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CN109647554A - Hemostasis examination chip and hemostasis examination method - Google Patents

Hemostasis examination chip and hemostasis examination method Download PDF

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Publication number
CN109647554A
CN109647554A CN201910025010.3A CN201910025010A CN109647554A CN 109647554 A CN109647554 A CN 109647554A CN 201910025010 A CN201910025010 A CN 201910025010A CN 109647554 A CN109647554 A CN 109647554A
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blood
blood sample
microchannel
hemostasis examination
collecting chamber
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Pending
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CN201910025010.3A
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Chinese (zh)
Inventor
邓治杨
杨雁婷
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Individual
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Priority to CN201910025010.3A priority Critical patent/CN109647554A/en
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502753Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/80Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood groups or blood types or red blood cells
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Molecular Biology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Dispersion Chemistry (AREA)
  • Immunology (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

The invention discloses a kind of hemostasis examination chips, including microchannel, microchannel includes the accommodating chamber for accommodating red blood cell, and accommodating chamber is distributed in space array, and is equipped between two adjacent accommodating chambers and can be used for the communicating passage that red blood cell passes through while playing barrier effect to the flowing of red blood cell;One end of microchannel is equipped with the first blood sample cavity, the other end is equipped with the collecting chamber for collecting blood plasma;Collecting chamber is equipped with coupled the second logical blood sample cavity.The invention also discloses a kind of hemostasis examination methods, it is characterized by comprising following steps: 1) the first blood sample being instilled the first blood sample cavity, the red blood cell and blood plasma of the first blood sample are separated using microchannel, the blood plasma isolated is deposited in collecting chamber;2) when blood plasma is full of collecting chamber, the second blood sample is instilled into the second blood sample cavity, the second blood sample enters in collecting chamber;3) Coagulation test between the first blood sample and the second blood sample is detected.

Description

Hemostasis examination chip and hemostasis examination method
Technical field
The invention belongs to hemostasis examination technical fields, are specifically a kind of hemostasis examination chip and hemostasis examination method.
Background technique
Its blood and the blood of contributor can be carried out blood coagulation before carrying out treatment of blood transfusion by the patient for clinically needing to transfuse blood Experiment, test both whether blood coagulation, the only blood of not blood coagulation, patient can be conveyed to.Current hemostasis examination method master If first measuring patient blood type, the antigen of erythrocyte surface is different in the blood of different blood groups, can only generate in human body with Its different antibody, for example, erythrocyte surface antigen is agglutinogen A in A type blood, blood plasma contains anti-B agglutinin, red in Type B blood Cell surface antigen is agglutinogen B, and blood plasma contains anti-A agglutinin, and there are two kinds of agglutinogens of A, B on AB type erythrocyte surface, O-shaped Then two kinds of antigens all do not have on erythrocyte surface.
The testing principle of blood group is: when red blood cell and known standard plasma in blood to be measured mix, being according to red blood cell No appearance agglutination judges which kind of antigen erythrocyte surface to be measured contains, to judge type blood to be measured.When red blood cell to be measured and Standard A type blood plasma mixedly appears agglutination, mixes with standard Type B blood plasma and is not aggregated, and blood to be measured is Type B blood;When to be measured red Cell and the mixing of standard A type blood plasma are not aggregated, mixedly appear agglutination with standard Type B blood plasma, blood to be measured is A type blood;When Red blood cell to be measured and standard A type/Type B blood plasma mixing are all aggregated, and blood to be measured is O-shaped blood, if on the contrary be not all aggregated, Blood to be measured is AB type blood.Clinically detection abo blood group is mainly the reagent that anti-A and anti-B are added dropwise on glass slide, blood to be measured It respectively with reagent hybrid reaction, observes, is drawing a conclusion under the microscope.But this method needs microscopical auxiliary, and Abo blood group detection reagent is basic demand.
Summary of the invention
In view of this, can directly be examined the purpose of the present invention is to provide a kind of hemostasis examination chip and hemostasis examination method It surveys whether two kinds of blood can generate blood coagulation phenomenon, and then directly judges whether the blood of contributor matches with the blood of patient.
In order to achieve the above objectives, the invention provides the following technical scheme:
A kind of hemostasis examination chip, including microchannel, the microchannel includes the accommodating chamber for accommodating red blood cell, described Accommodating chamber is distributed in space array, and is equipped between two adjacent accommodating chambers and be can be used for red blood cell across simultaneously to red thin The communicating passage of barrier effect is played in the flowing of born of the same parents;
One end of the microchannel is equipped with the first blood sample cavity, the other end is equipped with the collecting chamber for collecting blood plasma;
Further include the second blood sample cavity, is connected between the second blood sample sample cavity and the collecting chamber using capillary It is logical.
Further, the inner wall of the accommodating chamber and communicating passage all has hydrophily.
Further, the geometric dimension of the accommodating chamber is greater than the geometric dimension of red blood cell, and the size model of the accommodating chamber It encloses for 7.6-9.2um;The size range of the communicating passage is 2.8-3.4um.
Further, it is logical that the separation circulated for isolated blood plasma is equipped between the microchannel and the collecting chamber Road.
Further, accumulation is equipped with microballon in the microchannel, forms the accommodating chamber between the microballon and is connected to described Channel.
Further, the microchannel is accumulated close to the side of the split tunnel is equipped with big microballon, outside the big microballon Diameter is greater than the height of the split tunnel.
Further, the outer diameter of the small microballon is 9-11um, and the outer diameter of the big microballon is 80-120um.
Further, the collecting chamber is equipped with venthole.
It further, further include the functional layer of substrate and setting on the substrate, the microchannel, the first blood sample cavity It is arranged in the functional layer with collecting chamber.
The invention also provides a kind of hemostasis examination methods using hemostasis examination chip as described above, it is characterised in that: Include the following steps:
1) the first blood sample is instilled into the first blood sample cavity, separates the first blood sample using the microchannel Red blood cell and blood plasma, the blood plasma isolated is deposited in the collecting chamber;
2) when blood plasma is full of the collecting chamber, the second blood sample is instilled into the second blood sample cavity, the second blood Liquid sample is entered in the collecting chamber by the capillary;
3) Coagulation test between the first blood sample and the second blood sample is detected.
The beneficial effects of the present invention are:
Hemostasis examination chip of the invention, by the way that microchannel, when the first blood sample is by microchannel, the first blood is arranged Blood plasma in liquid sample can be by the accommodating chamber of connection and communicating passage quickly through and since communicating passage is to red in blood Cell has barrier effect, and therefore, the flow rate of blood plasma is faster than the flow rate of red blood cell, so that blood plasma is separated, And red blood cell slowly flows, and will not block microchannel;Isolated blood plasma is deposited in collecting chamber, then in the second blood sample cavity The second blood sample of interior instillation after the second blood sample enters collecting chamber, is carried out with the blood plasma that the first blood sample is isolated Reaction, can be detected whether Coagulation test occurs between the first blood sample and the second blood sample.
Detailed description of the invention
In order to keep the purpose of the present invention, technical scheme and beneficial effects clearer, the present invention provides following attached drawing and carries out Illustrate:
Fig. 1 is the structural schematic diagram of hemostasis examination chip embodiment 1 of the present invention;
Fig. 2 is the A detail drawing of Fig. 1;
Fig. 3 is the top view of Fig. 1;
Fig. 4 is the pictorial diagram of the hemostasis examination chip of the present embodiment;
Fig. 5 is the blood plasma separating effect figure of the hemostasis examination chip of the present embodiment;
Fig. 6 is effect picture when the present embodiment accumulates blood plasma in collecting chamber;
Fig. 7 is macrograph when generating red blood cell blood coagulation phenomenon;
Fig. 8 is micro- sem observation figure when generating red blood cell blood coagulation phenomenon;
Fig. 9 is macrograph when not generating red blood cell blood coagulation phenomenon;
Figure 10 is micro- sem observation figure when not generating red blood cell blood coagulation phenomenon;
Figure 11 is the structural schematic diagram of hemostasis examination chip embodiment 2 of the present invention;
Figure 12 is the B detail drawing of Figure 11;
Figure 13 is the C-C cross-sectional view of Figure 11;
Figure 14 is the top view of Figure 11.
Specific embodiment
The present invention will be further explained below with reference to the attached drawings and specific examples, so that those skilled in the art can be with It better understands the present invention and can be practiced, but illustrated embodiment is not as a limitation of the invention.
Embodiment 1
As shown in Figure 1, being the structural schematic diagram of hemostasis examination chip embodiment 1 of the present invention.The hemostasis examination of the present embodiment Chip, including microchannel 10, microchannel 10 include the accommodating chamber 11 for accommodating red blood cell, and accommodating chamber 11 is in space array point Cloth, and between two adjacent accommodating chambers 11 be equipped with can be used for red blood cell pass through simultaneously barrier effect is played to the flowing of red blood cell Communicating passage 12.One end of microchannel 10 is equipped with the first blood sample cavity 20, the other end is equipped with the collection for collecting blood plasma The collecting chamber 30 of chamber 30, the present embodiment is equipped with venthole 31;The hemostasis examination chip of the present embodiment further include the second blood into Sample chamber 70 is connected between second blood sample sample cavity 70 and collecting chamber 30 using capillary 71.The microchannel 10 of the present embodiment with The split tunnel 40 to circulate for isolated blood plasma is equipped between collecting chamber 30.
Specifically, accumulation is equipped with microballon 13 in microchannel 10, accommodating chamber 11 and communicating passage 12 are formed between microballon 13.It is micro- Channel 10 is equipped with big microballon 14 close to the accumulation of the side of split tunnel 40, and the outer diameter of big microballon 14 is greater than the height of split tunnel 40 Degree, big microballon 14 primarily serve the effect of limit, prevent microballon 13 from entering in split tunnel 40.Preferably, small microballon is outer Diameter is 9-11um, and the outer diameter of big microballon is 80-120um.The outer diameter of the small microballon of the present embodiment is 10um, and the outer diameter of big microballon is 100um.Since microballon 13 is spherical in shape, there are size variation, big areas for the size of the hole formed between microballon 13 and microballon 13 Domain forms accommodating chamber 11, and small channel forms communicating passage 12.And hole will form the structure of similar capillary, bead surface warp Crossing surface treatment has strongly hydrophilic, and blood plasma will receive the effect of capillary force, advances towards the direction of concave meniscus.Capillary is made It is firmly inversely proportional with the radius of capillary, therefore the size for controlling microballon is also most important to enhancing capillary force.
The hemostasis examination chip of the present embodiment further includes the functional layer 60 of substrate 50 and setting on this base substrate 50, microchannel 10, blood sample cavity 20 and collecting chamber 30 are arranged in functional layer 60.The substrate 50 of the present embodiment is made of glass, function Layer 60 is made of PDMS.
Hemostasis examination method using the hemostasis examination chip of the present embodiment is as follows, includes the following steps:
1) the first blood sample is instilled into the first blood sample cavity 20, after the first blood sample enters microchannel, in microballon Under the action of the hole formed between 13, the red blood cell and blood plasma point of the first blood sample are separated, blood plasma rate faster, and is isolated Blood plasma be deposited in collecting chamber 30;
2) when blood plasma is full of collecting chamber 30, the second blood sample is instilled into the second blood sample cavity 70, in capillary channel Under 71 capillarity, the second blood sample is entered in collecting chamber 30;
3) Coagulation test between the first blood sample and the second blood sample is detected.
The hemostasis examination chip of the present embodiment, by the way that microchannel, when the first blood sample is by microchannel, first is arranged Blood plasma in blood sample can be by the accommodating chamber of connection and communicating passage quickly through and since communicating passage is in blood Red blood cell has barrier effect, and therefore, the flow rate of blood plasma is faster than the flow rate of red blood cell, so that blood plasma be isolated Come, and red blood cell slowly flows, and will not block microchannel;Isolated blood plasma is deposited in collecting chamber, then the second blood into Sample the second blood sample of intracavitary instillation, after the second blood sample enters collecting chamber, the blood plasma isolated with the first blood sample It is reacted, can be detected and Coagulation test whether occurs between the first blood sample and the second blood sample, as illustrated in figures 6-10.
Embodiment 2
It as shown in figure 11, is the structural schematic diagram of hemostasis examination chip embodiment 2 of the present invention.The hemostasis examination of the present embodiment Chip, including microchannel 10, microchannel 10 include the accommodating chamber 11 for accommodating red blood cell, and accommodating chamber 11 is in space array point Cloth, and between two adjacent accommodating chambers 11 be equipped with can be used for red blood cell pass through simultaneously barrier effect is played to the flowing of red blood cell Communicating passage 12.One end of microchannel 10 is equipped with the first blood sample cavity 20, the other end is equipped with the collection for collecting blood plasma The collecting chamber 30 of chamber 30, the present embodiment is equipped with venthole 31.The hemostasis examination chip of the present embodiment further include the second blood into Sample chamber 70 is connected between second blood sample sample cavity 70 and collecting chamber 30 using capillary 71.The microchannel 10 of the present embodiment with The split tunnel 40 to circulate for isolated blood plasma is equipped between collecting chamber 30.
The hemostasis examination chip of the present embodiment further includes the functional layer 60 of substrate 50 and setting on this base substrate 50, microchannel 10, blood sample cavity 20 and collecting chamber 30 are arranged in functional layer 60.The substrate 50 of the present embodiment is made of glass, function Layer 60 is made of PDMS.
Further, the inner wall of accommodating chamber 11 and communicating passage 12 all has hydrophily.The geometric dimension of accommodating chamber 11 is greater than The geometric dimension of red blood cell, and the size range of accommodating chamber 11 is 7.6-9.2um;The size range of communicating passage 12 is 2.8- The geometric dimension of 3.4um, communicating passage 12 are slightly larger than or are slightly less than the geometric dimension of red blood cell, play certain blocking to red blood cell Effect.
Hemostasis examination method using the hemostasis examination chip of the present embodiment is as follows, includes the following steps:
1) the first blood sample is instilled into the first blood sample cavity 20, after the first blood sample enters microchannel, accommodated Under the hole effect that chamber 11 and communicating passage 12 are formed, communicating passage to the barrier effect of red blood cell make red blood cell flow rate compared with Slowly, the flow rate of blood plasma is very fast, separates red blood cell and blood plasma, and the blood plasma isolated is deposited in collecting chamber 30;
2) when blood plasma is full of collecting chamber 30, the second blood sample is instilled into the second blood sample cavity 70, in capillary channel Under 71 capillarity, the second blood sample is entered in collecting chamber 30;
3) Coagulation test between the first blood sample and the second blood sample is detected.
The hemostasis examination chip of the present embodiment, by the way that microchannel, when the first blood sample is by microchannel, first is arranged Blood plasma in blood sample can be by the accommodating chamber of connection and communicating passage quickly through and since communicating passage is in blood Red blood cell has barrier effect, and therefore, the flow rate of blood plasma is faster than the flow rate of red blood cell, so that blood plasma be isolated Come, and red blood cell slowly flows, and will not block microchannel;Isolated blood plasma is deposited in collecting chamber, then the second blood into Sample the second blood sample of intracavitary instillation, after the second blood sample enters collecting chamber, the blood plasma isolated with the first blood sample It is reacted, can be detected whether Coagulation test occurs between the first blood sample and the second blood sample.
Embodiment described above is only to absolutely prove preferred embodiment that is of the invention and being lifted, protection model of the invention It encloses without being limited thereto.Those skilled in the art's made equivalent substitute or transformation on the basis of the present invention, in the present invention Protection scope within.Protection scope of the present invention is subject to claims.

Claims (10)

1. a kind of hemostasis examination chip, it is characterised in that: including microchannel (10), the microchannel (10) includes red for accommodating The accommodating chamber (11) of cell, the accommodating chamber (11) are distributed in space array, and between two adjacent accommodating chambers (11) Equipped with can be used for red blood cell and pass through simultaneously to play the flowing of red blood cell the communicating passage (12) of barrier effect;
One end of the microchannel (10) is equipped with the first blood sample cavity (20), the other end is equipped with the collecting chamber for collecting blood plasma (30);
Further include the second blood sample cavity (70), hair is used between the second blood sample sample cavity (70) and the collecting chamber (30) Tubule (71) is connected.
2. hemostasis examination chip according to claim 1, it is characterised in that: the accommodating chamber (11) and communicating passage (12) Inner wall all have hydrophily.
3. hemostasis examination chip according to claim 1, it is characterised in that: the geometric dimension of the accommodating chamber (11) is greater than The geometric dimension of red blood cell, and the size range of the accommodating chamber (11) is 7.6-9.2um;The size of the communicating passage (12) Range is 2.8-3.4um.
4. hemostasis examination chip according to claim 1, it is characterised in that: the microchannel (10) and the collecting chamber (30) split tunnel (40) to circulate for isolated blood plasma is equipped between.
5. hemostasis examination chip according to claim 4, it is characterised in that: accumulation is equipped with microballon in the microchannel (10) (13), the accommodating chamber (11) and the communicating passage (12) are formed between the microballon (13).
6. hemostasis examination chip according to claim 5, it is characterised in that: the microchannel (10) is logical close to the separation The side accumulation in road (40) is equipped with big microballon (14), and the outer diameter of the big microballon (14) is greater than the height of the split tunnel (40) Degree.
7. hemostasis examination chip according to claim 6, it is characterised in that: the outer diameter of the small microballon is 9-11um, institute The outer diameter for stating big microballon is 80-120um.
8. hemostasis examination chip according to claim 1-7, it is characterised in that: the collecting chamber (30) is equipped with Venthole (31).
9. hemostasis examination chip according to claim 8, it is characterised in that: further include substrate (50) and setting in the base Functional layer (60) on bottom (50), the microchannel (10), the first blood sample cavity (20) and collecting chamber (30) are arranged at institute It states in functional layer (60).
10. a kind of hemostasis examination method using the hemostasis examination chip as described in claim any one of 1-9, it is characterised in that: Include the following steps:
1) the first blood sample is instilled into the first blood sample cavity (20), separates the first blood using the microchannel (10) The red blood cell and blood plasma of sample, the blood plasma isolated are deposited in the collecting chamber (30);
2) when blood plasma is full of the collecting chamber (30), the second blood sample is instilled into the second blood sample cavity (70), the Two blood samples are entered in the collecting chamber (30) by the capillary (71);
3) Coagulation test between the first blood sample and the second blood sample is detected.
CN201910025010.3A 2019-01-11 2019-01-11 Hemostasis examination chip and hemostasis examination method Pending CN109647554A (en)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101137908A (en) * 2005-03-07 2008-03-05 可乐丽股份有限公司 Microchannel array, manufacturing method thereof, and blood measurement method using same
CN102350379A (en) * 2011-07-04 2012-02-15 大连理工大学 Micro fluid control whole blood preprocessing chip based on naturally-deposited filling column
CN103285949A (en) * 2013-05-27 2013-09-11 苏州扬清芯片科技有限公司 Micro-fluidic serum extracting chip
WO2014182844A1 (en) * 2013-05-07 2014-11-13 Micronics, Inc. Microfluidic devices and methods for performing serum separation and blood cross-matching
CN205517821U (en) * 2016-03-31 2016-08-31 苏州市博纳泰科生物技术有限公司 Whole blood separating mechanism
CN207366327U (en) * 2017-09-08 2018-05-15 深圳市太赫兹科技创新研究院有限公司 A kind of whole blood blood plasma piece-rate system
CN108761100A (en) * 2018-04-17 2018-11-06 杭州电子科技大学 The automatic cross match blood test method of unknown blood group

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101137908A (en) * 2005-03-07 2008-03-05 可乐丽股份有限公司 Microchannel array, manufacturing method thereof, and blood measurement method using same
CN102350379A (en) * 2011-07-04 2012-02-15 大连理工大学 Micro fluid control whole blood preprocessing chip based on naturally-deposited filling column
WO2014182844A1 (en) * 2013-05-07 2014-11-13 Micronics, Inc. Microfluidic devices and methods for performing serum separation and blood cross-matching
CN103285949A (en) * 2013-05-27 2013-09-11 苏州扬清芯片科技有限公司 Micro-fluidic serum extracting chip
CN205517821U (en) * 2016-03-31 2016-08-31 苏州市博纳泰科生物技术有限公司 Whole blood separating mechanism
CN207366327U (en) * 2017-09-08 2018-05-15 深圳市太赫兹科技创新研究院有限公司 A kind of whole blood blood plasma piece-rate system
CN108761100A (en) * 2018-04-17 2018-11-06 杭州电子科技大学 The automatic cross match blood test method of unknown blood group

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Application publication date: 20190419