temperature.
For example, referring to fig. 6, two curves corresponding to red blood cells and platelets/immature platelets are the correspondence between a preset temperature value and a first light intensity of an optical signal corresponding to the red blood cells and a second light intensity of an optical signal corresponding to the platelets/immature platelets. The fluorescence signal intensity (e.g., referred to as first intensity) of red blood cells (RBCs, including reticulocytes RET) in the RET channel as a function of ambient temperature can be plotted as curve V R =f 1 (t) and the fluorescence signal intensity of platelets (PLT, including immature platelets) (e.g., referred to as second intensity) as a function of ambient temperature can be represented by curve V P =f 2 (t) wherein V R For RBC fluorescence signal intensity, V P The fluorescence signal intensity of PLT, t is the ambient temperature. f (f) 1 (t)、f 2 (t) may be a function, formulated, or when not formulated, may be in the form of an array of t-V。f 1 (t)、f 2 (t) is obtained, for example, by a fluorescence temperature drift test.
Exemplary, as shown in FIG. 6, V R =f 1 (t)、V P =f 2 (t) is approximately linear and can be expressed by a linear formula, i.e. V R =f 1 (t)=a 1 t+b 1 ,V P =f 2 (t)=a 2 t+b 2 Wherein a is 1 、b 1 、a 2 、b 2 Is constant, for example, obtained by linear fitting in a fluorescence signal temperature drift test.
Exemplary, preset reference temperature t 0 The temperature may be 25℃and is not limited to this. Reference temperature t 0 The fluorescence signal intensity of the corresponding RBC is V R (t 0 ) PLT has a fluorescent signal intensity of V P (t 0 ). Specifically, the temperature compensation is to adjust the intensity of the optical signal indicated by the electrical signal at other temperatures, such as the current ambient temperature, to be consistent with the intensity of the light corresponding to the reference temperature.
For example, when the temperature value representing the temperature of the sample liquid to be measured is detected as t, the first compensation coefficient g corresponding to the temperature value t can be determined R The method comprises the following steps:
Figure BDA0003404505790000121
wherein f 1 (t) represents the first light intensity, V, of the optical signal corresponding to the first particle (such as RBC, including reticulocyte RET) at the temperature value t R (t 0 ) And the first compensation coefficient is determined according to the ratio of the first light intensity corresponding to the reference temperature to the first light intensity of the optical signal corresponding to the first particle at the temperature value t.
For example, when the temperature value representing the temperature of the sample liquid to be measured is detected as t, it may be determined that the second compensation coefficient corresponding to the temperature value t is:
Figure BDA0003404505790000122
wherein f 2 (t) represents the second intensity of the optical signal corresponding to the second particle (e.g., platelet PLT, including immature platelets) at the temperature value t, V P (t 0 ) And the second compensation coefficient is determined according to the ratio of the second light intensity corresponding to the reference temperature to the second light intensity of the optical signal corresponding to the second particle at the temperature value t.
By differentially performing different temperature compensation on the electrical signals corresponding to different particles, for example, compensating the electrical signals corresponding to the first particles according to a first compensation coefficient and compensating the electrical signals corresponding to the second particles according to a second compensation coefficient, the accuracy of analysis results is improved, for example, the centers of gravity of different particle clusters, such as the centers of gravity of erythrocyte particle clusters and the centers of gravity of platelet particle clusters, can be kept unchanged at different environmental temperatures. Illustratively, different temperature compensation is differentially performed on different cell subsets of the same channel, improving the accuracy of the analysis results of the channel.
In some embodiments, the signal processing device 40 is configured to: distinguishing at least two particles in the first particles according to the electric signals subjected to the compensation processing based on the first compensation coefficient to obtain an analysis result of the first particles; and/or distinguishing at least two particles in the second particles according to the electric signals after the compensation processing based on the second compensation coefficient, so as to obtain an analysis result of the second particles.
In an exemplary embodiment, in the electrical signals after the first compensation coefficient compensation process, at least the electrical signals corresponding to the first particles have a better temperature compensation effect, and different particles in the first particles can be more accurately distinguished based on the electrical signals after the first compensation coefficient compensation process. Likewise, the electrical signal after the compensation process based on the second compensation coefficient can also more accurately distinguish different particles in the second particles.
In some embodiments, the signal processing device 40 is configured to perform compensation processing on the particles passing through the detection area based on the first compensation coefficient, and distinguish between a first particle and a second particle in the particles and at least two particles in the first particle according to the electrical signal after compensation processing based on the first compensation coefficient, so as to obtain an analysis result of the first particle; and compensating the electric signal corresponding to the second particles based on the second compensation coefficient, and distinguishing at least two particles in the second particles according to the electric signal compensated based on the second compensation coefficient to obtain an analysis result of the second particles.
For example, the particles passing through the detection area are subjected to non-differential compensation (which may be referred to as first-stage compensation) based on the first compensation coefficient, so that the electrical signal corresponding to the first particle is better and fully compensated in temperature, and the electrical signal corresponding to the second particle is partially compensated; according to the electric signals after the compensation processing based on the first compensation coefficient, the types of the examples corresponding to the electric signals can be distinguished more accurately; and then, based on a second compensation coefficient, carrying out compensation processing (which can be called second-stage compensation) on the electric signal corresponding to the second particles after the compensation processing based on the first compensation coefficient, so that the electric signal corresponding to the second particles is also better and fully subjected to temperature compensation. According to the electric signals corresponding to the first particles after the sufficient temperature compensation, at least two particles in the first particles can be accurately distinguished, and an accurate analysis result of the first particles is obtained; according to the electric signals corresponding to the second particles after the sufficient temperature compensation, at least two particles in the second particles can be accurately distinguished, and an accurate analysis result of the second particles can be obtained.
For example, referring to fig. 7 and 8, the signal processing apparatus 40 includes an amplifying circuit 41, an analog-to-digital conversion circuit 42, and a gain setting circuit 43. The photodetector 33 is configured to detect a light output electrical signal generated by the particles passing through the detection region after being irradiated with light, such as a fluorescence output fluorescence electrical signal generated by the fluorescence detector 331, where the scattered light detector 33 and the side scattered light detector 333 output a forward scattered photoelectric signal and a side scattered photoelectric signal, respectively, by forward scattered light and side scattered light of the particles passing through the detection region. The amplifying circuit 41 is used for amplifying the analog signal output by the photodetector 33, such as the fluorescence detector 331, and the analog-to-digital conversion circuit 42 is used for converting the analog signal amplified by the amplifying circuit 41 into a digital signal. For example, as shown in fig. 7, each photodetector 33 corresponds to a respective amplifying circuit 41 and an analog-to-digital conversion circuit 42, and the plurality of amplifying circuits 41 and the plurality of analog-to-digital conversion circuits 42 process the analog signals output by the plurality of photodetectors 33 in parallel; of course, the present invention is not limited thereto, and for example, one analog-to-digital conversion circuit 42 processes analog signals output from different photodetectors 33 in a time-sharing manner.
Illustratively, the signal processing device 40 is configured to control the gain setting circuit 43 to adjust the gain of the photodetector 33 and/or to adjust the gain of the amplifying circuit 41 based on the first compensation coefficient, so as to perform compensation processing on the analog signal, i.e. perform compensation processing on particles passing through the detection zone based on the first compensation coefficient. For example, as shown in fig. 7, the signal processing device 40 is configured to control the gain setting circuit 43 to adjust the gain of the photodetector 33 based on the first compensation coefficient; the photoelectric conversion sensitivity of the SiPMT is compensated to be the reference temperature t, for example, by adjusting the gain setting circuit 43 0 First compensation coefficient g of photoelectric conversion sensitivity R Multiple times. As shown in fig. 8, the signal processing device 40 is configured to control the gain setting circuit 43 to adjust the gain of the amplifying circuit 41 based on the first compensation coefficient; the gain of the amplifying circuit 41 is compensated to the reference temperature t, for example by adjusting the gain setting circuit 43 0 First compensation coefficient g of lower gain R Multiple times.
For example, referring to fig. 9, the signal processing apparatus 40 includes an amplifying circuit 41 and an analog-to-digital conversion circuit 42, where the amplifying circuit 41 is configured to amplify an analog signal output by the photodetector 33, and the analog-to-digital conversion circuit 42 is configured to convert the analog signal amplified by the amplifying circuit 41 into a digital signal; the signal processing means 40 is configured to perform compensation processing on the digital signal based on the first compensation coefficient. For example, as shown in fig. 9, the signal processing device 40 includes a first digital amplifier for performing compensation processing on the digital signal based on the first compensation coefficient; for example compensating the gain of the first digital amplifier to a reference temperature t 0 First compensation coefficient g of lower gain R Multiple times. For example, the first digital amplifier may be an amplifier implemented by an algorithm.
As illustrated in fig. 7 to 9, the signal processing apparatus 40 further includes a processor 44, and the processor 44 is configured to perform compensation processing on the digital signal. Processor 44 includes a temperature compensation controller and a data processor and may also include a first digital amplifier. Wherein the temperature compensation controller is configured to determine a first compensation coefficient and a second compensation coefficient according to the temperature value, and control the gain setting circuit 43 to adjust the gain of the photodetector 33 and/or adjust the gain of the amplifying circuit 41 based on the first compensation coefficient, or adjust the gain of the first digital amplifier based on the first compensation coefficient; the data processor is used for obtaining the analysis result of at least the first particles and the second particles according to the electric signals after compensation processing. It will be appreciated that the temperature compensation controller, the data processor, and the first digital amplifier may all be implemented by software algorithms.
The processor 44 in the signal processing device 40 is further configured to perform compensation processing on the digital signal corresponding to the second particle based on the second compensation coefficient. As shown in fig. 7 and 8, the signal processing device 40 is configured to control the gain setting circuit 43 to adjust the gain of the photodetector 33 and/or to adjust the gain of the amplifying circuit 41 based on the first compensation coefficient (first-stage compensation), and to perform compensation processing on the digital signal corresponding to the second particle based on the second compensation coefficient (second-stage compensation). As shown in fig. 9, the signal processing device 40 is configured to perform compensation processing (first-stage compensation) on the digital signal corresponding to each particle passing through the detection region based on the first compensation coefficient; and performing compensation processing (second-stage compensation) on the digital signal corresponding to the second particle based on the second compensation coefficient.
In some embodiments, please refer to fig. 7 to 9 in combination with fig. 10, the signal processing device 40 is configured to obtain, by using the pulse recognition unit and the channel scatter diagram generating unit, a scatter diagram of the current detection channel based on the processed electric signal compensated by the first compensation coefficient; the parameter calculation unit can distinguish first particles from at least two particles in the first particles in a scatter diagram of the current detection channel to obtain an analysis result of the first particles; and by the second particle scattergram generating unit, the second particles can be distinguished from the scattergram of the current detection channel; the second digital amplifier may perform compensation processing on the electrical signal corresponding to the second particle based on the second compensation coefficient, and the parameter calculation unit may distinguish at least two particles in the second particle based on the electrical signal after the compensation processing of the second compensation coefficient, so as to obtain an analysis result of the second particle. It will be appreciated that the pulse recognition unit, the channel scatter plot generation unit, the second particle scatter plot generation unit, the second digital amplifier, the parameter calculation unit may all be implemented by a software algorithm.
For example, analog pulse signals corresponding to the cell particles in the RET channel (such as analog signals of the fluorescent electric signal FL, the forward scattering photoelectric signal FSC, and the side scattering photoelectric signal SSC) are converted into digital pulses by the analog-to-digital conversion circuit 42, and in the data processor, pulse recognition is performed first in the pulse recognition unit, and a pulse peak height value of FSC, SSC, FL corresponding to each particle is output. Then, in the RET channel scattergram generating unit, a RET channel scattergram is generated based on the three-way pulse peak height values.
As shown in fig. 3, in the RET channel scatter diagram, there is a significant difference between the red blood cells and the regions where the platelets are distributed, and a dividing line is provided between two clusters in the FSC and FL directions, so that the platelets can be individually divided to obtain a PLT scatter diagram, which is a function of the PLT scatter diagram generating unit (i.e., the second particle scatter diagram generating unit). And then digitally amplifying the FL peak height value in the PLT scatter diagram to obtain a PLT scatter diagram after temperature compensation, and then calculating parameters such as IPF and the like according to the PLT scatter diagram after temperature compensation.
When the first particles and the second particles are distinguished from each other or at least two of the first particles and at least two of the second particles are distinguished from each other by the electric signal, the distinction may be made without using a scatter diagram, for example, the distinction may be made by other particle classification algorithms such as a clustering algorithm, or the like.
Illustratively, the electrical signals corresponding to the particles of the detection channel are subjected to two-stage temperature compensation according to the particle type, wherein the first-stage compensation performs gain adjustment on the electrical signals of all the particles (such as red blood cells and platelets) according to the temperature drift characteristics of the first particles (such as red blood cells) along with the temperature change, and the second-stage compensation performs digital amplification on the pulse peak height data of the second particles (such as platelets) in the scatter diagram of the current detection channel along with the temperature change in the processor 44.
Illustratively, the electrical signal corresponding to the second particle is compensated based on a ratio of the second compensation coefficient to the first compensation coefficient. For example, when the first compensation is performed, the electric signals corresponding to the first particles and the second particles are compensated according to the first compensation coefficient, such as the fluorescent intensity of red blood cells is amplified, and the fluorescent intensity of platelets is amplified by g R Doubling; thus, for example, the gain of the second digital amplifier can be compensated to the reference temperature t when the electric signal corresponding to the second particle is compensated for the second time 0 K times the gain:
Figure BDA0003404505790000161
wherein g R Represents a first compensation coefficient g p Representing a second compensation coefficient.
Illustratively, since the first compensation is performed before the second compensation, the second compensation has a smaller amount of computation, such as a lower performance requirement on the processor 44, and lower hardware cost.
Illustratively, the reagent includes a diluent for spherically treating the blood sample and a dye for staining the blood sample. For example, the test channel is a RET channel. The signal processing device 40 is configured to distinguish between the erythrocyte particle group particles and the platelet particle group particles in the particles passing through the detection area, and at least the erythrocytes and the reticulocytes in the erythrocyte particle group particles according to the electric signals compensated based on the first compensation coefficient, so as to obtain an analysis result of the erythrocyte particle group; and compensating the electric signals corresponding to the platelet particle group particles based on the second compensation coefficient, and distinguishing at least platelets and immature platelets in the platelet particle group particles according to the electric signals compensated based on the second compensation coefficient to obtain an analysis result of at least the platelet particle group. It will be appreciated that the aforementioned first particles comprise erythrocyte particle population particles and the second particles comprise platelet particle population particles; at least two of the first particles comprise erythrocytes and reticulocytes and at least two of the second particles comprise platelets and immature platelets. Of course, the present invention is not limited thereto, and the first particles include platelet particle group particles, and the second particles include erythrocyte particle group particles; at least two of the first particles comprise platelets and immature platelets and at least two of the second particles comprise erythrocytes and reticulocytes. For example, the analysis result of the population of red blood cell particles comprises at least the number of said red blood cells and/or said reticulocytes, and the analysis result of the population of platelet particles comprises at least the number of said platelets and/or said immature platelets.
For example, the signal processing device 40 is configured to perform compensation processing on the fluorescent electric signal generated by the fluorescent detector 331 in the light detector 33 based on the first compensation coefficient and the second compensation coefficient; and obtaining an analysis result of at least the erythrocyte particle group and the platelet particle group according to the scattered light signals generated by the scattered light detectors in the light detectors and the compensated processed fluorescent electric signals. For example, in RET channels, the temperature has little effect on the scattered light signal, and compensation may not be needed or otherwise adaptively compensated; the temperature has a relatively large influence on the fluorescent signal, and different particles can be distinguished accurately by carrying out compensation processing on the fluorescent electric signal based on the first compensation coefficient and the second compensation coefficient.
Example two
Illustratively, the reagent includes a hemolyzing agent for hemolyzing the blood sample and a staining solution for staining the blood sample; for example, the test channel is a DIFF channel. The signal processing device 40 is configured to distinguish, according to the electric signal compensated based on the first compensation coefficient, the leukocyte subset particles and the blood shadow region particle group particles in the particles passing through the detection region, and at least two particles in the leukocyte subset particles, so as to obtain an analysis result of the leukocyte subset; and compensating the electric signals corresponding to the particles of the particle group of the blood shadow area based on the second compensation coefficient, and distinguishing at least the particles of the particle group of the blood shadow area from reticulocytes according to the electric signals compensated based on the second compensation coefficient to obtain an analysis result of the particle group of the blood shadow area; wherein at least two of the leukocyte subpopulation particles are selected from at least two of the following: lymphocytes, monocytes, eosinophils, neutrophils, basophils, naive granulocytes.
FIG. 11 is a scatter plot of DIFF channels of an embodiment with platelets (including immature platelets) in frame number 1 and reticulocytes in frame number 2. The DIFF channel can simultaneously measure leukocytes (including lymphocytes, monocytes, neutrophils, eosinophils, basophils, strangles, naive cells, etc.), platelets (PLT), reticulocytes (RET), etc. Platelets, reticulocytes and white blood cells have different temperature drift characteristics. By compensating the electric signals of the particle groups based on at least the first compensation coefficient and the second compensation coefficient, respectively, white blood cells (and internal classification thereof), platelets, packed red blood cells, and the like can be accurately measured from the electric signals after the compensation process.
In the DIFF channel, taking temperature compensation of the fluorescent electric signal as an example, the photoelectric conversion sensitivity of the sipt is adjusted by the gain setting circuit 43 according to the current temperature based on the first compensation coefficient to perform first-stage compensation of the particle electric signal of the entire DIFF channel. Then, a platelet/RET digital amplifier is arranged in the data processor, the second-stage compensation is carried out on fluorescent electric signals corresponding to the particles (including PLT and RET) in the blood shadow area of the DIFF channel based on the second compensation coefficient, and the compensated electric signals are identified through algorithm so as to identify the PLT and RET.
The inventor of the application also finds that in the DIFF channel, forward scattered light and fluorescence of various particles are greatly influenced by temperature, and forward scattered photoelectric signals and fluorescence electric signals can be compensated according to corresponding compensation coefficients, so that the accuracy of sample analysis results is improved. For example, the first compensation coefficient comprises a first fluorescence compensation coefficient and/or a first forward scattered light compensation coefficient, and the second compensation coefficient comprises a second fluorescence compensation coefficient and/or a second forward scattered light compensation coefficient; the signal processing device 40 is used for performing compensation processing on the fluorescent electric signal generated by the fluorescent detector 331 in the light detector 33 based on the first fluorescent compensation coefficient and the second fluorescent compensation coefficient; and further for compensating the forward scattered-light signal generated by the forward scattered-light detector 332 in the light detector 33 based on the first forward scattered-light compensation coefficient and/or the second forward scattered-light compensation coefficient; the signal processing device 40 is configured to obtain an analysis result of at least the leukocyte subpopulation and the particle swarm in the blood shadow region according to the forward scattering photoelectric signal after compensation processing and the fluorescence electric signal after compensation processing. It will be appreciated that the forward scattered photoelectric signal may be first-order compensated and/or second-order compensated; for example, the first-stage compensation may be performed only on the fluorescence electric signal, and the second-stage compensation may be performed on the forward scattered photoelectric signal and the fluorescence electric signal, which is not limited to this.
