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 blood cell analysis technical field, relate in particular to a kind of chip type blood cell analyzer and method.
Background technology
The information that blood cell analysis obtains can contribute to diagnosis, the antidiastole disease relevant with hematological system, contribute to analysing patient's condition, observe the curative effect, judging prognosis, for prevent disease provides foundation, instruct clinical application and carry out clinic study, therefore haemocyte check (being routine blood test) becomes first of three large routine inspections in clinical examination (routine blood test, routine urinalysis, just conventional), and its clinical practice is also extensive.After nineteen fifty-three Mr. Ku Erte invention electrical impedance method blood-counter system, various automatic blood cell analysers are come out one after another, and the blood cell analysis technology is developed rapidly.
At present, traditional cellanalyzer is bulky, expensive and complicated operation, need the special messenger to use and carry out periodic maintenance, the measurement reagent price supporting with it is also more expensive, generally be applicable to the more more concentrated hospital inspection section office of test samples, and for different medical units such as village's clinics, often sample size is little, and sample disperses very much on time dimension, the situation that significant discomfort occurs, do not meet the analytical instrument microminiaturization, the demand for development of integrated and portability, and can not meet village's clinic, clinic, community or individual family etc. are than the user demand of subsection.Therefore should overcome tradition check kind equipment shortcoming, meet again the demand of different medical unit to measuring means, current urgent need is developed portability, simple to operateization, the cellanalyzer of the just-in-time of reporting the result, and is applicable to Site Detection, emergency analysis, domestic. applications and primary care.
Summary of the invention
The invention provides a kind of chip type blood cell analyzer and method, be intended to solve bulky, the expensive and complicated operation of existing cellanalyzer, can not meet the technical matters of the user demand of less medical institutions.
Technical scheme provided by the invention is: a kind of chip type blood cell analyzer, comprise the blood cell analysis chip, described blood cell analysis chip comprises leucocyte/hemoglobin analysis chip and red blood cell/blood platelet analysis chip, described leucocyte/hemoglobin analysis chip adopts electrical impedance, high frequency conductance and laser light scattering detection technique to be detected leucocyte, and described red blood cell/blood platelet analysis chip adopts sheath stream technology, electrical impedance technology or unsteady boundary mark technology to count respectively red blood cell and blood platelet.
Technical scheme of the present invention also comprises: described leucocyte/hemoglobin analysis chip adopts described impedance bioelectrical measurement leucocyte volume; Adopt described high frequency conductance technology reacting cells internal structural information; Adopt described laser scattering technology analysis of cells particle information.
Technical scheme of the present invention also comprises: described leucocyte/hemoglobin analysis chip adopts the concentration of colorimetric determination haemoglobin; The detection mode of the concentration of described detection haemoglobin is: colorimetric measure the absorbance of blood sample under the specific wavelength of 530-550nm.
Technical scheme of the present invention also comprises: on described leucocyte/hemoglobin analysis chip, be provided with liquid storage tank, waste liquid pool, detection zone, colorimetric pool and flow sensor, described liquid storage tank is for storing detection reagent, described waste liquid pool is for storing the blood sample through detecting, described detection zone is detected for the leucocyte to process, determine each subgroup character of leucocyte, described colorimetric pool is for detection of the concentration of haemoglobin in blood sample, and described flow sensor is for making the interior corresponding fluids of liquid storage tank quantitative.
Technical scheme of the present invention also comprises: on described red blood cell/blood platelet analysis chip, be provided with liquid storage tank, waste liquid pool, detection zone and flow sensor, described liquid storage tank is for storing detection reagent, described waste liquid pool is for storing the blood sample through detecting, the two ends up and down of described detection zone apply steady current, cell through electrical impedance and process produces electronic impulse, according to the height of pulse, red blood cell and blood platelet are counted respectively, described flow sensor is for making the interior corresponding fluids of liquid storage tank quantitative; Wherein, described red blood cell and enumeration of thrombocytes mode are: the measurement by impulse magnitude determines cell volume, and the number by recording impulse obtains Cytometric result; Difference setting threshold according to blood platelet and erythrocyte volume, to be defined as red blood cell higher than the pulse signal of threshold value, to be defined as blood platelet lower than the pulse signal of threshold value, and pass through the number of produced electronic impulse and big or smallly carry out red blood cell and enumeration of thrombocytes and measure analysis.
Technical scheme of the present invention also comprises: described liquid storage tank input mode comprises that Micropump, electrokinetic injection, positive pressure drive sample introduction, Ngatively pressurized sampling or electric osmose sample introduction.
Technical scheme of the present invention also comprises: described blood cell analysis chip material comprises quartz, glass, monocrystalline silicon or macromolecule polymeric material.
Another technical scheme provided by the invention is: a kind of chip type blood cell analysis method comprises:
Step a: adopt electrical impedance, high frequency conductance and laser light scattering detection technique to be detected the leucocyte on leucocyte/hemoglobin analysis chip;
Step b: the concentration that adopts the colorimetric determination haemoglobin;
Step c: adopt sheath stream technology, electrical impedance technology or unsteady boundary mark technology to count respectively red blood cell and blood platelet on red blood cell/blood platelet analysis chip.
Technical scheme of the present invention also comprises: in described a, described leucocyte detection mode comprises: adopt described impedance bioelectrical measurement leucocyte volume, adopt described high frequency conductance technology reacting cells internal structural information, adopt described laser scattering technology analysis of cells particle information.
Technical scheme of the present invention also comprises: in described step b, the detection mode of the concentration of described detection haemoglobin is: colorimetric measure the absorbance of blood sample under the specific wavelength of 530-550nm.
Technical scheme of the present invention has following advantage or beneficial effect: technical scheme of the present invention has following advantage or beneficial effect: the chip type blood cell analyzer of the embodiment of the present invention and method are by utilizing the blood cell analysis chip to realize the somatotype of haemocyte, have simple in structure, volume is little, cost is low, easy to operate, easy care, easily transportation, chip are the advantage such as discardable by mistake, meet the demand for development of analytical instrument microminiaturization, integrated and portability, be particularly useful for the use of Site Detection, emergency analysis, domestic. applications and different medical unit.
The accompanying drawing explanation
Accompanying drawing 1 is the structural representation of the chip type blood cell analyzer of the embodiment of the present invention;
The detection schematic diagram of the leucocyte of accompanying drawing 2 embodiment of the present invention/hemoglobin analysis chip;
The detection schematic diagram of the red blood cell of accompanying drawing 3 embodiment of the present invention/blood platelet analysis chip;
Accompanying drawing 4 is process flow diagrams of the chip type blood cell analysis method of the embodiment of the present invention;
Accompanying drawing 5 is process flow diagrams of the leucocyte detection method of the embodiment of the present invention.
Embodiment
In order to make purpose of the present invention, technical scheme and advantage clearer, below in conjunction with drawings and Examples, the present invention is further elaborated.Should be appreciated that specific embodiment described herein, only in order to explain the present invention, is not intended to limit the present invention.
Referring to Fig. 1, is the structural representation of the chip type blood cell analyzer of the embodiment of the present invention.The chip type blood cell analyzer of the embodiment of the present invention comprises the blood cell analysis chip, and the blood cell analysis chip comprises leucocyte/hemoglobin analysis chip and red blood cell/blood platelet analysis chip; Wherein,
Leucocyte/hemoglobin analysis chip is used for adopting the physics detection techniques such as electrical impedance, high frequency conductance and laser light scattering to be detected leucocyte, particularly,
Seeing also Fig. 2, is the detection schematic diagram of the leucocyte/hemoglobin analysis chip of the embodiment of the present invention.Leucocyte/hemoglobin analysis chip is provided with liquid storage tank, waste liquid pool, detection zone, colorimetric pool and flow sensor, liquid storage tank is for storing detection reagent, waste liquid pool is for storing the blood sample through detecting, detection zone carries out one by one, VCS(volume, conductivity, scatter simultaneously, triple for the leucocyte to process, the V-low frequency wave, the analysis of cells volume; The C-high frequency waves, the analysis of cells caryogram; S-laser, the particle characteristics of analysis of cells; VCS detects and uses V, C, tri-kinds of probes of S, a certain site at detection zone, the single-row leucocyte passed through is carried out to one by one, detection and three dimensional analysis simultaneously, triple, to determine its subgroup character) detect, and by determination data as calculated machine process to determine each subgroup character of leucocyte, colorimetric pool is for detection of the concentration of haemoglobin, and flow sensor is for making the interior corresponding fluids of each liquid storage tank quantitative.Wherein, the quantity of liquid storage tank and flow sensor can be arranged according to the detection demand, testing process is: under the quantitative effect of flow sensor C1 to C7, by anticoagulation (being the most frequently used in visiting work and one of most important anti-coagulants and reagent), dilution (has certain pH, appropriate osmotic pressure and the balanced electrolyte solution of conductivity, with the human body haemocyte, dilute by a certain percentage, can make the human body haemocyte keep the normal physiological form, and disperse to be difficult for reuniting) and hemolytic agent (haemoglobin detected components and erythrocyte hemolysis agent, hemolytic agent is hypotonic, acid, the solution that contains appropriate wetting agent, red blood cell in the rapid dissolved destruction blood of energy, discharge haemoglobin and form with it stable compound) distinguish sample introduction to liquid storage tank S1, R1, R2, whole blood suitably dilutes, and because hemolytic agent osmotic pressure official post erythrocytolysis destroys, add leucocyte stabilizing agent (a kind of high oozing by liquid storage tank R5, the solution of alkalescence, in energy and hemolytic agent, stabilized leukocyte makes it to keep or approach the original physiologic form) in and the effect of hemolytic agent, make leukocyte surface, endochylema and cell volume return to ortho states substantially, the sheath fluid sample introduction is to liquid storage tank R6, blood sample is under the effect of sheath fluid stream, leucocyte is in line and passes through one by one detection zone A1, leucocyte to process carries out one by one, simultaneously, triple VCS detects (V-low frequency wave, the analysis of cells volume, the C-high frequency waves, the analysis of cells caryogram, S-laser, the particle characteristics of analysis of cells, VCS detects and uses V, C, tri-kinds of probes of S, a certain site at detection zone, the single-row leucocyte passed through is carried out to one by one, simultaneously, triple detection and three dimensional analysis, to determine its subgroup character), and by determination data as calculated machine process to determine each subgroup character of leucocyte.Because different classes of cell can present obvious difference in information characteristic such as volume, surface characteristics, inner structures, these information characteristic are defined into and take VCS in the formed three-dimensional scatter diagram of three-dimensional coordinate, five class leucocytes can form specific cell mass in three dimensions, account for the number percent of total white blood cells by calculating certain group of cell quantities, can obtain five leukocyte differential count results; Simultaneously, due to RBC(Red Blood Cell, red blood cell count(RBC), referring to mean constant of red blood cell contained in unit volume blood) dissolved destruction discharges haemoglobin, haemoglobin reacts with hemolytic agent and forms stable haemoglobin compound, the haemoglobin compound enters haemoglobin test macro-colorimetric pool E, colorimetric measure its absorbance under the specific wavelength of 530-550nm, in the variation of absorbance and liquid, the content of haemoglobin is proportional, can record thus the concentration of haemoglobin; In embodiments of the present invention, to leukocytic detection except five leukocyte differential counts, can also measure and analyze the parameter such as volume, caryoplasm ratio, cell granulations characteristic of neutrophil leucocyte, for understanding the difference of bacterium perception disease and Other diseases, also there is granulophilocyte analytic function and t lymphocyte subset cluster analysis function.
Electrical impedance detects as according to the Ku Erte theory of electrical impedance, measuring the leucocyte volume, measuring method is: certain low-frequency current is by two electrodes of sensor, because cell is non-conducting, when cell passes through two electrodes, inter-electrode impedance moment increase, the electric pulse that the formation amplitude is directly proportional to cell volume, measure the volume of cell according to the size of pulse, according to the number of pulse, carry out cell count; Through the electronic selection to impulse magnitude that various cell produces, can the different types of cell of incomplete differentiation, effectively distinguish the comparatively significant lymphocyte of volume difference in size and monocyte, but the pulse height produced due to cell dissimilar but that volume is identical is identical, therefore only depend on cell volume not distinguish fully, and then utilize high-frequency electrical inducing defecation by enema and suppository and laser light scattering to analyze the leucocyte inner structure.
The high frequency conductance technology is for the reacting cells internal structural information, and concrete reactive mode is: although cell membrane can not make low-frequency current pass through, can pass through high-frequency current; Add a radio frequency (high frequency) generator on electrode, cell membrane has conduction to high-frequency current, form around alternating electromagnetic field during by cell when electric current, form electromagnetic wave, because the difference between the inner structures such as ratio, particle and nucleocytoplasmic ratio of nucleus, slurry is distinguished to some extent to the conduction parameter of high-frequency current, the electromagnetic field formed around it is not identical yet, by cell, to the conduction parameter of high-frequency current and the variable quantity of electromagnetic field, can reflect nuclear internal structural information; And can distinguish leaflet core and non-segmented cell, for distinguishing the close and cell colony that inner structure is different of volume, as lymphocyte and basophilic granulocyte.
Laser scattering technology is used for the analysis of cells particle information: the concrete analysis mode is: by one-wavelength laser, each cell is scanned, analysis of cells film surface characteristics and inner structure, survey grain pattern and density situation in intracellular nucleic leaflet situation and endochylema, detect the light scattering characteristic of cell 10 ° of-70 ° of wide range, and distinguish the different cell colony of particle characteristics according to the light scattering characteristic of cell, the thin scattered light than particle that for example the cell endoparticle is thick is stronger, distinguish whereby the neutrophilia in granulocyte, three kinds of cells of acidophilia and basophilla.
Red blood cell/blood platelet analysis chip is for adopting sheath stream technology, electrical impedance technology or unsteady boundary mark technology to count respectively red blood cell and blood platelet; Seeing also Fig. 3, is the detection schematic diagram of the red blood cell/blood platelet analysis chip of the embodiment of the present invention.Be provided with liquid storage tank, waste liquid pool, detection zone and flow sensor on red blood cell/blood platelet analysis chip, liquid storage tank is for storing detection reagent, waste liquid pool is for storing the blood sample through detecting, the two ends up and down of detection zone apply steady current, through electrical impedance technology detect make through cell produce electronic impulse, according to the height of pulse, red blood cell and blood platelet are counted respectively, flow sensor is for making the interior corresponding fluids of each liquid storage tank quantitative; Wherein, the quantity of liquid storage tank and flow sensor can be arranged according to the detection demand.Concrete testing process is: under the quantitative effect of flow sensor C8 to C13, the anticoagulation sample introduction is to liquid storage tank S2, the dilution sample introduction is to liquid storage tank R5, quantitatively whole blood sample dilutes by proper proportion through quantitative dilution, the first sheath fluid (dilution) sample introduction is to the R6 liquid storage tank, the second sheath fluid (dilution) sample introduction is to the R7 liquid storage tank, blood sample is under quantitative sheath fluid stream effect, cell is single arrangement and passes through one by one the aperture of detection zone A2 middle and lower reaches, the two ends up and down of detection zone A2 apply steady current, detect (being that each cell produces electronic impulse proportional to cell volume) and flow into waste liquid pool W2 through electrical impedance, red blood cell and enumeration of thrombocytes mode are: the measurement by impulse magnitude determines cell volume, and the number by recording impulse obtains Cytometric result, due to blood platelet (blood platelet, PLT) with erythrocyte volume, obvious difference is arranged, difference setting threshold according to blood platelet and erythrocyte volume, to be defined as red blood cell higher than the pulse signal of threshold value, pulse signal lower than threshold value is defined as blood platelet, thereby passes through the number of produced electronic impulse and big or smallly carry out red blood cell and enumeration of thrombocytes and measure analysis, wherein, the quantity of leucocyte impact can be ignored.The present invention accelerates stream of cells by the speed of detection zone by the mode that adopts secondary sheath stream, improve and detect cell quantity, simultaneously accurate chip structure and pressure equilibrium are controlled, make the diameter of stream of cells be stabilized in the width be close with haemocyte, guarantee that cell is single arrangement and accepts the electrical impedance detection under hydrodynamic action, assurance is carried out one by one, is measured accurately and rapidly a large amount of cells, and shortens the time of pattern detection.
Sheath stream technology is specially: for fear of cell in testing process, occur side by side or lateral flow district after testing, and the phenomenons such as cell backflow, turbulent flow or eddy current are brought the detection error, adopt sheath stream technology, be that the cell suspension sample is under the effect of swiftly flowing sheath fluid lateral compression effect, form the similar compression flow form that enters the sheath shape, guarantee the coated lower stream of cells that form single arrangement of sample cell at sheath fluid, pass through successively detection zone; Sheath stream technology can be applicable to two kinds of cell count principles: one is theory of electrical impedance, and sheath flows by carrying out cell count in the sensitizing range of detection zone; Another kind is the laser counting principle, and cell liquid stream chamber is longer, with laser vertical, intersects, and laser beam produces light scattering after to each cell irradiation of flowing through, and utilizes this principle to carry out cell count; The boundary mark technology of floating is: because various intercellular boundaries can be with the cell actual size left or move right, therefore be called the boundary mark technology of floating; In normal specimen, red blood cell and volume of platelets differ larger, generally by red blood cell and hematoblastic boundary due to 35fl, large is red blood cell, little is blood platelet, also has to take that 30fl or 20fl be boundary; But under some pathologic condition, may there is large blood platelet to surpass the 35fl boundary, cause blood platelet to leak meter and make Lower result; Otherwise, if erythrocyte volume (as hypoferric anemia or Mediterranean property anaemia) less than normal may be blood platelet by part microcyte error count, make platelet count higher; For result accurate, calculating instrument utilizes computing machine to find the histogram minimum point between 5-35fl, be decided to be red blood cell and hematoblastic boundary with this, histogrammic boundary mark can be made corresponding adjustment automatically according to the variation of cell mass, can make thus counted numerical value tally with the actual situation.
In embodiments of the present invention, the liquid storage tank sample introduction adopts Micropump, electrokinetic injection, positive pressure to drive the various ways such as sample introduction, Ngatively pressurized sampling or electric osmose sample introduction, the blood cell analysis chip can be made by materials such as quartz, glass, monocrystalline silicon, high molecular polymerizations, such as polymetylmethacrylate, polydimethylsiloxane or polycarbonate etc.; Can be by adding the suitable modes such as adjuvant to alleviate or to avoid the chip microchannel surface to adsorb haemocyte in chip microchannel modifying inner surface, chip material modification or solution; Simultaneously, the present invention, except being applied to medical industry, is equally applicable to relate in the diameter of measurement of species particle or liquid that atomic quantity is carried out quantitatively and the industry such as analysis qualitatively, for example, in physico-chemical analysis in pure water, measure the content of its impurity and bacterium; Or the measurement of the degree of purity of various industrial high purity liquid or demarcation etc.
Referring to Fig. 4, is the process flow diagram of the chip type blood cell analysis method of the embodiment of the present invention.The chip type blood cell analysis method of the embodiment of the present invention comprises:
Step 400: detect the leucocyte on leucocyte/hemoglobin analysis chip by anticoagulation, dilution, hemolytic agent, leucocyte stabilizing agent and sheath fluid etc., and each subgroup character of definite leucocyte;
In step 400, the leucocyte testing process is: by anticoagulation, dilution and hemolytic agent difference sample introduction are to liquid storage tank S1, R1, R2, whole blood suitably dilutes, and because hemolytic agent osmotic pressure official post erythrocytolysis destroys, by liquid storage tank R5, add in the leucocyte stabilizing agent and the effect of hemolytic agent, make leukocyte surface, endochylema and cell volume return to ortho states substantially, the sheath fluid sample introduction is to the R6 liquid storage tank, blood sample is under the effect of sheath fluid stream, leucocyte is in line and passes through one by one detection zone A1, leucocyte to process carries out one by one, simultaneously, triple VCS detects, and by determination data as calculated machine process to determine each subgroup character of leucocyte.Because different classes of cell can present obvious difference in information characteristic such as volume, surface characteristics, inner structures, these information characteristic are defined into and take VCS in the formed three-dimensional scatter diagram of three-dimensional coordinate, five class leucocytes can form specific cell mass in three dimensions, account for the number percent of total white blood cells by calculating certain group of cell quantities, can obtain five leukocyte differential count results; In embodiments of the present invention, to leukocytic detection except five leukocyte differential counts, can also measure and analyze the parameter such as volume, caryoplasm ratio, cell granulations characteristic of neutrophil leucocyte, for understanding the difference of bacterium perception disease and Other diseases, also there is granulophilocyte analytic function and t lymphocyte subset cluster analysis function; Wherein, VCS detects and is: V-low frequency wave, analysis of cells volume; The C-high frequency waves, the analysis of cells caryogram; S-laser, the particle characteristics of analysis of cells; VCS detects and uses V, C, tri-kinds of probes of S, in a certain site of detection zone, the single-row leucocyte passed through is carried out to one by one, detection and three dimensional analysis simultaneously, triple, to determine its subgroup character; Specifically seeing also Fig. 5, is the process flow diagram of the leucocyte detection method of the embodiment of the present invention.The leucocyte detection method of the embodiment of the present invention comprises the following steps:
Step 401: adopt impedance bioelectrical measurement leucocyte volume;
In step 401, the leucocyte volume measuring method is: certain low-frequency current is by two electrodes of sensor, because cell is non-conducting, when cell passes through two electrodes, inter-electrode impedance moment increase, the electric pulse that the formation amplitude is directly proportional to cell volume, measure the volume of cell according to the size of pulse, according to the number of pulse, carry out cell count; Through the electronic selection to impulse magnitude that various cell produces, can the different types of cell of incomplete differentiation, effectively distinguish the comparatively significant lymphocyte of volume difference in size and monocyte, but the pulse height produced due to cell dissimilar but that volume is identical is identical, therefore only depend on cell volume not distinguish fully, and then utilize high-frequency electrical inducing defecation by enema and suppository and laser light scattering to analyze the leucocyte inner structure.
Step 402: by high frequency conductance technology reacting cells internal structural information;
In step 402, concrete reactive mode is: although cell membrane can not make low-frequency current pass through, can pass through high-frequency current; Add a radio frequency (high frequency) generator on electrode, cell membrane has conduction to high-frequency current, form around alternating electromagnetic field during by cell when electric current, form electromagnetic wave, because the difference between the inner structures such as ratio, particle and nucleocytoplasmic ratio of nucleus, slurry is distinguished to some extent to the conduction parameter of high-frequency current, the electromagnetic field formed around it is not identical yet, by cell, to the conduction parameter of high-frequency current and the variable quantity of electromagnetic field, can reflect nuclear internal structural information; And can distinguish leaflet core and non-segmented cell, for distinguishing the close and cell colony that inner structure is different of volume, as lymphocyte and basophilic granulocyte.
Step 403: by laser scattering technology analysis of cells particle information;
In step 403, the concrete analysis mode is: by one-wavelength laser, each cell is scanned, analysis of cells film surface characteristics and inner structure, survey grain pattern and density situation in intracellular nucleic leaflet situation and endochylema, detect the light scattering characteristic of cell 10 ° of-70 ° of wide range, and distinguish the different cell colony of particle characteristics according to the light scattering characteristic of cell, the thin scattered light than particle that for example the cell endoparticle is thick is stronger, distinguishes whereby neutrophilia, acidophilia and three kinds of cells of basophilla in granulocyte.
Step 500: the concentration that adopts COLORIMETRY METHOD IN HEMOGLOBIN DETERMINATION;
In step 500, because the dissolved destruction of red blood cell discharges haemoglobin, haemoglobin reacts with hemolytic agent and forms stable haemoglobin compound, the haemoglobin compound enters haemoglobin test macro-colorimetric pool E, colorimetric measure its absorbance under the specific wavelength of 530-550nm, in the variation of absorbance and liquid, the content of haemoglobin is proportional, can record thus the concentration of haemoglobin;
Step 600: adopt sheath stream technology, electrical impedance technology or unsteady boundary mark technology to count respectively red blood cell and blood platelet on red blood cell/blood platelet analysis chip;
In step 600, red blood cell and platelet count process are: the anticoagulation sample introduction is to liquid storage tank S2, the dilution sample introduction is to liquid storage tank R5, quantitatively whole blood sample dilutes by proper proportion through quantitative dilution, the first sheath fluid sample introduction is to the R6 liquid storage tank, the second sheath fluid sample introduction is to the R7 liquid storage tank, blood sample is under quantitative sheath fluid stream effect, cell is single arrangement and passes through one by one the aperture of detection zone A2 middle and lower reaches, the two ends up and down of detection zone A2 apply steady current, detect (being that each cell produces electronic impulse proportional to cell volume) and flow into waste liquid pool W2 through electrical impedance, C8 to C13 is flow sensor, for making the interior corresponding fluids of each liquid storage tank quantitative, red blood cell and enumeration of thrombocytes mode are: the measurement by impulse magnitude determines cell volume, and the number by recording impulse obtains Cytometric result, due to blood platelet (blood platelet, PLT) with erythrocyte volume, obvious difference is arranged, difference setting threshold according to blood platelet and erythrocyte volume, to be defined as red blood cell higher than the pulse signal of threshold value, pulse signal lower than threshold value is defined as blood platelet, thereby passes through the number of produced electronic impulse and big or smallly carry out red blood cell and enumeration of thrombocytes and measure analysis, wherein, the quantity of leucocyte impact can be ignored.
Technical scheme of the present invention has following advantage or beneficial effect: the chip type blood cell analyzer of the embodiment of the present invention and method are by utilizing the blood cell analysis chip to realize the somatotype of haemocyte, have simple in structure, volume is little, cost is low, easy to operate, easy care, easily transportation, chip are the advantage such as discardable by mistake, meet the demand for development of analytical instrument microminiaturization, integrated and portability, be particularly useful for the use of Site Detection, emergency analysis, domestic. applications and different medical unit.
The foregoing is only preferred embodiment of the present invention, not in order to limit the present invention, all any modifications of doing within the spirit and principles in the present invention, be equal to and replace and improvement etc., within all should being included in protection scope of the present invention.
Claims (10)
1. a chip type blood cell analyzer, it is characterized in that, comprise the blood cell analysis chip, described blood cell analysis chip comprises leucocyte/hemoglobin analysis chip and red blood cell/blood platelet analysis chip, described leucocyte/hemoglobin analysis chip adopts electrical impedance, high frequency conductance and laser light scattering detection technique to be detected leucocyte, and described red blood cell/blood platelet analysis chip adopts sheath stream technology, electrical impedance technology or unsteady boundary mark technology to count respectively red blood cell and blood platelet.
2. chip type blood cell analyzer according to claim 1, is characterized in that, described leucocyte/hemoglobin analysis chip adopts described impedance bioelectrical measurement leucocyte volume; Adopt described high frequency conductance technology reacting cells internal structural information; Adopt described laser scattering technology analysis of cells particle information.
3. chip type blood cell analyzer according to claim 2, is characterized in that, described leucocyte/hemoglobin analysis chip adopts the concentration of colorimetric determination haemoglobin; The detection mode of the concentration of described detection haemoglobin is: colorimetric measure the absorbance of blood sample under the wavelength of 530-550nm.
4. chip type blood cell analyzer according to claim 3, it is characterized in that, be provided with liquid storage tank, waste liquid pool, detection zone, colorimetric pool and flow sensor on described leucocyte/hemoglobin analysis chip, described liquid storage tank is for storing detection reagent, described waste liquid pool is for storing the blood sample through detecting, described detection zone is detected for the leucocyte to process, determine each subgroup character of leucocyte, described colorimetric pool is for detection of the concentration of haemoglobin in blood sample, and described flow sensor is for making the interior corresponding fluids of liquid storage tank quantitative.
5. chip type blood cell analyzer according to claim 1, it is characterized in that, be provided with liquid storage tank, waste liquid pool, detection zone and flow sensor on described red blood cell/blood platelet analysis chip, described liquid storage tank is for storing detection reagent, described waste liquid pool is for storing the blood sample through detecting, the two ends up and down of described detection zone apply steady current, through electrical impedance technology detect make through cell produce electronic impulse, according to the height of pulse, red blood cell and blood platelet are counted respectively, described flow sensor is for making the interior corresponding fluids of liquid storage tank quantitative; Wherein, described red blood cell and enumeration of thrombocytes mode are: the measurement by impulse magnitude determines cell volume, and the number by recording impulse obtains Cytometric result; Difference setting threshold according to blood platelet and erythrocyte volume, to be defined as red blood cell higher than the pulse signal of threshold value, to be defined as blood platelet lower than the pulse signal of threshold value, and pass through the number of produced electronic impulse and big or smallly carry out red blood cell and enumeration of thrombocytes and measure analysis.
6. according to the described chip type blood cell analyzer of claim 4 or 5, it is characterized in that, described liquid storage tank input mode comprises that Micropump, electrokinetic injection, positive pressure drive sample introduction, Ngatively pressurized sampling or electric osmose sample introduction.
7. according to the described chip type blood cell analyzer of claim 1 to 5 any one, it is characterized in that, described blood cell analysis chip material comprises quartz, glass, monocrystalline silicon or macromolecule polymeric material.
8. a chip type blood cell analysis method comprises:
Step a: adopt electrical impedance, high frequency conductance and laser light scattering detection technique to be detected the leucocyte on leucocyte/hemoglobin analysis chip;
Step b: the concentration that adopts the colorimetric determination haemoglobin;
Step c: adopt sheath stream technology, electrical impedance technology or unsteady boundary mark technology to count respectively red blood cell and blood platelet on red blood cell/blood platelet analysis chip.
9. chip type blood cell analysis method according to claim 8, it is characterized in that, in described a, described leucocyte detection mode comprises: adopt described impedance bioelectrical measurement leucocyte volume, adopt described high frequency conductance technology reacting cells internal structural information, adopt described laser scattering technology analysis of cells particle information.
10. chip type blood cell analysis method according to claim 9, is characterized in that, in described step b, the detection mode of the concentration of described detection haemoglobin is: colorimetric measure the absorbance of blood sample under the wavelength of 530-550nm.
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