CN103471980A - Chip-type hemocyte analyzing device and method - Google Patents
Chip-type hemocyte analyzing device and method Download PDFInfo
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Abstract
The invention belongs to the technical field of hemocyte analysis, and particularly relates to a chip-type hemocyte analyzing device and a chip-type hemocyte analyzing method. The chip-type hemocyte analyzing device comprises a hemocyte analysis chip, the hemocyte analysis chip comprises a leucocyte/haematoglobin analysis chip and an erythrocyte/thrombocyte analysis chip, the leucocyte/haematoglobin analysis chip detects leucocytes by adopting an electrical impedance, high frequency conductance and laser scattering detection technology, and the erythrocyte/thrombocyte analysis chip respectively accounts the erythrocyte and thrombocyte by adopting a sheath flow technology, an electrical impedance technology or a floating landmark technology. According to the invention, typing of the hematocytes is realized by using the hematocyte analysis chip, the chip-type hemocyte analyzing device has the advantages of simple structure, small size, low cost, high convenience in operation, high easiness in maintenance and transportation, disposable property and the like, meets the development requirement on analyzer miniaturization, integration and portability, and is particularly suitable for field detection, emergency analysis, domestic application and basic medical units.
Description
Technical Field
The invention belongs to the technical field of blood cell analysis, and particularly relates to a chip type blood cell analysis device and method.
Background
The information obtained by blood cell analysis can help to diagnose, differential diagnose and disease related to the blood system, help to analyze the state of an illness, observe the curative effect and judge the prognosis, provide basis for preventing diseases, guide clinical medication and carry out clinical medical research, so the blood cell test (i.e. the blood routine) becomes the first of three routine tests (the blood routine, the urine routine and the stool routine) in clinical tests, and the clinical application of the blood cell test is also the most extensive. Since the invention of the electrical impedance cytometry by Coulter in 1953, various automatic blood cell analyzers were developed in succession, and the blood cell analysis technology was rapidly developed.
At present, the traditional blood cell analyzer is large in size, high in price and complex in operation, needs to be used by a specially-assigned person for periodic maintenance, is expensive in price of a measuring reagent matched with the blood cell analyzer, is generally suitable for hospital inspection departments with more and more concentrated inspection samples, is small in sample amount for basic medical units such as village health rooms and the like, is very dispersed in time dimension, has obvious uncomfortable conditions, does not meet the development requirements of miniaturization, integration and portability of the analyzer, and cannot meet the use requirements of smaller units such as village health rooms, community clinics or personal families and the like. Therefore, the defects of the traditional detection equipment are overcome, the requirements of the primary medical unit on detection means are met, and the portable blood cell analyzer with simple operation and instant report results is urgently needed to be developed, so that the blood cell analyzer is suitable for field detection, emergency analysis, household application and primary medical treatment.
Disclosure of Invention
The invention provides a chip type blood cell analysis device and method, and aims to solve the technical problems that an existing blood cell analyzer is large in size, high in price and complex in operation, and cannot meet the use requirements of smaller medical units.
The technical scheme provided by the invention is as follows: a chip type blood cell analysis device comprises a blood cell analysis chip, wherein the blood cell analysis chip comprises a white blood cell/hemoglobin analysis chip and a red blood cell/platelet analysis chip, the white blood cell/hemoglobin analysis chip detects white blood cells by adopting an electrical impedance, high-frequency conductance and laser scattering detection technology, and the red blood cell/platelet analysis chip respectively counts red blood cells and platelets by adopting a sheath flow technology, an electrical impedance technology or a floating landmark technology.
The technical scheme of the invention also comprises: the leucocyte/hemoglobin analysis chip adopts the electrical impedance to measure the volume of the leucocyte and adopts the high-frequency conductance technology to react the internal structure information of the cell; and analyzing cell particle information by using the laser scattering technology.
The technical scheme of the invention also comprises: the leucocyte/hemoglobin analysis chip detects the concentration of hemoglobin by a colorimetric method; the detection mode for detecting the concentration of the hemoglobin is as follows: the color was measured at specific wavelengths of 530-550nm and the absorbance value of the blood sample was determined.
The technical scheme of the invention also comprises: be provided with liquid storage tank, waste liquid pond, detection zone, color comparison pond and flow sensor on the leucocyte/hemoglobin analysis chip, the liquid storage tank is used for saving detect reagent, the waste liquid pond is used for saving the blood sample through the detection, the detection zone is used for detecting the leucocyte of process, confirms each subgroup nature of leucocyte, the color comparison pond is arranged in detecting the concentration of haemoglobin in the blood sample, flow sensor is used for making corresponding fluid ration in the liquid storage pond.
The technical scheme of the invention also comprises: the erythrocyte/platelet analysis chip is provided with a liquid storage tank, a waste liquid tank, a detection area and a flow sensor, wherein the liquid storage tank is used for storing a detection reagent, the waste liquid tank is used for storing a detected blood sample, constant current is applied to the upper end and the lower end of the detection area, an electronic pulse is generated with passing cells through electrical impedance, erythrocytes and platelets are respectively counted according to the height of the pulse, and the flow sensor is used for quantifying corresponding fluid in the liquid storage tank; wherein, the counting mode of the red blood cells and the platelets is as follows: measuring the cell volume by measuring the pulse size, and recording the number of pulses to obtain a cell counting result; a threshold value is set according to the difference between the volumes of the platelets and the red blood cells, pulse signals higher than the threshold value are defined as red blood cells, pulse signals lower than the threshold value are defined as platelets, and counting and volume analysis of the red blood cells and the platelets are carried out according to the number and the size of generated electronic pulses.
The technical scheme of the invention also comprises: the sample introduction mode of the liquid storage tank comprises a micro pump, electric sample introduction, forward pressure drive sample introduction, negative pressure sample introduction or electroosmosis sample introduction.
The technical scheme of the invention also comprises: the blood cell analysis chip material comprises quartz, glass, monocrystalline silicon or high molecular polymer material.
The other technical scheme provided by the invention is as follows: a chip-based blood cell analysis method comprising:
step a: detecting the leucocytes on the leucocyte/hemoglobin analysis chip by adopting an electrical impedance, high-frequency conductance and laser scattering detection technology;
step b: detecting the concentration of hemoglobin by a colorimetric method;
step c: and respectively counting the red blood cells and the blood platelets on the red blood cell/blood platelet analysis chip by adopting a sheath flow technology, an electrical impedance technology or a floating landmark technology.
The technical scheme of the invention also comprises: in the a, the leukocyte detection means comprises: and measuring the volume of the white blood cells by adopting the electrical impedance, reflecting the internal structure information of the cells by adopting the high-frequency conductance technology, and analyzing the particle information of the cells by adopting the laser scattering technology.
The technical scheme of the invention also comprises: in the step b, the detection method for detecting the concentration of hemoglobin is as follows: the color was measured at specific wavelengths of 530-550nm and the absorbance value of the blood sample was determined.
The technical scheme of the invention has the following advantages or beneficial effects: the technical scheme of the invention has the following advantages or beneficial effects: the chip type blood cell analysis device and the method of the embodiment of the invention realize the typing of blood cells by utilizing the blood cell analysis chip, have the advantages of simple structure, small volume, low cost, convenient operation, easy maintenance, easy transportation, disposable chip and the like, meet the development requirements of miniaturization, integration and portability of an analysis instrument, and are particularly suitable for field detection, emergency analysis, household application and use of primary medical units.
Drawings
FIG. 1 is a schematic structural view of a chip-type blood cell analyzer according to an embodiment of the present invention;
FIG. 2 is a schematic diagram of the detection of the leukocyte/hemoglobin analysis chip according to the embodiment of the present invention;
FIG. 3 is a schematic diagram of the detection of the red blood cell/platelet analysis chip according to the embodiment of the present invention;
FIG. 4 is a flow chart of a chip-based blood cell analysis method according to an embodiment of the present invention;
FIG. 5 is a flow chart of a method for detecting leukocytes according to an embodiment of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Fig. 1 is a schematic structural diagram of a chip-type blood cell analyzer according to an embodiment of the invention. The chip type blood cell analysis device comprises a blood cell analysis chip, wherein the blood cell analysis chip comprises a leucocyte/hemoglobin analysis chip and a red blood cell/platelet analysis chip; wherein,
the leucocyte/hemoglobin analysis chip is used for detecting leucocytes by adopting physical detection technologies such as electrical impedance, high-frequency conductance, laser scattering and the like, and particularly,
please refer to fig. 2, which is a schematic diagram illustrating the detection of the leukocyte/hemoglobin analysis chip according to the embodiment of the present invention. The leucocyte/hemoglobin analysis chip is provided with a liquid storage tank, a waste liquid tank, a detection zone, a colorimetric tank and a flow sensor, wherein the liquid storage tank is used for storing a detection reagent, the waste liquid tank is used for storing a detected blood sample, the detection zone is used for carrying out one-by-one simultaneous and triple VCS (volume, conductivity, scatter, V-low frequency wave and cell volume analysis on the passing leucocytes, C-high frequency wave and cell karyotype analysis, S-laser and cell particle characteristics analysis, the VCS detection is that three probes V, C, S are used for carrying out one-by-one simultaneous and triple detection and three-dimensional analysis on the passing single-line leucocytes at a certain position of the detection zone so as to determine the subgroup property) detection, and the measured data is processed by a computer to determine the property of each subgroup of the leucocytes, the colorimetric pool is used for detecting the concentration of the hemoglobin, and the flow sensor is used for quantifying the corresponding fluid in each liquid storage pool. The number of the liquid storage tanks and the number of the flow sensors can be set according to detection requirements; the detection process comprises the following steps: under the quantitative action of flow sensors C1-C7, anticoagulant (one of the most common and important anticoagulants and reagents in clinical examination), diluent (electrolyte balance liquid with certain pH, proper osmotic pressure and conductivity, which is diluted with human blood cells in a certain proportion to keep the human blood cells in normal physiological form and disperse and not easily aggregate) and hemolytic agent (hemoglobin detection component and erythrocyte hemolytic agent, which is hypotonic and acidic solution containing a proper amount of wetting agent, can rapidly dissolve and destroy erythrocytes in blood, release hemoglobin and form stable compounds with the erythrocytes) are respectively injected into liquid storage tanks S1, R1 and R2, whole blood is properly diluted, and erythrocytes are dissolved and destroyed due to osmotic pressure difference of hemolytic agent, and then leukocyte stabilizer (a hypertonic and alkaline solution, which can neutralize hemolytic agent, is added into liquid storage tank R5, stabilizing leukocytes to keep or approach original physiological shape) and neutralizing hemolytic agent to restore leukocyte surface, cytoplasm and cell volume to original state, feeding sheath fluid into reservoir R6, allowing blood sample to pass through detection area A1 under the action of sheath fluid flow, and performing one-by-one, simultaneous and triple VCS detection (V-low frequency, analyzing cell volume; c-high frequency wave, analyzing cell nuclear type; s-laser, analyzing the particle characteristics of the cells; the VCS uses V, C, S probes to perform one-by-one, simultaneous, triple detection and three-dimensional analysis on a single column of white blood cells passing through at a certain position in a detection area so as to determine the properties of the subpopulations of the white blood cells), and the measured data is processed by a computer to determine the properties of each subpopulation of the white blood cells. Because different types of cells show obvious difference in characteristic information such as volume, surface characteristics, internal structure and the like, the characteristic information is defined into a three-dimensional scatter diagram formed by taking VCS as a three-dimensional coordinate, five types of white blood cells can form a specific cell group in a three-dimensional space, and five white blood cell classification results can be obtained by calculating the percentage of the number of the cells of a certain group to the total number of the white blood cells; meanwhile, because RBC (Red Blood Cell, Red Blood Cell count, which means the number of Red Blood cells contained in a unit volume of Blood) is dissolved and destroyed to release hemoglobin, the hemoglobin reacts with a hemolytic agent to form a stable hemoglobin compound, the hemoglobin compound enters a hemoglobin test system, namely a colorimetric pool E, and is subjected to colorimetry at a specific wavelength of 530-550nm and the absorbance value is measured, and the change of absorbance is proportional to the content of hemoglobin in liquid, so that the concentration of hemoglobin can be measured; in the embodiment of the invention, in addition to five white blood cell classifications, the white blood cell detection can also measure and analyze parameters such as the volume, the nuclear plasma proportion, the cell granule characteristics and the like of neutrophils, is used for understanding the difference between bacterial susceptibility diseases and other diseases, and also has the reticulocyte analysis function and the T lymphocyte subpopulation analysis function.
The electrical impedance detection is used for measuring the volume of white blood cells according to the Coulter electrical impedance principle, and the measuring method comprises the following steps: a certain low-frequency current passes through the two electrodes of the sensor, and due to the non-conductivity of the cells, when the cells pass through the two electrodes, the impedance between the electrodes is instantly increased to form electric pulses with the amplitude in direct proportion to the volume of the cells, the volume of the cells is measured according to the size of the pulses, and the cells are counted according to the number of the pulses; through the electronic selection of the pulse size generated by various cells, different types of cells can be incompletely distinguished, lymphocytes and monocytes with more obvious volume size difference can be effectively distinguished, but the cells with different types and the same volume can not be completely distinguished only by the cell volume because the pulse amplitudes generated by the cells with the different types and the same volume are the same, and then the internal structure of the white blood cells is analyzed by a high-frequency conductance method and laser scattering.
The high-frequency conductance technology is used for reacting the internal structure information of cells, and the specific reaction mode is as follows: although the cell wall cannot pass low frequency current, it can pass high frequency current; the electrode is provided with a radio frequency (high frequency) generator, the cell membrane has conductivity to the high frequency current, when the current passes through the cell, an alternating electromagnetic field is formed around the cell to form electromagnetic waves, the conductivity parameters of the high frequency current are different due to the difference of the internal structures such as the proportion of cell nucleus and pulp, particles, nuclear-to-mass ratio and the like, the electromagnetic field formed around the cell is different, and the internal structure information of the cell nucleus can be reflected by the conductivity parameters of the cell to the high frequency current and the variable quantity of the electromagnetic field; and can distinguish between the nucleus of the divided leaf and the cells without the leaf nucleus, and is used for distinguishing the cell populations with similar volumes and different internal structures, such as lymphocytes and basophils.
Laser scattering techniques were used to analyze cell particle information: the specific analysis mode is as follows: scanning each cell by monochromatic laser, analyzing the surface characteristics and the internal structure of the cell membrane, detecting the inner cell core leaf division condition and the particle structure and density condition in cytoplasm, detecting the light scattering characteristics of the cell in a wide angle range of 10-70 degrees, and distinguishing cell populations with different particle characteristics according to the light scattering characteristics of the cell, for example, the light scattering characteristics of coarse particles in the cell are stronger than those of fine particles, thereby distinguishing three types of neutrophilic, acidophilic and basophilic cells in the granulocyte.
The erythrocyte/platelet analysis chip is used for respectively counting erythrocytes and platelets by adopting a sheath flow technology, an electrical impedance technology or a floating landmark technology; FIG. 3 is a schematic diagram of the detection of the erythrocyte/platelet analysis chip according to the embodiment of the invention. The erythrocyte/platelet analysis chip is provided with a liquid storage tank, a waste liquid tank, a detection area and a flow sensor, wherein the liquid storage tank is used for storing a detection reagent, the waste liquid tank is used for storing a detected blood sample, constant current is applied to the upper end and the lower end of the detection area, the passing cells generate electronic pulse through the detection of an electrical impedance technology, the erythrocyte and the platelet are respectively counted according to the height of the pulse, and the flow sensor is used for quantifying the corresponding fluid in each liquid storage tank; wherein, the quantity of liquid storage tank and flow sensor can set up according to the measuring demand. The specific detection process is as follows: under the quantitative action of flow sensors C8-C13, anticoagulated blood is fed into a liquid storage tank S2, diluent is fed into a liquid storage tank R5, a quantitative whole blood sample is diluted by the quantitative diluent according to a proper proportion, first sheath liquid (diluent) is fed into the liquid storage tank R6, second sheath liquid (diluent) is fed into the liquid storage tank R7, the cells of the blood sample are arranged singly under the action of the quantitative sheath liquid flow and pass through pores at the downstream in a detection area A2 one by one, constant current is applied to the upper end and the lower end of the detection area A2, and the blood sample flows into a waste liquid tank W2 through electrical impedance detection (namely, each cell generates electronic pulse proportional to the cell volume); the red blood cells and platelets were counted: measuring the cell volume by measuring the pulse size, and recording the number of pulses to obtain a cell counting result; because the volume of Platelets (PLTs) is obviously different from that of red blood cells, a threshold value is set according to the volume difference of the platelets and the red blood cells, pulse signals higher than the threshold value are defined as red blood cells, and pulse signals lower than the threshold value are defined as platelets, so that the counting and volume analysis of the red blood cells and the platelets can be carried out according to the number and the size of generated electronic pulses; among these, the influence of the number of leukocytes was negligible. The invention accelerates the speed of cell flow passing through the detection area by adopting a secondary sheath flow mode, improves the number of detected cells, simultaneously stabilizes the diameter of the cell flow at the width close to that of blood cells by adopting an accurate chip structure and pressure balance control, ensures that the cells are singly arranged under the action of fluid dynamics to receive electrical impedance detection, ensures that a large number of cells are accurately and quickly measured one by one, and shortens the time of sample detection.
The sheath flow technology specifically comprises the following steps: in order to avoid the phenomenon that cells flow through a detection area in parallel or in a lateral direction in the detection process and the phenomenon of cell backflow, turbulence or eddy current brings detection errors, a sheath flow technology is adopted, namely, a cell suspension sample forms a compressed flow form similar to a sheath shape under the action of a sheath liquid lateral extrusion effect flowing at a high speed, so that the sample cells are ensured to form a single arranged cell flow under the coating of the sheath liquid and sequentially pass through the detection area; sheath flow technology can be applied to two cell counting principles: one is the principle of electrical impedance, and the sheath flow passes through a sensitive area of a detection area to count cells; the other is a laser counting principle, a cell flow chamber is longer and is vertically intersected with laser, laser beams irradiate each cell flowing through to generate light scattering, and the cell counting is carried out by utilizing the principle; the floating landmark technique is: since the boundaries between various cells can move left or right with the actual size of the cell, the technique is called floating landmark; the volume difference between red blood cells and platelets in a normal specimen is large, the limit between the red blood cells and the platelets is generally 35fl, the large red blood cells and the small platelets are also 30fl or 20 fl; but in some pathological cases it may be that large platelets exceed the 35fl limit, causing a platelet leaky meter with low results; conversely, if the volume of red blood cells is small (e.g., iron deficiency anemia or thalassemia), some of the small red blood cells may be miscalculated as platelets, resulting in a high platelet count; in order to obtain accurate results, the counting instrument uses a computer to search the lowest point of the histogram between 5fl and 35fl, so as to define the boundary between red blood cells and platelets, and the landmarks of the histogram are automatically adjusted according to the change of the cell group, thereby enabling the counted value to be in accordance with the actual situation.
In the embodiment of the invention, the sample injection of the liquid storage pool adopts various modes such as micropump, electric sample injection, forward pressure driven sample injection, negative pressure sample injection or electroosmosis sample injection, etc., and the blood cell analysis chip can be made of quartz, glass, monocrystalline silicon, high polymer polymerization and other materials, such as polymethyl methacrylate (PMMA), Polydimethylsiloxane (PDMS) or Polycarbonate (PC); the adsorption of the surface of the chip microchannel to blood cells can be reduced or avoided by means of surface modification of the chip microchannel, chip material modification or adding proper additives into solution; meanwhile, the invention is also applicable to industries such as quantitative and qualitative analysis related to measuring the diameter of substance particles or the number of micro-particles in liquid, for example, physicochemical analysis in pure water, and the content of impurities and bacteria in the pure water is measured; or the measurement or calibration of the purity of various industrial high-purity liquids.
FIG. 4 is a flowchart of a chip-based blood cell analysis method according to an embodiment of the present invention. The chip type blood cell analysis method provided by the embodiment of the invention comprises the following steps:
step 400: detecting leucocytes on the leucocyte/hemoglobin analysis chip through anticoagulation, diluent, hemolytic agent, leucocyte stabilizing agent, sheath fluid and the like, and determining the properties of each subgroup of the leucocytes;
in step 400, the white blood cell detection process is: anticoagulant, diluent and hemolytic agent are respectively injected into liquid storage tanks S1, R1 and R2, whole blood is properly diluted, red blood cells are dissolved and destroyed due to osmotic pressure difference of hemolytic agent, then white blood cell stabilizing agent is added into the liquid storage tank R5 to neutralize hemolytic agent, the surface, cytoplasm and cell volume of the white blood cells are basically recovered to original states, sheath liquid is injected into the liquid storage tank R6, white blood cells of a blood sample are arranged in a line and pass through a detection zone A1 one by one under the action of sheath liquid flow, one by one, simultaneous and triple VCS detection is carried out on the passing white blood cells, and the measured data is processed by a computer to determine the properties of each subgroup of the white blood cells. Because different types of cells show obvious difference in characteristic information such as volume, surface characteristics, internal structure and the like, the characteristic information is defined into a three-dimensional scatter diagram formed by taking VCS as a three-dimensional coordinate, five types of white blood cells can form a specific cell group in a three-dimensional space, and five white blood cell classification results can be obtained by calculating the percentage of the number of the cells of a certain group to the total number of the white blood cells; in the embodiment of the invention, in addition to five white blood cell classifications, the white blood cell detection can also determine and analyze parameters such as the volume, the nuclear plasma proportion, the cell particle characteristics and the like of neutrophils, is used for understanding the difference between bacterial susceptibility diseases and other diseases, and also has the reticulocyte analysis function and the T lymphocyte subset analysis function; wherein the VCS is detected as: v-low frequency wave, analyzing cell volume; c-high frequency wave, analyzing cell nuclear type; s-laser, analyzing the particle characteristics of the cells; the VCS detection is that V, C, S three probes are used to perform one-by-one, simultaneous, triple detection and three-dimensional analysis on a single column of white blood cells passing through a certain position in a detection area so as to determine the subgroup properties; referring to FIG. 5, a flowchart of a method for detecting leukocytes according to an embodiment of the invention is shown. The leukocyte detection method of the embodiment of the invention comprises the following steps:
step 401: measuring the volume of the white blood cells by adopting electrical impedance;
in step 401, the leukocyte volume measurement method is: a certain low-frequency current passes through the two electrodes of the sensor, and due to the non-conductivity of the cells, when the cells pass through the two electrodes, the impedance between the electrodes is instantly increased to form electric pulses with the amplitude in direct proportion to the volume of the cells, the volume of the cells is measured according to the size of the pulses, and the cells are counted according to the number of the pulses; through the electronic selection of the pulse size generated by various cells, different types of cells can be incompletely distinguished, lymphocytes and monocytes with more obvious volume size difference can be effectively distinguished, but the cells with different types and the same volume can not be completely distinguished only by the cell volume because the pulse amplitudes generated by the cells with the different types and the same volume are the same, and then the internal structure of the white blood cells is analyzed by a high-frequency conductance method and laser scattering.
Step 402: reacting the internal structure information of the cells by a high-frequency conductance technology;
in step 402, the specific reaction method is as follows: although the cell wall cannot pass low frequency current, it can pass high frequency current; the electrode is provided with a radio frequency (high frequency) generator, the cell membrane has conductivity to the high frequency current, when the current passes through the cell, an alternating electromagnetic field is formed around the cell to form electromagnetic waves, the conductivity parameters of the high frequency current are different due to the difference of the internal structures such as the proportion of cell nucleus and pulp, particles, nuclear-to-mass ratio and the like, the electromagnetic field formed around the cell is different, and the internal structure information of the cell nucleus can be reflected by the conductivity parameters of the cell to the high frequency current and the variable quantity of the electromagnetic field; and can distinguish between the nucleus of the divided leaf and the cells without the leaf nucleus, and is used for distinguishing the cell populations with similar volumes and different internal structures, such as lymphocytes and basophils.
Step 403: analyzing cell particle information by a laser scattering technology;
in step 403, the specific analysis manner is: scanning each cell by monochromatic laser, analyzing the surface characteristics and the internal structure of the cell membrane, detecting the inner cell core leaf division condition and the particle structure and density condition in cytoplasm, detecting the light scattering characteristics of the cell in a wide angle range of 10-70 degrees, and distinguishing cell populations with different particle characteristics according to the light scattering characteristics of the cell, for example, the light scattering characteristics of coarse particles in the cell are stronger than those of fine particles, thereby distinguishing three types of neutrophilic, acidophilic and basophilic cells in the granulocyte.
Step 500: measuring the concentration of hemoglobin by a colorimetric method;
in step 500, since the red blood cells are lysed and destroyed to release hemoglobin, the hemoglobin reacts with a hemolytic agent to form a stable hemoglobin compound, the hemoglobin compound enters a hemoglobin test system, namely a cuvette E, and is subjected to colorimetry at a specific wavelength of 530-550nm and the absorbance value is measured, wherein the change of the absorbance is proportional to the content of the hemoglobin in the liquid, and thus the concentration of the hemoglobin can be measured;
step 600: respectively counting the red blood cells and the blood platelets on the red blood cell/blood platelet analysis chip by adopting a sheath flow technology, an electrical impedance technology or a floating landmark technology;
in step 600, the red blood cell and platelet count process is: anticoagulated blood is injected into a liquid storage tank S2, diluent is injected into a liquid storage tank R5, a quantitative whole blood sample is diluted by quantitative diluent according to a proper proportion, a first sheath liquid is injected into a R6 liquid storage tank, a second sheath liquid is injected into a R7 liquid storage tank, cells of the blood sample are arranged singly and pass through small holes at the downstream of a detection area A2 one by one under the action of quantitative sheath liquid flow, constant current is applied to the upper end and the lower end of a detection area A2, the blood sample flows into a waste liquid tank W2 through electrical impedance detection (namely each cell generates electronic pulse proportional to the volume of the cell), and C8-C13 are flow sensors and are used for quantifying corresponding fluid in each liquid storage tank; the red blood cells and platelets were counted: measuring the cell volume by measuring the pulse size, and recording the number of pulses to obtain a cell counting result; because the volume of Platelets (PLTs) is obviously different from that of red blood cells, a threshold value is set according to the volume difference of the platelets and the red blood cells, pulse signals higher than the threshold value are defined as red blood cells, and pulse signals lower than the threshold value are defined as platelets, so that the counting and volume analysis of the red blood cells and the platelets can be carried out according to the number and the size of generated electronic pulses; among these, the influence of the number of leukocytes was negligible.
The technical scheme of the invention has the following advantages or beneficial effects: the chip type blood cell analysis device and the method of the embodiment of the invention realize the typing of blood cells by utilizing the blood cell analysis chip, have the advantages of simple structure, small volume, low cost, convenient operation, easy maintenance, easy transportation, disposable chip and the like, meet the development requirements of miniaturization, integration and portability of an analysis instrument, and are particularly suitable for field detection, emergency analysis, household application and use of primary medical units.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (10)
1. A chip type blood cell analysis device is characterized by comprising a blood cell analysis chip, wherein the blood cell analysis chip comprises a white blood cell/hemoglobin analysis chip and a red blood cell/platelet analysis chip, the white blood cell/hemoglobin analysis chip detects white blood cells by adopting an electrical impedance, high-frequency conductance and laser scattering detection technology, and the red blood cell/platelet analysis chip respectively counts the red blood cells and the platelets by adopting a sheath flow technology, an electrical impedance technology or a floating landmark technology.
2. The chip-type hemocyte analyzer of claim 1, wherein the leucocyte/hemoglobin analysis chip measures the volume of leucocytes using the electrical impedance; and analyzing cell particle information by using the laser scattering technology.
3. The chip-type blood cell analyzer according to claim 2, wherein the leukocyte/hemoglobin analysis chip detects the concentration of hemoglobin by a colorimetric method; the detection mode for detecting the concentration of the hemoglobin is as follows: the color was taken at a wavelength of 530-550nm and the absorbance value of the blood sample was determined.
4. The chip-type hemocyte analyzing device of claim 3, wherein a liquid storage tank for storing a detection reagent, a waste liquid storage tank for storing a detected blood sample, a detection zone for detecting passing white blood cells and determining properties of each subpopulation of white blood cells, a colorimetric tank for detecting a concentration of hemoglobin in the blood sample, and a flow sensor for quantifying a corresponding fluid in the liquid storage tank are disposed on the leucocyte/hemoglobin analyzing chip.
5. The chip-type blood cell analyzer according to claim 1, wherein a liquid reservoir for storing a detection reagent, a waste liquid reservoir for storing a detected blood sample, a detection area for applying a constant current to upper and lower ends of the detection area, an electrical impedance technique for detecting passing cells to generate an electrical pulse, and a flow sensor for quantifying the amount of fluid in the liquid reservoir; wherein, the counting mode of the red blood cells and the platelets is as follows: measuring the cell volume by measuring the pulse size, and recording the number of pulses to obtain a cell counting result; a threshold value is set according to the difference between the volumes of the platelets and the red blood cells, pulse signals higher than the threshold value are defined as red blood cells, pulse signals lower than the threshold value are defined as platelets, and counting and volume analysis of the red blood cells and the platelets are carried out according to the number and the size of generated electronic pulses.
6. The chip-type hemocyte analyzing device of claim 4 or 5, wherein the reservoir sample introduction manner comprises a micro pump, an electric sample introduction, a forward pressure-driven sample introduction, a negative pressure sample introduction or an electroosmotic sample introduction.
7. The chip-type hemocyte analyzing device according to any one of claims 1 to 5, wherein the hemocyte analyzing chip material comprises quartz, glass, single crystal silicon or a polymeric material.
8. A chip-based blood cell analysis method comprising:
step a: detecting the leucocytes on the leucocyte/hemoglobin analysis chip by adopting an electrical impedance, high-frequency conductance and laser scattering detection technology;
step b: detecting the concentration of hemoglobin by a colorimetric method;
step c: and respectively counting the red blood cells and the blood platelets on the red blood cell/blood platelet analysis chip by adopting a sheath flow technology, an electrical impedance technology or a floating landmark technology.
9. The chip-based blood cell analysis method according to claim 8, wherein the leukocyte detection means in the step a comprises: and measuring the volume of the white blood cells by adopting the electrical impedance, reflecting the internal structure information of the cells by adopting the high-frequency conductance technology, and analyzing the particle information of the cells by adopting the laser scattering technology.
10. The chip-based blood cell analysis method according to claim 9, wherein in the step b, the hemoglobin concentration is detected by a detection method comprising: the color was taken at a wavelength of 530-550nm and the absorbance value of the blood sample was determined.
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