Example III
Illustratively, the reagent includes a hemolyzing agent for hemolyzing the blood sample and a staining solution for staining the blood sample; for example, the test channel is a WNB channel. The signal processing device 40 is configured to distinguish, according to the electric signal compensated based on the first compensation coefficient, the white blood cell population particles and nucleated red blood cells in the particles passing through the detection region, and at least basophils in the white blood cell population particles, so as to obtain an analysis result of the white blood cell population; and compensating the electric signal corresponding to the nucleated red blood cells based on the second compensation coefficient, and obtaining an analysis result of at least the nucleated red blood cells according to the electric signal compensated based on the second compensation coefficient.
A scatter plot of WNB channels in one embodiment is shown in fig. 12. The WNB channels can simultaneously measure leukocytes (including basophils, nucleated erythrocytes (NRBC) and the like). Wherein the NRBC has different temperature drift characteristics than the basophils. By compensating the electric signals of each particle group according to at least the first compensation coefficient and the second compensation coefficient, white blood cells, basophils and nucleated red blood cells can be accurately measured according to the electric signals after compensation treatment.
Taking temperature compensation of fluorescent electric signals as an example in the WNB channel, based on a first compensation coefficient, the photoelectric conversion sensitivity of the SiPMT is adjusted by the gain setting circuit 43 according to the current temperature to perform first-stage compensation on particle electric signals of the whole WNB channel, and the electric signals after the first-stage compensation can distinguish white blood cells and NRBC cells. Then, a basophil digital amplifier is arranged in the data processor, the fluorescent electric signals corresponding to the white blood cell population particles (including basophils) are subjected to second-stage compensation based on the second compensation coefficient, and the compensated electric signals are identified in the white blood cell population through an algorithm to distinguish the basophils.
For example, the signal processing device 40 is configured to perform compensation processing on the fluorescent electric signal generated by the fluorescent detector 331 in the light detector 33 based on the first compensation coefficient and the second compensation coefficient; and obtaining an analysis result of at least the white blood cell population and the nucleated red blood cells based on the scattered light signals generated by the scattered light detectors 33 of the light detectors 33 and the compensated processed fluorescent electrical signals.
Example IV
In other embodiments, please refer to fig. 13 and 14, in which the signal processing device 40 is configured to perform compensation processing on the particles passing through the detection area based on the first compensation coefficient, and distinguish a first particle from at least two particles in the first particles according to the electrical signal after the compensation processing based on the first compensation coefficient, so as to obtain an analysis result of the first particle; and performing compensation processing on particles passing through the detection area based on the second compensation coefficient, and distinguishing second particles from at least two particles in the second particles according to the electric signals subjected to the compensation processing based on the second compensation coefficient to obtain an analysis result of the second particles.
The signal processing device 40 performs parallel compensation and processing on the particles passing through the detection region according to a first compensation coefficient and a second compensation coefficient, specifically, obtains an analysis result of the first particles according to an electric signal after compensation processing based on the first compensation coefficient, and obtains an analysis result of the second particles according to an electric signal after compensation processing based on the second compensation coefficient.
The temperature compensation effect of the electrical signal corresponding to at least the first particle in the electrical signal after the first compensation coefficient compensation processing is better, and different particles in the first particle can be more accurately distinguished based on the electrical signal after the first compensation coefficient compensation processing; similarly, in the electrical signals subjected to the second compensation coefficient compensation processing, at least the electrical signals corresponding to the second particles have better temperature compensation effect, and different particles in the second particles can be more accurately distinguished based on the electrical signals subjected to the second compensation coefficient compensation processing.
For example, referring to fig. 13, the signal processing apparatus 40 includes an amplifying circuit 41, an analog-to-digital conversion circuit 42, and a processor 44, where the amplifying circuit 41 is configured to amplify an analog signal output by the photodetector 33, and the analog-to-digital conversion circuit 42 is configured to convert the analog signal amplified by the amplifying circuit 41 into a digital signal.
Referring to fig. 14, a processor 44 in the signal processing device 40 is configured to perform compensation processing on a digital signal corresponding to particles passing through the detection area based on the first compensation coefficient; and compensating the digital signal corresponding to the particles passing through the detection area based on the second compensation coefficient. As shown in fig. 14, in the data processor, the third digital amplifier performs compensation processing on the digital signal corresponding to the particle passing through the detection area based on the first compensation coefficient, while the fourth digital amplifier performs compensation processing on the digital signal corresponding to the particle passing through the detection area based on the second compensation coefficient; the digital signals after the compensation processing of the digital amplifiers are subjected to pulse recognition in the corresponding pulse recognition units, and the pulse peak height value of FSC, SSC, FL corresponding to each particle is output. Then, a scatter diagram is generated at the first scatter diagram generating unit according to the three-way pulse peak height values corresponding to the third digital amplifier, and a scatter diagram is generated at the second scatter diagram generating unit according to the three-way pulse peak height values corresponding to the fourth digital amplifier. The parameter calculation unit distinguishes first particles and at least two particles in the first particles according to the scatter diagram generated by the first scatter diagram generation unit, so as to obtain an analysis result of the first particles, and distinguishes second particles and at least two particles in the second particles according to the scatter diagram generated by the second scatter diagram generation unit, so as to obtain an analysis result of the second particles.
For example, referring to fig. 15, the signal processing apparatus 40 includes a first amplifying circuit 411, a second amplifying circuit 412, an analog-to-digital conversion circuit 42, and a gain setting circuit 43, where the first amplifying circuit 411 and the second amplifying circuit 412 are respectively used for amplifying the analog signal output by the photodetector 33, and the analog-to-digital conversion circuit 42 is used for converting the analog signal amplified by the first amplifying circuit 411 and the second amplifying circuit 412 into a digital signal.
As shown in fig. 15, the signal processing device 40 is configured to control the gain setting circuit 43 to adjust the gain of the first amplifying circuit 411 based on the first compensation coefficient, so as to perform compensation processing on the analog signal of the particle passing through the detection region; and controlling the gain setting circuit 43 to adjust the gain of the second amplifying circuit 412 based on the second compensation coefficient, thereby performing compensation processing on the analog signal of the particle passing through the detection region.
It can be understood that, when the particles passing through the detection area are compensated in parallel according to the first compensation coefficient and the second compensation coefficient, and the analysis result of the first particles is obtained according to the electric signal after the compensation process based on the first compensation coefficient, and the analysis result of the second particles is obtained according to the electric signal after the compensation process based on the second compensation coefficient, the digital signal may be compensated in parallel, or the analog signal may be compensated.
In other embodiments, referring to fig. 13 and 16, the signal processing device 40 is configured to distinguish the first particle from the second particle in the particles according to the electrical signal of the particles passing through the detection region; and compensating the electric signal corresponding to the first particles based on the first compensation coefficient, and distinguishing at least two particles in the first particles according to the electric signal compensated based on the first compensation coefficient to obtain an analysis result of the first particles; and/or compensating the electric signal corresponding to the second particles based on the second compensation coefficient, and distinguishing at least two particles in the second particles according to the electric signal compensated based on the second compensation coefficient to obtain an analysis result of the second particles.
For example, the first particles and the second particles may be first distinguished according to the electric signal not subjected to compensation processing, and then the electric signal corresponding to the first particles is subjected to compensation processing according to the first compensation coefficient in parallel, and the electric signal corresponding to the second particles is subjected to compensation processing according to the second compensation coefficient. At least two kinds of particles in the first particles can be accurately distinguished according to the electric signals corresponding to the first particles after the compensation process based on the first compensation coefficient, and at least two kinds of particles in the second particles can be accurately distinguished according to the electric signals corresponding to the second particles after the compensation process based on the second compensation coefficient.
As shown in fig. 13, the signal processing device 40 includes an amplifying circuit 41, an analog-to-digital conversion circuit 42, and a processor 44, the amplifying circuit 41 is configured to amplify the analog signal output from the photodetector 33, and the analog-to-digital conversion circuit 42 is configured to convert the analog signal amplified by the amplifying circuit 41 into a digital signal.
As shown in fig. 16, the processor 44 in the signal processing device 40 is configured to perform compensation processing on the digital signal corresponding to the first particle based on the first compensation coefficient; and compensating the digital signal corresponding to the second particle based on the second compensation coefficient. As shown in fig. 16, in the data processor, first, the pulse recognition unit performs pulse recognition on the digital signal of the particle passing through the detection region, and outputs a pulse peak height value of FSC, SSC, FL corresponding to each particle. Then, in a third scatter diagram generating unit, a scatter diagram, such as a scatter diagram of the first particles, is generated according to the three pulse peak height values; and generating another scatter plot, such as a scatter plot of the second particles, in parallel at a fourth scatter plot generating unit, based on the three-way pulse peak height values; the fifth digital amplifier performs compensation processing on the electric signals corresponding to the first particles based on the first compensation coefficient, and the sixth digital amplifier performs compensation processing on the electric signals corresponding to the second particles based on the second compensation coefficient; the parameter calculation unit distinguishes at least two particles in the first particles according to the electric signal after the compensation processing based on the first compensation coefficient to obtain an analysis result of the first particles, and distinguishes at least two particles in the second particles according to the electric signal after the compensation processing based on the second compensation coefficient to obtain an analysis result of the second particles.
Referring to fig. 14 to 16, the electrical signals are synchronously compensated based on the first compensation coefficient and the second compensation coefficient, and the analysis result of the first particles is obtained according to the electrical signals compensated based on the first compensation coefficient, and the analysis result of the second particles is obtained according to the electrical signals compensated based on the second compensation coefficient; it will be appreciated that these approaches may be referred to as parallel compensation.
Example five
Illustratively, the reagent includes a diluent for spherically treating the blood sample and a dye for staining the blood sample; for example, the test channel is a RET channel. When parallel compensation is performed, the signal processing means 40 are arranged to: distinguishing the erythrocyte particle group particles in the particles passing through the detection area from at least erythrocytes and reticulocytes in the erythrocyte particle group particles according to the electric signals compensated based on the first compensation coefficient, so as to obtain an analysis result of at least erythrocyte particle groups; and distinguishing platelet particle group particles in the particles passing through the detection area from at least platelets and immature platelets in the platelet particle group particles according to the electric signals compensated based on the second compensation coefficient, so as to obtain an analysis result of at least the platelet particle group.
For example, the signal processing device 40 is configured to perform compensation processing on the fluorescent electric signal generated by the fluorescent detector 331 in the light detector 33 based on the first compensation coefficient and the second compensation coefficient; and obtaining an analysis result of at least the erythrocyte particle group and the platelet particle group according to the scattered light signals generated by the scattered light detectors in the light detectors and the compensated processed fluorescent electric signals. Illustratively, in RET channels, the temperature has little effect on the scattered light signal, and compensation may not be required or otherwise adaptively compensated; the temperature has a relatively large influence on the fluorescent signal, and different particles can be distinguished accurately by carrying out compensation processing on the fluorescent electric signal based on the first compensation coefficient and the second compensation coefficient.
Example six
Illustratively, the reagent includes a hemolyzing agent for hemolyzing the blood sample and a staining solution for staining the blood sample; for example, the test channel is a DIFF channel. When parallel compensation is performed, the signal processing means 40 are arranged to: distinguishing white blood cell subset particles in the particles passing through the detection zone from at least two particles in the white blood cell subset particles according to the electric signals compensated based on the first compensation coefficient, so as to obtain an analysis result of the white blood cell subset; distinguishing the particles of the blood shadow area particle group from the particles passing through the detection area according to the electric signals compensated by the second compensation coefficient, and at least the particles of the blood platelet particle group and the reticulocytes in the particles of the blood shadow area particle group to obtain an analysis result of at least the particles of the blood shadow area; wherein at least two of the leukocyte subpopulation particles are selected from at least two of the following: lymphocytes, monocytes, eosinophils, neutrophils, basophils, naive granulocytes.
For example, the first compensation coefficient comprises a first fluorescence compensation coefficient and/or a first forward scattered light compensation coefficient, and the second compensation coefficient comprises a second fluorescence compensation coefficient and/or a second forward scattered light compensation coefficient; the signal processing device 40 is used for performing compensation processing on the fluorescent electric signal generated by the fluorescent detector 331 in the light detector 33 based on the first fluorescent compensation coefficient and the second fluorescent compensation coefficient; and further for compensating the forward scattered-light signal generated by the forward scattered-light detector 332 in the light detector 33 based on the first forward scattered-light compensation coefficient and/or the second forward scattered-light compensation coefficient; the signal processing device 40 is configured to obtain an analysis result of at least the leukocyte subpopulation and the particle swarm in the blood shadow region according to the forward scattering photoelectric signal after compensation processing and the fluorescence electric signal after compensation processing. It will be appreciated that the forward scattered photoelectric signal may be first-order compensated and/or second-order compensated; for example, the first-stage compensation may be performed only on the fluorescence electric signal, and the second-stage compensation may be performed on the forward scattered photoelectric signal and the fluorescence electric signal, which is not limited to this.
Example seven
Illustratively, the reagent includes a hemolyzing agent for hemolyzing the blood sample and a staining solution for staining the blood sample; for example, the test channel is a WNB channel. When parallel compensation is performed, the signal processing means 40 are arranged to: distinguishing the white blood cell population particles in the particles passing through the detection zone from at least basophils in the white blood cell population particles according to the electric signals compensated based on the first compensation coefficient, so as to obtain an analysis result of the white blood cell population; and distinguishing nucleated red blood cells in the particles passing through the detection region according to the electric signals compensated based on the second compensation coefficient, so as to obtain an analysis result of at least the nucleated red blood cells.
For example, the signal processing device 40 is configured to perform compensation processing on the fluorescent electric signal generated by the fluorescent detector 331 in the light detector 33 based on the first compensation coefficient and the second compensation coefficient; and obtaining an analysis result of at least the white blood cell population and the nucleated red blood cells based on the scattered light signals generated by the scattered light detectors 33 of the light detectors 33 and the compensated processed fluorescent electrical signals.
In some embodiments, the signal processing device 40 is further configured to determine a third compensation coefficient according to the temperature value, perform compensation processing on the electrical signal after compensation processing based on the first compensation coefficient and/or the second compensation coefficient based on the third compensation coefficient, and obtain an analysis result of the third particle according to the electrical signal after compensation processing based on the third compensation coefficient.
For example, the electrical signal compensated based on the first compensation coefficient and/or compensated based on the second compensation coefficient may be further compensated based on a third compensation coefficient; for example, after at least two kinds of particles of the second particles are distinguished from the electrical signal after the compensation process based on the second compensation coefficient, at least one kind of particles of the at least two kinds of particles, such as an electrical signal corresponding to a third particle, may be subjected to a third compensation, and at least two kinds of particles of the three kinds of particles may be distinguished from the electrical signal after the third compensation. By differentially carrying out different temperature compensation on the electric signals corresponding to different particles, the accuracy of analysis results and the refinement degree of particle distinction are improved.
According to the sample analyzer provided by the embodiment of the application, the temperature value representing the temperature of the sample liquid to be measured is obtained, the first compensation coefficient and the second compensation coefficient are determined according to the temperature value, the electric signal is subjected to compensation processing based on the first compensation coefficient and the second compensation coefficient, and the electric signal is output by the light detector 33 after detecting the particles passing through the detection area and being irradiated by light; because the electric signals corresponding to different particles in the sample liquid to be detected are differentially subjected to different temperature compensation based on the first compensation coefficient and the second compensation coefficient, the influence of different temperature drift characteristics of different particles on the sample analysis result can be eliminated, and the accuracy of the analysis result is improved.
Example eight
Referring to fig. 1 in conjunction with the foregoing examples, in some embodiments, a sample analyzer includes:
a sampling device 10 comprising a sampling needle for drawing a blood sample to be tested;
a sample preparation part 20 having a reaction well 21 for receiving a portion of the blood sample to be measured sucked by the sampling device 10, and a reagent supply part 22 for supplying a reagent to the reaction well 21 so that the portion of the blood sample to be measured is mixed with the reagent in the reaction well 21 to prepare a sample solution to be measured; the sample liquid to be detected at least comprises first particles and second particles; wherein the second particles and the first particles are different particles;
an optical measurement device 30 comprising a flow cell 31, a light source 32, and a light detector 33, wherein the light source 32 is used for emitting a light beam to irradiate a detection area of the flow cell 31, the flow cell 31 is communicated with the reaction cell 21, so that each particle in a sample liquid to be measured in the reaction cell 21 can pass through the detection area of the flow cell 31, and the light detector 33 is used for detecting fluorescence generated by the particles passing through the detection area after being irradiated with light to output a fluorescence electric signal;
the signal processing device 40 is configured to obtain a temperature value representing a temperature of the sample liquid to be measured, determine a first compensation coefficient and a second compensation coefficient according to the temperature value, and perform compensation processing on the fluorescent electric signal based on the first compensation coefficient and the second compensation coefficient; and distinguishing the erythrocyte particle group particles from the platelet particle group particles in the particles passing through the detection zone according to the fluorescence electric signals after compensation treatment to obtain an analysis result of at least the erythrocyte particle group and the platelet particle group.
Illustratively, the signal processing device 40 is configured to distinguish between erythrocytes and reticulocytes in the erythrocyte population particles, and obtain an analysis result of the erythrocyte population; and/or
And distinguishing platelets from immature platelets in the platelet particle group particles to obtain an analysis result of the platelet particle group.
For the fluorescent electric signal, two sets of different temperature compensation modes are used for red blood cells (including reticulocytes) and platelets (including immature platelets) in the RET measurement channel, and gains of the red blood cell signals and the platelet signals are respectively adjusted according to the environment temperature, so that the center of gravity of the red blood cell particle cluster and the center of gravity of the platelet particle cluster are kept unchanged at different environment temperatures, the influence of different temperature drift characteristics of different particles on a sample analysis result can be eliminated, and the accuracy of the analysis result is improved.
Example nine
The signal processing device 40 of the sample analyzer is used for obtaining a temperature value representing the temperature of the sample liquid to be measured, and determining a first compensation coefficient and a second compensation coefficient according to the temperature value; adjusting a first classification parameter based on the first compensation coefficient, and adjusting a second classification parameter based on the second compensation coefficient; and distinguishing at least two particles in the first particles according to the electric signal based on the adjusted first classification parameter to obtain an analysis result of the first particles; and distinguishing at least two particles in the second particles according to the electric signals based on the adjusted second classification parameters to obtain analysis results of the second particles. Illustratively, the processor 44 adjusts a first classification parameter based on the first compensation coefficient and adjusts a second classification parameter based on the second compensation coefficient.
According to the embodiment of the application, the temperature value representing the temperature of the sample liquid to be tested is obtained, the first compensation coefficient and the second compensation coefficient are determined according to the temperature value, and the classification parameters for classifying and identifying different particles are differentially adjusted based on the first compensation coefficient and the second compensation coefficient; for example, the first classification parameter adjusted based on the first compensation coefficient is more consistent with the temperature drift characteristic of the first particle, and the second classification parameter adjusted based on the second compensation coefficient is more consistent with the temperature drift characteristic of the second particle.
The particles are classified and identified based on the adjusted classification parameters, so that the influence of different temperature drift characteristics of different particles on a sample analysis result can be eliminated, and the accuracy of the analysis result is improved. It can be appreciated that the embodiments of the present application and the foregoing embodiments are based on the same inventive concept to eliminate the influence of the temperature drift characteristics of different particles on the analysis result of the sample.
Exemplary classification parameters for distinguishing between different particles include at least one of: the boundary (e.g., slope and/or intercept of the boundary), electrical signal threshold or electrical signal boundary value, and the range of values of the electrical signal that distinguish a particular particle on the scatter plot, although not limited thereto.
Referring to fig. 17, the left scatter plot is a RET scatter plot at a reference temperature, and the right scatter plot is a RET scatter plot at a current ambient temperature (e.g., 40 ℃). As shown in fig. 17, the upper diagonal line in the RET scattergram is a boundary line for distinguishing at least two kinds of particles (e.g., erythrocytes and reticulocytes) among the particles of the erythrocyte particle group (first particles), and the particles on the right side of the diagonal line are reticulocytes. As shown in fig. 17, the vertical line on the lower side of the RET scattergram is a boundary line for distinguishing at least two particles (e.g., platelets and immature platelets) among the particles (second particles) of the platelet particle group, and the particles on the right side of the vertical line are immature platelets.
Referring to fig. 17, at least the expansion degree in the fluorescence direction is different at different temperatures, and the variation of the expansion degree of different particles is different; for example, at high temperatures, the fluorescence signal intensity decays and the scatter plot compresses in the fluorescence direction (FL). For example, by adjusting the classification parameters to move the boundary of different particles in the first particles to the left, such as adjusting the threshold of RET algorithm boundary, at least two particles in the first particles can still be selected; similarly, moving the boundary between two particles in the second particle to the left, such as adjusting the threshold of the boundary of the immature platelet algorithm, also allows for the screening of at least two particles in the second particle (e.g., immature platelets), which is also a temperature compensated approach.
Since the temperature drift characteristics of the first particle and the second particle, such as the erythrocyte particle group particle and the platelet particle group particle, are not consistent, the algorithmic demarcation line of the different particles (such as erythrocytes and reticulocytes) in the first particle is not consistent with the amplitude of the adjustment of the algorithmic demarcation line of the different particles (such as platelets/immature platelets) in the second particle with temperature changes.
For example, the algorithmic demarcation of erythrocytes and reticulocytes can be expressed as follows:
y=f R (x,t)
the algorithmic demarcation of platelets/immature platelets can be expressed as follows:
y=f P (x,t)
wherein x represents the horizontal axis fluorescence FL in the scatter diagram, y represents the vertical axis forward scattered light FSC in the scatter diagram, and the algorithm boundary between the red blood cells and the reticulocyte and the algorithm boundary between the platelets/immature platelets are all functions of the temperature t.
For example, as shown in fig. 17, the boundary between erythrocytes and reticulocytes in the erythrocyte population particles is represented as follows:
y=k R (t)x+b R
the boundary between platelets and immature platelets in the platelet particle population particles is represented as follows:
x=b P (t)
where k represents the slope of the dividing line, which varies with temperature, and b represents the intercept of the dividing line.
For example, reference temperature t 0 The fluorescent signal intensity of erythrocyte particle swarm particles at (e.g. 25 ℃) is V R (t 0 ) The slope of the algorithm boundary line on the scatter diagram is k 1 Dividing line y=k 1 x+b R . The fluorescence signal intensity becomes V at 40℃ambient temperature R (t) (considering that the scattered light signal intensity has not changed), then the slope k of the algorithmic boundary at 40 ℃ can be determined R (t) the following:
Figure BDA0003404505790000271
when the fluorescence signal intensity becomes half of 25 ℃ at 40 ℃, the time division gradient at 40 ℃ is also adjusted to 2 times of the time division gradient at 25 ℃, i.e. the first compensation coefficient of the gradient when the corresponding boundary gradient of the first particles is adjusted to the reference temperature. It was confirmed that the boundary between erythrocytes and reticulocytes in the erythrocyte population particles at 40℃ambient temperature was represented as follows:
Figure BDA0003404505790000272
for example, reference temperature t 0 Platelet particle population particles with a fluorescence signal intensity of V at (e.g., 25 ℃ C.) P (t 0 ) The algorithm dividing line on the scatter diagram is x=b 1 . The fluorescence signal intensity becomes V at the ambient temperature t P (t) (considering that the scattered light signal intensity is unchanged), then it can be determined that the algorithm boundary adjusts to:
Figure BDA0003404505790000273
when the fluorescence signal intensity of the platelet particle group particles becomes one third of 25 ℃ at 40 ℃, the intercept of the boundary line corresponding to the platelet particle group particles at 40 ℃ is adjusted to one third of the intercept at 25 ℃.
The first compensation coefficient and the second compensation coefficient are determined according to the temperature value, and the classification parameters for classifying and identifying different particles are differentially adjusted based on the first compensation coefficient and the second compensation coefficient, so that the particles are classified and identified based on the adjusted classification parameters, the influence of different temperature drift characteristics of different particles on a sample analysis result can be eliminated, and the accuracy of the analysis result is improved. For example, when the temperature is changed, the gain of the holding circuit is not changed, the signal intensity of the electric signal is not subjected to temperature compensation, the algorithm boundary is adjusted through the first compensation coefficient and the second compensation coefficient, and the algorithm threshold is subjected to temperature compensation, so that the same effect can be achieved.
For example, in the DIFF channel and the WNB channel, the particles are divided by an area surrounded by a plurality of boundary lines, and classification parameters (such as slope and/or intercept) corresponding to one or more boundary lines may be adjusted according to corresponding compensation coefficients.
Examples ten
The signal processing device 40 is configured to obtain a temperature value representing a temperature of the sample liquid to be measured, and determine a first compensation coefficient and a second compensation coefficient according to the temperature value; and carrying out compensation processing on the particles passing through the detection area based on the first compensation coefficient, and distinguishing at least two particles in the first particles according to the electric signals subjected to the compensation processing based on the first compensation coefficient to obtain an analysis result of the first particles.
Illustratively, the first particles and the second particles, and at least two of the first particles, are distinguished from each other according to the electrical signal after compensation processing based on the first compensation coefficient.
The processor 44 in the signal processing device 40 is further configured to adjust a second classification parameter based on the second compensation coefficient, and distinguish at least two particles in the second particles according to the compensated electrical signal corresponding to the second particles based on the adjusted second classification parameter, so as to obtain an analysis result of the second particles. The influence of different temperature drift characteristics of different particles on the analysis result of the sample can be eliminated, and the accuracy of the analysis result is improved. It can be appreciated that the embodiments of the present application and the foregoing embodiments are based on the same inventive concept to eliminate the influence of the temperature drift characteristics of different particles on the analysis result of the sample.
Illustratively, the compensating process is performed on the particles passing through the detection zone based on the first compensation coefficient, and the gain setting circuit 43 may be controlled to adjust the gain of the photodetector 33 and/or adjust the gain of the amplifying circuit 41 based on the first compensation coefficient, so as to perform the compensating process on the analog signal of the particles passing through the detection zone; or the digital signal corresponding to the particles passing through the detection zone may be subjected to compensation processing based on the first compensation coefficient.
Illustratively, by performing compensation processing on the particles passing through the detection zone based on the first compensation coefficient, for example, gain adjustment is performed on the electrical signals of all particles (e.g., including red blood cells, platelets) according to the temperature drift characteristics of the first particles (e.g., red blood cells) with temperature change; the temperature compensation effect of the electric signal corresponding to at least the first particles in the electric signal after the first compensation coefficient compensation treatment is good, and different particles in the first particles can be distinguished more accurately based on the electric signal after the first compensation coefficient compensation treatment.
For example, referring to fig. 18, the left scatter plot is a RET scatter plot at the current ambient temperature (e.g., 40 ℃), and the middle scatter plot is a RET scatter plot after compensating the electrical signal based on the first compensation coefficient. For example, the electrical signal of the particles of the whole RET channel is amplified by a first compensation factor, i.e., a first order compensation, according to the temperature drift characteristics of the red blood cell pellet. After this compensation is performed, differentiation of erythrocytes from packed erythrocytes can be achieved. The first compensation coefficient is, for example:
Figure BDA0003404505790000291
because the temperature drift characteristics of the first particles and the second particles, such as erythrocyte particle group particles and platelet particle group particles, are not consistent, the electric signals of the second particles (such as platelet particle group particles) after the first-stage compensation are still compensated in place, for example, smaller g p /g R The accuracy of distinguishing different particles in the second particles is low only according to the electric signals of the second particles after the first-stage compensation.
In some embodiments, the reagent comprises a diluent for spherically treating the blood sample and a dye for staining the blood sample; the signal processing device is used for distinguishing erythrocyte particle group particles and platelet particle group particles in particles passing through the detection area and at least erythrocytes and reticulocytes in the erythrocyte particle group particles according to the electric signals compensated based on the first compensation coefficient, so as to obtain an analysis result of the erythrocyte particle group; and distinguishing at least platelets and immature platelets in the platelet particle group particles according to the compensated electric signals corresponding to the platelet particle group particles based on the adjusted second classification parameters, so as to obtain an analysis result of at least the platelet particle group.
In some embodiments, the reagent comprises a hemolysis agent for hemolysis treatment of the blood sample and a staining solution for staining the blood sample; the signal processing device is used for distinguishing white blood cell subset particles and blood shadow region particle group particles in particles passing through the detection region and at least two particles in the white blood cell subset particles according to the electric signals compensated based on the first compensation coefficient, so as to obtain analysis results of the white blood cell subset; and distinguishing at least platelet particle group particles and reticulocytes in the platelet particle group particles according to the compensated electric signals corresponding to the platelet particle group particles based on the adjusted second classification parameters, so as to obtain an analysis result of at least the platelet particle group.
Wherein at least two of the leukocyte subpopulation particles are selected from at least two of the following: lymphocytes, monocytes, eosinophils, neutrophils, basophils, naive granulocytes.
In some embodiments, the reagent comprises a hemolysis agent for hemolysis treatment of the blood sample and a staining solution for staining the blood sample; the signal processing device is used for distinguishing white blood cell group particles and nucleated red blood cells in particles passing through the detection area and at least basophils in the white blood cell group particles according to the electric signals compensated based on the first compensation coefficient to obtain an analysis result of the white blood cell group; and obtaining an analysis result of at least the nucleated red blood cells according to the compensated electrical signals corresponding to the nucleated red blood cells based on the adjusted second classification parameters.
The second classification parameters are adjusted based on the second compensation coefficients, so that the adjusted second classification parameters are more in line with the temperature drift characteristics of the second particles; when at least two particles in the second particles are distinguished according to the compensated electric signals corresponding to the second particles based on the adjusted second classification parameters, the influence of the difference of the temperature drift characteristics of the second particles and the first particles on the analysis result of the sample can be eliminated, and the accuracy of the analysis result is improved.
Referring to fig. 18, the right scatter diagram is a RET scatter diagram in which the electric signal is compensated based on the first compensation coefficient, a white solid line in the scatter diagram indicates a boundary between two kinds of the second particles at the reference temperature, and a white dotted line indicates a boundary adjusted based on the second compensation coefficient.
For example, the algorithmic demarcation of platelets from immature platelets at the reference temperature uses x=b 1 When the ambient temperature is t, the boundary line adjusted based on the second compensation coefficient is as follows:
Figure BDA0003404505790000301
for example, in the DIFF channel and the WNB channel, the particles are divided by an area surrounded by a plurality of boundary lines, and classification parameters (such as slope and/or intercept) corresponding to one or more boundary lines may be adjusted according to the second compensation coefficient.
Example eleven
Referring to fig. 19 in combination with the foregoing embodiments, fig. 19 is a flow chart of a method for analyzing a blood sample according to an embodiment of the present application. The analysis method may be applied to the aforementioned sample analyzer, for example, but is not limited thereto.
As shown in fig. 19, the analysis method of the blood sample according to the embodiment of the present application includes steps S110 to S150.
S110, acquiring an electric signal of light output generated by a light detector after detecting particles passing through a detection area after being irradiated by light, wherein a sample liquid to be detected passing through the detection area at least comprises first particles and second particles, and the second particles and the first particles are different particles;
S120, obtaining a temperature value representing the temperature of the sample liquid to be tested;
s130, determining a first compensation coefficient and a second compensation coefficient according to the temperature value;
s140, performing compensation processing on the electric signal based on the first compensation coefficient and the second compensation coefficient;
s150, obtaining analysis results of at least the first particles and the second particles according to the electric signals after the compensation processing.
In some embodiments, the acquiring the electrical signal of the light output of the particles passing through the detection zone after being illuminated by the light comprises: at least a fluorescence electric signal is obtained, which is output by the fluorescence detector to detect fluorescence generated by the particles passing through the detection region after being irradiated with light.
Illustratively, the obtaining the analysis result of at least the first particle and the second particle according to the electrical signal after the compensation processing includes: and distinguishing erythrocyte particle group particles from platelet particle group particles in particles passing through the detection zone according to the fluorescence electric signals after compensation treatment, so as to obtain an analysis result of at least the erythrocyte particle group and the platelet particle group.
The specific principle and implementation of the method for analyzing a blood sample provided in the embodiment of the present application are similar to those of the sample analyzer in the foregoing embodiment, and are not repeated here.
It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.
It should also be understood that the term "and/or" as used in this application and the appended claims refers to any and all possible combinations of one or more of the associated listed items, and includes such combinations.
While the invention has been described with reference to certain preferred embodiments, it will be understood by those skilled in the art that various changes and substitutions of equivalents may be made and equivalents will be apparent to those skilled in the art without departing from the scope of the invention. Therefore, the protection scope of the present application shall be subject to the protection scope of the claims.

Claims (32)

1. A sample analyzer, comprising:
a sampling device comprising a sampling needle for sucking a blood sample to be tested;
a sample preparation part having a reaction cell for receiving a portion of a blood sample to be measured sucked by the sampling device and a reagent supply part for supplying a reagent to the reaction cell so that the portion of the blood sample to be measured is mixed with the reagent in the reaction cell to prepare a sample liquid to be measured; the sample liquid to be detected at least comprises first particles and second particles; wherein the second particles and the first particles are different particles;
The optical measuring device comprises a flow chamber, a light source and a light detector, wherein the light source is used for emitting light beams to irradiate a detection area of the flow chamber, the flow chamber is communicated with the reaction tank, so that each particle in a sample liquid to be measured in the reaction tank can pass through the detection area of the flow chamber, and the light detector is used for detecting a light output electric signal generated by the particles passing through the detection area after the particles are irradiated by light;
the signal processing device is used for obtaining a temperature value representing the temperature of the sample liquid to be detected, determining a first compensation coefficient and a second compensation coefficient according to the temperature value, carrying out compensation processing on the electric signal based on the first compensation coefficient and the second compensation coefficient, and obtaining an analysis result of at least the first particle and the second particle according to the electric signal after the compensation processing.
2. The sample analyzer of claim 1, wherein the light detector comprises at least two of a fluorescence detector, a forward scatter detector, a side scatter detector; the electrical signals include at least two of fluorescent electrical signals, forward scattered photoelectric signals, and side scattered photoelectric signals.
3. The sample analyzer of claim 1, wherein the signal processing device is configured to:
Distinguishing at least two particles in the first particles according to the electric signals subjected to the compensation processing based on the first compensation coefficient to obtain an analysis result of the first particles; and/or
And distinguishing at least two particles in the second particles according to the electric signals after the compensation processing based on the second compensation coefficient, so as to obtain an analysis result of the second particles.
4. The sample analyzer according to claim 1, wherein the signal processing means is configured to perform compensation processing on particles passing through the detection region based on the first compensation coefficient, and to distinguish between first particles and second particles among the particles and at least two particles among the first particles based on the electrical signal after the compensation processing based on the first compensation coefficient, to obtain an analysis result of the first particles; and
and carrying out compensation processing on the electric signals corresponding to the second particles based on the second compensation coefficients, and distinguishing at least two particles in the second particles according to the electric signals subjected to the compensation processing based on the second compensation coefficients to obtain analysis results of the second particles.
5. The sample analyzer according to claim 1, wherein the signal processing means is configured to perform compensation processing on particles passing through the detection area based on the first compensation coefficient, and to distinguish between a first particle of the particles and at least two particles of the first particles based on the electrical signal after the compensation processing based on the first compensation coefficient, to obtain an analysis result of the first particles; and
And carrying out compensation processing on particles passing through the detection area based on the second compensation coefficient, and distinguishing second particles in the particles and at least two particles in the second particles according to the electric signals subjected to the compensation processing based on the second compensation coefficient to obtain an analysis result of the second particles.
6. The sample analyzer of claim 1, wherein the signal processing device is configured to distinguish between first particles and second particles of the particles based on an electrical signal of the particles passing through the detection zone; and
performing compensation processing on the electric signals corresponding to the first particles based on the first compensation coefficient, and distinguishing at least two particles in the first particles according to the electric signals subjected to the compensation processing based on the first compensation coefficient to obtain an analysis result of the first particles; and/or
And carrying out compensation processing on the electric signals corresponding to the second particles based on the second compensation coefficients, and distinguishing at least two particles in the second particles according to the electric signals subjected to the compensation processing based on the second compensation coefficients to obtain analysis results of the second particles.
7. The sample analyzer of claim 4, wherein the electrical signal comprises an analog signal and a digital signal; the signal processing device comprises an amplifying circuit, an analog-to-digital conversion circuit and a gain setting circuit, wherein the amplifying circuit is used for amplifying an analog signal output by the optical detector, and the analog-to-digital conversion circuit is used for converting the analog signal amplified by the amplifying circuit into a digital signal;
The signal processing device is used for controlling the gain setting circuit to adjust the gain of the light detector and/or adjust the gain of the amplifying circuit based on the first compensation coefficient so as to carry out compensation processing on the analog signal; and
and carrying out compensation processing on the digital signal corresponding to the second particle based on the second compensation coefficient.
8. The sample analyzer of claim 4, wherein the electrical signal comprises an analog signal and a digital signal; the signal processing device comprises an amplifying circuit and an analog-to-digital conversion circuit, wherein the amplifying circuit is used for amplifying an analog signal output by the optical detector, and the analog-to-digital conversion circuit is used for converting the analog signal amplified by the amplifying circuit into a digital signal;
the signal processing device is used for carrying out compensation processing on the digital signal based on the first compensation coefficient; and
and carrying out compensation processing on the digital signal corresponding to the second particle based on the second compensation coefficient.
9. The sample analyzer of claim 5, wherein the electrical signal comprises an analog signal and a digital signal; the signal processing device comprises a first amplifying circuit, a second amplifying circuit, an analog-to-digital conversion circuit and a gain setting circuit, wherein the first amplifying circuit and the second amplifying circuit are respectively used for amplifying analog signals output by the optical detector, and the analog-to-digital conversion circuit is used for converting the analog signals amplified by the first amplifying circuit and the second amplifying circuit into digital signals;
The signal processing device is used for controlling the gain setting circuit to adjust the gain of the first amplifying circuit based on the first compensation coefficient so as to carry out compensation processing on the analog signals of the particles passing through the detection area; and
and controlling the gain setting circuit to adjust the gain of the second amplifying circuit based on the second compensation coefficient, thereby performing compensation processing on the analog signal of the particle passing through the detection region.
10. The sample analyzer of claim 5, wherein the electrical signal comprises an analog signal and a digital signal; the signal processing device comprises an amplifying circuit, an analog-to-digital conversion circuit and a processor, wherein the amplifying circuit is used for amplifying an analog signal output by the optical detector, and the analog-to-digital conversion circuit is used for converting the analog signal amplified by the amplifying circuit into a digital signal;
the processor is used for carrying out compensation processing on the digital signals corresponding to the particles passing through the detection zone based on the first compensation coefficient; and
and carrying out compensation processing on the digital signals corresponding to the particles passing through the detection zone based on the second compensation coefficient.
11. The sample analyzer of claim 6, wherein the electrical signal comprises an analog signal and a digital signal; the signal processing device comprises an amplifying circuit, an analog-to-digital conversion circuit and a processor, wherein the amplifying circuit is used for amplifying an analog signal output by the optical detector, and the analog-to-digital conversion circuit is used for converting the analog signal amplified by the amplifying circuit into a digital signal;
The processor is used for carrying out compensation processing on the digital signal corresponding to the first particle based on the first compensation coefficient; and
and carrying out compensation processing on the digital signal corresponding to the second particle based on the second compensation coefficient.
12. The sample analyzer according to any one of claims 1 to 11, wherein the signal processing device is further configured to determine a third compensation coefficient according to the temperature value, perform compensation processing on the electrical signal after compensation processing based on the first compensation coefficient and/or the second compensation coefficient based on the third compensation coefficient, and obtain an analysis result of a third particle according to the electrical signal after compensation processing based on the third compensation coefficient.
13. The sample analyzer of any one of claims 1-4, 7-8, wherein the reagent comprises a diluent for sphericizing a blood sample and a dye for staining the blood sample;
the signal processing device is used for distinguishing erythrocyte particle group particles and platelet particle group particles in particles passing through the detection area and at least erythrocytes and reticulocytes in the erythrocyte particle group particles according to the electric signals compensated based on the first compensation coefficient, so as to obtain an analysis result of the erythrocyte particle group; and
And compensating the electric signals corresponding to the platelet particle group particles based on the second compensation coefficient, and distinguishing at least platelets and immature platelets in the platelet particle group particles according to the electric signals compensated based on the second compensation coefficient to obtain an analysis result of at least the platelet particle group.
14. The sample analyzer of any one of claims 1-3, 5, 6, 9-11, wherein the reagent comprises a diluent for spherically treating the blood sample and a dye for staining the blood sample; the signal processing device is used for:
distinguishing the erythrocyte particle group particles in the particles passing through the detection area from at least erythrocytes and reticulocytes in the erythrocyte particle group particles according to the electric signals compensated based on the first compensation coefficient, so as to obtain an analysis result of at least erythrocyte particle groups; and
and distinguishing platelet particle group particles in the particles passing through the detection area from at least platelets and immature platelets in the platelet particle group particles according to the electric signals compensated based on the second compensation coefficient, so as to obtain an analysis result of at least the platelet particle group.
15. The sample analyzer of claim 13 or 14, wherein the signal processing device is configured to perform compensation processing on the fluorescent electrical signal generated by the fluorescent detector in the light detector based on the first compensation coefficient and the second compensation coefficient; and obtaining an analysis result of at least the erythrocyte particle group and the platelet particle group according to the scattered light signals generated by the scattered light detectors in the light detectors and the compensated processed fluorescent electric signals.
16. The sample analyzer of any one of claims 1-4, 7-8, wherein the reagent comprises a hemolyzing agent for hemolyzing the blood sample and a staining solution for staining the blood sample;
the signal processing device is used for distinguishing white blood cell subset particles and blood shadow region particle group particles in particles passing through the detection region and at least two particles in the white blood cell subset particles according to the electric signals compensated based on the first compensation coefficient, so as to obtain analysis results of the white blood cell subset; and
compensating the electric signals corresponding to the particles of the particle group of the blood shadow area based on the second compensation coefficient, and distinguishing at least the particles of the particle group of the blood shadow area from reticulocytes according to the electric signals compensated based on the second compensation coefficient to obtain an analysis result of the particle group of the blood shadow area;
Wherein at least two of the leukocyte subpopulation particles are selected from at least two of the following: lymphocytes, monocytes, eosinophils, neutrophils, basophils, naive granulocytes.
17. The sample analyzer of any one of claims 1-3, 5, 6, 9-11, wherein the reagent comprises a hemolyzing agent for hemolyzing the blood sample and a staining solution for staining the blood sample; the signal processing device is used for:
distinguishing white blood cell subset particles in the particles passing through the detection zone from at least two particles in the white blood cell subset particles according to the electric signals compensated based on the first compensation coefficient, so as to obtain an analysis result of the white blood cell subset; and
distinguishing blood shadow region particle group particles from at least blood platelet particle group particles and reticulocytes in the blood shadow region particle group particles in the particles passing through the detection region according to the electric signals compensated based on the second compensation coefficient, so as to obtain an analysis result of at least the blood shadow region particle group;
wherein at least two of the leukocyte subpopulation particles are selected from at least two of the following: lymphocytes, monocytes, eosinophils, neutrophils, basophils, naive granulocytes.
18. The sample analyzer of claim 16 or 17, wherein the first compensation coefficient comprises a first fluorescence compensation coefficient and/or a first forward scattered light compensation coefficient, and the second compensation coefficient comprises a second fluorescence compensation coefficient and/or a second forward scattered light compensation coefficient; the signal processing device is used for carrying out compensation processing on fluorescent electric signals generated by a fluorescent detector in the optical detector based on the first fluorescent compensation coefficient and the second fluorescent compensation coefficient; the device is also used for compensating forward scattered photoelectric signals generated by forward scattered light detectors in the light detectors based on the first forward scattered light compensation coefficient and/or the second forward scattered light compensation coefficient;
the signal processing device is used for obtaining an analysis result of at least the leukocyte subpopulation and the particle swarm in the blood shadow area according to the forward scattering photoelectric signal after compensation processing and the fluorescence electric signal after compensation processing.
19. The sample analyzer of any one of claims 1-4, 7-8, wherein the reagent comprises a hemolyzing agent for hemolyzing the blood sample and a staining solution for staining the blood sample;
The signal processing device is used for distinguishing white blood cell group particles and nucleated red blood cells in particles passing through the detection area and at least basophils in the white blood cell group particles according to the electric signals compensated based on the first compensation coefficient to obtain an analysis result of the white blood cell group; and
and compensating the electric signal corresponding to the nucleated red blood cells based on the second compensation coefficient, and obtaining an analysis result of at least the nucleated red blood cells according to the electric signal compensated based on the second compensation coefficient.
20. The sample analyzer of any one of claims 1-3, 5, 6, 9-11, wherein the reagent comprises a hemolyzing agent for hemolyzing the blood sample and a staining solution for staining the blood sample; the signal processing device is used for:
distinguishing the white blood cell population particles in the particles passing through the detection zone from at least basophils in the white blood cell population particles according to the electric signals compensated based on the first compensation coefficient, so as to obtain an analysis result of the white blood cell population; and
and distinguishing nucleated red blood cells in the particles passing through the detection area according to the electric signals compensated based on the second compensation coefficient, so as to obtain an analysis result of at least the nucleated red blood cells.
21. The sample analyzer of claim 19 or 20, wherein the signal processing device is configured to perform compensation processing on fluorescent electrical signals generated by a fluorescent detector in the light detector based on the first compensation coefficient and the second compensation coefficient; and obtaining an analysis result of at least the white blood cell population and the nucleated red blood cells according to the scattered light signals generated by the scattered light detectors in the light detectors and the compensated processed fluorescent electrical signals.
22. The sample analyzer of any one of claims 1-21, further comprising a temperature detection device, wherein the signal processing device is configured to obtain a temperature value detected by the temperature detection device; or alternatively
The signal processing means is for acquiring the temperature value from a temperature detection means other than the sample analyzer.
23. The sample analyzer of any one of claims 1-21, wherein the signal processing device is configured to determine the corresponding first compensation coefficient and second compensation coefficient according to the temperature value based on a correspondence between a preset temperature value and the first compensation coefficient and the second compensation coefficient.
24. A sample analyzer, comprising:
a sampling device comprising a sampling needle for sucking a blood sample to be tested;
a sample preparation part having a reaction cell for receiving a portion of a blood sample to be measured sucked by the sampling device and a reagent supply part for supplying a reagent to the reaction cell so that the portion of the blood sample to be measured is mixed with the reagent in the reaction cell to prepare a sample liquid to be measured; the sample liquid to be detected at least comprises first particles and second particles; wherein the second particles and the first particles are different particles;
the optical measuring device comprises a flow chamber, a light source and a light detector, wherein the light source is used for emitting light beams to irradiate a detection area of the flow chamber, the flow chamber is communicated with the reaction tank, so that each particle in a sample liquid to be measured in the reaction tank can pass through the detection area of the flow chamber, and the light detector is used for detecting fluorescent output fluorescent electric signals generated by the particles passing through the detection area after the particles are irradiated by light;
the signal processing device is used for obtaining a temperature value representing the temperature of the sample liquid to be detected, determining a first compensation coefficient and a second compensation coefficient according to the temperature value, and carrying out compensation processing on the fluorescent electric signal based on the first compensation coefficient and the second compensation coefficient; and distinguishing the erythrocyte particle group particles from the platelet particle group particles in the particles passing through the detection zone according to the fluorescence electric signals after compensation treatment to obtain an analysis result of at least the erythrocyte particle group and the platelet particle group.
25. The sample analyzer of claim 24, wherein the signal processing device is configured to distinguish between red blood cells and reticulocytes in the population of red blood cell particles to obtain an analysis result of the population of red blood cell particles; and/or
And distinguishing platelets from immature platelets in the platelet particle group particles to obtain an analysis result of the platelet particle group.
26. A sample analyzer, comprising:
a sampling device comprising a sampling needle for sucking a blood sample to be tested;
a sample preparation part having a reaction cell for receiving a portion of a blood sample to be measured sucked by the sampling device and a reagent supply part for supplying a reagent to the reaction cell so that the portion of the blood sample to be measured is mixed with the reagent in the reaction cell to prepare a sample liquid to be measured; the sample liquid to be detected at least comprises first particles and second particles; wherein the second particles and the first particles are different particles;
the optical measuring device comprises a flow chamber, a light source and a light detector, wherein the light source is used for emitting light beams to irradiate a detection area of the flow chamber, the flow chamber is communicated with the reaction tank, so that each particle in a sample liquid to be measured in the reaction tank can pass through the detection area of the flow chamber, and the light detector is used for detecting a light output electric signal generated by the particles passing through the detection area after the particles are irradiated by light;
The signal processing device is used for obtaining a temperature value representing the temperature of the sample liquid to be detected, and determining a first compensation coefficient and a second compensation coefficient according to the temperature value; adjusting a first classification parameter based on the first compensation coefficient, and adjusting a second classification parameter based on the second compensation coefficient; and distinguishing at least two particles in the first particles according to the electric signal based on the adjusted first classification parameter to obtain an analysis result of the first particles; and distinguishing at least two particles in the second particles according to the electric signals based on the adjusted second classification parameters to obtain analysis results of the second particles.
27. A sample analyzer, comprising:
a sampling device comprising a sampling needle for sucking a blood sample to be tested;
a sample preparation part having a reaction cell for receiving a portion of a blood sample to be measured sucked by the sampling device and a reagent supply part for supplying a reagent to the reaction cell so that the portion of the blood sample to be measured is mixed with the reagent in the reaction cell to prepare a sample liquid to be measured; the sample liquid to be detected at least comprises first particles and second particles; wherein the second particles and the first particles are different particles;
The optical measuring device comprises a flow chamber, a light source and a light detector, wherein the light source is used for emitting light beams to irradiate a detection area of the flow chamber, the flow chamber is communicated with the reaction tank, so that each particle in a sample liquid to be measured in the reaction tank can pass through the detection area of the flow chamber, and the light detector is used for detecting a light output electric signal generated by the particles passing through the detection area after the particles are irradiated by light;
the signal processing device is used for obtaining a temperature value representing the temperature of the sample liquid to be detected, and determining a first compensation coefficient and a second compensation coefficient according to the temperature value; carrying out compensation processing on particles passing through the detection area based on the first compensation coefficient, and distinguishing at least two particles in the first particles according to the electric signals subjected to the compensation processing based on the first compensation coefficient to obtain an analysis result of the first particles;
the signal processing device is further configured to adjust a second classification parameter based on the second compensation coefficient, and distinguish at least two particles in the second particles according to the compensated electrical signal corresponding to the second particles based on the adjusted second classification parameter, so as to obtain an analysis result of the second particles.
28. The sample analyzer of claim 27, wherein the reagent comprises a diluent for spherically treating the blood sample and a dye for staining the blood sample;
the signal processing device is used for distinguishing erythrocyte particle group particles and platelet particle group particles in particles passing through the detection area and at least erythrocytes and reticulocytes in the erythrocyte particle group particles according to the electric signals compensated based on the first compensation coefficient, so as to obtain an analysis result of the erythrocyte particle group; and
and distinguishing at least platelets and immature platelets in the platelet particle group particles according to the compensated electric signals corresponding to the platelet particle group particles based on the adjusted second classification parameters, so as to obtain an analysis result of at least the platelet particle group.
29. The sample analyzer of claim 27, wherein the reagent comprises a hemolyzing agent for hemolyzing the blood sample and a dye solution for staining the blood sample;
the signal processing device is used for distinguishing white blood cell subset particles and blood shadow region particle group particles in particles passing through the detection region and at least two particles in the white blood cell subset particles according to the electric signals compensated based on the first compensation coefficient, so as to obtain analysis results of the white blood cell subset; and
Distinguishing at least platelet particle swarm particles and reticulocytes in the platelet particle swarm particles according to the compensated electric signals corresponding to the platelet particle swarm particles on the basis of the adjusted second classification parameters, and obtaining an analysis result of at least the platelet particle swarm;
wherein at least two of the leukocyte subpopulation particles are selected from at least two of the following: lymphocytes, monocytes, eosinophils, neutrophils, basophils, naive granulocytes.
30. The sample analyzer of claim 27, wherein the reagent comprises a hemolyzing agent for hemolyzing the blood sample and a dye solution for staining the blood sample;
the signal processing device is used for distinguishing white blood cell group particles and nucleated red blood cells in particles passing through the detection area and at least basophils in the white blood cell group particles according to the electric signals compensated based on the first compensation coefficient to obtain an analysis result of the white blood cell group; and
and obtaining an analysis result of at least the nucleated red blood cells according to the compensated electric signals corresponding to the nucleated red blood cells based on the adjusted second classification parameters.
31. A method of analyzing a blood sample, comprising:
acquiring an electric signal of light output generated by a light detector after detecting particles passing through a detection area by light irradiation, wherein a sample liquid to be detected passing through the detection area at least comprises first particles and second particles, and the second particles and the first particles are different particles;
acquiring a temperature value representing the temperature of a sample liquid to be measured;
determining a first compensation coefficient and a second compensation coefficient according to the temperature value;
performing compensation processing on the electric signal based on the first compensation coefficient and the second compensation coefficient;
and obtaining an analysis result of at least the first particles and the second particles according to the electric signals after the compensation treatment.
32. The method of claim 31, wherein the acquiring the electrical signal of the light output of the light detector generated by the particles passing through the detection zone after being illuminated by the light comprises: at least acquiring a fluorescence electric signal output by fluorescence detector for detecting fluorescence generated by particles passing through a detection area after being irradiated by light;
the analysis result of at least the first particle and the second particle is obtained according to the electric signal after compensation processing, and the method comprises the following steps:
And distinguishing erythrocyte particle group particles from platelet particle group particles in particles passing through the detection zone according to the fluorescence electric signals after compensation treatment, so as to obtain an analysis result of at least the erythrocyte particle group and the platelet particle group.
CN202111508951.6A 2021-12-10 2021-12-10 Sample analyzer and method for analyzing blood sample Pending CN116256304A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111508951.6A CN116256304A (en) 2021-12-10 2021-12-10 Sample analyzer and method for analyzing blood sample

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111508951.6A CN116256304A (en) 2021-12-10 2021-12-10 Sample analyzer and method for analyzing blood sample

Publications (1)

Publication Number Publication Date
CN116256304A true CN116256304A (en) 2023-06-13

Family

ID=86684918

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111508951.6A Pending CN116256304A (en) 2021-12-10 2021-12-10 Sample analyzer and method for analyzing blood sample

Country Status (1)

Country Link
CN (1) CN116256304A (en)

Similar Documents

Publication Publication Date Title
US7390662B2 (en) Method and apparatus for performing platelet measurement
CN107202903B (en) Sample analyzer and sample analyzing method thereof
KR101941310B1 (en) Identifying and enumerating early granulated cells (egc)
US8828737B2 (en) Use of focused light scattering techniques in biological applicationa
EP1714146B1 (en) Method of measurement of nucleated red blood cells
JP3793685B2 (en) Automatic analysis system and method
JP6232046B2 (en) Urine sample analyzer and urine sample analysis method
JP6116502B2 (en) Sample analyzer and sample analysis method
AU2006210424A1 (en) Methods and devices for characterizing particles in clear and turbid media
JP5937780B2 (en) Fluorescence spectrum correction method and fluorescence spectrum measuring apparatus
US6979570B2 (en) Particle analyzer and particle analyzing method
US8996317B2 (en) Sample analyzer, computer program product for a sample analyzer and method for analyzing a sample
CN108279229B (en) Whole blood CRP detection device
US8349256B2 (en) Blood cell analyzer, blood cell analyzing method, and computer program product
CN114450589A (en) Method for analyzing red blood cells in blood sample and blood analysis system
CN114252386A (en) Sample detection method and sample analyzer
EP0467952B1 (en) Method for screening cells or formed bodies with populations expressing selected characteristics utilizing one sensing parameter
CN116256304A (en) Sample analyzer and method for analyzing blood sample
JPH05322882A (en) Blood analyzing instrument
CN113495050A (en) Cell sorting method, sorting device, and program
JP7319986B2 (en) Analysis method for biological sample containing living cells and analyzer for implementing the analysis method
CN105334191B (en) Method and device for correcting hemoglobin concentration and volume of single red blood cell
CN115201154A (en) Method for detecting blood sample and sample analyzer
CN116026728A (en) Blood analyzer and blood analysis method
Longanbach et al. Since the 1980s, automated blood cell analysis has virtu-ally replaced manual hemoglobin, hematocrit, and cell

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication