WO2019010788A1 - Blood separation pretreatment chip and blood separation device - Google Patents

Blood separation pretreatment chip and blood separation device Download PDF

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Publication number
WO2019010788A1
WO2019010788A1 PCT/CN2017/100741 CN2017100741W WO2019010788A1 WO 2019010788 A1 WO2019010788 A1 WO 2019010788A1 CN 2017100741 W CN2017100741 W CN 2017100741W WO 2019010788 A1 WO2019010788 A1 WO 2019010788A1
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WIPO (PCT)
Prior art keywords
blood
array
microcolumn
cells
diameter
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PCT/CN2017/100741
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French (fr)
Chinese (zh)
Inventor
韩琳
丁庆
刘荣跃
杨彬
李辰
Original Assignee
华讯方舟科技有限公司
深圳市太赫兹科技创新研究院有限公司
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Publication of WO2019010788A1 publication Critical patent/WO2019010788A1/en

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/502707—Containers 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 the manufacture of the container or its components
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/502753—Containers 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers 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
    • B01L3/502761—Containers 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 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0636—Integrated biosensor, microarrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped

Definitions

  • the embodiments of the present invention belong to the field of biomedical technology, and in particular, to a blood separation pretreatment chip and a blood separation device.
  • the therapeutic effect can be through various markers in the blood.
  • the results of the reaction are measured.
  • the blood sample of a cancer patient is detected by a blood tester, which can realize the non-injury test of the cancer patient, monitor the patient's condition, and provide an important basis for the doctor and the doctor to adjust the reasonable treatment plan for accurate medical treatment. Testing provides a solid foundation.
  • biomolecules other than proteins, miRNAs and the like in the blood also contain a large number of cells of different sizes.
  • serum needs to be separated from the blood.
  • the traditional method of serum separation is to freeze the blood sample for a period of time, and then separate the blood sample by a centrifuge. This method of serum separation requires a large amount of blood and is prolonged, which seriously reduces the detection efficiency of blood samples.
  • Embodiments of the present invention provide a blood separation pretreatment chip and a blood separation device, which are capable of rapidly separating a very small amount of blood samples and improving the detection efficiency of blood samples.
  • An embodiment of the present invention provides a blood separation pretreatment chip including at least one microcolumn array sequentially arranged along a blood flow direction, each of the microcolumn arrays having different column spacings, the at least one The column spacing of the microcolumn array is sequentially decreased according to the arrangement order of the at least one microcolumn array, and the at least one microcolumn array includes at least an array of red blood cell trapping micropillars;
  • the red blood cell trapping microcolumn array intercepts red blood cells in the blood to filter red blood cells in the blood; [0007] blood flows in from the inlet of the blood separation pretreatment chip, and is sequentially intercepted and filtered by the at least one microcolumn array to obtain plasma containing less than a predetermined amount of red blood cells and platelets from the blood separation pretreatment The exit of the chip flows out.
  • the at least one microcolumn array comprises a tumor cell trapping microcolumn array, a monocyte trapping microcolumn array, a leukocyte truncated microcolumn array, and the red blood cell trapping microcolumn arranged in sequence along the blood flow direction.
  • the tumor cell entrapment microcolumn array intercepts tumor cells in the blood to filter tumor cells in the blood; the monocyte traps microcolumn arrays against monocytes in the blood Performing entrapment to filter monocytes in the blood; the leukocyte-retaining microcolumn array intercepts leukocytes in the blood to filter leukocytes in the blood;
  • the blood flows in from the inlet of the blood separation pretreatment chip, sequentially passes through the tumor cell intercepting microcolumn array, the monocyte trapping microcolumn array, the leukocyte-retained microcolumn array, and the red blood cell
  • the microcolumn array is trapped, and tumor cells, monocytes, white blood cells, and red blood cells in the blood are intercepted and filtered, and plasma containing less than a predetermined amount of red blood cells and platelets is obtained from the outlet of the blood separation pretreatment chip.
  • the array of micropillars comprises a plurality of rows of microcolumns arranged in sequence along the direction of blood flow, and any two adjacent rows of the microcolumns are misaligned.
  • the column spacing of the tumor cell-retaining microcolumn array is less than or equal to the diameter of the tumor cells and greater than the diameter of monocytes, white blood cells, red blood cells, and platelets in the blood.
  • the column spacing of the monocyte trapped microcolumn array is less than or equal to the diameter of the monocyte and greater than the diameter of leukocytes, red blood cells, and platelets in the blood.
  • the column spacing of the leukocyte-retaining microcolumn array is less than or equal to the diameter of the leukocytes and greater than the diameter of red blood cells and platelets in the blood.
  • the column spacing of the array of red blood cell trapped micropillars is less than or equal to the diameter of the red blood cells and greater than the diameter of the platelets in the blood.
  • the array of micropillars is any one of a cylindrical array, an elliptical cylinder array, or a polygonal cylinder array.
  • Another aspect of an embodiment of the present invention further provides a blood separation device comprising the above-mentioned blood separation pre-treatment
  • the microchip includes a microfluidic chip, and the microfluidic chip is provided with a microchannel connected to an outlet of the blood separation pretreatment chip;
  • the micro flow channel includes a plurality of micro flow channel units arranged in a periodic manner, and the plurality of micro flow channel units are connected end to end in sequence;
  • the micro flow channel unit includes a first semi-annular micro flow channel and a second semi-annular micro flow channel, and the inlets of the first semi-annular micro flow channel outlet and the second semi-annular micro flow channel are seamless Docking;
  • the micro flow channel performs inertial focusing treatment on the blood after the pretreatment , to obtain high purity plasma.
  • a difference between an outer diameter and an inner diameter of the first semi-annular microchannel is equal to a circumscribed diameter at any position on the first semi-annular microchannel, the second semicircular micro
  • the difference between the outer diameter and the inner diameter of the flow passage is smaller than the maximum circular cut diameter of the second semi-annular micro flow passage, and the outer diameter of the first semi-annular micro flow passage is smaller than the inner diameter of the second semi-annular micro flow passage.
  • At least one microcolumn array including an array of red blood cell trapping micropillars for trapping and filtering red blood cells is sequentially disposed along the blood flow direction, and at least one column spacing of each microcolumn array is different, so that at least one The column spacing of the microcolumn array is sequentially decreased in accordance with the arrangement order of the at least one microcolumn array, so that blood flows in from the inlet of the blood separation pretreatment chip, and sequentially passes through the interception and filtration of the at least one microcolumn array to obtain a low content.
  • the plasma of the preset amount of red blood cells and platelets flows out from the outlet of the blood separation pretreatment chip, so that a rapid separation of a very small amount of blood sample can be achieved, and the detection efficiency of the blood sample can be improved.
  • FIG. 1 is a schematic perspective view of a blood separation pretreatment chip according to an embodiment of the present invention.
  • FIG. 2 is a plan view of a blood separation pretreatment chip according to an embodiment of the present invention.
  • FIG. 3 is a schematic structural view of a blood separation device according to an embodiment of the present invention.
  • FIG. 4 is a front elevational view of a micro flow channel chip according to an embodiment of the present invention.
  • an embodiment of the present invention provides a blood separation pretreatment chip 10, which comprises four microcolumn arrays arranged in sequence along a blood flow direction, and four microcolumn arrays respectively contain tumor cell retention microscopy.
  • Column array 1 mononuclear cell retention microcolumn array 2, white blood cell retention microcolumn array 3, and red blood cell retention microcolumn array 4; the column spacing of each microcolumn array is different, and the column spacing of the four microcolumn arrays is microscopic
  • the order of arrangement of the column arrays is sequentially decreased, that is, the column spacing of the tumor cell intercepting microcolumn array 1 > the column spacing of the mononuclear cell retention microcolumn array IJ2 > the column spacing of the white blood cell microcolumn array IJ3 > the red blood cell intercepting microcolumn array ⁇ IJ4 column spacing.
  • the column spacing specifically refers to the width of the gap between any adjacent two microcolumns in the direction perpendicular to the blood flow direction in any microcolumn array, the column in this embodiment
  • the spacing specifically refers to the lateral column spacing.
  • any adjacent two of the microcolumn arrays in a direction parallel to the flow of blood can be set according to actual needs, and the longitudinal column spacing can be equal to the lateral column spacing.
  • the micropillar array can be any of a cylindrical array, an elliptical cylinder array, or a polygonal cylinder array. Only the case where the micropillar array is a cylindrical array is exemplarily shown in Fig. 1.
  • the working principle of the blood separation pretreatment chip provided in this embodiment is:
  • the tumor cell entrapment microcolumn array intercepts tumor cells in the blood to filter tumor cells in the blood;
  • the monocyte trap microcolumn array intercepts monocytes in the blood to filter mononuclear blood The cells;
  • the leukocyte-retaining microcolumn array intercepts white blood cells in the blood to filter white blood cells in the blood;
  • the red blood cell intercepting microcolumn array intercepts red blood cells in the blood to filter red blood cells in the blood;
  • the blood separation pretreatment chip includes at least one microcolumn array and the at least one microcolumn array includes at least an array of red blood cell trapping microcolumns for trapping and filtering red blood cells, and blood is separated from the blood.
  • the inlet flow of the processing chip is sequentially intercepted and filtered by at least one microcolumn array to obtain plasma containing less than a predetermined amount of red blood cells and platelets from the outlet of the blood separation pretreatment chip.
  • setting the blood separation pretreatment chip includes at least an array of red blood cell trapping microcolumns, which can intercept and filter all cells in the blood to obtain a content lower than a preset amount. Plasma of red blood cells and platelets.
  • the filtered plasma also contains less than a predetermined amount of red blood cells because the red blood cells are flat, and the column spacing cannot be smaller than the size of all red blood cells due to the limitation of the manufacturing process. Therefore, some red blood cells cannot be effectively trapped.
  • the amount of the preset amount can be determined by the number of microcolumn arrays and the column spacing. The smaller the column spacing, the smaller the preset amount.
  • the number and type of microcolumn arrays included in the blood separation pretreatment chip can be set according to actual needs. For example, if you only need to intercept and filter tumor cells, you can only set the tumor size. The cell is trapped in the microcolumn array; only the monocyte trapping microcolumn array can be set only by intercepting and filtering the monocytes. The same type of micro-column array can also be set at the same time to enhance the interception filtering effect.
  • the present invention provides at least one microcolumn by sequentially arranging at least one microcolumn array including an array of red blood cell trapped micropillars for trapping and filtering red blood cells along the blood flow direction, and making the column spacing of each microcolumn array different
  • the column spacing of the array is sequentially decreased in accordance with the arrangement order of the at least one microcolumn array, so that blood flows in from the inlet of the blood separation pretreatment chip, sequentially passes through the interception and filtration of the at least one microcolumn array, and the content is lower than the pre-prepared
  • the amount of red blood cells and platelets of plasma flow out from the outlet of the blood separation pretreatment chip, which can achieve rapid separation of a very small amount of blood samples and improve the detection efficiency of blood samples.
  • this embodiment exemplarily shows the size structure of each microcolumn in the blood separation pretreatment chip 10.
  • the four microcolumn arrays each include a plurality of rows of microcolumns arranged in sequence along the blood flow direction, and any two adjacent rows of microcolumns are misaligned.
  • the misalignment arrangement specifically means that the adjacent two rows of microcolumns are not disposed opposite each other, but are arranged at a certain distance from each other, so that the entire microcolumn array forms an oblique array, obliquely
  • the degree of tilt of the array can be set according to actual needs.
  • each row of microcolumns in a microcolumn array can also be positioned facing up.
  • the blood cells can easily flow out along the unlineed straight line gap, thereby reducing the interception and filtering effect on blood cells.
  • each microcolumn array in order to achieve a better hematofiltration effect, it is desirable to have a column spacing of each microcolumn array that is smaller than the diameter of the blood cells that it needs to intercept and filter.
  • the column spacing of the tumor cell-retaining microcolumn array is less than or equal to the diameter of the tumor cells and greater than the diameter of monocytes, white blood cells, red blood cells, and platelets in the blood.
  • the diameter of the tumor cells is usually 17 ⁇ m to 52 ⁇ m, and therefore, the column spacing of the tumor cell-carrying microcolumn array should be less than or equal to 17 ⁇ m or slightly larger than 17 ⁇ m to achieve entrapment of most tumor cells.
  • the column spacing of the tumor cell trapped microcolumn array can range from 17 ⁇ to 25 ⁇ .
  • the column spacing of the tumor cell-retaining microcolumn array 1 is 20 ⁇ m, and the diameter of the tumor cell-retaining micro-column is 20 ⁇ m.
  • the cross-sectional size and height of each microcolumn in the tumor cell-retaining microcolumn array may be set according to actual needs, for example, the height may be greater than 52 ⁇ m ; when the tumor cells intercept the microcolumn width in the microcolumn array The range is 10 ⁇ 30 ⁇ , for example, 10 ⁇ , 15 ⁇ , 20 ⁇ , 25 ⁇ or 30 ⁇ ; when the microcolumn is a cylindrical crucible, the microcolumn width refers to the diameter of the cylinder; when the microcolumn is a square cylinder, the microcolumn width refers to the square column Square side length.
  • the column spacing of the monocyte trapped microcolumn array is less than or equal to the diameter of the monocytes and greater than the diameter of the white blood cells, red blood cells, and platelets in the blood.
  • the diameter of the monocytes is usually 15 ⁇ m to 25 ⁇ m, and therefore, the column spacing of the mononuclear-trapped microcolumn array should be less than or equal to 15 ⁇ m or slightly more than 15 ⁇ m to achieve a majority of monocytes. Interception.
  • the column spacing of the mononuclear-retained microcolumn array can range from 15 ⁇ to 17 ⁇ .
  • the column spacing of the mononuclear cell retention microcolumn array 1 is 15 ⁇ m, and the diameter of the mononuclear cell retention microcolumn is 18 ⁇ m.
  • the cross-sectional size and height of each microcolumn in the mononuclear cell retention microcolumn array can be set according to actual needs, for example, the height can be greater than 25 ⁇ m ; when the mononuclear cells are trapped in the microcolumn array
  • the width of the column ranges from 10 ⁇ to 30 ⁇ , for example, 10 ⁇ , 15 ⁇ , 20 ⁇ , 25 ⁇ or 30 ⁇ ; when the microcolumn is a cylindrical crucible, the microcolumn width refers to the diameter of the cylinder; when the microcolumn is a square cylinder, the microcolumn width refers to The square side of the square column is long.
  • the column spacing of the leukocyte-retaining microcolumn array is less than or equal to the diameter of the leukocytes and greater than the diameter of the red blood cells and platelets in the blood.
  • the diameter of the white blood cells is usually 7 ⁇ 10 ⁇ , 12 ⁇ 20 ⁇ or 14 ⁇ 20 ⁇
  • the column spacing of the leukocyte-retained microcolumn array should be less than or equal to 7 ⁇ or slightly greater than 7 ⁇ to achieve retention of most white blood cells.
  • the column spacing of a white blood cell trapped microcolumn array can be 7 ⁇ 1
  • the column spacing of the leukocyte-retaining micro-column array ij l is 10 ⁇ m, and the diameter of the leukocyte-retaining micro-column is 12 ⁇ m.
  • the cross-sectional size and height of each microcolumn in the leukocyte-retaining micro-column array can be set according to actual needs, for example, the height can be greater than 20 ⁇ m ;
  • the micro-column width in the white blood cell-carrying micro-column array is 5 ⁇ ⁇ 25 ⁇ , for example, 5 ⁇ , 10 ⁇ , 15 ⁇ , 20 ⁇ or 25 ⁇ ; when the microcolumn is a cylindrical crucible, The microcolumn width refers to the diameter of the cylinder; when the microcolumn is a square column, the microcolumn width refers to the square side length of the square column.
  • the column spacing of the array of red blood cell trapped micropillars is less than or equal to the diameter of the red blood cells and greater than the diameter of the platelets in the blood.
  • the diameter of the red blood cells is usually 6 ⁇ to 8 ⁇ . Therefore, the column spacing of the red blood cell trapping microcolumn array should be less than or equal to 6 ⁇ or slightly larger than 6 ⁇ to achieve entrapment of most red blood cells.
  • the column spacing of the erythrocyte-intercepting microcolumn array can range from 4 ⁇ to 7 ⁇ .
  • the column spacing of the red blood cell trapping microcolumn ij ij l is 5 ⁇ m, and the diameter of the red blood cell trapping microcolumn is 10 ⁇ m.
  • the cross-sectional size and height of each microcolumn in the red blood cell trapping microcolumn array can be set according to actual needs, for example, the height can be greater than 8 ⁇ m ;
  • the microcolumn width in the red blood cell trapping microcolumn array is 5 ⁇ ⁇ 25 ⁇ , for example, 5 ⁇ , 10 ⁇ , 15 ⁇ , 20 ⁇ or 25 ⁇ ;
  • the microcolumn width refers to the diameter of the cylinder; when the microcolumn is a square cylinder, the microcolumn width refers to the square of the square column Side length.
  • an embodiment of the present invention further provides a blood separation device including the blood separation pretreatment chip 10, further comprising a microfluidic chip 20, and the microfluidic chip 20 is disposed on the microfluidic chip 20 A microchannel 21 connected to the outlet of the blood separation pretreatment chip 10 and a plasma outlet and a blood cell outlet connected to the outlet of the microchannel.
  • the direction of the solid arrow in FIG. 3 indicates the direction of the blood main flow.
  • the micro flow path 21 includes a plurality of micro flow path units 211 (the portion where the dotted circles are shown in FIG. 3 is a micro flow path unit), and the plurality of micro flow path units 211 are connected end to end in sequence.
  • the microchannel unit 211 includes a first semi-annular microchannel and a second semi-annular microchannel, and the inlets of the first annular microchannel outlet and the second semicircular microchannel are seamlessly docked.
  • the size of the micro flow channel can be set according to actual needs.
  • the difference between the outer diameter and the inner diameter of the first semi-annular microchannel is equal to the circumscribed diameter at any point on the first semi-annular microchannel, and the outer diameter of the second semi-circular microchannel is The difference between the inner diameters is smaller than the maximum circumscribed diameter of the second semicircular microchannel, and the outer diameter of the first semicircular microchannel is smaller than the inner diameter of the second semicircular microchannel
  • the working principle of the blood separation device is as follows: [0069] After the blood is passed through the blood separation pretreatment chip and pretreated, the microfluidic chip enters the microchannel through the inlet of the microfluidic chip, and the microchannel performs inertial focusing treatment on the pretreated blood to obtain high purity plasma and blood cells. High-purity plasma flows out through the plasma outlet, and blood cells flow out through the blood cell outlet.
  • the inertial focusing process specifically refers to: filtering the residual small-sized cells or particles in the plasma by inertial focusing, and the particles such as cells flow in the micro-flow channel, in addition to being driven by the mainstream driving force,
  • the shear force caused by the difference in velocity gradient of the fluid and the Wall Effect Lift Force caused by the closed channel wall are combined, and the shear force and the wall lift are combined into an inertial force.
  • the cells Under the action of inertial force, the cells will migrate at a fixed position in the microchannel, so they can be used to separate platelets and a small amount of red blood cells in plasma to obtain high-purity plasma.
  • FIG. 4 a specific size structure of the micro flow path 21 is exemplarily shown in the present embodiment.
  • a specific size structure of the micro flow path 21 is exemplarily shown in the present embodiment.
  • only two cycles of the micro flow channel unit are shown by way of example.
  • the difference between the outer diameter R3 and the inner diameter R4 of the second semicircular microchannel is smaller than the maximum circumscribed diameter L2 of the second semicircular microchannel, that is, R3-R4 ⁇ L2;
  • the outer diameter R1 of the first annular microchannel is smaller than the first
  • the circumscribed diameter L1 at any position on the first semicircular microchannel is smaller than the maximum secant diameter L2 of the second semicircular microchannel, that is, LI ⁇ L2

Abstract

A blood separation pretreatment chip and a blood separation device. The blood separation pretreatment chip comprises at least one micropillar array arranged in succession along the direction of blood flow, pillar spacings in each said micropillar array are different from each other, the pillar spacings of said at least one micropillar array decrease in succession according to the arrangement sequence of said at least one micropillar array, and said at least one micropillar array at least comprises a red blood cell trapping micropillar array. Said red blood cell trapping micropillar array traps red blood cells in blood, so as to filter red blood cells in blood. Blood flows in from the inlet of said blood separation pretreatment chip and is subjected to trapping and filtration by means of said at least one micropillar array in sequence, so as to obtain a plasma comprising less than a predetermined amount of red blood cells and platelets, which flows out from the outlet of said blood separation pretreatment chip. Said chip and device can achieve rapid separation of a very small amount of a blood sample, increasing the detection efficiency of the blood sample.

Description

说明书 发明名称：一种血液分离预处理芯片及血液分离装置 技术领域  Description: A blood separation pretreatment chip and a blood separation device
[0001] 本发明实施例属于生物医学技术领域， 尤其涉及一种血液分离预处理芯片及血 液分离装置。  [0001] The embodiments of the present invention belong to the field of biomedical technology, and in particular, to a blood separation pretreatment chip and a blood separation device.
背景技术  Background technique
[0002] 在癌症病人的治疗过程中， 治疗效果的好坏可以通过血液中的各种标志物分子  [0002] In the treatment of cancer patients, the therapeutic effect can be through various markers in the blood.
(如蛋白、 miRNA (MicroRNA, 非编码单链 RNA分子） ） 的反应结果来衡量 。 通常， 是利用血液检测仪对癌症病人的血液样本进行检测， 可以实现对癌症 病人的无损伤检测， 实吋监测病人的病情， 为医生及吋调整合理的治疗方案提 供重要依据， 为精准的医疗检测提供坚实的基础。  (As protein, miRNA (MicroRNA, non-coding single-stranded RNA molecules)) the results of the reaction are measured. Usually, the blood sample of a cancer patient is detected by a blood tester, which can realize the non-injury test of the cancer patient, monitor the patient's condition, and provide an important basis for the doctor and the doctor to adjust the reasonable treatment plan for accurate medical treatment. Testing provides a solid foundation.
[0003] 然而， 血液中除了蛋白、 miRNA等生物分子还含有大量不同尺寸的细胞。 为了 提高生物分子的检测灵敏度和可靠性， 需要将血清从血液中分离出来。 传统的 血清分离方法是把血液样本先冷置一段吋间， 然后用离心机对血液样本进行分 离。 这种血清分离方法需要耗费大量血液且耗吋较长， 严重降低了血液样本的 检测效率。  [0003] However, biomolecules other than proteins, miRNAs and the like in the blood also contain a large number of cells of different sizes. In order to improve the detection sensitivity and reliability of biomolecules, serum needs to be separated from the blood. The traditional method of serum separation is to freeze the blood sample for a period of time, and then separate the blood sample by a centrifuge. This method of serum separation requires a large amount of blood and is prolonged, which seriously reduces the detection efficiency of blood samples.
技术问题  technical problem
[0004] 本发明实施例提供一种血液分离预处理芯片及血液分离装置， 能够对极少量的 血液样本进行快速分离， 提高血液样本的检测效率。  Embodiments of the present invention provide a blood separation pretreatment chip and a blood separation device, which are capable of rapidly separating a very small amount of blood samples and improving the detection efficiency of blood samples.
问题的解决方案  Problem solution
技术解决方案  Technical solution
[0005] 本发明实施例一方面提供一种血液分离预处理芯片， 其包括沿血液流向依次排 列的至少一个微柱阵列， 每个所述微柱阵列的柱间距均不相同， 所述至少一个 微柱阵列的柱间距按照所述至少一个微柱阵列的排列顺序依次减小， 所述至少 一个微柱阵列至少包括红细胞截留微柱阵列；  [0005] An embodiment of the present invention provides a blood separation pretreatment chip including at least one microcolumn array sequentially arranged along a blood flow direction, each of the microcolumn arrays having different column spacings, the at least one The column spacing of the microcolumn array is sequentially decreased according to the arrangement order of the at least one microcolumn array, and the at least one microcolumn array includes at least an array of red blood cell trapping micropillars;
[0006] 所述红细胞截留微柱阵列对所述血液中的红细胞进行截留， 以过滤所述血液中 的红细胞； [0007] 血液从所述血液分离预处理芯片的入口流入， 依次经过所述至少一个微柱阵列 的截留和过滤， 得到含有低于预设量的红细胞和血小板的血浆从所述血液分离 预处理芯片的出口流出。 [0006] the red blood cell trapping microcolumn array intercepts red blood cells in the blood to filter red blood cells in the blood; [0007] blood flows in from the inlet of the blood separation pretreatment chip, and is sequentially intercepted and filtered by the at least one microcolumn array to obtain plasma containing less than a predetermined amount of red blood cells and platelets from the blood separation pretreatment The exit of the chip flows out.
[0008] 在一个实施例中， 所述至少一个微柱阵列包括沿血液流向依次排列的肿瘤细胞 截留微柱阵列、 单核细胞截留微柱阵列、 白细胞截留微柱阵列和所述红细胞截 留微柱阵列； [0008] In one embodiment, the at least one microcolumn array comprises a tumor cell trapping microcolumn array, a monocyte trapping microcolumn array, a leukocyte truncated microcolumn array, and the red blood cell trapping microcolumn arranged in sequence along the blood flow direction. Array
[0009] 所述肿瘤细胞截留微柱阵列对所述血液中的肿瘤细胞进行截留， 以过滤所述血 液中的肿瘤细胞； 所述单核细胞截留微柱阵列对所述血液中的单核细胞进行截 留， 以过滤所述血液中的单核细胞； 所述白细胞截留微柱阵列对所述血液中的 白细胞进行截留， 以过滤所述血液中的白细胞；  [0009] the tumor cell entrapment microcolumn array intercepts tumor cells in the blood to filter tumor cells in the blood; the monocyte traps microcolumn arrays against monocytes in the blood Performing entrapment to filter monocytes in the blood; the leukocyte-retaining microcolumn array intercepts leukocytes in the blood to filter leukocytes in the blood;
[0010] 所述血液从所述血液分离预处理芯片的入口流入， 依次经过所述肿瘤细胞截留 微柱阵列、 所述单核细胞截留微柱阵列、 所述白细胞截留微柱阵列和所述红细 胞截留微柱阵列， 对所述血液中的肿瘤细胞、 单核细胞、 白细胞和红细胞进行 截留并过滤后， 得到含有低于预设量的红细胞和血小板的血浆从血液分离预处 理芯片的出口流出。  [0010] the blood flows in from the inlet of the blood separation pretreatment chip, sequentially passes through the tumor cell intercepting microcolumn array, the monocyte trapping microcolumn array, the leukocyte-retained microcolumn array, and the red blood cell The microcolumn array is trapped, and tumor cells, monocytes, white blood cells, and red blood cells in the blood are intercepted and filtered, and plasma containing less than a predetermined amount of red blood cells and platelets is obtained from the outlet of the blood separation pretreatment chip.
[0011] 在一个实施例中， 所述微柱阵列包括沿血液流向依次排列的多排微柱， 任意相 邻的两排所述微柱均错位排列。  [0011] In one embodiment, the array of micropillars comprises a plurality of rows of microcolumns arranged in sequence along the direction of blood flow, and any two adjacent rows of the microcolumns are misaligned.
[0012] 在一个实施例中， 所述肿瘤细胞截留微柱阵列的柱间距小于或等于所述肿瘤细 胞的直径且大于所述血液中的单核细胞、 白细胞、 红细胞和血小板的直径。  [0012] In one embodiment, the column spacing of the tumor cell-retaining microcolumn array is less than or equal to the diameter of the tumor cells and greater than the diameter of monocytes, white blood cells, red blood cells, and platelets in the blood.
[0013] 在一个实施例中， 所述单核细胞截留微柱阵列的柱间距小于或等于所述单核细 胞的直径且大于所述血液中的白细胞、 红细胞和血小板的直径。  [0013] In one embodiment, the column spacing of the monocyte trapped microcolumn array is less than or equal to the diameter of the monocyte and greater than the diameter of leukocytes, red blood cells, and platelets in the blood.
[0014] 在一个实施例中， 所述白细胞截留微柱阵列的柱间距小于或等于所述白细胞的 直径且大于所述血液中的红细胞和血小板的直径。 [0014] In one embodiment, the column spacing of the leukocyte-retaining microcolumn array is less than or equal to the diameter of the leukocytes and greater than the diameter of red blood cells and platelets in the blood.
[0015] 在一个实施例中， 所述红细胞截留微柱阵列的柱间距小于或等于所述红细胞的 直径且大于所述血液中的血小板的直径。 [0015] In one embodiment, the column spacing of the array of red blood cell trapped micropillars is less than or equal to the diameter of the red blood cells and greater than the diameter of the platelets in the blood.
[0016] 在一个实施例中， 所述微柱阵列为圆柱阵列、 椭圆柱阵列或多边形柱体阵列中 的任一种。 [0016] In one embodiment, the array of micropillars is any one of a cylindrical array, an elliptical cylinder array, or a polygonal cylinder array.
[0017] 本发明实施例另一方面还提供一种血液分离装置， 其包括上述的血液分离预处 理芯片， 还包括微流控芯片， 所述微流控芯片上设置有与所述血液分离预处理 芯片的出口连接的微流道； [0017] Another aspect of an embodiment of the present invention further provides a blood separation device comprising the above-mentioned blood separation pre-treatment The microchip includes a microfluidic chip, and the microfluidic chip is provided with a microchannel connected to an outlet of the blood separation pretreatment chip;
[0018] 所述微流道包括周期性排列的多个微流道单元， 所述多个微流道单元依次首尾 连接；  [0018] the micro flow channel includes a plurality of micro flow channel units arranged in a periodic manner, and the plurality of micro flow channel units are connected end to end in sequence;
[0019] 所述微流道单元包括第一半环形微流道和第二半环形微流道， 所述第一半环形 微流道出口和所述第二半环形微流道的入口无缝对接；  [0019] the micro flow channel unit includes a first semi-annular micro flow channel and a second semi-annular micro flow channel, and the inlets of the first semi-annular micro flow channel outlet and the second semi-annular micro flow channel are seamless Docking;
[0020] 血液流经所述血液分离预处理芯片被预处理之后， 流入所述微流控芯片上的所 述微流道， 所述微流道对所述预处理之后的血液进行惯性聚焦处理， 得到高纯 度的血浆。 [0020] after the blood is pretreated by the blood separation pretreatment chip, flowing into the micro flow channel on the microfluidic chip, the micro flow channel performs inertial focusing treatment on the blood after the pretreatment , to obtain high purity plasma.
[0021] 在一个实施例中， 所述第一半环形微流道的外径与内径之差等于所述第一半环 形微流道上任一处的环切直径， 所述第二半环形微流道的外径与内径之差小于 所述第二半环形微流道的最大环切直径， 所述第一半环形微流道的外径小于所 述第二半环形微流道的内径。  [0021] In one embodiment, a difference between an outer diameter and an inner diameter of the first semi-annular microchannel is equal to a circumscribed diameter at any position on the first semi-annular microchannel, the second semicircular micro The difference between the outer diameter and the inner diameter of the flow passage is smaller than the maximum circular cut diameter of the second semi-annular micro flow passage, and the outer diameter of the first semi-annular micro flow passage is smaller than the inner diameter of the second semi-annular micro flow passage.
发明的有益效果  Advantageous effects of the invention
有益效果  Beneficial effect
[0022] 本发明实施例通过沿血液流向依次设置包括用于截留并过滤红细胞的红细胞截 留微柱阵列的至少一个微柱阵列， 并使每个微柱阵列的柱间距均不相同， 使至 少一个微柱阵列的柱间距按照至少一个微柱阵列的排列顺序依次减小， 使血液 从所述血液分离预处理芯片的入口流入， 依次经过所述至少一个微柱阵列的截 留和过滤， 得到含有低于预设量的红细胞和血小板的血浆从血液分离预处理芯 片的出口流出， 可以实现对极少量的血液样本的快速分离， 提高血液样本的检 测效率。  [0022] In the embodiment of the present invention, at least one microcolumn array including an array of red blood cell trapping micropillars for trapping and filtering red blood cells is sequentially disposed along the blood flow direction, and at least one column spacing of each microcolumn array is different, so that at least one The column spacing of the microcolumn array is sequentially decreased in accordance with the arrangement order of the at least one microcolumn array, so that blood flows in from the inlet of the blood separation pretreatment chip, and sequentially passes through the interception and filtration of the at least one microcolumn array to obtain a low content. The plasma of the preset amount of red blood cells and platelets flows out from the outlet of the blood separation pretreatment chip, so that a rapid separation of a very small amount of blood sample can be achieved, and the detection efficiency of the blood sample can be improved.
对附图的简要说明  Brief description of the drawing
附图说明  DRAWINGS
[0023] 为了更清楚地说明本发明实施例中的技术方案， 下面将对实施例描述中所需要 使用的附图作简单地介绍， 显而易见地， 下面描述中的附图是本发明的一些实 施例， 对于本领域普通技术人员来讲， 在不付出创造性劳动的前提下， 还可以 根据这些附图获得其他的附图。 [0024] 图 1是本发明的一个实施例提供的血液分离预处理芯片的立体结构示意图；[0023] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly described below. Obviously, the drawings in the following description are some implementations of the present invention. For example, other drawings may be obtained from those of ordinary skill in the art in light of the inventive work. 1 is a schematic perspective view of a blood separation pretreatment chip according to an embodiment of the present invention;
[0025] 图 2是本发明的一个实施例提供的血液分离预处理芯片的俯视图； 2 is a plan view of a blood separation pretreatment chip according to an embodiment of the present invention; [0025] FIG.
[0026] 图 3是本发明的一个实施例提供的血液分离装置的结构示意图；  3 is a schematic structural view of a blood separation device according to an embodiment of the present invention;
[0027] 图 4是本发明的一个实施例提供的微流道芯片的主视图。  4 is a front elevational view of a micro flow channel chip according to an embodiment of the present invention.
本发明的实施方式 Embodiments of the invention
[0028] 为了使本技术领域的人员更好地理解本发明方案， 下面将结合本发明实施例中 的附图， 对本发明实施例中的技术方案进行清楚地描述， 显然， 所描述的实施 例是本发明一部分的实施例， 而不是全部的实施例。 基于本发明中的实施例， 本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例， 都应当属于本发明保护的范围。  The technical solutions in the embodiments of the present invention will be clearly described below in conjunction with the accompanying drawings in the embodiments of the present invention. It is an embodiment of the invention, but not all of the embodiments. All other embodiments obtained by a person of ordinary skill in the art based on the embodiments of the present invention without departing from the inventive scope are intended to fall within the scope of the invention.
[0029] 本发明的说明书和权利要求书及上述附图中的术语"包括"以及它们任何变形， 意图在于覆盖不排他的包含。 例如包含一系列步骤或单元的过程、 方法或系统 、 产品或设备没有限定于已列出的步骤或单元， 而是可选地还包括没有列出的 步骤或单元， 或可选地还包括对于这些过程、 方法、 产品或设备固有的其它步 骤或单元。 此外， 术语"第一"、 "第二 "和"第三"等是用于区别不同对象， 而非用 于描述特定顺序。  [0029] The term "comprising", and any variations thereof, in the specification and claims of the invention and the above description are intended to cover a non-exclusive inclusion. For example, a process, method or system, product or device comprising a series of steps or units is not limited to the listed steps or units, but optionally also includes steps or units not listed, or alternatively also includes Other steps or units inherent to these processes, methods, products or equipment. Further, the terms "first", "second", "third", etc. are used to distinguish different objects, and are not intended to describe a particular order.
[0030] 如图 1所示， 本发明的一个实施例提供一种血液分离预处理芯片 10， 其包括沿 血液流向依次排列的四个微柱阵列， 四个微柱阵列分别为肿瘤细胞截留微柱阵 列 1、 单核细胞截留微柱阵列 2、 白细胞截留微柱阵列 3和红细胞截留微柱阵列 4 ； 每个微柱阵列的柱间距均不相同， 并且四个微柱阵列的柱间距按照微柱阵列 的排列顺序依次减小， 即肿瘤细胞截留微柱阵列 1的柱间距〉单核细胞截留微柱 阵歹 IJ2的柱间距〉白细胞截留微柱阵歹 IJ3的柱间距〉红细胞截留微柱阵歹 IJ4的柱间 距。  [0030] As shown in FIG. 1, an embodiment of the present invention provides a blood separation pretreatment chip 10, which comprises four microcolumn arrays arranged in sequence along a blood flow direction, and four microcolumn arrays respectively contain tumor cell retention microscopy. Column array 1, mononuclear cell retention microcolumn array 2, white blood cell retention microcolumn array 3, and red blood cell retention microcolumn array 4; the column spacing of each microcolumn array is different, and the column spacing of the four microcolumn arrays is microscopic The order of arrangement of the column arrays is sequentially decreased, that is, the column spacing of the tumor cell intercepting microcolumn array 1 > the column spacing of the mononuclear cell retention microcolumn array IJ2 > the column spacing of the white blood cell microcolumn array IJ3 > the red blood cell intercepting microcolumn array柱IJ4 column spacing.
[0031] 在本实施例中， 柱间距具体是指任一微柱阵列中， 与血液流向垂直的方向上的 任意相邻的两个微柱之间的空隙的宽度， 本实施例中的柱间距具体是指横向柱 间距。  [0031] In the present embodiment, the column spacing specifically refers to the width of the gap between any adjacent two microcolumns in the direction perpendicular to the blood flow direction in any microcolumn array, the column in this embodiment The spacing specifically refers to the lateral column spacing.
[0032] 在具体应用中， 任一微柱阵列中， 与血液流向平行的方向上的任意相邻的两个 微柱之间的空隙的宽度 （即纵向柱间距） 可以根据实际需要设定， 纵向柱间距 可以等于横向柱间距。 [0032] In a particular application, any adjacent two of the microcolumn arrays in a direction parallel to the flow of blood The width of the gap between the microcolumns (ie, the longitudinal column spacing) can be set according to actual needs, and the longitudinal column spacing can be equal to the lateral column spacing.
[0033] 在具体应用中， 微柱阵列可以为圆柱阵列、 椭圆柱阵列或多边形柱体阵列中的 任一种。 图 1中仅示例性的示出微柱阵列为圆柱阵列的情况。  [0033] In a particular application, the micropillar array can be any of a cylindrical array, an elliptical cylinder array, or a polygonal cylinder array. Only the case where the micropillar array is a cylindrical array is exemplarily shown in Fig. 1.
[0034] 本实施例所提供的血液分离预处理芯片的工作原理为： [0034] The working principle of the blood separation pretreatment chip provided in this embodiment is:
[0035] 肿瘤细胞截留微柱阵列对血液中的肿瘤细胞进行截留， 以过滤血液中的肿瘤细 胞； 单核细胞截留微柱阵列对血液中的单核细胞进行截留， 以过滤血液中的单 核细胞； 白细胞截留微柱阵列对血液中的白细胞进行截留， 以过滤血液中的白 细胞； 红细胞截留微柱阵列对血液中的红细胞进行截留， 以过滤血液中的红细 胞；  [0035] The tumor cell entrapment microcolumn array intercepts tumor cells in the blood to filter tumor cells in the blood; the monocyte trap microcolumn array intercepts monocytes in the blood to filter mononuclear blood The cells; the leukocyte-retaining microcolumn array intercepts white blood cells in the blood to filter white blood cells in the blood; the red blood cell intercepting microcolumn array intercepts red blood cells in the blood to filter red blood cells in the blood;
[0036] 血液从血液分离预处理芯片的入口流入， 依次经过肿瘤细胞截留微柱阵列、 单 核细胞截留微柱阵列、 白细胞截留微柱阵列和红细胞截留微柱阵列， 对血液中 的肿瘤细胞、 单核细胞、 白细胞和红细胞进行截留并过滤后， 得到含有低于预 设量的红细胞和血小板的血浆从血液分离预处理芯片的出口流出。  [0036] blood flows from the inlet of the blood separation pretreatment chip, and sequentially passes through the tumor cell interception microcolumn array, the monocyte trapped microcolumn array, the leukocyte-retained microcolumn array, and the red blood cell-retained microcolumn array, for tumor cells in the blood, After the monocytes, white blood cells, and red blood cells are intercepted and filtered, plasma containing less than a predetermined amount of red blood cells and platelets is obtained from the outlet of the blood separation pretreatment chip.
[0037] 在一个实施例中， 血液分离预处理芯片包括至少一个微柱阵列且这至少一个微 柱阵列中至少包括用于截留并过滤红细胞的红细胞截留微柱阵列， 血液从所述 血液分离预处理芯片的入口流入， 依次经过至少一个微柱阵列的截留和过滤， 得到含有低于预设量的红细胞和血小板的血浆从血液分离预处理芯片的出口流 出。  [0037] In one embodiment, the blood separation pretreatment chip includes at least one microcolumn array and the at least one microcolumn array includes at least an array of red blood cell trapping microcolumns for trapping and filtering red blood cells, and blood is separated from the blood. The inlet flow of the processing chip is sequentially intercepted and filtered by at least one microcolumn array to obtain plasma containing less than a predetermined amount of red blood cells and platelets from the outlet of the blood separation pretreatment chip.
[0038] 由于红细胞是血液中尺寸最小的细胞， 因此， 设定血液分离预处理芯片至少包 括红细胞截留微柱阵列， 可以对血液中的所有细胞进行截留和过滤， 以得到含 有低于预设量的红细胞和血小板的血浆。  [0038] Since the red blood cells are the smallest cells in the blood, setting the blood separation pretreatment chip includes at least an array of red blood cell trapping microcolumns, which can intercept and filter all cells in the blood to obtain a content lower than a preset amount. Plasma of red blood cells and platelets.
[0039] 在本实施例中， 过滤后的血浆中之所以还含有低于预设量的红细胞是因为红细 胞是扁平状的， 由于制作工艺的限制， 柱间距没法做到小于所有红细胞的尺寸 ， 因此会有部分红细胞无法被有效截留。 在柱间距的可控范围内， 预设量的多 少具体可以由微柱阵列的数量和柱间距来决定， 柱间距越小， 预设量越小。  [0039] In the present embodiment, the filtered plasma also contains less than a predetermined amount of red blood cells because the red blood cells are flat, and the column spacing cannot be smaller than the size of all red blood cells due to the limitation of the manufacturing process. Therefore, some red blood cells cannot be effectively trapped. Within the controllable range of the column spacing, the amount of the preset amount can be determined by the number of microcolumn arrays and the column spacing. The smaller the column spacing, the smaller the preset amount.
[0040] 在具体应用中， 血液分离预处理芯片所包括的微柱阵列的数量及种类可以根据 实际需要进行设置。 例如， 只需要截留和过滤肿瘤细胞， 则可以只设定肿瘤细 胞截留微柱阵列； 只需要截留和过滤单核细胞， 则可以只设定单核细胞截留微 柱阵列。 同一种类型的微柱阵列也可以同吋设置多个， 以加强截留过滤效果。 [0040] In a specific application, the number and type of microcolumn arrays included in the blood separation pretreatment chip can be set according to actual needs. For example, if you only need to intercept and filter tumor cells, you can only set the tumor size. The cell is trapped in the microcolumn array; only the monocyte trapping microcolumn array can be set only by intercepting and filtering the monocytes. The same type of micro-column array can also be set at the same time to enhance the interception filtering effect.
[0041] 本发明通过沿血液流向依次设置包括用于截留并过滤红细胞的红细胞截留微柱 阵列的至少一个微柱阵列， 并使每个微柱阵列的柱间距均不相同， 使至少一个 微柱阵列的柱间距按照至少一个微柱阵列的排列顺序依次减小， 使血液从所述 血液分离预处理芯片的入口流入， 依次经过所述至少一个微柱阵列的截留和过 滤， 得到含有低于预设量的红细胞和血小板的血浆从血液分离预处理芯片的出 口流出， 可以实现对极少量的血液样本的快速分离， 提高血液样本的检测效率 [0041] The present invention provides at least one microcolumn by sequentially arranging at least one microcolumn array including an array of red blood cell trapped micropillars for trapping and filtering red blood cells along the blood flow direction, and making the column spacing of each microcolumn array different The column spacing of the array is sequentially decreased in accordance with the arrangement order of the at least one microcolumn array, so that blood flows in from the inlet of the blood separation pretreatment chip, sequentially passes through the interception and filtration of the at least one microcolumn array, and the content is lower than the pre-prepared The amount of red blood cells and platelets of plasma flow out from the outlet of the blood separation pretreatment chip, which can achieve rapid separation of a very small amount of blood samples and improve the detection efficiency of blood samples.
[0042] 如图 2所示， 本实施例示例性的示出了血液分离预处理芯片 10中各微柱的尺寸 结构。 在本实施例中， 四个微柱阵列均包括沿血液流向依次排列的多排微柱， 任意相邻的两排微柱均错位排列。 As shown in FIG. 2, this embodiment exemplarily shows the size structure of each microcolumn in the blood separation pretreatment chip 10. In this embodiment, the four microcolumn arrays each include a plurality of rows of microcolumns arranged in sequence along the blood flow direction, and any two adjacent rows of microcolumns are misaligned.
[0043] 在本实施例中， 错位排列具体是指相邻的两排微柱并不是正对着设置， 而是相 互错幵一定距离设置， 使整个微柱阵列构成一个斜向阵列， 斜向阵列的倾斜程 度可以根据实际需要设定。 通过使每个微柱阵列中相邻排的微柱错位排列， 可 以提高对血细胞的截留和过滤效果。 [0043] In this embodiment, the misalignment arrangement specifically means that the adjacent two rows of microcolumns are not disposed opposite each other, but are arranged at a certain distance from each other, so that the entire microcolumn array forms an oblique array, obliquely The degree of tilt of the array can be set according to actual needs. By displacing the adjacent columns of microcolumns in each microcolumn array, the retention and filtration of blood cells can be improved.
[0044] 在具体应用中， 微柱阵列中的每排微柱也可以正对设置。 只是若微柱阵列中的 每排微柱都正对设置， 形成一个矩形阵列， 则血细胞很容易顺着没有遮挡的直 线缝隙流出， 从而降低对血细胞的截留和过滤效果。 [0044] In a particular application, each row of microcolumns in a microcolumn array can also be positioned facing up. However, if each row of microcolumns in the microcolumn array is positioned correctly to form a rectangular array, the blood cells can easily flow out along the unlineed straight line gap, thereby reducing the interception and filtering effect on blood cells.
[0045] 在具体应用中， 为了实现较好的血细胞过滤效果， 需要使每个微柱阵列的柱间 距都小于其所需要截留和过滤的血细胞的直径。 [0045] In a particular application, in order to achieve a better hematofiltration effect, it is desirable to have a column spacing of each microcolumn array that is smaller than the diameter of the blood cells that it needs to intercept and filter.
[0046] 在一个实施例中， 肿瘤细胞截留微柱阵列的柱间距小于或等于肿瘤细胞的直径 且大于血液中的单核细胞、 白细胞、 红细胞和血小板的直径。 In one embodiment, the column spacing of the tumor cell-retaining microcolumn array is less than or equal to the diameter of the tumor cells and greater than the diameter of monocytes, white blood cells, red blood cells, and platelets in the blood.
[0047] 在具体应用中， 肿瘤细胞的直径通常为 17μηι~52μιη， 因此， 肿瘤细胞截留微柱 阵列的柱间距应当小于或等于 17μηι或略大于 17μηι， 以实现对绝大部分肿瘤细胞 的截留。 例如， 肿瘤细胞截留微柱阵列的柱间距可以在 17μηι~25μιη范围内。 [0047] In a specific application, the diameter of the tumor cells is usually 17 μm to 52 μm, and therefore, the column spacing of the tumor cell-carrying microcolumn array should be less than or equal to 17 μm or slightly larger than 17 μm to achieve entrapment of most tumor cells. For example, the column spacing of the tumor cell trapped microcolumn array can range from 17 μηι to 25 μιη.
[0048] 如图 2所示， 在本实施例中， 肿瘤细胞截留微柱阵列 1的柱间距为 20μηι， 肿瘤 细胞截留微柱直径为 20μηι。 [0049] 在具体应用中， 肿瘤细胞截留微柱阵列中的各微柱的截面尺寸和高度可以根据 实际需要设定， 例如， 高度可以大于 52μηι; 当肿瘤细胞截留微柱阵列中的微柱 宽度范围为 10~30μηι， 例如， 10μηι、 15μηι、 20μηι、 25μηι或 30μηι; 当微柱为圆 柱吋， 微柱宽度是指圆柱的直径； 当微柱为方柱吋， 微柱宽度是指方柱的方形 边长。 As shown in FIG. 2, in the present embodiment, the column spacing of the tumor cell-retaining microcolumn array 1 is 20 μm, and the diameter of the tumor cell-retaining micro-column is 20 μm. [0049] In a specific application, the cross-sectional size and height of each microcolumn in the tumor cell-retaining microcolumn array may be set according to actual needs, for example, the height may be greater than 52 μm ; when the tumor cells intercept the microcolumn width in the microcolumn array The range is 10~30μηι, for example, 10μηι, 15μηι, 20μηι, 25μηι or 30μηι; when the microcolumn is a cylindrical crucible, the microcolumn width refers to the diameter of the cylinder; when the microcolumn is a square cylinder, the microcolumn width refers to the square column Square side length.
[0050] 在一个实施例中， 单核细胞截留微柱阵列的柱间距小于或等于单核细胞的直径 且大于血液中的白细胞、 红细胞和血小板的直径。  [0050] In one embodiment, the column spacing of the monocyte trapped microcolumn array is less than or equal to the diameter of the monocytes and greater than the diameter of the white blood cells, red blood cells, and platelets in the blood.
[0051] 在具体应用中， 单核细胞的直径通常为 15μηι~25μιη， 因此， 单核细胞截留微柱 阵列的柱间距应当小于或等于 15μηι或略大于 15μηι， 以实现对绝大部分单核细胞 的截留。 例如， 单核细胞截留微柱阵列的柱间距可以在 15μηι~17μιη范围内。  [0051] In a specific application, the diameter of the monocytes is usually 15 μm to 25 μm, and therefore, the column spacing of the mononuclear-trapped microcolumn array should be less than or equal to 15 μm or slightly more than 15 μm to achieve a majority of monocytes. Interception. For example, the column spacing of the mononuclear-retained microcolumn array can range from 15 μηι to 17 μιη.
[0052] 如图 2所示， 在本实施例中， 单核细胞截留微柱阵列 1的柱间距为 15μηι， 单核 细胞截留微柱的直径为 18μηι。  As shown in FIG. 2, in the present embodiment, the column spacing of the mononuclear cell retention microcolumn array 1 is 15 μm, and the diameter of the mononuclear cell retention microcolumn is 18 μm.
[0053] 在具体应用中， 单核细胞截留微柱阵列中的各微柱的截面尺寸和高度可以根据 实际需要设定， 例如， 高度可以大于 25μηι; 当单核细胞截留微柱阵列中的微柱 的宽度范围为 10μηι~30μιη， 例如， 10μηι、 15μηι、 20μηι、 25μηι或 30μηι; 当微柱 为圆柱吋， 微柱宽度是指圆柱的直径； 当微柱为方柱吋， 微柱宽度是指方柱的 方形边长。 [0053] In a specific application, the cross-sectional size and height of each microcolumn in the mononuclear cell retention microcolumn array can be set according to actual needs, for example, the height can be greater than 25 μm ; when the mononuclear cells are trapped in the microcolumn array The width of the column ranges from 10μηι to 30μιη, for example, 10μηι, 15μηι, 20μηι, 25μηι or 30μηι; when the microcolumn is a cylindrical crucible, the microcolumn width refers to the diameter of the cylinder; when the microcolumn is a square cylinder, the microcolumn width refers to The square side of the square column is long.
[0054] 在一个实施例中， 白细胞截留微柱阵列的柱间距小于或等于白细胞的直径且大 于血液中的红细胞和血小板的直径。  [0054] In one embodiment, the column spacing of the leukocyte-retaining microcolumn array is less than or equal to the diameter of the leukocytes and greater than the diameter of the red blood cells and platelets in the blood.
[0055] 在具体应用中， 白细胞的直径通常为 7μηι~10 μηι、 12μηι~20 μηι或 14μηι~20 μηι[0055] In a specific application, the diameter of the white blood cells is usually 7μηι~10 μηι, 12μηι~20 μηι or 14μηι~20 μηι
， 因此， 白细胞截留微柱阵列的柱间距应当小于或等于 7μηι或略大于 7μηι， 以实 现对绝大部分白细胞的截留。 例如， 白细胞截留微柱阵列的柱间距可以在 7μηι~1Therefore, the column spacing of the leukocyte-retained microcolumn array should be less than or equal to 7μηι or slightly greater than 7μηι to achieve retention of most white blood cells. For example, the column spacing of a white blood cell trapped microcolumn array can be 7μηι~1
4μηι范围内。 Within the range of 4μηι.
[0056] 如图 2所示， 在本实施例中， 白细胞截留微柱阵歹 ij l的柱间距为 10μηι， 白细胞 截留微柱的直径为 12μηι。  As shown in FIG. 2, in the present embodiment, the column spacing of the leukocyte-retaining micro-column array ij l is 10 μm, and the diameter of the leukocyte-retaining micro-column is 12 μm.
[0057] 在具体应用中， 白细胞截留微柱阵列中的各微柱的截面尺寸和高度可以根据实 际需要设定， 例如， 高度可以大于 20μηι; 白细胞截留微柱阵列中的微柱宽度范 围为 5μηι~25μιη， 例如， 5μηι、 10μηι、 15μηι、 20μηι或 25μηι; 当微柱为圆柱吋， 微柱宽度是指圆柱的直径； 当微柱为方柱吋， 微柱宽度是指方柱的方形边长。 [0057] In a specific application, the cross-sectional size and height of each microcolumn in the leukocyte-retaining micro-column array can be set according to actual needs, for example, the height can be greater than 20 μm ; the micro-column width in the white blood cell-carrying micro-column array is 5 μηι ~25μιη, for example, 5μηι, 10μηι, 15μηι, 20μηι or 25μηι; when the microcolumn is a cylindrical crucible, The microcolumn width refers to the diameter of the cylinder; when the microcolumn is a square column, the microcolumn width refers to the square side length of the square column.
[0058] 在一个实施例中， 红细胞截留微柱阵列的柱间距小于或等于红细胞的直径且大 于血液中的血小板的直径。  [0058] In one embodiment, the column spacing of the array of red blood cell trapped micropillars is less than or equal to the diameter of the red blood cells and greater than the diameter of the platelets in the blood.
[0059] 在具体应用中， 红细胞的直径通常为 6μηι~8 μιη因此， 红细胞截留微柱阵列的 柱间距应当小于或等于 6μηι或略大于 6μηι， 以实现对绝大部分红细胞的截留。 例 如， 红细胞截留微柱阵列的柱间距可以在 4μηι~7μιη范围内。 [0059] In a specific application, the diameter of the red blood cells is usually 6 μηι to 8 μηη. Therefore, the column spacing of the red blood cell trapping microcolumn array should be less than or equal to 6 μηι or slightly larger than 6 μηι to achieve entrapment of most red blood cells. For example, the column spacing of the erythrocyte-intercepting microcolumn array can range from 4μηι to 7μιη.
[0060] 如图 2所示， 在本实施例中， 红细胞截留微柱阵歹 ij l的柱间距为 5μηι， 红细胞截 留微柱的直径为 10μηι。 As shown in FIG. 2, in the present embodiment, the column spacing of the red blood cell trapping microcolumn ij ij l is 5 μm, and the diameter of the red blood cell trapping microcolumn is 10 μm.
[0061] 在具体应用中， 红细胞截留微柱阵列中的各微柱的截面尺寸和高度可以根据实 际需要设定， 例如， 高度可以大于 8μηι; 红细胞截留微柱阵列中的微柱宽度范围 为 5μηι~25μιη， 例如， 例如， 5μηι、 10μηι、 15μηι、 20μηι或 25μηι; 当微柱为圆柱 吋， 微柱宽度是指圆柱的直径； 当微柱为方柱吋， 微柱宽度是指方柱的方形边 长。 [0061] In a specific application, the cross-sectional size and height of each microcolumn in the red blood cell trapping microcolumn array can be set according to actual needs, for example, the height can be greater than 8 μm ; the microcolumn width in the red blood cell trapping microcolumn array is 5 μηι ~25μιη, for example, 5μηι, 10μηι, 15μηι, 20μηι or 25μηι; When the microcolumn is a cylindrical crucible, the microcolumn width refers to the diameter of the cylinder; when the microcolumn is a square cylinder, the microcolumn width refers to the square of the square column Side length.
[0062] 如图 3所示， 本发明的一个实施例还提供一种血液分离装置， 其包括上述的血 液分离预处理芯片 10， 还包括微流控芯片 20， 微流控芯片 20上设置有与血液分 离预处理芯片 10的出口连接的微流道 21以及与微流道的出口连接的血浆出口和 血细胞出口。  As shown in FIG. 3, an embodiment of the present invention further provides a blood separation device including the blood separation pretreatment chip 10, further comprising a microfluidic chip 20, and the microfluidic chip 20 is disposed on the microfluidic chip 20 A microchannel 21 connected to the outlet of the blood separation pretreatment chip 10 and a plasma outlet and a blood cell outlet connected to the outlet of the microchannel.
[0063] 图 3中实心箭头方向表示血液主流方向。  [0063] The direction of the solid arrow in FIG. 3 indicates the direction of the blood main flow.
[0064] 微流道 21包括周期性排列的多个微流道单元 211 (图 3中虚线圈起来的部分即为 一个微流道单元） ， 多个微流道单元 211依次首尾连接。  The micro flow path 21 includes a plurality of micro flow path units 211 (the portion where the dotted circles are shown in FIG. 3 is a micro flow path unit), and the plurality of micro flow path units 211 are connected end to end in sequence.
[0065] 微流道单元 211包括第一半环形微流道和第二半环形微流道， 第一半环形微流 道出口和第二半环形微流道的入口无缝对接。 [0065] The microchannel unit 211 includes a first semi-annular microchannel and a second semi-annular microchannel, and the inlets of the first annular microchannel outlet and the second semicircular microchannel are seamlessly docked.
[0066] 在具体应用中， 微流道的尺寸可以根据实际需要进行设定。 [0066] In a specific application, the size of the micro flow channel can be set according to actual needs.
[0067] 在一个实施例中， 第一半环形微流道的外径与内径之差等于第一半环形微流道 上任一处的环切直径， 第二半环形微流道的外径与内径之差小于第二半环形微 流道的最大环切直径， 第一半环形微流道的外径小于第二半环形微流道的内径 [0067] In one embodiment, the difference between the outer diameter and the inner diameter of the first semi-annular microchannel is equal to the circumscribed diameter at any point on the first semi-annular microchannel, and the outer diameter of the second semi-circular microchannel is The difference between the inner diameters is smaller than the maximum circumscribed diameter of the second semicircular microchannel, and the outer diameter of the first semicircular microchannel is smaller than the inner diameter of the second semicircular microchannel
[0068] 本实施例所提供的血液分离装置的工作原理为： [0069] 血液流经血液分离预处理芯片被预处理之后， 通过微流控芯片的入口流入微流 道， 微流道对预处理之后的血液进行惯性聚焦处理， 得到高纯度的血浆和血细 胞， 高纯度的血浆经血浆出口流出， 血细胞经血细胞出口流出。 [0068] The working principle of the blood separation device provided in this embodiment is as follows: [0069] After the blood is passed through the blood separation pretreatment chip and pretreated, the microfluidic chip enters the microchannel through the inlet of the microfluidic chip, and the microchannel performs inertial focusing treatment on the pretreated blood to obtain high purity plasma and blood cells. High-purity plasma flows out through the plasma outlet, and blood cells flow out through the blood cell outlet.
[0070] 在具体应用中， 惯性聚焦处理具体是指： 通过惯性聚焦来过滤血浆中残余的小 尺寸细胞或颗粒， 细胞等颗粒在微流道中流动吋， 除了受到主流驱动力向前流 动， 还在垂直方向受到由流体的速度梯度差导致的剪切力和闭合的通道壁带来 的壁面升力 （Wall Effect Lift Force) 的影响， 剪切力和壁面升力合成为惯性力。 在惯性力作用下， 细胞将会在微流道内的固定位置迁移， 因此可用来分离血浆 中的血小板和少量红细胞从而得到高纯度的血浆。  [0070] In a specific application, the inertial focusing process specifically refers to: filtering the residual small-sized cells or particles in the plasma by inertial focusing, and the particles such as cells flow in the micro-flow channel, in addition to being driven by the mainstream driving force, In the vertical direction, the shear force caused by the difference in velocity gradient of the fluid and the Wall Effect Lift Force caused by the closed channel wall are combined, and the shear force and the wall lift are combined into an inertial force. Under the action of inertial force, the cells will migrate at a fixed position in the microchannel, so they can be used to separate platelets and a small amount of red blood cells in plasma to obtain high-purity plasma.
[0071] 如图 4所示， 本实施例中示例性的示出了微流道 21的具体尺寸结构。 图 4中为了 示意方便， 仅示例性的示出两个周期的微流道单元。  As shown in FIG. 4, a specific size structure of the micro flow path 21 is exemplarily shown in the present embodiment. For the convenience of the illustration in Fig. 4, only two cycles of the micro flow channel unit are shown by way of example.
[0072] 在本实施例中， 第一半环形微流道的外径 R1与内径 R2之差等于第一半环形微 流道上任一处的环切直径 Ll， 即 R1-R2=L1 ; 第二半环形微流道的外径 R3与内径 R4之差小于第二半环形微流道的最大环切直径 L2， 即 R3-R4< L2; 第一半环形 微流道的外径 R1小于第二半环形微流道的内径 R4， 即 R1 < R4; 第一半环形微流 道上任一处的环切直径 L1小于第二半环形微流道的最大环切直径 L2， 即 LI < L2  [0072] In this embodiment, the difference between the outer diameter R1 and the inner diameter R2 of the first semi-annular microchannel is equal to the circumscribed diameter L1 at any position on the first semi-annular microchannel, that is, R1-R2=L1; The difference between the outer diameter R3 and the inner diameter R4 of the second semicircular microchannel is smaller than the maximum circumscribed diameter L2 of the second semicircular microchannel, that is, R3-R4< L2; the outer diameter R1 of the first annular microchannel is smaller than the first The inner diameter R4 of the second half annular microchannel, that is, R1 < R4; the circumscribed diameter L1 at any position on the first semicircular microchannel is smaller than the maximum secant diameter L2 of the second semicircular microchannel, that is, LI < L2
[0073] 以上所述仅为本发明的较佳实施例而已， 并不用以限制本发明， 凡在本发明的 精神和原则之内所作的任何修改、 等同替换和改进等， 均应包含在本发明的保 护范围之内。 The above is only the preferred embodiment of the present invention, and is not intended to limit the present invention. Any modifications, equivalents, and improvements made within the spirit and scope of the present invention should be included in the present invention. Within the scope of protection of the invention.

Claims

权利要求书 Claim
[权利要求 1] 一种血液分离预处理芯片， 其特征在于， 包括沿血液流向依次排列的 至少一个微柱阵列， 每个所述微柱阵列的柱间距均不相同， 所述至少 一个微柱阵列的柱间距按照所述至少一个微柱阵列的排列顺序依次减 小， 所述至少一个微柱阵列至少包括红细胞截留微柱阵列； 所述红细胞截留微柱阵列对所述血液中的红细胞进行截留， 以过滤所 述血液中的红细胞；  [Claim 1] A blood separation pretreatment chip, comprising: at least one microcolumn array arranged in sequence along a blood flow direction, each of the microcolumn arrays having a different column pitch, the at least one microcolumn The column spacing of the array is sequentially decreased according to the arrangement order of the at least one microcolumn array, the at least one microcolumn array comprising at least an array of red blood cell trapping microcolumns; the red blood cell intercepting microcolumn array intercepting red blood cells in the blood To filter red blood cells in the blood;
血液从所述血液分离预处理芯片的入口流入， 依次经过所述至少一个 微柱阵列的截留和过滤， 得到含有低于预设量的红细胞和血小板的血 浆从所述血液分离预处理芯片的出口流出。  Blood flows from the inlet of the blood separation pretreatment chip, and is sequentially intercepted and filtered by the at least one microcolumn array to obtain plasma containing less than a predetermined amount of red blood cells and platelets from the blood separation pretreatment chip outlet. Flow out.
[权利要求 2] 如权利要求 1所述的血液分离预处理芯片， 其特征在于， 所述至少一 个微柱阵列包括沿血液流向依次排列的肿瘤细胞截留微柱阵列、 单核 细胞截留微柱阵列、 白细胞截留微柱阵列和所述红细胞截留微柱阵列 所述肿瘤细胞截留微柱阵列对所述血液中的肿瘤细胞进行截留， 以过 滤所述血液中的肿瘤细胞； 所述单核细胞截留微柱阵列对所述血液中 的单核细胞进行截留， 以过滤所述血液中的单核细胞； 所述白细胞截 留微柱阵列对所述血液中的白细胞进行截留， 以过滤所述血液中的白 细胞；  [Claim 2] The blood separation pretreatment chip according to claim 1, wherein the at least one microcolumn array comprises a tumor cell trapping microcolumn array and a monocyte trapping microcolumn array arranged in sequence along the blood flow direction. a leukocyte-retaining microcolumn array and the erythrocyte-retaining micro-column array, the tumor cell-retaining micro-column array intercepting tumor cells in the blood to filter tumor cells in the blood; the monocyte trapping micro a column array intercepts monocytes in the blood to filter mononuclear cells in the blood; the leukocyte-retaining microcolumn array intercepts leukocytes in the blood to filter leukocytes in the blood ;
所述血液从所述血液分离预处理芯片的入口流入， 依次经过所述肿瘤 细胞截留微柱阵列、 所述单核细胞截留微柱阵列、 所述白细胞截留微 柱阵列和所述红细胞截留微柱阵列， 对所述血液中的肿瘤细胞、 单核 细胞、 白细胞和红细胞进行截留并过滤后， 得到含有低于预设量的红 细胞和血小板的血浆从血液分离预处理芯片的出口流出。  The blood flows in from the inlet of the blood separation pretreatment chip, and sequentially passes through the tumor cell intercepting microcolumn array, the monocyte trapping microcolumn array, the leukocyte truncated microcolumn array, and the red blood cell trapping microcolumn The array, after trapping and filtering the tumor cells, monocytes, white blood cells, and red blood cells in the blood, obtains plasma containing less than a predetermined amount of red blood cells and platelets from the outlet of the blood separation pretreatment chip.
[权利要求 3] 如权利要求 1所述的血液分离预处理芯片， 其特征在于， 所述微柱阵 列包括沿血液流向依次排列的多排微柱， 任意相邻的两排所述微柱均 错位排列。  [Claim 3] The blood separation pretreatment chip according to claim 1, wherein the microcolumn array comprises a plurality of rows of microcolumns arranged in sequence along the blood flow direction, and any two adjacent rows of the microcolumns are Misplaced.
[权利要求 4] 如权利要求 1~3任一项所述的血液分离预处理芯片， 其特征在于， 所 述肿瘤细胞截留微柱阵列的柱间距小于或等于所述肿瘤细胞的直径且 大于所述血液中的单核细胞、 白细胞、 红细胞和血小板的直径。 [Claim 4] The blood separation pretreatment chip according to any one of claims 1 to 3, wherein The column spacing of the tumor cell-retaining microcolumn array is less than or equal to the diameter of the tumor cells and greater than the diameter of monocytes, white blood cells, red blood cells, and platelets in the blood.
[权利要求 5] 如权利要求 1~3任一项所述的血液分离预处理芯片， 其特征在于， 所 述单核细胞截留微柱阵列的柱间距小于或等于所述单核细胞的直径且 大于所述血液中的白细胞、 红细胞和血小板的直径。  [Claim 5] The blood separation pretreatment chip according to any one of claims 1 to 3, wherein a column spacing of the monocyte-carrying microcolumn array is less than or equal to a diameter of the monocyte and Greater than the diameter of white blood cells, red blood cells and platelets in the blood.
[权利要求 6] 如权利要求 1~3任一项所述的血液分离预处理芯片， 其特征在于， 所 述白细胞截留微柱阵列的柱间距小于或等于所述白细胞的直径且大于 所述血液中的红细胞和血小板的直径。 The blood separation pretreatment chip according to any one of claims 1 to 3, wherein a column spacing of the leukocyte-retaining microcolumn array is smaller than or equal to a diameter of the white blood cell and larger than the blood. The diameter of red blood cells and platelets.
[权利要求 7] 如权利要求 1~3任一项所述的血液分离预处理芯片， 其特征在于， 所 述红细胞截留微柱阵列的柱间距小于或等于所述红细胞的直径且大于 所述血液中的血小板的直径。 The blood separation pretreatment chip according to any one of claims 1 to 3, wherein a column pitch of the red blood cell trapping microcolumn array is smaller than or equal to a diameter of the red blood cell and larger than the blood. The diameter of the platelets in it.
[权利要求 8] 如权利要求 1所述的血液分离预处理芯片， 其特征在于， 所述微柱阵 列为圆柱阵列、 椭圆柱阵列或多边形柱体阵列中的任一种。 [Claim 8] The blood separation pretreatment chip according to claim 1, wherein the microcolumn array is any one of a cylindrical array, an elliptical cylinder array, or a polygonal cylinder array.
[权利要求 9] 一种血液分离装置， 其特征在于， 包括如权利要求 1~8任一项所述的 血液分离预处理芯片， 还包括微流控芯片， 所述微流控芯片上设置有 与所述血液分离预处理芯片的出口连接的微流道以及与所述微流道的 出口连接的血浆出口和血细胞出口； [Claim 9] A blood separation device comprising the blood separation pretreatment chip according to any one of claims 1 to 8, further comprising a microfluidic chip, wherein the microfluidic chip is provided with a microchannel connected to an outlet of the blood separation pretreatment chip and a plasma outlet and a blood cell outlet connected to an outlet of the microchannel;
所述微流道包括周期性排列的多个微流道单元， 所述多个微流道单元 依次首尾连接；  The micro flow channel includes a plurality of micro flow channel units arranged in a periodic manner, and the plurality of micro flow channel units are connected end to end in sequence;
所述微流道单元包括第一半环形微流道和第二半环形微流道， 所述第 一半环形微流道出口和所述第二半环形微流道的入口无缝对接； 血液流经所述血液分离预处理芯片被预处理之后， 通过所述微流控芯 片的入口流入所述微流道， 所述微流道对所述预处理之后的血液进行 惯性聚焦处理， 得到高纯度的血浆和血细胞， 所述高纯度的血浆经所 述血浆出口流出， 所述血细胞经所述血细胞出口流出。  The micro flow channel unit includes a first semi-annular micro flow channel and a second semi-annular micro flow channel, and the first semi-annular micro flow channel outlet and the second semi-annular micro flow channel inlet are seamlessly docked; After flowing through the blood separation pretreatment chip, the micro flow channel is flowed through the inlet of the microfluidic chip, and the micro flow channel performs inertial focusing treatment on the blood after the pretreatment to obtain high Purity of plasma and blood cells, the high purity plasma exiting through the plasma outlet, and the blood cells flow out through the blood cell outlet.
[权利要求 10] 如权利要求 9所述的血液分离装置， 其特征在于， 所述第一半环形微 流道的外径与内径之差等于所述第一半环形微流道上任一处的环切直 径， 所述第二半环形微流道的外径与内径之差小于所述第二半环形微 流道的最大环切直径， 所述第一半环形微流道的外径小于所述第二半 环形微流道的内径。 [Claim 10] The blood separation device according to claim 9, wherein a difference between an outer diameter and an inner diameter of the first semicircular microchannel is equal to any one of the first semicircular microchannels a circumscribed diameter, a difference between an outer diameter and an inner diameter of the second semi-annular microchannel is smaller than the second semicircular micro The maximum circumscribed diameter of the flow channel, the outer diameter of the first semi-annular microchannel being smaller than the inner diameter of the second semi-annular microchannel.
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