CN103170377B - Hemocyte analysis chip and system for using chip thereof - Google Patents
Hemocyte analysis chip and system for using chip thereof Download PDFInfo
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- CN103170377B CN103170377B CN201110430735.4A CN201110430735A CN103170377B CN 103170377 B CN103170377 B CN 103170377B CN 201110430735 A CN201110430735 A CN 201110430735A CN 103170377 B CN103170377 B CN 103170377B
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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 liquid storage pool, a second liquid storage pool, a third liquid storage pool, a first fluid passage, a second fluid passage and a detection channel. The first liquid storage pool is used for storing a hemocyte suspension, the second liquid storage pool is used for storing a solution which is capable of changing the specific performance of the hemocyte suspension, and the third liquid storage pool is used for storing waste liquid. The first liquid storage pool is connected to the third liquid storage pool through the first fluid passage and the detection channel, and the second liquid storage pool is connected to the third liquid storage pool through the second fluid passage and the detection channel. The first fluid passage and the second fluid passage are intersected with the detection channel at a same position. A small detection hole is provided on the detection channel. 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 microflow control technique and apply the system of this chip.
Background technology
Blood flows through each tissue and the organ of human body, the interaction between each tissue and organ of human body, to influence each other be realized by the adjustment of neural, body fluid and balance, and this balance is reflected in the aspect such as various physical parameters, physiological parameter of blood.The information that blood test obtains can contribute to the disease diagnosed, antidiastole is relevant with hematological system, contributes to analysing patient's condition, observe the curative effect, judging prognosis, for prevent disease provides foundation, instructs clinical application and carry out clinic study.Blood cell Epidemiological Analysis is not only the Main Basis of the various disease of diagnosis hemopoietic system, also important information can be provided to the diagnosis and differential diagnosis of other system disease, therefore haemocyte inspection (i.e. blood routine examination) has become first of three large routine inspections in clinical examination (routine blood test, routine urinalysis, just routine), and its clinical practice is also extensive.
Haemocyte inspection field, invented particle counting technology from early 1950s Mr. Ku Erte, manufactured First cellanalyzer and be applied to clinical since, the development of cellanalyzer has the history of 50 years.At present, cellanalyzer has become one of hospital clinical inspection application instrument widely, and it mainly can be divided into three classification and five classification cellanalyzers, and Cleaning Principle is electrical impedance, radio frequency and laser light scattering etc. mainly.
Three current classification cellanalyzer many employings electrical impedance methods.The principle that electrical impedance detects is: the character non-conducting according to haemocyte, detects in the resistance variations by causing during aperture suspended particulate in electrolyte solution.Specific practice is, arranges an aperture in cell suspension to be measured, and respectively there is an electrode applying certain voltage the both sides of aperture, if the electric current of supply and impedance are stable, according to Ohm's law, are also constant by the voltage of aperture.When the cell of in suspension is by aperture, because the conductibility of haemocyte is minimum, the conduction property of haemocyte is lower than isotonic electrolyte, the resistance in aperture induction zone is in circuit increased, causes voltage change instantaneously and occur a pulse signal.The degree that voltage increases depends on the volume of cell, and the volume of cell is larger, and the voltage change caused is larger, and the pulse amplitude of generation is higher.Can be measured the volume of cell by the measurement of paired pulses amplitude, the number of recording impulse can obtain Cytometric result.Through to various haemocyte produce the electronic selection of impulse magnitude, different types of haemocyte can be distinguished and analyze.
Current blood cell analysis is generally carried out through specific people under given conditions by commercially available cellanalyzer.The volume of this kind of cellanalyzer is large, cost is high, maintenance is wasted time and energy, can only analyze a sample at every turn, has strict demand simultaneously, need through professional training to operator, and limitation is comparatively large, is difficult to popularize.
For solving the problem, industry is now just putting forth effort to develop the cellanalyzer based on microflow control technique.The initial form of microfluidic analysis technology is micro-full analytical system (the miniaturized total analysis systems based on micro electronmechanical process technology that proposes first of Manz and Widmer of early 1990s Switzerland, μ TAS), its objective is and the function of assay laboratory is transferred in portable analytical equipment, even be integrated on the chip of heart size, adapt to the demand for development of microminiaturized, integrated, the portability of analytical instrument, automation, for the realization of " individualizing ", " family oriented " assay laboratory creates advantage.Micro-fluidic chip (microfluidic chip) is most active field and frontier development in μ TAS, and be widely used in the fields such as immunoassay, DNA analysis, analysis of protein, PCR (Polymerase Chain Reaction, PCR), cell sorting and single cell analysis.Micro-fluidic chip carries out cell research be more and more subject to people's attention, be applied to cell chulture, cell count and category filter, the aspect such as interactional research and single cell analysis of constituent analysis in born of the same parents, molecular ion and cell, micro-fluidic chip shows good application potential in medical diagnosis on disease, becomes and develops ideal platform that is quick, efficient, low cost medical diagnosis on disease technology.
Cellanalyzer based on micro-fluidic chip can improve the shortcomings such as traditional cellanalyzer volume is large, price, maintenance is wasted time and energy, flux is low, operation easier is large, thus improve analysis throughput, reduction operation easier, reduction volume, and micro-fluidic chip cost is low, can single use, by mistake and discardable, and reduce price and the maintenance cost of cellanalyzer, therefore micro-fluidic chip has good application prospect in blood cell analysis, is applicable 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 microflow control technique and apply the system of this chip.
Blood cell analysis chip provided by the invention comprises at least one micro-fluidic chip, this micro-fluidic chip comprises the first liquid storage tank, second liquid storage tank, 3rd liquid storage tank, first liquid passage, second liquid passage and sense channel, first liquid storage tank is for storing blood cell suspension, second liquid storage tank can change the solution of blood cell suspension particular characteristic for storing, 3rd liquid storage tank is for storing waste liquid, first liquid storage tank is connected with the 3rd liquid storage tank with sense channel by first liquid passage, second liquid storage tank is connected with the 3rd liquid storage tank with sense channel by second liquid passage, first liquid passage and second liquid passage and sense channel cross at same position, sense channel is provided with the detection aperture that haemocyte can be made to pass through.
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 detection unit and signal processing system, electrical impedance detection unit comprises is located at detection multiple electrode of aperture both sides and the detector for voltage change between detecting electrode, and the voltage change that signal processing system is used for detecting according to electrical impedance detection unit carries out cell analysis.
In one embodiment of the invention, described second liquid storage tank, the first liquid storage tank and the 3rd liquid storage tank ecto-entad are configured on micro-fluidic chip successively.
In one embodiment of the invention, described first liquid storage tank has multiple, these first liquid storage tanks are uniformly distributed in around the 3rd liquid storage tank, and the 3rd liquid storage tank is connected with these first liquid storage tanks with many articles of first liquid passages by the many articles of sense channels radially extended by the 3rd liquid storage tank.
In one embodiment of the invention, the quantity of described second liquid storage tank is one, and the liquid in described second liquid storage tank passes through second liquid channel allocation in sense channel in the mode that multi-grade mean distributes.
In one embodiment of the invention, described second liquid passage has multiple level from outside to inside, the quantity of the second liquid passage of each internal layer is the twice of adjacent outer second liquid number of channels, each outer field second liquid passage is all connected with adjacent two internal layer second liquid passages, and the second liquid passage of innermost layer is connected with sense channel with first liquid passage.
In one embodiment of the invention, the connection between the second liquid passage of innermost layer and sense channel is that Y type connects, T-shaped connection or
type connects.
In one embodiment of the invention, described blood cell analysis chip comprises two micro-fluidic chips, these two micro-fluidic chips are respectively white blood cell detection chip and red blood cell/platelets analysis chip, first liquid storage tank of described white blood cell detection chip is blood sample liquid storage tank, second liquid storage tank is erythrocyte cracked liquid liquid storage tank, 3rd liquid storage tank is waste liquid pool, first liquid passage is blood sample channel, second liquid passage is erythrocyte cracked liquid passage, first liquid storage tank of described red blood cell/platelets analysis chip is blood sample liquid storage tank, second liquid storage tank is sheath fluid liquid storage tank, 3rd liquid storage tank is waste liquid pool, first liquid passage is blood sample channel, second liquid passage is sheath fluid passage.
In one embodiment of the invention, described blood cell analysis chip comprises a micro-fluidic chip, described micro-fluidic chip is integrated with white blood cell detection chip and red blood cell/platelets analysis chip, described white blood cell detection chip and red blood cell/platelets analysis chip are divided into the both sides of micro-fluidic chip, its two sense channels sharing a waste liquid pool and be positioned at two chip interface, these two sense channels are connected with the second liquid passage of white blood cell detection chip with red blood cell/platelets analysis chip simultaneously.
In one embodiment of the invention, described blood cell analysis chip is counted the cell by detecting aperture by electrical impedance method.
Blood cell analysis system of the present invention has that structure is simple, 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 applicable 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, in order to technological means of the present invention can be better understood, and can be implemented according to the content of description, and can become apparent to allow above and other object of the present invention, feature and advantage, below especially exemplified by preferred embodiment, and coordinate accompanying drawing, be described in detail as follows.
Accompanying drawing explanation
Figure 1 shows that the schematic diagram of cellanalyzer of the present invention.
Figure 2 shows that the schematic diagram of the first embodiment of blood cell analysis chip in Fig. 1.
The schematic diagram of the second embodiment of the chip of blood cell analysis shown in Fig. 3.
The schematic diagram of the 3rd embodiment of the chip of blood cell analysis shown in Fig. 4.
Detailed description of the invention
For further setting forth the present invention for the technological means reaching predetermined goal of the invention and take and effect, below in conjunction with accompanying drawing and preferred embodiment, the blood cell analysis chip propose foundation the present invention and the system detailed description of the invention applying this chip, structure, feature and effect thereof, be described in detail as follows.
Figure 1 shows that the schematic diagram of blood cell analysis system of the present invention.As shown in Figure 1, this blood cell analysis system 100 is the high flux blood cell analysis systems based on microfluidic analysis technology, and it comprises blood cell analysis chip 10, electrical impedance detection unit 20, signal processing system 30 and display 40.
Wherein, blood cell analysis chip 10 by quartz, glass, monocrystalline silicon, macromolecule polymeric material as polymethyl methacrylate (PolymethylMethacrylate, PMMA), dimethyl silicone polymer (polydimethylsiloxane, PDMS), Merlon (Polycarbonate, etc. PC) make, which is provided with many sense channel F1-F8 that multiple band detects aperture 110, L1-L8 (as shown in Figure 2).Electrical impedance detection unit 20 comprises high voltage source 21, multiple electrode 22 and detector (not shown).These electrodes 22 are placed in the both sides of the detection aperture 110 of sense channel respectively, and the output of high voltage source 21 connects the electrode 22 on blood cell analysis chip 10, and detector is used for the change of voltage between detecting electrode 22.Signal processing system 30 is embedded in main frame, for according to the voltage change between the electrode 22 of electrical impedance detection unit 20, analyzes the haemocyte by detecting aperture 110, determines kind and the quantity of the haemocyte by detecting aperture 110.Display 40 is 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 comprises two discoid micro-fluidic chips, and these two micro-fluidic chips are respectively white blood cell detection chip 11 and red blood cell/platelets analysis chip 12.White blood cell detection chip 11 has same structure with red blood cell/platelets analysis chip 12, and they comprise the first liquid storage tank, the second liquid storage tank, the 3rd liquid storage tank and first liquid passage, second liquid passage and sense channel respectively.
When micro-fluidic chip is white blood cell detection chip 11, the first liquid storage tank is blood sample liquid storage tank A1-A8, and it is for storing blood cell suspension.Second liquid storage tank is erythrocyte cracked liquid liquid storage tank B, and the erythrocyte cracked liquid stored in it can change the performance of blood cell suspension.3rd liquid storage tank is waste liquid pool C, for storing the waste liquid after detection.First liquid passage is blood sample channel D1-D8, second liquid passage is erythrocyte cracked liquid passage E1-E4, and sense channel is F1-F8.When micro-fluidic chip is red blood cell/platelets analysis chip 12, first liquid storage tank is blood sample liquid storage tank G1-G8, second liquid storage tank is sheath fluid liquid storage tank H, 3rd liquid storage tank is waste liquid pool I, first liquid passage is blood sample channel J1-J8, second liquid passage is sheath fluid passage K1-K4, and sense channel is L1-L8.Embodiment shown in Fig. 2 comprises eight the first liquid storage tanks, the second liquid storage tank, the 3rd liquid storage tank, and the first liquid passage of suitable quantity, second liquid passage and sense channel.That is, white blood cell detection chip 11 and red blood cell/platelets analysis chip 12 are the blood cell analysis chip 10 of 8 passages, and it can be analyzed 8 blood samples.
More specific detail is carried out to the structure of blood cell analysis chip 10 of the present invention below, because the structure of white blood cell detection chip 11 is identical with the structure of red blood cell/platelets analysis chip 12, therefore, be hereafter only described for the structure of white blood cell detection chip 11 to micro-fluidic chip.
In white blood cell detection chip 11, waste liquid pool is positioned at the center of white blood cell detection chip 11, and blood sample liquid storage tank A1-A8 is uniformly distributed in around waste liquid pool C.Waste liquid pool C is connected with blood sample liquid storage tank A1-A8 with blood sample channel D1-D8 by the sense channel F1-F8 radially extended by waste liquid pool C.Erythrocyte cracked liquid liquid storage tank B is positioned at the outermost of white blood cell detection chip 11, its erythrocyte cracked liquid passage E1-E4 by multistage distribution and blood sample channel D1-D8 crosses in the junction of blood sample channel D1-D8 and sense channel F1-F8, by erythrocyte cracked liquid uniform distribution in sense channel F1-F8.
Specifically, from distribution mode, erythrocyte cracked liquid passage E1-E4 is divided into four levels from outside to inside, and wherein, outer field erythrocyte cracked liquid passage outwards offsets certain distance relative to the erythrocyte cracked liquid passage of internal layer respectively.From effect and bearing of trend, erythrocyte cracked liquid passage E1-E4 can be divided into extension passage and interface channel.Extension passage extends, for the circumferential distribution erythrocyte cracked liquid along white blood cell detection chip 11 along the circumference of white blood cell detection chip 11 and concentric circles thereof.Interface channel roughly extends along the depth direction of white blood cell detection chip 11, for connecting erythrocyte cracked liquid liquid storage tank B and erythrocyte cracked liquid passage E1-E4, or the extension passage of the erythrocyte cracked liquid passage of connection adjacent layer, or connect erythrocyte cracked liquid passage E1-E4 and blood sample channel D1-D8 and sense channel F1-F8.
In each layer passage of erythrocyte cracked liquid, the first level erythrocyte cracked liquid passage E1 comprises an extension passage, and this extension passage is semicircle.Second level erythrocyte cracked liquid passage E2 comprises two extension passages, and these two extension passages are the circular arc that central angle is right angle.Third level erythrocyte cracked liquid passage E3 comprises four extension passages, and they are the circular arc that central angle is miter angle.Fourth stage erythrocyte cracked liquid passage E4 comprises eight extension passages, and they are the circular arc that central angle is less than 22.5 degree of angles.
The extension passage of fourth stage erythrocyte cracked liquid passage E4 lays respectively between two adjacent blood sample liquid storage tanks, and its interface channel by inclination and blood sample channel D 1-D8 and sense channel F1-F8 cross in the junction of blood sample channel D1-D8 and sense channel F1-F8.The extension passage of third level erythrocyte cracked liquid passage E3 lays respectively between two adjacent fourth stage passage E4, and its two ends are connected with the middle part of fourth stage extension passage respectively by the interface channel of radial direction.The extension passage of second level erythrocyte cracked liquid passage E2 lays respectively between two adjacent third level passage E3, and its two ends are connected with the middle part of third level extension passage respectively by the interface channel of radial direction.The extension passage of first order erythrocyte cracked liquid passage E1 is between the passage E2 of the second level, its two ends are connected with the middle part of second level extension passage respectively by the interface channel of radial direction, and are connected with erythrocyte cracked liquid liquid storage tank B by radial interface channel in the middle part of it.In the present embodiment, the extension passage of fourth stage erythrocyte cracked liquid passage E4 is crossed in the junction of blood sample channel D1-D8 and sense channel F1-F8 by the interface channel that tilts and blood sample channel D1-D8 and sense channel F1-F8, makes fourth stage erythrocyte cracked liquid passage E4 be similar to Y type with the connection of sense channel F1-F8 and is connected; Understandable, in other embodiments of the invention, fourth stage erythrocyte cracked liquid passage can without the need to arranging interface channel, and extension passage is crossed in the junction of blood sample channel and sense channel with blood sample channel and sense channel directly to front extending to, in this case, blood sample liquid storage tank can the extension passage of fourth stage erythrocyte cracked liquid passage relatively slightly to outer setting, the connection of erythrocyte cracked liquid passage and sense channel is similar to T-shaped connection; In another embodiment of the present invention, the extension passage of fourth stage erythrocyte cracked liquid passage crosses in the junction of blood sample channel and sense channel by the interface channel of L-type and blood sample channel and sense channel, like this, being connected to become of erythrocyte cracked liquid passage and sense channel
type connects.
Introducing in detail below utilizes blood cell analysis system 100 to carry out the process of blood cell analysis:
When carrying out white blood cell count(WBC), anticoagulation sample introduction is to the blood sample liquid storage tank A1-A8 of white blood cell detection chip 11, erythrocyte cracked liquid sample introduction is to erythrocyte cracked liquid liquid storage tank B, make anticoagulation and erythrocyte cracked liquid flow out from the liquid storage tank of correspondence simultaneously, it is made to mix at sense channel F1-F8, after mixing, under the effect of erythrocyte cracked liquid, erythrocyte membrane in blood breaks, discharge hemoglobin, only leave the nubbin that erythrocyte membrane is small, leucocyte in blood is in line, leucocyte is one by one by the detection aperture 110 of sense channel F1-F8 middle and lower reaches, waste liquid pool C is flowed into after electrical impedance detects.Because the conductive properties of haemocyte is lower than isotonic electrolyte, when haemocyte is by detecting aperture 110, the voltage detecting aperture 110 place changes, detector will receive a pulse signal, the size of this pulse signal is determined by the size of the blood cell volume detecting aperture 110, the number of pulse signal is determined by the number of the haemocyte detecting aperture 110, then, the signal transmission that receives to signal processing system 30, makes signal processing system 30 can carry out white blood cell count(WBC) and volumetric analysis according to the quantity of pulse signal and size by detector.
When carrying out red blood cell/platelet count, anticoagulation sample introduction is to the blood sample liquid storage tank G1-G8 of red blood cell/platelets analysis chip 12, sheath fluid sample introduction is to the sheath fluid liquid storage tank H of red blood cell/platelets analysis chip 12, make anticoagulation and sheath fluid flow out from liquid storage tank simultaneously, it is made to mix at sense channel L1-L8, after mixing, under the effect of sheath fluid, unicellular in blood is in line, cell, one by one by the detection aperture 110 of sense channel L1-L8 middle and lower reaches, flows into waste liquid pool I after electrical impedance detects.Because the conductive properties of haemocyte is lower than isotonic electrolyte, when haemocyte is by detecting aperture 110, the voltage detecting aperture 110 place changes, detector will receive a pulse signal, the size of pulse signal is determined by the size of the blood cell volume detecting aperture 110, the number of pulse signal is determined by the number of the haemocyte detecting aperture 110, because blood platelet and erythrocyte volume have obvious difference, therefore, threshold value can be set, pulse signal higher than threshold value is defined as corresponding with red blood cell, otherwise it is then corresponding with blood platelet, thus make signal processing system 30 can carry out red blood cell/platelet count and volumetric analysis according to the quantity of pulse signal and size.
Blood cell analysis system of the present invention, utilizes micro-fluidic and electrical impedance detection technique, can carry out accurate counting, realize haemocyte three classification analysis to the red blood cell/blood platelet in anticoagulation and leucocyte.Certainly, blood cell analysis system of the present invention also in conjunction with technology such as laser, radio frequency and chemical stainings, can realize the analysis of haemocyte five classification analysis and other relevant parameters of routine blood test.
Further, blood cell analysis system of the present invention also has that structure is simple, 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 applicable to the uses such as hospital, clinic, community and individual family.
In addition, it should be noted that, in the embodiment shown in Figure 2, adopt the blood cell analysis chip 10 of 8 passages to analyze 8 blood samples simultaneously, understandably, in the present invention, the quantity of sense channel is not limited to this, is illustrated in figure 3 the blood cell analysis chip 10a of 32 passages.In the embodiment shown in fig. 3, blood cell analysis chip 10a comprises 32 the first liquid storage tanks, the first liquid passage of the second liquid storage tank, the 3rd liquid storage tank and a suitable quantity, second liquid passage and sense channel.
In the embodiment shown in fig. 3, second liquid passage is divided into 6 levels from outside to inside.The second liquid passage of the first level comprises an extension passage, and this extension passage is semicircle.The second liquid passage of the second level comprises two extension passages, and these two extension passages are the circular arc that central angle is right angle.The second liquid passage of the third level comprises four extension passages, and they are the circular arc that central angle is miter angle.The second liquid passage of the fourth stage comprises eight extension passages, and they are the circular arc that central angle is 22.5 degree of angles.The second liquid passage of level V comprises 16 extension passages, and they are the circular arc that central angle is 11.25 degree of angles.The second liquid passage of the 6th grade comprises 32 articles of extension passages, and they are central angle is the circular arc being less than 5.6 degree of angles.
The second liquid extension passage of the 6th grade is between adjacent two blood sample liquid storage tanks, and its two ends are crossed in the junction of blood sample channel and sense channel by the interface channel that tilts and blood sample channel and sense channel.The second liquid extension passage of level V lays respectively between two adjacent the 6th grade of passages, and its two ends are connected with the middle part of the 6th grade of extension passage respectively by the interface channel of radial direction.The second liquid extension passage of the fourth stage lays respectively between two adjacent level V passages, and its two ends are connected with the middle part of level V extension passage respectively by the interface channel of radial direction.The second liquid extension passage of the third level lays respectively between two adjacent fourth stage passages, and its two ends are connected with the middle part of fourth stage extension passage respectively by the interface channel of radial direction.The second liquid extension passage of the second level is between adjacent two third level passages, and its two ends are connected with the middle part of third level extension passage respectively by the interface channel of radial direction.The second liquid extension passage of the first order is between the passage of the second level, and its two ends are connected with the middle part of second level extension passage respectively by the interface channel of radial direction, and is connected with the second liquid storage tank by radial interface channel in the middle part of it.
Known by the embodiment shown in Fig. 2 and Fig. 3, blood cell analysis chip 10 of the present invention also can adopt the sense channel of other quantity, when adopting the sense channel of other quantity, second liquid passage need meet following condition: second liquid passage is divided into multiple level from outside to inside, the quantity of the second liquid passage of internal layer is the twice of adjacent outer second liquid number of channels, each outer field second liquid passage is all connected with adjacent two internal layer second liquid passages, outermost second liquid passage is connected with the second liquid storage tank, the second liquid passage of innermost layer is connected with sense channel with first liquid passage.
In the embodiment shown in Fig. 2 and Fig. 3, blood cell analysis system 100 utilizes two discoidal micro-fluidic chips to carry out red blood cell/platelet count and white blood cell count(WBC) respectively, be appreciated that, in other embodiments of the invention, blood cell analysis system 100 also can utilize a discoidal micro-fluidic chip to carry out red blood cell/platelet count and white blood cell count(WBC) simultaneously, improves the integration degree of haemocyte detection chip.The embodiment that a micro-fluidic chip carries out red blood cell/platelet count and white blood cell count(WBC) is simultaneously shown in Fig. 4.Embodiment shown in Fig. 4 and embodiment illustrated in fig. 2 to be maximumly distinguished as, white blood cell detection chip 11b and red blood cell/platelets analysis chip 12b is divided into the both sides of blood cell analysis chip 10b, described white blood cell detection chip 11b and red blood cell/platelets analysis chip 12b shares a waste liquid pool C and is positioned at two sense channels F3, F7 of two chip interface, and these two sense channels F3, F7 are connected with the second liquid passage of red blood cell/platelets analysis chip 12b with white blood cell detection chip 11b simultaneously.Specifically, in the embodiment shown in fig. 4,8 blood sample liquid storage tank A1-A8 of micro-fluidic chip be uniformly distributed in be positioned at chip center waste liquid pool C around.Second liquid storage tank comprises the erythrocyte cracked liquid liquid storage tank B and sheath fluid liquid storage tank H that lay respectively at the micro-fluidic chip left and right sides.Corresponding with erythrocyte cracked liquid liquid storage tank B and sheath fluid liquid storage tank H, second liquid passage comprises erythrocyte cracked liquid passage and sheath fluid passage, and erythrocyte cracked liquid passage is corresponding with erythrocyte cracked liquid liquid storage tank B and sheath fluid liquid storage tank H with the position of sheath fluid passage.Label is the sense channel corresponding white blood cell detection chip 11b of F1, F2, F8, can carry out normal white blood cell count(WBC).Label is the corresponding red blood cell/platelets analysis chip 12b of sense channel of F4, F5, F6, can carry out normal red blood cell/platelet count.Label is the sense channel of F3 and F7 is the passage that white blood cell detection chip 11b and red blood cell/platelets analysis chip 12b shares, the one side inflow erythrocyte cracked liquid of these two sense channels F3, F7, one side inflow sheath fluid, due to the difference of the liquid component of inflow, the effect of passage F3 is different from passage F1, F2, F8, the effect of passage F7 is different from passage F4, F5, F6, and passage F3 and F7 can be used for doing check experiment, as examination criteria particle or charge thing.
For second liquid passage, in the embodiment shown in fig. 4, second liquid passage is divided into 3 levels from outside to inside.The second liquid passage of the first order comprises two extension passages, and these two extension passages are the circular arc that central angle is right angle.The second liquid passage of the second level comprises four extension passages, and they are the circular arc that central angle is miter angle.The second liquid passage of the third level comprises eight extension passages, and they are the circular arc that central angle is less than 22.5 degree of angles.
The second liquid extension passage of the third level lays respectively between two adjacent blood sample liquid storage tanks, and its two ends are crossed in the junction of blood sample channel and sense channel by the interface channel that tilts and blood sample channel and sense channel.The second liquid extension passage of the second level lays respectively between two adjacent third level passages, and its two ends are connected with the middle part of third level extension passage respectively by the interface channel of radial direction.The second liquid extension passage of the first order lays respectively between two adjacent second level passages, its two ends are connected with the middle part of second level extension passage respectively by the interface channel of radial direction, and are connected with the second corresponding liquid storage tank by radial interface channel in the middle part of it.
Finally it should be noted that, in the embodiment shown in Fig. 2 to Fig. 4 of the present invention, blood cell analysis chip is disc, understandably, in other embodiments of the invention, the shape of blood cell analysis chip can be square, the polygon such as hexagon, octagon, as long as enable the various reservoir on blood cell analysis chip and fluid passage arrange to be similar to mode of the present invention, and the liquid in the second liquid storage tank is passed through second liquid channel allocation to sense channel in the mode that multi-grade mean distributes.
In addition, the micro-valve of Micropump, electrokinetic injection, positive pressure can be adopted 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 at the channel inner surface of blood cell analysis chip through ad hoc fashion modification, or chip material modification, to keep the hydrophobicity of channel inner surface, or add suitable additive in the solution, alleviate or avoid the channel surface absorption haemocyte of blood cell analysis chip, prevent the channel blockage of blood cell analysis chip.
The above, it is only preferred embodiment of the present invention, not any pro forma restriction is done to the present invention, although the present invention discloses as above with preferred embodiment, but and be not used to limit the present invention, any those skilled in the art, do not departing within the scope of technical solution of the present invention, make a little change when the technology contents of above-mentioned announcement can be utilized or be modified to the Equivalent embodiments of equivalent variations, in every case be do not depart from technical solution of the present invention content, according to any simple modification that 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 (8)
1. a blood cell analysis chip, comprise at least one micro-fluidic chip, it is characterized in that: this micro-fluidic chip comprises the first liquid storage tank, second liquid storage tank, 3rd liquid storage tank, first liquid passage, second liquid passage and sense channel, first liquid storage tank is for storing blood cell suspension, second liquid storage tank can change the solution of blood cell suspension particular characteristic for storing, 3rd liquid storage tank is for storing waste liquid, first liquid storage tank is connected with the 3rd liquid storage tank with sense channel by first liquid passage, second liquid storage tank is connected with the 3rd liquid storage tank with sense channel by second liquid passage, first liquid passage and second liquid passage and sense channel cross at same position, described sense channel is provided with the detection aperture that haemocyte can be made to pass through, described blood cell analysis chip is counted the cell by detecting aperture by electrical impedance method,
Described first liquid storage tank has multiple, and these first liquid storage tanks are uniformly distributed in around the 3rd liquid storage tank, and the 3rd liquid storage tank is connected with these first liquid storage tanks with many articles of first liquid passages by the many articles of sense channels radially extended by the 3rd liquid storage tank.
2. blood cell analysis chip as claimed in claim 1, is characterized in that: described second liquid storage tank, the first liquid storage tank and the 3rd liquid storage tank ecto-entad are configured on micro-fluidic chip successively.
3. blood cell analysis chip as claimed in claim 1, is characterized in that: the quantity of described second liquid storage tank is one, and the liquid in described second liquid storage tank passes through second liquid channel allocation in sense channel in the mode that multi-grade mean distributes.
4. blood cell analysis chip as claimed in claim 1, it is characterized in that: described second liquid passage has multiple level from outside to inside, the quantity of the second liquid passage of each internal layer is the twice of adjacent outer second liquid number of channels, each outer field second liquid passage is all connected with adjacent two internal layer second liquid passages, and the second liquid passage of innermost layer is connected with sense channel with first liquid passage.
5. blood cell analysis chip as claimed in claim 4, is characterized in that: the connection between the second liquid passage of innermost layer and sense channel is that Y type connects, T-shaped connection or
type connects.
6. blood cell analysis chip as claimed in claim 1, it is characterized in that: described blood cell analysis chip comprises two micro-fluidic chips, these two micro-fluidic chips are respectively white blood cell detection chip and red blood cell/platelets analysis chip, first liquid storage tank of described white blood cell detection chip is blood sample liquid storage tank, second liquid storage tank is erythrocyte cracked liquid liquid storage tank, 3rd liquid storage tank is waste liquid pool, first liquid passage is blood sample channel, second liquid passage is erythrocyte cracked liquid passage, first liquid storage tank of described red blood cell/platelets analysis chip is blood sample liquid storage tank, second liquid storage tank is sheath fluid liquid storage tank, 3rd liquid storage tank is waste liquid pool, first liquid passage is blood sample channel, second liquid passage is sheath fluid passage.
7. blood cell analysis chip as claimed in claim 1, it is characterized in that: described blood cell analysis chip comprises a micro-fluidic chip, described micro-fluidic chip is integrated with white blood cell detection chip and red blood cell/platelets analysis chip, described white blood cell detection chip and red blood cell/platelets analysis chip are divided into the both sides of micro-fluidic chip, its two sense channels sharing a waste liquid pool and be positioned at two chip interface, these two sense channels are connected with the second liquid passage of white blood cell detection chip with red blood cell/platelets analysis chip simultaneously.
8. a blood cell analysis system, it is characterized in that: this blood cell analysis system comprises the blood cell analysis chip according to any one of claim 1 to 7, and electrical impedance detection unit and signal processing system, electrical impedance detection unit comprises is located at detection multiple electrode of aperture both sides and the detector for voltage change between detecting electrode, and the voltage change that signal processing system is used for detecting according to electrical impedance detection unit carries out cell analysis.
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| CN103471982B (en) * | 2013-08-23 | 2015-11-25 | 深圳中科强华科技有限公司 | Blood cell analysis chip, analyzer and analysis method |
| CN103471980B (en) * | 2013-08-23 | 2015-08-26 | 深圳中科强华科技有限公司 | A kind of chip type blood cell analyzer and method |
| 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 |
| CN103472034B (en) * | 2013-08-23 | 2015-10-28 | 深圳中科强华科技有限公司 | Blood cell analysis chip, analyzer and analysis method |
| CN103528935B (en) * | 2013-10-15 | 2017-01-25 | 深圳中科强华科技有限公司 | Liquid path system for blood cell analyzer and blood cell analyzer |
| US10175225B2 (en) | 2014-09-29 | 2019-01-08 | C A Casyso Ag | Blood testing system and method |
| US10843185B2 (en) | 2017-07-12 | 2020-11-24 | Ca Casyso Gmbh | Autoplatelet cartridge device |
| CN107541452B (en) * | 2017-09-20 | 2023-12-15 | 杭州梓晶生物有限公司 | Microfluidic chip and chip assembly |
| 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 |
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