CN103175950A - Hemocyte analysis chip and system for using chip thereof - Google Patents
Hemocyte analysis chip and system for using chip thereof Download PDFInfo
- Publication number
- CN103175950A CN103175950A CN2011104307960A CN201110430796A CN103175950A CN 103175950 A CN103175950 A CN 103175950A CN 2011104307960 A CN2011104307960 A CN 2011104307960A CN 201110430796 A CN201110430796 A CN 201110430796A CN 103175950 A CN103175950 A CN 103175950A
- Authority
- CN
- China
- Prior art keywords
- storage tank
- liquid storage
- liquid
- passage
- chip
- 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.)
- Granted
Links
Images
Abstract
The invention provides a hemocyte analysis chip and an analysis system. The system comprises the chip, an electrical impedance detection unit and a signal processing system. The chip comprises a first detection chip and a second detection chip. The first detection chip comprises a blood sample channel, an erythrocyte lysate channel, a continuous phase channel and a first detection channel. The second detection chip comprises the blood sample channel, the continuous phase channel and a second detection channel. The blood sample channel, the erythrocyte lysate channel and the continuous phase channel of the first detection chip are communicated, and a communication position is connected with the first detection channel, the blood sample channel of the second detection chip is communicated with the continuous phase channel, and the communication position is connected with second detection channel, a small disperse aperture is provided between the connection positions of first detection channel and the second detection channel and the fluid passage, and a small detection aperture is provided at the position far from the small disperse aperture. The electrical impedance detection unit and the signal processing system use an electrical impedance method for analyzing hemocyte.
Description
Technical field
The present invention relates to a kind of blood cell analysis chip based on micro-fluidic drop technology and use the system of this chip.
Background technology
Blood flow is through each tissue and the organ of human body, each tissue of human body and the interaction between organ, to influence each other be to realize by adjusting and balance neural, body fluid, and this balance is reflected in the aspects such as the various physical parameters, physiological parameter of blood.The disease that the information that blood test obtains can help to diagnose, antidiastole is relevant with hematological system helps analysing patient's condition, observe the curative effect, judging prognosis, for prevent disease provides foundation, instructs clinical application and carries out clinic study.The blood cell Epidemiological Analysis is not only the Main Basis of diagnosis hemopoietic system various diseases, diagnosis and differential diagnosis to the other system disease also can provide important information, therefore haemocyte check (being blood routine examination) has become first of three large routine inspections in clinical examination (routine blood test, routine urinalysis, just conventional), and its clinical practice is also extensive.
In haemocyte check field, invented the particle counting technology from early 1950s Mr. Ku Erte, made the First cellanalyzer and be applied to clinical since, the development of the cellanalyzer history of existing 50 years.At present, cellanalyzer has become the hospital clinical check and has used one of instrument very widely, and it mainly can be divided into three classification and five classification cellanalyzers, and detecting principle is mainly electrical impedance, radio frequency and laser light scattering etc.
Although various high-grade cellanalyzers are come out one after another in the world at present, but still adopt electrical impedance method as the basis of blood count and cubing.The principle that electrical impedance detects is: the character non-conducting according to haemocyte, the resistance variations that suspended particle in electrolyte solution is caused by aperture the time detects.Specific practice is, an aperture is set in cell suspension to be measured, and respectively there is an electrode that applies certain voltage the both sides of aperture, if electric current and the impedance supplied with are stable, according to Ohm law, the voltage by aperture is also constant.When a cell in suspension passes through aperture, because the conduction of haemocyte is minimum, the conduction property of haemocyte is lower than waiting electrolytic solution that oozes, and makes the increase of the resistance in the aperture induction zone in circuit, and moment causes change in voltage and a pulse signal occurs.The degree that voltage increases depends on the volume of cell, and the volume of cell is larger, and the change in voltage that causes is larger, and the pulse-response amplitude of generation is higher.Can measure the volume of cell by the measurement of paired pulses amplitude, the number of recording impulse can obtain Cytometric result.Through the electronic selection to impulse magnitude that various haemocyte produces, can distinguish different types of haemocyte and analyze.
Present blood cell analysis generally carries out through the specific people under given conditions by commercially available cellanalyzer.The volume of this class cellanalyzer is large, cost is high, maintenance is wasted time and energy, can only analyze a sample at every turn, simultaneously the operator is had strict demand, needs through professional training, and limitation is larger, is difficult to popularize.
For addressing the above problem, industry is now just putting forth effort to develop the cellanalyzer based on microflow control technique.The initial form of microfluidic analysis technology be early 1990s Switzerland Manz and Widmer propose first take micro electronmechanical process technology as the basis micro-full analytical system (miniaturized total analysis systems, μ TAS), its objective is the function of assay laboratory is transferred in portable analytical equipment, even be integrated on the chip of heart size, adapt to that analytical instrument is microminiaturized, integrated, the demand for development of portability, robotization, for advantage has been created in the realization of " individualizing ", " family oriented " assay laboratory.
Micro-fluidic drop technology is as a branch technique of micro-fluidic chip, the liquid (disperse phase) that is intended on micro-fluidic chip to handle micro volume is scattered in external phase with the form of micro volume unit, become volume one by one only to receive the drop of upgrading sample dispersion, realize compartmentalization, the microminiaturization of sample, avoid the pollution of sample room, simultaneously because the surface-to-volume ratio of drop is larger, be beneficial to mass transfer, chemical reaction velocity improves, biochemical reaction test period shortening.Due to the external phase of selecting and the difference of disperse phase, drop is divided into water-in-oil type and oil-in-water type two classes, and wherein the water-in-oil type drop is take water as disperse phase, and oil phase is external phase; The oil-in-water type drop is take oil phase as disperse phase, and water is external phase.The generation of drop has initiatively and passive dual mode, active method is to rely on external force (electric field force, Pneumatic pressure, heat, ultrasonic etc.) to realize the controlling of drop, and passive rule is to rely on the modes such as special channel architecture such as T-shaped passage, double-T shaped passage, flow focusing to realize controlling drop.Sample flow in micro-fluidic chip is subject to the restriction of channel architecture, and the design of passage can affect the flow direction of sample, also can utilize the flow direction of the acting force control drop of electric field, magnetic field, ultrasound wave, surface wave and dielectric field etc. simultaneously.At present, micro-fluidic chip can be realized Highgrade integration, as can integrated multiple detecting device (electrochemical detector, fluorescence detector etc.), also can Integrated electrode, the functional part such as temperature sensor, so along with the development of micro-fluidic liquid drop control technology its range of application that reaches its maturity constantly enlarges, as synthetic in albumen crystallization, single cell analysis, DNA analysis, PCR (Polymerase Chain Reaction, PCR), quantum dot, biomedical imaging etc.Than traditional continuous fluid technology, micro-fluidic drop technology not only reduces the consumption of reagent sample, accelerates mixing velocity, can avoid the problems such as the diffusion of sample and cross pollution simultaneously.
In view of the many advantages that the micro-fluidic chip technology has, hope can have a kind of novel cellanalyzer based on the micro-fluidic chip technology of microminiaturization, or even for the micro-fluidic chip special cellanalyzer of a certain biochemical analysis function.Based on the cellanalyzer of micro-fluidic chip can improve that traditional cellanalyzer volume is large, the shortcoming such as price, maintenance are wasted time and energy, operation easier is large, thereby reduce operation easier, reduce volume, and the micro-fluidic chip cost is low, can disposablely use, with discardable after namely, and price and the maintenance cost of reduction cellanalyzer, therefore micro-fluidic chip has application prospect preferably aspect blood cell analysis, is fit to clinic, universal community, individual family etc. and carries out blood cell analysis mensuration.
Summary of the invention
Therefore, the invention provides a kind of blood cell analysis chip based on micro-fluidic drop technology and use the system of this chip.
blood cell analysis chip provided by the invention comprises the first detection chip and the second detection chip at least, this first detection chip comprises the first liquid storage tank, the second liquid storage tank, the 3rd liquid storage tank, the 4th liquid storage tank and the first liquid passage that is connected with above-mentioned liquid storage tank respectively, the second liquid passage, the 3rd fluid passage and the first sense channel, this second detection chip comprises the first liquid storage tank, the 3rd liquid storage tank, the 4th liquid storage tank and the first liquid passage that is connected with above-mentioned liquid storage tank respectively, the 3rd fluid passage and the second sense channel, wherein, the first liquid storage tank is used for storing blood cell suspension, the second liquid storage tank is used for storing the solution that can change the blood cell suspension particular characteristic, the 3rd liquid storage tank is used for storing external phase liquid, the 4th liquid storage tank is used for storing waste liquid, the first liquid passage of the first detection chip, the second liquid passage, one end of the 3rd fluid passage is connected and its connected position is connected with the first sense channel, the first liquid passage of the second a detection chip and end of the 3rd fluid passage is connected and its connected position and the second sense channel intersect, the first sense channel and the second sense channel are provided with dispersion apertures with being connected of fluid passage between the position, and in being provided with the detection aperture near the position of establishing the 4th liquid storage tank.
The present invention also provides a kind of blood cell analysis system, this blood cell analysis system comprises above-mentioned blood cell analysis chip, and electrical impedance detecting unit and signal processing system, the electrical impedance detecting unit comprises a plurality of electrodes of being located at aperture both sides and the detecting device that changes for detection of inter-electrode voltage, and signal processing system is used for carrying out cell analysis according to the change in voltage that the electrical impedance detecting unit detects.
In one embodiment of the invention, the first liquid passage of described the first detection chip and second liquid passage be communicated with before the 3rd fluid passage is connected.
In one embodiment of the invention, each fluid passage of described the first detection chip and the second detection chip includes an extension, and at least one fluid passage of the first detection chip and the second detection chip comprises that the position that is connected of each fluid passage of the first detection chip and the second detection chip is positioned on this connecting portion by the extended connecting portion of extension bending of correspondence.
In one embodiment of the invention, the extension of each fluid passage of described the first detection chip is parallel to each other, and the extension of each fluid passage of described the second detection chip also is parallel to each other.
in one embodiment of the invention, described the first detection chip all has two the 3rd liquid storage tanks and two three fluid passages corresponding with the 3rd liquid storage tank with the second detection chip, the 3rd liquid storage tank and the 3rd fluid passage of described the first detection chip lay respectively at the first liquid storage tank, the both sides of the second liquid storage tank and first liquid passage and second liquid passage, with the first liquid storage tank, the second liquid storage tank and first liquid passage and second liquid passage are surrounded, the 3rd liquid storage tank of described the first detection chip and the 3rd fluid passage lay respectively at the both sides of the first liquid storage tank and first liquid passage, the first liquid storage tank and first liquid passage are wrapped in wherein.
In one embodiment of the invention, the width of described first liquid passage, second liquid passage and the 3rd fluid passage is the 10-500 micron, the width of described the first sense channel and the second sense channel is the 50-2000 micron, and the height of all liq passage and sense channel is the 10-200 micron.
In one embodiment of the invention, the width of described dispersion apertures and detection aperture is the 5-200 micron.
In one embodiment of the invention, described the first detection chip and the second detection chip are respectively leucocyte detection chip and red blood cell/platelets analysis chip, described the first liquid storage tank is the blood sample liquid storage tank, the second liquid storage tank is the erythrocyte cracked liquid liquid storage tank, the 3rd liquid storage tank is the external phase liquid storage tank, and the 4th liquid storage tank is waste liquid pool, and the first liquid passage is the blood sample passage, the second liquid passage is the erythrocyte cracked liquid passage, and the 3rd fluid passage is the external phase passage.
In one embodiment of the invention, described blood cell analysis chip is counted the cell by aperture by electrical impedance method.
That blood cell analysis of the present invention system has is simple in structure, volume is little, easy to operate, cost is low, i.e. discardable, the advantage such as analysis speed is fast, many samples detect simultaneously of chip, is fit to the uses such as hospital, clinic, community and individual family.
Above-mentioned explanation is only the general introduction of technical solution of the present invention, for can clearer understanding technological means of the present invention, and can be implemented according to the content of instructions, and for above and other purpose of the present invention, feature and advantage can be become apparent, below especially exemplified by preferred embodiment, and the cooperation accompanying drawing, be described in detail as follows.
Description of drawings
Figure 1 shows that the schematic diagram of cellanalyzer of the present invention.
Figure 2 shows that the schematic diagram of blood cell analysis chip in Fig. 1.
Figure 3 shows that the formation schematic diagram of drop in the leucocyte detection chip of Fig. 2.
Figure 4 shows that the formation schematic diagram of drop in the red blood cell of Fig. 2/platelets analysis chip.
Embodiment
Reach for further setting forth the present invention technological means and the effect that predetermined goal of the invention is taked, below in conjunction with accompanying drawing and preferred embodiment, the blood cell analysis chip that foundation the present invention is proposed and system's embodiment, structure, feature and the effect thereof of using this chip are described in detail as follows.
Figure 1 shows that the schematic diagram of blood cell analysis of the present invention system.As shown in Figure 1, this blood cell analysis system 100 is based on the blood cell analysis system of microfluidic analysis platform, and it comprises blood cell analysis chip 10, electrical impedance detecting unit 20, signal processing system 30 and display 40.
Wherein, blood cell analysis chip 10 is by quartz, glass, monocrystalline silicon, macromolecule polymeric material such as polymethylmethacrylate (PolymethylMethacrylate, PMMA), dimethyl silicone polymer (polydimethylsiloxane, PDMS), polycarbonate (Polycarbonate, PC) etc. make, which is provided with sense channel E1, K1 (as shown in Figure 2) that band detects aperture F, M.Electrical impedance detecting unit 20 comprises high-voltage power supply 21, a plurality of electrode 22 and detecting device (not shown).These electrodes 22 are placed in the detection aperture F of sense channel E1, K1, the both sides of M, and the output terminal of high-voltage power supply 21 connects the electrode 22 on blood cell analysis chip 10, and detecting device is for detection of the variation of voltage between electrode 22.Signal processing system 30 is embedded in main frame, is used for according to the change in voltage between the electrode 22 of electrical impedance detecting unit 20, to analyzing by the haemocyte that detects aperture F, M, determines kind and quantity by the haemocyte that detects aperture F, M.Display 40 is used for showing the result of blood cell analysis.
Figure 2 shows that the schematic diagram of blood cell analysis chip.As shown in Figure 2, blood cell analysis chip 10 is micro-fluidic chip, and it comprises the first detection chip and the second detection chip with similar structures, and these two detection chip are respectively leucocyte detection chip 11 and red blood cell/platelets analysis chip 12.
Leucocyte detection chip 11 comprises one first liquid storage tank, one second liquid storage tank, two the 3rd liquid storage tanks, one the 4th liquid storage tanks and a first liquid passage that is connected with above-mentioned liquid storage tank respectively, a second liquid passage, two the 3rd fluid passages and one first sense channel.In the present embodiment, the first liquid storage tank is blood sample liquid storage tank A, and it is used for storing blood cell suspension.The second liquid storage tank is erythrocyte cracked liquid liquid storage tank B, and in it, erythrocyte cracked liquid of storage can change the performance of blood cell suspension.The 3rd liquid storage tank is external phase liquid storage tank C, D, and the external phase liquid that stores in it can be oil or water-fast organic reagent.The 4th liquid storage tank is waste liquid pool E, is used for storing the waste liquid after detecting.Corresponding with above-mentioned liquid storage tank, the first liquid passage is blood sample passage A1, and the second liquid passage is that erythrocyte cracked liquid channel B 1, the three fluid passage is external phase channel C 1, D1, and the first sense channel is E1.
In above-mentioned leucocyte detection chip 11, external phase liquid storage tank C, D and external phase channel C 1, D1 lay respectively at the blood sample passage A1 of blood sample liquid storage tank A, erythrocyte cracked liquid liquid storage tank B and correspondence, the both sides of erythrocyte cracked liquid channel B 1, and blood sample liquid storage tank A, erythrocyte cracked liquid liquid storage tank B and corresponding blood sample passage A1, erythrocyte cracked liquid channel B 1 are wrapped in wherein.Above-mentioned passage A1, B1, C1, D1 comprise respectively the extension that parallels with the first sense channel E1 and bend rear edge perpendicular to the extended connecting portion of the direction of extension by extension.The connecting portion of above-mentioned passage A1, B1, C1, D1 all extends to the inboard of leucocyte detection chip 11, the connecting portion of above-mentioned passage A1, B1, C1, D1 is intersected at the middle part of leucocyte detection chip 11, the connected position of above-mentioned passage A1, B1, C1, D1 is positioned on above-mentioned connecting portion.Here need to prove, the extension of blood sample passage A1 and erythrocyte cracked liquid channel B 1 is shorter towards the length of the other side's inboard, make blood sample passage A1 intersect before the position that is connected that arrives A1, B1, C1, four passages of D1 with erythrocyte cracked liquid channel B 1, thereby make blood sample and erythrocyte cracked liquid mix before converging with disperse phase liquid.Intersect by a microchannel that is provided with dispersion apertures G between the connected position of passage A1, B1, C1, D1 and the first sense channel E1, detect aperture F and be located at the upper position near waste liquid pool E of the first sense channel E1.Be appreciated that, in an embodiment of the present invention, be not to be that all passage A1, B1, C1, D1 need to arrange connecting portion, arranging of connecting portion need to be adjusted according to the position at the connected position of A1, B1, C1, four passages of D1, just align with wherein certain passage when the connected position of A1, B1, C1, four passages of D1, this passage need not to arrange connecting portion.
Red blood cell/platelets analysis chip 12 comprises one first liquid storage tank, two the 3rd liquid storage tanks, one the 4th liquid storage tanks and a first liquid passage that is connected with above-mentioned liquid storage tank respectively, two the 3rd fluid passages and one second sense channel.In the present embodiment, the first liquid storage tank is blood sample liquid storage tank H, and the 3rd liquid storage tank is external phase liquid storage tank I, J, and the 4th liquid storage tank is waste liquid pool K.Corresponding with above-mentioned liquid storage tank, the first liquid passage is blood sample passage H1, and the 3rd fluid passage is external phase passage I1, J1, and the second sense channel is K1.
In above-mentioned red blood cell/platelets analysis chip 12, external phase liquid storage tank I, J and external phase passage I1, J1 are positioned at the both sides of the blood sample passage H1 of blood sample liquid storage tank H and correspondence, and blood sample liquid storage tank H and corresponding blood sample passage H1 are wrapped in wherein.Above-mentioned passage H1, I1, J1 include the extension that parallels with the second sense channel K1, and passage I1, J1 also comprise by edge after the extension bending perpendicular to the extended connecting portion of the direction of extension.The connecting portion of passage I1, J1 all extends to the inboard of red blood cell/platelets analysis chip 12, the connecting portion of passage I1, J1 and the extension of passage H1 are intersected at the middle part of red blood cell/platelets analysis chip 12, the connected position of passage H1, I1, J1 is positioned on the connecting portion of passage I1, J1.Intersect by a microchannel that is provided with dispersion apertures L between the connected position of passage H1, I1, J1 and the second sense channel K1, detect aperture M and be located at the upper position near waste liquid pool K of the second sense channel K1.
Below introduce in detail and utilize blood cell analysis system 100 to carry out the process of blood cell analysis:
as shown in Figure 3, when carrying out the leucocyte detection, the anticoagulation sample introduction is to blood sample liquid storage tank A, the erythrocyte cracked liquid sample introduction is to erythrocyte cracked liquid liquid storage tank B, water-fast organic reagent arrives external phase liquid storage tank C as the external phase sample introduction, D, make anticoagulation, erythrocyte cracked liquid, flow out from corresponding liquid storage tank when consecutive identical, because the inboard of blood sample passage A1 and erythrocyte cracked liquid channel B 1 is shorter, make blood sample at first contact with erythrocyte cracked liquid, disperse phase (blood sample of fusion and erythrocyte cracked liquid) and external phase are converged at dispersion apertures G place, because the slype at dispersion apertures G place makes the sectional area of passage with respect to passage A1, B1, C1, the connected position of D1 reduces suddenly, and make the mobile generation significant change of liquid, caused the unstable of interface, add surface tension, the effect of shearing force and external phase pressure, the disperse phase front end is in dispersion apertures G place is broken into the drop that contains cell of micro volume unit and is scattered in external phase, and each drop comprises a cell at the most, erythrocyte membrane in drop breaks under the effect of erythrocyte cracked liquid, discharge haemoglobin, only stay the small nubbin of erythrocyte membrane, comprising single celled drop is in line, pass through one by one the detection aperture F of the first sense channel E1 middle and lower reaches, detect and inflow waste liquid pool E through electrical impedance.The electrolytic solution that oozes than grade due to the conductive properties of haemocyte is low, when the drop that comprises haemocyte passes through to detect aperture F, the voltage at detection aperture F place changes, detecting device will receive a pulse signal, the size of this pulse signal depends on the volume size by the haemocyte that detects aperture F, the number of pulse signal depends on the blood cell number by detection aperture F, thereby carries out white blood cell count(WBC) and measure analysis according to number and the size of pulse signal.
as shown in Figure 4, when carrying out red blood cell/platelets analysis, the anticoagulation sample introduction is to blood sample liquid storage tank H, water-fast organic reagent arrives external phase liquid storage tank I as the external phase sample introduction, J, make anticoagulation, liquid storage tank from correspondence when consecutive identical flows out, disperse phase (blood sample) and external phase are converged at dispersion apertures L place, because the slype at dispersion apertures L place makes the sectional area of passage with respect to passage H1, I1, the connected position of J1 reduces suddenly, and make the mobile generation significant change of liquid, caused the unstable of interface, add surface tension, the effect of shearing force and external phase pressure, during the drop that contains cell that the disperse phase front end is broken into the micro volume unit at dispersion apertures L place is scattered in external phase, and each drop comprises a haemocyte at the most, comprising single celled drop is in line, pass through one by one the detection aperture M5 of the second sense channel K1 middle and lower reaches, detect and inflow waste liquid pool K4 through electrical impedance.the electrolytic solution that oozes than grade due to the conductive properties of haemocyte is low, when the drop that comprises haemocyte passes through to detect aperture M, detection aperture M place voltage changes, detecting device will receive a pulse signal, the size of this pulse signal depends on the size by the blood cell volume that detects aperture M, the number of pulse signal depends on the number by the haemocyte that detects aperture M, because blood platelet and erythrocyte volume have obvious difference, setting threshold, to be defined as higher than the pulse signal of threshold value corresponding with red blood cell, otherwise be defined as corresponding with blood platelet, thereby carry out red blood cell/platelet count and measure analysis according to number and the size of pulse signal.
By above narration as can be known, blood cell analysis of the present invention system utilizes micro-fluidic and the electrical impedance detection technique, can carry out accurate counting to the red blood cell/blood platelet in anticoagulation and leucocyte, realizes haemocyte three classification analysises.Certainly, blood cell analysis of the present invention system also can in conjunction with technology such as laser, radio frequency and chemical stainings, realize the analysis of haemocyte five classification analysises and other correlation parameters of routine blood test.
And that blood cell analysis of the present invention system also has is simple in structure, volume is little, easy to operate, cost is low, i.e. discardable, the advantage such as analysis speed is fast, many samples detect simultaneously of chip, is fit to the uses such as hospital, clinic, community and individual family.
In the present invention, the generation of micro-fluidic drop has initiatively and passive dual mode, the External Force Actings such as active method can adopt when forming drop that Pneumatic pressure, electricity are wetting, dielectrophoresis, ultrasonic, ultracentrifugation power, the Micro Channel Architecture such as that passive means can adopt when forming drop is T-shaped, double-T shaped, flow focusing.When utilizing passive means to form drop, the organic reagent that external phase liquid adopts can be silicone oil, glycerine, kerosene, paraffin, dimethyl sulfoxide, liquid dimethyl silicone polymer (polydimethylsiloxane, PDMS), fluorinated oil, oleic acid, sunflower oil, decane, n-tetradecane, n-hexadecane etc.When utilizing passive means to form drop, also can add suitable surfactant (as sorbitol anhydride oleate (Span 80), laurate) in external phase liquid, the stable droplet to increase its hydrophobicity, and the viscosity of external phase liquid 1-500 centipoise (cp), concentration 0-10 times of critical micelle concentration preferably preferably.When utilizing passive means to form drop, external phase microchannel width 10-500 micron (μ m), the wide 10-500 micron in disperse phase microchannel, pore widths 5-200 micron, detect microchannel width 50-2000 micron, detect aperture width 5-200 micron, microchannel height 10-200 micron.When utilizing passive means to form drop, external phase and disperse phase two-phase flow speed ratio value are 1: 1-500: 1, and the external phase flow velocity is preferably little liter/min of 0-1000 (μ L/min), and the disperse phase flow velocity is preferably little liter/min of 0-1000.
In addition, can adopt the little valve of Micropump, electrokinetic injection, positive pressure to drive the various ways such as sample introduction, Ngatively pressurized sampling, electric osmose sample introduction when the liquid storage tank that Liquid sample introduction is extremely corresponding.In blood cell analysis chip of the present invention, can be at the channel inner surface of blood cell analysis chip through the ad hoc fashion modification, perhaps chip material modification, to keep the hydrophobicity of channel inner surface, perhaps add suitable adjuvant in solution, alleviate or avoid the channel surface absorption haemocyte of blood cell analysis chip, prevent that the passage of blood cell analysis chip from stopping up.
the above, it is only preferred embodiment of the present invention, be not that the present invention is done any pro forma restriction, although the present invention discloses as above with preferred embodiment, yet be not to limit the present invention, any those skilled in the art, within not breaking away from the technical solution of the present invention scope, when the technology contents that can utilize above-mentioned announcement is made a little change or is modified to the equivalent embodiment of equivalent variations, in every case be not break away from the technical solution of the present invention content, any simple modification that foundation technical spirit of the present invention is done above embodiment, equivalent variations and modification, all still belong in the scope of technical solution of the present invention.
Claims (10)
1. blood cell analysis chip, it is characterized in that: this blood cell analysis chip comprises the first detection chip and the second detection chip at least, this first detection chip comprises the first liquid storage tank, the second liquid storage tank, the 3rd liquid storage tank, the 4th liquid storage tank and the first liquid passage that is connected with above-mentioned liquid storage tank respectively, the second liquid passage, the 3rd fluid passage and the first sense channel, this second detection chip comprises the first liquid storage tank, the 3rd liquid storage tank, the 4th liquid storage tank and the first liquid passage that is connected with above-mentioned liquid storage tank respectively, the 3rd fluid passage and the second sense channel, wherein, the first liquid storage tank is used for storing blood cell suspension, the second liquid storage tank is used for storing the solution that can change the blood cell suspension particular characteristic, the 3rd liquid storage tank is used for storing external phase liquid, the 4th liquid storage tank is used for storing waste liquid, the first liquid passage of the first detection chip, the second liquid passage, one end of the 3rd fluid passage is connected and its connected position is connected with the first sense channel, the first liquid passage of the second a detection chip and end of the 3rd fluid passage is connected and its connected position and the second sense channel intersect, the first sense channel and the second sense channel are provided with dispersion apertures with being connected of fluid passage between the position, and in being provided with the detection aperture near the position of establishing the 4th liquid storage tank.
2. blood cell analysis chip as claimed in claim 1 is characterized in that: the first liquid passage of described the first detection chip and second liquid passage be communicated with before the 3rd fluid passage is connected.
3. blood cell analysis chip as claimed in claim 1, it is characterized in that: each fluid passage of described the first detection chip and the second detection chip includes an extension, and at least one fluid passage of the first detection chip and the second detection chip comprises that the position that is connected of each fluid passage of the first detection chip and the second detection chip is positioned on this connecting portion by the extended connecting portion of extension bending of correspondence.
4. blood cell analysis chip as claimed in claim 3, it is characterized in that: the extension of each fluid passage of described the first detection chip is parallel to each other, and the extension of each fluid passage of described the second detection chip also is parallel to each other.
5. blood cell analysis chip as claimed in claim 1, it is characterized in that: described the first detection chip all has two the 3rd liquid storage tanks and two three fluid passages corresponding with the 3rd liquid storage tank with the second detection chip, the 3rd liquid storage tank and the 3rd fluid passage of described the first detection chip lay respectively at the first liquid storage tank, the both sides of the second liquid storage tank and first liquid passage and second liquid passage, with the first liquid storage tank, the second liquid storage tank and first liquid passage and second liquid passage are surrounded, the 3rd liquid storage tank of described the second detection chip and the 3rd fluid passage lay respectively at the both sides of the first liquid storage tank and first liquid passage, the first liquid storage tank and first liquid passage are wrapped in wherein.
6. blood cell analysis chip as claimed in claim 1, it is characterized in that: the width of described first liquid passage, second liquid passage and the 3rd fluid passage is the 10-500 micron, the width of described the first sense channel and the second sense channel is the 50-2000 micron, and the height of all liq passage and sense channel is the 10-200 micron.
7. blood cell analysis chip as claimed in claim 1 is characterized in that: described dispersion apertures and the width that detects aperture are the 5-200 micron.
8. blood cell analysis chip as claimed in claim 1, it is characterized in that: described the first detection chip and the second detection chip are respectively leucocyte detection chip and red blood cell/platelets analysis chip, described the first liquid storage tank is the blood sample liquid storage tank, the second liquid storage tank is the erythrocyte cracked liquid liquid storage tank, the 3rd liquid storage tank is the external phase liquid storage tank, the 4th liquid storage tank is waste liquid pool, the first liquid passage is the blood sample passage, the second liquid passage is the erythrocyte cracked liquid passage, and the 3rd fluid passage is the external phase passage.
9. blood cell analysis chip as claimed in claim 1, it is characterized in that: described blood cell analysis chip is counted the cell by aperture by electrical impedance method.
10. blood cell analysis system, it is characterized in that: this blood cell analysis system comprises blood cell analysis chip as claimed in any one of claims 1-9 wherein, and electrical impedance detecting unit and signal processing system, the electrical impedance detecting unit comprises a plurality of electrodes of being located at aperture both sides and the detecting device that changes for detection of inter-electrode voltage, and signal processing system is used for carrying out cell analysis according to the change in voltage that the electrical impedance detecting unit detects.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110430796.0A CN103175950B (en) | 2011-12-20 | 2011-12-20 | Hemocyte analysis chip and system for using chip thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110430796.0A CN103175950B (en) | 2011-12-20 | 2011-12-20 | Hemocyte analysis chip and system for using chip thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103175950A true CN103175950A (en) | 2013-06-26 |
| CN103175950B CN103175950B (en) | 2015-04-22 |
Family
ID=48635949
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110430796.0A Active CN103175950B (en) | 2011-12-20 | 2011-12-20 | Hemocyte analysis chip and system for using chip thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103175950B (en) |
Cited By (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103472216A (en) * | 2013-08-23 | 2013-12-25 | 深圳中科强华科技有限公司 | Hemocyte analysis chip, analyzer and analysis method |
| CN103471980A (en) * | 2013-08-23 | 2013-12-25 | 深圳中科强华科技有限公司 | Chip-type hemocyte analyzing device and method |
| CN103528935A (en) * | 2013-10-15 | 2014-01-22 | 深圳中科强华科技有限公司 | Liquid line system applied to hematology analyzer and hematology analyzer |
| CN103472034B (en) * | 2013-08-23 | 2015-10-28 | 深圳中科强华科技有限公司 | A kind of blood cell analysis chip, analyser and analytical approach |
| CN105879935A (en) * | 2015-01-18 | 2016-08-24 | 宁波大学 | Low-cost syphilis diagnosis microfluidic device delivering liquid flow through interface characteristic |
| CN106483059A (en) * | 2016-10-13 | 2017-03-08 | 中国人民解放军第三军医大学第附属医院 | Terahertz fluidic cell sensor and its detection method for single or a small amount of living cells markless detection |
| CN107085104A (en) * | 2016-02-15 | 2017-08-22 | 葛宇杰 | Strong hydrophobic PDMS is selected as the controller used in syphilis diagnosis chip apparatus of substrate material |
| CN107085105A (en) * | 2016-02-15 | 2017-08-22 | 葛宇杰 | The strong hydrophobic controller used in syphilis diagnosis Multichannel device of its substrate of micro-fluidic chip |
| CN107085101A (en) * | 2016-02-15 | 2017-08-22 | 葛宇杰 | Strong hydrophobic PDMS as substrate material hypotype swine flu detection chip apparatus |
| CN107121545A (en) * | 2016-02-25 | 2017-09-01 | 葛宇杰 | Multichannel micro-fluidic chip device is used in the cholera diagnosis of dual drive coupling operating mode |
| CN107213930A (en) * | 2017-07-27 | 2017-09-29 | 深圳中科芯海智能科技有限公司 | A kind of micro-fluidic chip and particle analysis method for particle analysis |
| CN107615041A (en) * | 2015-10-07 | 2018-01-19 | Afi技术公司 | Check device, inspection system and inspection method |
| CN108160125A (en) * | 2017-11-27 | 2018-06-15 | 深圳华炎微测医疗科技有限公司 | Biochemistry detection micro-fluidic chip and biochemistry detection micro-fluidic chip system and their application |
| CN108344678A (en) * | 2018-04-25 | 2018-07-31 | 北京怡天佳瑞科技有限公司 | A kind of particulate matter detection means and detection method |
| CN108452854A (en) * | 2018-04-04 | 2018-08-28 | 苏州芯海智能科技有限公司 | A kind of micro-fluidic chip and its application |
| CN108535145A (en) * | 2018-03-09 | 2018-09-14 | 深圳市瑞图生物技术有限公司 | Quickly detect the method and device of granulophilocyte quantity in peripheral blood |
| CN108680503A (en) * | 2018-05-18 | 2018-10-19 | 王闯 | Liquid controls chip and system |
| CN109569752A (en) * | 2018-12-22 | 2019-04-05 | 北京工业大学 | A kind of micro-fluidic chip bearing flow for improving the limit after droplet capture |
| CN109612890A (en) * | 2018-12-28 | 2019-04-12 | 瑞芯智造(深圳)科技有限公司 | A kind of particle counting system and application, the method for detecting metal ion and particle |
| CN110711608A (en) * | 2019-09-23 | 2020-01-21 | 中国科学院上海微系统与信息技术研究所 | Microfluidic chip for cell detection and preparation method thereof |
| CN111182877A (en) * | 2017-07-12 | 2020-05-19 | Ca卡希索有限公司 | Automatic platelet cassette apparatus |
| CN111239027A (en) * | 2020-01-22 | 2020-06-05 | 深圳市锦瑞生物科技有限公司 | Blood particle detection method and blood analyzer |
| CN114713297A (en) * | 2021-01-04 | 2022-07-08 | 深圳华大生命科学研究院 | Micro-fluidic chip |
| CN115125185A (en) * | 2022-08-30 | 2022-09-30 | 中国海洋大学 | Preparation method of bivalve blood lymphocyte single cell suspension |
| CN115228516A (en) * | 2021-04-23 | 2022-10-25 | 中国石油化工股份有限公司 | Domain-limiting unit and method for regulating and controlling size distribution of dispersed phase in multiphase system |
| US11719688B2 (en) | 2014-09-29 | 2023-08-08 | C A Casyso Gmbh | Blood testing system and method |
| US11768211B2 (en) | 2008-12-23 | 2023-09-26 | C A Casyso Gmbh | Cartridge device for a measuring system for measuring viscoelastic characteristics of a sample liquid, a corresponding measuring system, and a corresponding method |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020137218A1 (en) * | 1995-12-18 | 2002-09-26 | Alec Mian | Devices and methods for using centripetal acceleration to drive fluid movement in a microfluidics system |
| WO2005022147A1 (en) * | 2003-08-28 | 2005-03-10 | Celula, Inc. | Methods and apparatus for sorting cells using an optical switch in a microfluidic channel network |
| US20050255600A1 (en) * | 2004-05-14 | 2005-11-17 | Honeywell International Inc. | Portable sample analyzer cartridge |
| CN1712927A (en) * | 2005-06-19 | 2005-12-28 | 中国海洋大学 | Particle analyzing chip with microflow control of single-cell algae |
| WO2010056859A1 (en) * | 2008-11-14 | 2010-05-20 | Beckman Coulter, Inc. | Monolithic optical flow cells and method of manufacture |
-
2011
- 2011-12-20 CN CN201110430796.0A patent/CN103175950B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020137218A1 (en) * | 1995-12-18 | 2002-09-26 | Alec Mian | Devices and methods for using centripetal acceleration to drive fluid movement in a microfluidics system |
| WO2005022147A1 (en) * | 2003-08-28 | 2005-03-10 | Celula, Inc. | Methods and apparatus for sorting cells using an optical switch in a microfluidic channel network |
| US20050255600A1 (en) * | 2004-05-14 | 2005-11-17 | Honeywell International Inc. | Portable sample analyzer cartridge |
| CN1712927A (en) * | 2005-06-19 | 2005-12-28 | 中国海洋大学 | Particle analyzing chip with microflow control of single-cell algae |
| WO2010056859A1 (en) * | 2008-11-14 | 2010-05-20 | Beckman Coulter, Inc. | Monolithic optical flow cells and method of manufacture |
Cited By (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11892459B2 (en) | 2008-12-23 | 2024-02-06 | C A Casyso Gmbh | Cartridge device for a measuring system for measuring viscoelastic characteristics of a sample liquid, a corresponding measuring system, and a corresponding method |
| US11879899B2 (en) | 2008-12-23 | 2024-01-23 | C A Casyso Gmbh | Cartridge device for a measuring system for measuring viscoelastic characteristics of a sample liquid, a corresponding measuring system, and a corresponding method |
| US11768211B2 (en) | 2008-12-23 | 2023-09-26 | C A Casyso Gmbh | Cartridge device for a measuring system for measuring viscoelastic characteristics of a sample liquid, a corresponding measuring system, and a corresponding method |
| CN103471980A (en) * | 2013-08-23 | 2013-12-25 | 深圳中科强华科技有限公司 | Chip-type hemocyte analyzing device and method |
| CN103472034B (en) * | 2013-08-23 | 2015-10-28 | 深圳中科强华科技有限公司 | A kind of blood cell analysis chip, analyser and analytical approach |
| CN103472216A (en) * | 2013-08-23 | 2013-12-25 | 深圳中科强华科技有限公司 | Hemocyte analysis chip, analyzer and analysis method |
| CN103528935A (en) * | 2013-10-15 | 2014-01-22 | 深圳中科强华科技有限公司 | Liquid line system applied to hematology analyzer and hematology analyzer |
| CN103528935B (en) * | 2013-10-15 | 2017-01-25 | 深圳中科强华科技有限公司 | Liquid line system applied to hematology analyzer and hematology analyzer |
| US11719688B2 (en) | 2014-09-29 | 2023-08-08 | C A Casyso Gmbh | Blood testing system and method |
| CN105879935A (en) * | 2015-01-18 | 2016-08-24 | 宁波大学 | Low-cost syphilis diagnosis microfluidic device delivering liquid flow through interface characteristic |
| CN107615041A (en) * | 2015-10-07 | 2018-01-19 | Afi技术公司 | Check device, inspection system and inspection method |
| CN107085101A (en) * | 2016-02-15 | 2017-08-22 | 葛宇杰 | Strong hydrophobic PDMS as substrate material hypotype swine flu detection chip apparatus |
| CN107085105A (en) * | 2016-02-15 | 2017-08-22 | 葛宇杰 | The strong hydrophobic controller used in syphilis diagnosis Multichannel device of its substrate of micro-fluidic chip |
| CN107085104A (en) * | 2016-02-15 | 2017-08-22 | 葛宇杰 | Strong hydrophobic PDMS is selected as the controller used in syphilis diagnosis chip apparatus of substrate material |
| CN107121545A (en) * | 2016-02-25 | 2017-09-01 | 葛宇杰 | Multichannel micro-fluidic chip device is used in the cholera diagnosis of dual drive coupling operating mode |
| CN106483059A (en) * | 2016-10-13 | 2017-03-08 | 中国人民解放军第三军医大学第附属医院 | Terahertz fluidic cell sensor and its detection method for single or a small amount of living cells markless detection |
| CN111182877A (en) * | 2017-07-12 | 2020-05-19 | Ca卡希索有限公司 | Automatic platelet cassette apparatus |
| US10843185B2 (en) | 2017-07-12 | 2020-11-24 | Ca Casyso Gmbh | Autoplatelet cartridge device |
| US11691142B2 (en) | 2017-07-12 | 2023-07-04 | Ca Casyso Gmbh | Autoplatelet cartridge device |
| CN111182877B (en) * | 2017-07-12 | 2021-11-05 | Ca卡希索有限公司 | Cartridge device and method for testing platelet activity in blood samples |
| CN107213930A (en) * | 2017-07-27 | 2017-09-29 | 深圳中科芯海智能科技有限公司 | A kind of micro-fluidic chip and particle analysis method for particle analysis |
| CN107213930B (en) * | 2017-07-27 | 2022-12-20 | 深圳中科芯海智能科技有限公司 | Microfluidic chip for particle analysis and particle analysis method |
| CN108160125A (en) * | 2017-11-27 | 2018-06-15 | 深圳华炎微测医疗科技有限公司 | Biochemistry detection micro-fluidic chip and biochemistry detection micro-fluidic chip system and their application |
| CN108535145A (en) * | 2018-03-09 | 2018-09-14 | 深圳市瑞图生物技术有限公司 | Quickly detect the method and device of granulophilocyte quantity in peripheral blood |
| CN108452854A (en) * | 2018-04-04 | 2018-08-28 | 苏州芯海智能科技有限公司 | A kind of micro-fluidic chip and its application |
| CN108344678A (en) * | 2018-04-25 | 2018-07-31 | 北京怡天佳瑞科技有限公司 | A kind of particulate matter detection means and detection method |
| US11467081B2 (en) | 2018-04-25 | 2022-10-11 | Nanjing Yitian Biotechnology Co., Ltd. | Particle detection device and detection method |
| CN108680503A (en) * | 2018-05-18 | 2018-10-19 | 王闯 | Liquid controls chip and system |
| CN109569752A (en) * | 2018-12-22 | 2019-04-05 | 北京工业大学 | A kind of micro-fluidic chip bearing flow for improving the limit after droplet capture |
| CN109569752B (en) * | 2018-12-22 | 2021-03-30 | 北京工业大学 | Microfluidic chip for improving ultimate bearing flow after liquid drop capture |
| CN109612890B (en) * | 2018-12-28 | 2021-02-02 | 瑞芯智造(深圳)科技有限公司 | Particle counting system, application of particle counting system and method for detecting metal ions and particles |
| CN109612890A (en) * | 2018-12-28 | 2019-04-12 | 瑞芯智造(深圳)科技有限公司 | A kind of particle counting system and application, the method for detecting metal ion and particle |
| CN110711608A (en) * | 2019-09-23 | 2020-01-21 | 中国科学院上海微系统与信息技术研究所 | Microfluidic chip for cell detection and preparation method thereof |
| CN111239027A (en) * | 2020-01-22 | 2020-06-05 | 深圳市锦瑞生物科技有限公司 | Blood particle detection method and blood analyzer |
| CN114713297A (en) * | 2021-01-04 | 2022-07-08 | 深圳华大生命科学研究院 | Micro-fluidic chip |
| CN114713297B (en) * | 2021-01-04 | 2023-10-03 | 深圳华大生命科学研究院 | Microfluidic Chip |
| CN115228516A (en) * | 2021-04-23 | 2022-10-25 | 中国石油化工股份有限公司 | Domain-limiting unit and method for regulating and controlling size distribution of dispersed phase in multiphase system |
| CN115125185A (en) * | 2022-08-30 | 2022-09-30 | 中国海洋大学 | Preparation method of bivalve blood lymphocyte single cell suspension |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103175950B (en) | 2015-04-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103175950B (en) | Hemocyte analysis chip and system for using chip thereof | |
| Yuan et al. | Recent progress of particle migration in viscoelastic fluids | |
| Vembadi et al. | Cell cytometry: Review and perspective on biotechnological advances | |
| Chung et al. | Recent advances in miniaturized microfluidic flow cytometry for clinical use | |
| Tang et al. | Microfluidic impedance cytometer with inertial focusing and liquid electrodes for high-throughput cell counting and discrimination | |
| Huh et al. | Microfluidics for flow cytometric analysis of cells and particles | |
| Yuan et al. | On-chip microparticle and cell washing using coflow of viscoelastic fluid and newtonian fluid | |
| CN103170377B (en) | Hemocyte analysis chip and system for using chip thereof | |
| Zhang et al. | Design of a single-layer microchannel for continuous sheathless single-stream particle inertial focusing | |
| CN103472216A (en) | Hemocyte analysis chip, analyzer and analysis method | |
| Bilican et al. | Focusing-free impedimetric differentiation of red blood cells and leukemia cells: A system optimization | |
| Chen et al. | Optical microflow cytometer for particle counting, sizing and fluorescence detection | |
| Chang et al. | Deformation-based droplet separation in microfluidics | |
| Choi et al. | Microfluidic high-throughput single-cell mechanotyping: Devices and applications | |
| CN112945637A (en) | Sampling device | |
| CN210752733U (en) | Micro-fluidic integrated chip that detects | |
| WO2008036083A1 (en) | Microfluidic flow cytometer and applications of same | |
| CN207614860U (en) | Microlayer model generating means | |
| Wu et al. | MEMS-based Coulter counter for cell counting and sizing using multiple electrodes | |
| CN108169129A (en) | A kind of method for realizing microballoon single-row sample introduction | |
| CN105628660B (en) | A kind of passive micro-valve POCT chips | |
| CN202951487U (en) | Micro-fluidic chip integrating functions of micro-cavity static polymerase chain reactions (PCRs) and capillary electrophoresis (CE) | |
| Shen et al. | A simple 3-D microelectrode fabrication process and its application in microfluidic impedance cytometry | |
| Mansor et al. | A Novel Integrated Dual Microneedle-Microfluidic Impedance Flow Cytometry for Cells Detection in Suspensions. | |
| CN112547143B (en) | Micro-fluidic chip and blood cell detection device |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |