WO2020252627A1 - 检测芯片及其制备方法 - Google Patents

检测芯片及其制备方法 Download PDF

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Publication number
WO2020252627A1
WO2020252627A1 PCT/CN2019/091555 CN2019091555W WO2020252627A1 WO 2020252627 A1 WO2020252627 A1 WO 2020252627A1 CN 2019091555 W CN2019091555 W CN 2019091555W WO 2020252627 A1 WO2020252627 A1 WO 2020252627A1
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WIPO (PCT)
Prior art keywords
detection
substrate
detection chip
chip according
diversion
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PCT/CN2019/091555
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English (en)
French (fr)
Inventor
殷雨丹
Original Assignee
京东方科技集团股份有限公司
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Publication date
Application filed by 京东方科技集团股份有限公司 filed Critical 京东方科技集团股份有限公司
Priority to PCT/CN2019/091555 priority Critical patent/WO2020252627A1/zh
Priority to EP19933242.0A priority patent/EP3984639A4/en
Priority to CN201980000847.0A priority patent/CN112399887B/zh
Priority to US16/767,464 priority patent/US20220050100A1/en
Publication of WO2020252627A1 publication Critical patent/WO2020252627A1/zh

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G01N33/54386—Analytical elements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
    • G01N33/525—Multi-layer analytical elements
    • 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
    • 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
    • B01L3/502746—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 means for controlling flow resistance, e.g. flow controllers, baffles
    • 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
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/025—Align devices or objects to ensure defined positions relative to each other
    • 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
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0689—Sealing
    • 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
    • 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
    • B01L2300/0848—Specific forms of parts of containers
    • B01L2300/0851—Bottom walls
    • 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
    • B01L2300/16—Surface properties and coatings
    • B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • B01L2300/165—Specific details about hydrophobic, oleophobic surfaces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/08—Regulating or influencing the flow resistance
    • B01L2400/084—Passive control of flow resistance
    • B01L2400/086—Passive control of flow resistance using baffles or other fixed flow obstructions

Definitions

  • the embodiment of the present disclosure relates to a detection chip and a preparation method thereof.
  • Microfluidic Chip has gradually become a research hotspot, and involves many disciplines such as biology, chemistry, medicine, fluids, electronics, materials, and machinery.
  • the microfluidic chip can process and manipulate trace amounts (for example, 10 -9 to 10 -18 liters) of fluids in tens to hundreds of micrometer scale channels.
  • trace amounts for example, 10 -9 to 10 -18 liters
  • the micro-scale structure of the microfluidic chip significantly increases the specific surface area of the fluid, that is, the ratio of surface area to volume, it causes a series of special effects related to the surface, such as laminar flow effect, surface tension, capillary effect, and rapid heat transfer Effect, diffusion effect, etc. Therefore, the microfluidic chip has superior performance that the macro-scale laboratory device does not have, and has broad application prospects.
  • At least one embodiment of the present disclosure provides a detection chip, which includes: a first substrate; a plurality of detection units located on the first substrate; at least one diversion dam located on the first substrate, the diversion dam It extends along the first path and is located between adjacent detection units.
  • the plurality of detection units are arranged in multiple rows, and the first path extends along the row direction.
  • the diversion dams are provided on both sides of each column of detection units.
  • the at least one diversion dam includes a plurality of diversion dams, and the plurality of diversion dams are parallel to each other.
  • the height of the diversion dam in the direction perpendicular to the first substrate is greater than the height of the detection unit in the direction perpendicular to the first substrate.
  • the detection chip provided by an embodiment of the present disclosure further includes a hydrophilic layer, wherein the hydrophilic layer covers the detection unit and the diversion dam.
  • the portion of the hydrophilic layer covering the detection unit includes a chemical modification group.
  • the detection chip provided by an embodiment of the present disclosure further includes a hydrophobic layer, wherein the hydrophobic layer is arranged on the first substrate, and the detection unit and the diversion dam are arranged on the hydrophobic layer.
  • the detection chip provided by an embodiment of the present disclosure further includes a second substrate, wherein the second substrate is disposed opposite to the first substrate and is spaced apart from the first substrate to provide a detection space.
  • the detection chip provided by an embodiment of the present disclosure further includes a sample inlet and a sample outlet, wherein the sample inlet and the sample outlet are provided on the second substrate.
  • the detection chip provided by an embodiment of the present disclosure further includes a detection area, wherein the multiple detection units are located in the detection area, the multiple detection units are arranged in multiple rows, and the sampling port and the The sample outlets are distributed on both sides of the detection area along the column direction.
  • the sample inlet and the sample outlet are axially or centrally symmetrically distributed along the column direction on both sides of the detection area.
  • the first substrate and/or the second substrate are glass substrates.
  • the detection chip provided by an embodiment of the present disclosure further includes a frame sealant, wherein the frame sealant is located between the first substrate and the second substrate and surrounds the diversion dam and the A detection unit.
  • the height of the diversion dam is 30% to 60% of the distance between the first substrate and the second substrate.
  • the width of the diversion dam is 50 micrometers to 200 micrometers, and the distance between the diversion dam and the adjacent detection unit is greater than or equal to 100 micrometers.
  • the length of the diversion dam is greater than or equal to the sum of the lengths of the plurality of detection units on the first path.
  • the cross-sectional shape of the diversion dam in a direction perpendicular to the first path is rectangular, square, trapezoidal or semicircular.
  • the material of the diversion dam includes photoresist.
  • the detection chip provided by an embodiment of the present disclosure further includes a positioning component, wherein the positioning component is located on the first substrate, and the hydrophobic layer is provided on the positioning component.
  • At least one embodiment of the present disclosure further provides a method for preparing a detection chip according to any one of the embodiments of the present disclosure, including: forming a plurality of detection units and at least one diversion dam on a first substrate; wherein the guide The flow dam extends along the first path and is located between adjacent detection units.
  • FIG. 1 is a schematic plan view of a detection chip provided by some embodiments of the disclosure.
  • FIG. 2 is a schematic cross-sectional view of the detection chip shown in FIG. 1;
  • FIG. 3 is a schematic diagram of flow field simulation of a detection chip provided by some embodiments of the present disclosure.
  • FIG. 4 is a schematic plan view of another detection chip provided by some embodiments of the disclosure.
  • FIG. 5 is a schematic cross-sectional view of the detection chip shown in FIG. 4.
  • FIG. 6 is a schematic flowchart of a method for preparing a detection chip provided by some embodiments of the disclosure.
  • the immunoassay chip is a commonly used microfluidic chip that can be used to detect cancer markers, heart markers, thyroid markers, gonadal markers, and other infectious disease markers.
  • the target antigen or antibody can be attached to the detection unit in the immunodetection chip, then the immunodetection chip is packaged, the solution to be detected is injected into the immunoassay chip, and the solution to be detected flows through the area where the detection unit is located. If there are markers in the solution to be tested, with the flow of the solution to be tested, these markers will bind to the antigen or antibody attached to the detection unit, so that the markers are fixed on the detection unit. Then, optical detection (for example, fluorescence detection) is performed on the detection unit, so that the immunological detection result can be obtained.
  • optical detection for example, fluorescence detection
  • the internal space of the immunoassay chip is of micrometer scale, the injection speed, injection volume, temperature and other factors of the solution to be tested have a greater influence on the flow field in the chip, so the stability and parallelism of the flow field in the chip are relatively high. Poor, it is not conducive to the combination of the marker in the solution to be tested with the target antigen or antibody on the detection unit, which will adversely affect the immunoassay result.
  • At least one embodiment of the present disclosure provides a detection chip and a preparation method thereof.
  • the detection chip can improve the stability and parallelism of the flow field, help improve the accuracy of the immune detection result, and has the advantages of small size, high throughput, etc. Features.
  • At least one embodiment of the present disclosure provides a detection chip, which includes a first substrate, a plurality of detection units, and at least one diversion dam.
  • a plurality of detection units are located on the first substrate, the diversion dam is located on the first substrate, and the diversion dam extends along the first path and is located between adjacent detection units.
  • FIG. 1 is a schematic plan view of a detection chip provided by some embodiments of the disclosure
  • FIG. 2 is a schematic cross-sectional view of the detection chip shown in FIG. 1.
  • the detection chip 100 includes a first substrate 110, a plurality of detection units 120 and at least one diversion dam 130.
  • the first substrate 110 functions as support, protection, etc., and may be a plastic substrate, a glass substrate, or a silicon substrate, or may be other applicable substrates, which are not limited in the embodiments of the present disclosure.
  • the first substrate 110 is a transparent substrate (for example, a glass substrate), so that light can pass through the transparent substrate without damage or with low loss, thereby improving the accuracy of subsequent optical inspections and reducing the need for additional optical inspection equipment. Claim.
  • a plurality of detection units 120 are located on the first substrate 110, and the detection units 120 are used, for example, to provide attachment positions for target antigens or antibodies.
  • the detection unit 120 has a convex shape, so that the target antigen or antibody attached thereto can bind or react with the marker in the solution to be detected flowing through the detection unit 120.
  • the detection unit 120 may also be in the shape of a groove or a plane, as long as it can ensure that the target antigen or antibody attached to the detection unit 120 can contact the solution to be detected flowing through the detection unit 120 And it can be combined with the marker in it.
  • the number of detection units 120 is not limited, and can be any number, for example, according to the type or concentration of the marker to be detected.
  • the diversion dam 130 is located on the first base plate 110, and the diversion dam 130 extends along the first path and is located between adjacent detection units 120.
  • the diversion dam 130 affects the flow field in the internal space of the detection chip 100, thereby improving the uniformity of the flow velocity at the location of different detection units 120, improving the parallelism of the flow field along the first path, and improving the stability of the flow field, so that The solution to be detected can stably and uniformly flow through the area where the detection unit 120 is located. Therefore, the marker in the solution to be detected can fully bind or react with the target antigen or antibody on the detection unit 120, thereby helping to improve the accuracy and reliability of the immunological detection result.
  • the detection chip 100 also has the characteristics of small size and high throughput.
  • the multiple detection units 120 are arranged in multiple columns, and the first path extends along the column direction Z.
  • Diversion dams 130 are provided on both sides of each column of detection units 120, and a plurality of diversion dams 130 are parallel to each other.
  • the parallelism of the flow field formed by the flow of the solution to be tested along the column direction Z is improved under the action of the diversion dam 130, so that the solution to be tested can be Stably and uniformly flow in the column direction Z.
  • the first path is not limited to extending along the column direction Z, and may also extend in any other direction.
  • the first path may extend along a straight line or a curve, which may be determined according to the flow path and flow mode of the solution to be detected, which is not limited in the embodiment of the present disclosure.
  • the diversion dam 130 when the first path extends along a straight line, the diversion dam 130 also extends along a straight line; when the first path extends along a curve, the diversion dam 130 also extends along a curve.
  • the multiple detection units 120 can be arranged in multiple rows along a straight line, or can be arranged in multiple groups along a curve, and the diversion dam 130 located between adjacent detection units 120 can extend along the arrangement direction of the detection units 120. .
  • the diversion dam 130 may be provided on both sides of each column of the detection unit 120, or only some columns of the detection unit 120 may be provided with the diversion dam 130, which can be based on It depends on the parallelism of the flow field that needs to be achieved, which is not limited in the embodiments of the present disclosure.
  • the flow field has good parallelism . If the target antigen or antibody on a detection unit 120 accidentally falls off, the fallen off target antigen or antibody will flow along the column direction Z, that is, flow in the area where the detection unit 120 is located, so it will not affect Other columns of detection units 120 can avoid crosstalk between different detection sites (ie, detection units 120) and avoid cross-contamination.
  • the number of diversion dams 130 is not limited, and may be one or more.
  • the diversion dam 130 can be located between the two rows of detection units 120, thereby reducing the The number of flow dams 130 makes the flow field have good parallelism.
  • the cross-sectional shape of the diversion dam 130 in the direction perpendicular to the first path may be a rectangle, a square, a trapezoid, a semicircle or other suitable shapes, such as a regular shape or an irregular shape.
  • the embodiment of the present disclosure does not limit this.
  • different cross-sectional shapes will have different effects on the flow field, so the cross-sectional shape of the diversion dam 130 can be determined according to the characteristics of the flow field.
  • both the diversion dam 130 and the detection unit 120 can be made of photoresist, for example, a photoresist that can be etched by a thick film.
  • the diversion dam 130 and the detection unit 120 may be formed in the same patterning process to simplify the production process.
  • the detection chip 100 further includes a hydrophilic layer 140 that covers the detection unit 120 and the diversion dam 130.
  • a hydrophilic layer 140 covers the detection unit 120 and the diversion dam 130.
  • the material of the hydrophilic layer 140 is silicon oxide, such as silicon dioxide (SiO2).
  • the hydrophilic layer 140 can also be made of other suitable inorganic or organic materials, as long as the surface of the hydrophilic layer 140 in contact with the solution to be tested is hydrophilic.
  • the hydrophilic layer 140 can be directly prepared using hydrophilic materials.
  • the hydrophilic layer 140 can be made of a material that is not hydrophilic. In this case, it is necessary to perform a hydrophilic treatment on the surface of the hydrophilic layer 140 in contact with the solution to be tested, so that the hydrophilic layer 140 It is hydrophilic.
  • a non-hydrophilic material such as silicon nitride
  • it can be hydrophilized, such as gel modification, ultraviolet radiation, plasma, and other methods.
  • it can be made non-hydrophilic.
  • the surface of the sexual material has hydrophilic groups to make it hydrophilic.
  • the portion of the hydrophilic layer 140 covering the detection unit 120 includes a chemical modification group 141.
  • the chemical modification group 141 can be obtained by a chemical modification treatment method, and can bind to the target antigen or antibody.
  • the target antigen or antibody can be firmly attached to the detection unit 120, and the target antigen or antibody will not fall off easily under the flow of the solution to be tested, thereby improving the accuracy of the immunological detection result.
  • the detection chip 100 further includes a hydrophobic layer 150.
  • the hydrophobic layer 150 is disposed on the first substrate 110, and the detection unit 120 and the diversion dam 130 are disposed on the hydrophobic layer 150.
  • the solution to be tested can flow more easily in the detection chip 100, and the markers in the solution to be tested can not easily adhere to the first substrate 110, so as to avoid the markers in the solution to be tested from being wasted .
  • the material of the hydrophobic layer 150 is resin or silicon nitride.
  • the hydrophobic layer 150 can also be made of other suitable inorganic or organic materials, as long as it is ensured that the side of the hydrophobic layer 150 away from the first substrate 110 is hydrophobic.
  • the hydrophobic layer 150 can be directly prepared using a hydrophobic material.
  • the hydrophobic layer 150 may be made of a material that does not have hydrophobicity. In this case, it is necessary to perform a hydrophobic treatment on the surface of the hydrophobic layer 150 away from the first substrate 110, so that the hydrophobic layer 150 is away from the first substrate.
  • the surface of 110 is hydrophobic.
  • the detection chip 100 further includes a second substrate 160.
  • the second substrate 160 is disposed opposite to the first substrate 110 and is spaced apart from the first substrate 110 to provide a detection space (ie, a liquid flow space).
  • the material of the second substrate 160 may be the same as or different from the material of the first substrate 110, which is not limited in the embodiment of the present disclosure.
  • the second substrate 160 is a transparent substrate (such as a glass substrate), so that light can pass through the transparent substrate without damage or with low loss, thereby improving the accuracy of subsequent optical inspections and reducing the need for additional optical inspection equipment. Claim.
  • the detection chip 100 further includes a sample inlet 171, a sample outlet 172 and a detection area 001.
  • a plurality of detection units 120 are located in the detection area 001, the plurality of detection units 120 are arranged in multiple rows, and the injection port 171 and the sample outlet 172 are distributed along the column direction Z on both sides of the detection area 001 (for example, located in the figure Upper and lower sides).
  • the solution to be detected may be injected into the sample inlet 171 by a micro-syringe pump or a pipette gun, and flow out from the sample outlet 172 after flowing through the plurality of detection units 120 along the column direction Z.
  • sample inlet 171 and the sample outlet 172 are symmetrically or centrally distributed along the Z axis in the column direction on both sides of the detection area 001, so that the parallelism and stability of the flow field can be further improved.
  • the embodiment of the present disclosure is not limited to this, and the sample inlet 171 and the sample outlet 172 may also be distributed asymmetrically, which may be determined according to the characteristics of the flow field and actual requirements.
  • the sample inlet 171 and the sample outlet 172 are provided on the second substrate 160.
  • the injection port 171 may be a through hole penetrating through the second substrate 160, and the shape of the through hole on a cross-section parallel to the second substrate 160 may be any suitable shape such as a circle, a rectangle, a square, etc. shape.
  • the sample outlet 172 may also be a through hole penetrating the second substrate 160, and the shape of the sample outlet 172 on a cross section parallel to the second substrate 160 may be the same as or different from the shape of the sample inlet 171.
  • FIG. 2 only schematically shows the arrangement of the injection port 171 on the second substrate 160, but the relative position of the injection port 171 and the detection unit 120 is not limited by the situation shown in FIG. 2 .
  • the detection chip 100 further includes a sealant 180, which is located between the first substrate 110 and the second substrate 160 and surrounds the diversion dam 130 And multiple detection units 120.
  • the first substrate 110, the second substrate 160, and the sealant 180 jointly define the flow space of the solution to be detected.
  • spacers can be mixed in the sealant 180, so that the spacing between the first substrate 110 and the second substrate 160 can be controlled by the spacers, and the compression strength of the detection chip 100 can be enhanced .
  • the height h1 of the diversion dam 130 in the direction perpendicular to the first substrate 110 is greater than the height h2 of the detection unit 120 in the direction perpendicular to the first substrate 110, so as to better regulate the flow.
  • the height h1 of the diversion dam 130 is 30% to 60% of the distance h0 between the first substrate 110 and the second substrate 160, such as 40% or 50%.
  • the distance h0 between the first substrate 110 and the second substrate 160 is 100 microns
  • the height h1 of the diversion dam 130 is 50 microns
  • the height h2 of the detection unit 120 is 3 microns
  • the height of h1 and h2 is 3 microns.
  • the height difference is large, which can better adjust the parallelism of the flow field.
  • the cross-sectional shape of the diversion dam 130 in a direction perpendicular to the first path (for example, the column direction Z) is a semicircle
  • the radius of the semicircle may be greater than or equal to the first substrate 110 Half of the distance h0 from the second substrate 160.
  • the width W1 of the diversion dam 130 is 50 micrometers to 200 micrometers, for example, 80 micrometers, 100 micrometers, or 150 micrometers.
  • the distance d between the diversion dam 130 and the adjacent detection unit 120 is greater than or equal to 100 microns.
  • the length L of the diversion dam 130 is greater than or equal to the sum of the lengths of the plurality of detection units 120 in the first path (for example, the column direction Z).
  • the length L of the diversion dam 130 is 1 cm.
  • the height h1 can guide the height of the flow dam 130 itself, and can also guide the sum of the heights of the flow dam 130 and the hydrophilic layer 140.
  • the height h2 can refer to the detection unit
  • the height of 120 itself can also refer to the sum of the heights of the detection unit 120 and the hydrophilic layer 140.
  • the width W1 and the spacing d may also take the thickness of the hydrophilic layer 140 into consideration.
  • the target antigen or antibody is attached to the detection unit 120 before the first substrate 110 and the second substrate 160 are paired.
  • a liquid containing a target antigen or antibody can be dropped on the detection unit 120. Due to the presence of the chemical modification group 141, the target antigen or antibody binds to the chemical modification group 141 and can be attached to the detection unit 120.
  • the first substrate 110 and the second substrate 160 are aligned with the frame sealant 180. Then, the solution to be tested is injected from the sample inlet 171 so that the solution to be tested flows through the detection area 001 and flows out from the sample outlet 172.
  • the marker in the solution to be detected flows through the detection unit 120, it will bind or react with the target antigen or antibody attached to the detection unit 120.
  • a bovine serum albumin (BSA) solution can be injected into the detection chip 100 to clean the internal space of the detection chip 100, so as to reduce the portion of the internal space of the detection chip 100 except for the detection unit 120. The adsorption, thereby improving the accuracy of subsequent detection.
  • an optical detection device is used to perform optical detection on the detection chip 100 to obtain an immunological detection result.
  • FIG. 3 is a schematic diagram of a flow field simulation of a detection chip provided by some embodiments of the present disclosure.
  • the simulation result is, for example, the simulation result of the detection chip 100 shown in FIG. 1 and FIG. 2.
  • FIG. 3 shows that, due to the provision of the diversion dam 130, the uniformity of the flow field distribution in different areas in the detection chip 100 is better.
  • the flow velocity in the area between the diversion dams 130 is relatively large, and the flow field has good stability and parallelism, thereby helping to improve the accuracy of the immunological detection results. degree.
  • FIG. 3 is a schematic diagram of a flow field simulation of a detection chip provided by some embodiments of the present disclosure.
  • the simulation result is, for example, the simulation result of the detection chip 100 shown in FIG. 1 and FIG. 2.
  • the flow velocity in the area adjacent to the diversion dam 130 and on both sides of the diversion dam 130 is relatively small, so it is necessary to keep the diversion dam 130 and the detection unit 120 at a certain distance (for example, the aforementioned distance d , And d is greater than or equal to 100 microns), so that the detection unit 120 avoids the area with a small flow velocity.
  • FIG. 4 is a schematic plan view of another detection chip provided by some embodiments of the present disclosure
  • FIG. 5 is a schematic cross-sectional view of the detection chip shown in FIG. 4.
  • the detection chip 200 of this embodiment is basically the same as the detection chip 100 shown in FIGS. 1 and 2.
  • the positioning component 190 is used to cooperate with a separately provided optical detection device to realize the positioning of the detection chip 200, thereby facilitating the optical detection device to perform optical detection on the detection chip 200.
  • the positioning member 190 is disposed on the first substrate 110 and is covered by the hydrophobic layer 150.
  • the positioning member 190 may be made of a metal material, such as molybdenum (Mo), or may be made of an opaque insulating material, which is not limited in the embodiment of the present disclosure.
  • Mo molybdenum
  • the optical positioning device of the optical detection device emits light for positioning.
  • the detection chip 200 is located at a preset position, since the positioning component 190 does not transmit light, the sensor set in the corresponding position The detected light intensity is very small or zero, so that it can be determined that the detection chip 200 is located at a preset position to achieve positioning.
  • optical detection equipment can be used to perform optical detection and signal reading of specific locations.
  • the specific site is a certain or certain detection unit 120 to which the target antigen or antibody is attached.
  • the positioning component 190 is located outside the detection area 001, for example, further outside the liquid flow space formed by the first substrate 110, the second substrate 160 and the sealant 180, so as to avoid affecting the optical detection.
  • a plurality of positioning components 190 are arranged on one side of the detection chip 200 and close to the edge of the detection chip 200. By providing multiple positioning members 190, the positioning accuracy can be improved.
  • the embodiment of the present disclosure is not limited to this, and the location of the positioning component 190 can be determined according to actual needs, for example, it can be placed on any side, any two sides, around or other suitable positions of the detection chip 200, which can be based on It depends on the positioning method of the matching optical detection equipment.
  • the number of positioning components 190 is also not limited, and can be any number, which can be determined according to actual needs.
  • At least one embodiment of the present disclosure also provides a method for preparing a detection chip, which can be used to prepare the detection chip described in any embodiment of the present disclosure.
  • the preparation method By using the preparation method, the stability and parallelism of the flow field inside the detection chip can be improved, and the accuracy of the immunological detection result can be improved, and the prepared detection chip has the characteristics of small size, high throughput and the like.
  • FIG. 6 is a schematic flowchart of a method for preparing a detection chip provided by some embodiments of the disclosure.
  • the preparation method includes the following operations.
  • Step S300 forming a plurality of detection units 120 and at least one diversion dam 130 on the first substrate 110, and the diversion dam 130 extends along the first path and is located between adjacent detection units 120.
  • photoresist may be used, and the detection unit 120 and the diversion dam 130 may be formed through processes such as exposure, development, and etching.
  • the preparation method may further include more steps, and the order between the steps is not limited and can be determined according to actual needs.
  • the detailed description and technical effects of the preparation method please refer to the above description of the detection chip 100/200, which will not be repeated here.

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Abstract

一种检测芯片及其制备方法，该检测芯片(100)包括第一基板(110)、多个检测单元(120)和至少一个导流坝(130)。多个检测单元(120)位于第一基板(110)上，导流坝(130)位于第一基板(110)上，导流坝(130)沿第一路径延伸且位于相邻的检测单元(120)之间。该检测芯片(100)可以提高流场的稳定性和平行性，有助于提高免疫检测结果的准确度，且具有体积小、高通量等特点。

Description

检测芯片及其制备方法 技术领域
本公开的实施例涉及一种检测芯片及其制备方法。
背景技术
随着生物化学检测技术的发展，微流控芯片(Microfluidic Chip)逐渐成为研究热点，并且涉及到生物、化学、医学、流体、电子、材料、机械等多个学科。微流控芯片可以在数十至数百微米尺度通道内处理和操纵微量(例如10 -9至10 -18升)流体。由于微流控芯片的微米级结构显著增大了流体的比表面积，即表面积与体积的比例，从而导致了一系列与表面有关的特殊效应，例如层流效应、表面张力、毛细效应、快速热传导效应、扩散效应等。因此，微流控芯片具有宏观尺度实验室装置所不具有的优越性能，具有广阔的应用前景。
发明内容
本公开至少一个实施例提供一种检测芯片，包括：第一基板；多个检测单元，位于所述第一基板上；至少一个导流坝，位于所述第一基板上，所述导流坝沿第一路径延伸且位于相邻的检测单元之间。
例如，在本公开一实施例提供的检测芯片中，所述多个检测单元排列为多列，所述第一路径沿列方向延伸。
例如，在本公开一实施例提供的检测芯片中，每列检测单元的两侧均设置有所述导流坝。
例如，在本公开一实施例提供的检测芯片中，所述至少一个导流坝包括多个导流坝，所述多个导流坝彼此平行。
例如，在本公开一实施例提供的检测芯片中，所述导流坝沿垂直于所述第一基板的方向的高度大于所述检测单元沿垂直于所述第一基板的方向的高度。
例如，本公开一实施例提供的检测芯片还包括亲水层，其中，所述亲水层覆盖所述检测单元和所述导流坝。
例如，在本公开一实施例提供的检测芯片中，所述亲水层覆盖所述检测单元的部分包括化学修饰基团。
例如，本公开一实施例提供的检测芯片还包括疏水层，其中，所述疏水层设置在所述第一基板上，所述检测单元和所述导流坝设置在所述疏水层上。
例如，本公开一实施例提供的检测芯片还包括第二基板，其中，所述第二基板与所述第一基板相对设置，且与所述第一基板间隔开以提供检测空间。
例如，本公开一实施例提供的检测芯片还包括进样口和出样口，其中，所述进样口和所述出样口设置在所述第二基板上。
例如，本公开一实施例提供的检测芯片还包括检测区域，其中，所述多个检测单元位于所述检测区域中，所述多个检测单元排列为多列，所述进样口和所述出样口沿列方向分布在所述检测区域的两侧。
例如，在本公开一实施例提供的检测芯片中，所述进样口和所述出样口沿所述列方向轴对称或中心对称分布在所述检测区域的两侧。
例如，在本公开一实施例提供的检测芯片中，所述第一基板和/或所述第二基板为玻璃基板。
例如，本公开一实施例提供的检测芯片还包括封框胶，其中，所述封框胶位于所述第一基板和所述第二基板之间，且围绕所述导流坝和所述多个检测单元。
例如，在本公开一实施例提供的检测芯片中，所述导流坝的高度为所述第一基板与所述第二基板之间的距离的30％至60％。
例如，在本公开一实施例提供的检测芯片中，所述导流坝的宽度为50微米至200微米，所述导流坝与相邻的检测单元的间距大于或等于100微米。
例如，在本公开一实施例提供的检测芯片中，所述导流坝的长度大于或等于所述多个检测单元在所述第一路径上的长度之和。
例如，在本公开一实施例提供的检测芯片中，所述导流坝在垂直于所述第一路径的方向上的截面形状为矩形、正方形、梯形或半圆形。
例如，在本公开一实施例提供的检测芯片中，所述导流坝的材料包括光刻胶。
例如，本公开一实施例提供的检测芯片还包括定位部件，其中，所述定位部件位于所述第一基板上，所述疏水层设置在所述定位部件上。
本公开至少一个实施例还提供一种如本公开任一实施例所述的检测芯片 的制备方法，包括：在第一基板上形成多个检测单元和至少一个导流坝；其中，所述导流坝沿第一路径延伸且位于相邻的检测单元之间。
附图说明
为了更清楚地说明本公开实施例的技术方案，下面将对实施例的附图作简单地介绍，显而易见地，下面描述中的附图仅仅涉及本公开的一些实施例，而非对本公开的限制。
图1为本公开一些实施例提供的一种检测芯片的平面示意图；
图2为如图1所示的检测芯片的剖面示意图；
图3为本公开一些实施例提供的一种检测芯片的流场仿真示意图；
图4为本公开一些实施例提供的另一种检测芯片的平面示意图；
图5为图4所示的检测芯片的剖面示意图；以及
图6为本公开一些实施例提供的一种检测芯片的制备方法的流程示意图。
具体实施方式
为使本公开实施例的目的、技术方案和优点更加清楚，下面将结合本公开实施例的附图，对本公开实施例的技术方案进行清楚、完整地描述。显然，所描述的实施例是本公开的一部分实施例，而不是全部的实施例。基于所描述的本公开的实施例，本领域普通技术人员在无需创造性劳动的前提下所获得的所有其他实施例，都属于本公开保护的范围。
除非另作定义，此处使用的技术术语或者科学术语应当为本公开所属领域内具有一般技能的人士所理解的通常意义。本公开中使用的“第一”、“第二”以及类似的词语并不表示任何顺序、数量或者重要性，而只是用来区分不同的组成部分。同样，“包括”或者“包含”等类似的词语意指出现该词前面的元件或者物件涵盖出现在该词后面列举的元件或者物件及其等同，而不排除其他元件或者物件。“连接”或者“相连”等类似的词语并非限定于物理的或者机械的连接，而是可以包括电性的连接，不管是直接的还是间接的。“上”、“下”、“左”、“右”等仅用于表示相对位置关系，当被描述对象的绝对位置改变后，则该相对位置关系也可能相应地改变。
免疫检测芯片是一种常用的微流控芯片，可以用于进行癌症标志物、心 脏标志物、甲状腺标志物、性腺标志物以及其他传染病标志物的检测。例如，可以使目标抗原或抗体附着在免疫检测芯片内的检测单元上，然后封装该免疫检测芯片，将待检测溶液注入免疫检测芯片，使待检测溶液流过检测单元所在的区域。若待检测溶液中存在标志物，随着待检测溶液的流动，则这些标志物会与附着在检测单元上的抗原或抗体结合，从而使标志物被固定到检测单元上。然后，对检测单元进行光学检测(例如荧光检测)，从而可以得到免疫检测结果。
然而，由于免疫检测芯片的内部空间为微米尺度，待检测溶液的注入速度、注入量、温度等因素对芯片内的流场的影响较大，因此芯片内的流场的稳定性和平行性较差，不利于待检测溶液中的标志物与检测单元上的目标抗原或抗体结合，从而会对免疫检测结果产生不利影响。
本公开至少一实施例提供一种检测芯片及其制备方法，该检测芯片可以提高流场的稳定性和平行性，有助于提高免疫检测结果的准确度，且具有体积小、高通量等特点。
下面，将参考附图详细地说明本公开的实施例。应当注意的是，不同的附图中相同的附图标记将用于指代已描述的相同的元件。
本公开至少一实施例提供一种检测芯片，该检测芯片包括第一基板、多个检测单元和至少一个导流坝。多个检测单元位于第一基板上，导流坝位于第一基板上，导流坝沿第一路径延伸且位于相邻的检测单元之间。
图1为本公开一些实施例提供的一种检测芯片的平面示意图，图2为如图1所示的检测芯片的剖面示意图。如图1和图2所示，检测芯片100包括第一基板110、多个检测单元120和至少一个导流坝130。
第一基板110起支撑、保护等作用，可以为塑料基板、玻璃基板或硅基板，也可以为其他适用的基板，本公开的实施例对此不作限制。例如，当采用玻璃基板时，成本较低；当采用硅基板时，性能较好。例如，第一基板110为透明基板(例如玻璃基板)，以使光线可以无损或损耗较低地穿过该透明基板，从而可以提高后续光学检测的准确性，降低对另行提供的光学检测设备的要求。
多个检测单元120位于第一基板110上，检测单元120例如用于为目标抗原或抗体提供附着位置。例如，在一些示例中，检测单元120为凸台形状，从而便于附着在其上的目标抗原或抗体与流过检测单元120的待检测溶液中 的标志物结合或反应。当然，本公开的实施例不限于此，检测单元120也可以为凹槽形状或者平面形状，只要能保证附着在检测单元120上的目标抗原或抗体能够与流过检测单元120的待检测溶液接触并能与其中的标志物结合即可。需要说明的是，本公开的实施例中，检测单元120的数量不受限制，可以为任意个数，例如根据需要检测的标志物的种类或浓度而定。
导流坝130位于第一基板110上，导流坝130沿第一路径延伸且位于相邻的检测单元120之间。导流坝130对检测芯片100的内部空间的流场产生影响，从而可以提高不同检测单元120所在位置的流速均一性，提高流场沿第一路径的平行性，提高流场的稳定性，使得待检测溶液能够稳定均匀地流过检测单元120所在的区域。因此，待检测溶液中的标志物能够与检测单元120上的目标抗原或抗体充分结合或反应，从而有助于提高免疫检测结果的准确度和可靠度。并且，该检测芯片100还具有体积小、高通量等特点。
例如，在一些示例中，如图1所示，多个检测单元120排列为多列，第一路径沿列方向Z延伸。每列检测单元120的两侧均设置有导流坝130，且多个导流坝130彼此平行。当待检测溶液沿列方向Z流过多个检测单元120时，在导流坝130的作用下，待检测溶液流动所形成的流场沿列方向Z的平行性得到提高，使得待检测溶液能够稳定均匀地沿列方向Z流动。
需要说明的是，本公开的实施例中，第一路径不限于沿列方向Z延伸，也可以沿其他任意的方向延伸。并且，第一路径可以沿直线延伸，也可以沿曲线延伸，这可以根据待检测溶液的流动路径和流动方式而定，本公开的实施例对此不作限制。例如，当第一路径沿直线延伸时，导流坝130也沿直线延伸；当第一路径沿曲线延伸时，导流坝130也沿曲线延伸。相应地，多个检测单元120可以沿直线排列为多列，也可以沿曲线排列为多组，位于相邻的检测单元120之间的导流坝130沿着检测单元120的排列方向延伸即可。
需要说明的是，本公开的实施例中，可以在每列检测单元120的两侧设置导流坝130，也可以仅在某些列检测单元120的两侧设置导流坝130，这可以根据需要达到的流场平行性而定，本公开的实施例对此不作限制。
例如，当每列检测单元120的两侧均设置有导流坝130时(例如，检测单元120和导流坝130设置为如图1所示的情形时)，流场具有较好的平行性。若某个检测单元120上的目标抗原或抗体意外脱落，该脱落的目标抗原或抗体会沿着列方向Z流动，也即是，在该列检测单元120所在的区域内流 动，因此不会影响其他列检测单元120，从而可以避免不同检测位点(即检测单元120)之间的串扰，避免交叉污染。
例如，导流坝130的数量不受限制，可以为一个或多个。例如，在一些示例中，若多个检测单元120仅排列为两列，则可以仅设置一个导流坝130，且使该导流坝130位于两列检测单元120之间，从而可以在减少导流坝130数量的同时使流场具有较好的平行性。
例如，导流坝130在垂直于第一路径(例如列方向Z)的方向上的截面形状可以为矩形、正方形、梯形、半圆形或其他适用的形状，例如可以为规则形状或不规则形状，本公开的实施例对此不作限制。例如，不同的截面形状会对流场产生不同程度的影响，因此可以根据流场的特点确定导流坝130的截面形状。
例如，导流坝130和检测单元120均可以采用光刻胶制备，该光刻胶例如为可厚膜刻蚀的光刻胶。例如，在一些示例中，可以在同一个构图工艺中形成导流坝130和检测单元120，以简化生产工艺。
例如，如图2所示，在一些示例中，该检测芯片100还包括亲水层140，亲水层140覆盖检测单元120和导流坝130。通过设置亲水层140，可以使待检测溶液更好地与检测单元120接触，从而便于待检测溶液中的标志物与检测单元120上的目标抗原或抗体结合。
例如，亲水层140的材料为硅氧化物，例如二氧化硅(SiO2)等。当然，本公开的实施例不限于此，亲水层140也可以采用其他合适的无机或有机材料制备，只要保证亲水层140与待检测溶液接触的表面具有亲水性即可。例如，亲水层140可以采用亲水性材料直接制备。又例如，亲水层140可以采用不具有亲水性的材料制备，在这种情况下，需要在亲水层140与待检测溶液接触的表面进行亲水化处理，从而使该亲水层140具有亲水性。例如，若采用非亲水性材料，例如氮化硅等，可以对其进行亲水化处理，例如采用凝胶化改性法、紫外辐射法、等离子体法等方法，例如可以使非亲水性材料的表面具有亲水基团，以使其具有亲水性。
例如，如图2所示，在一些示例中，亲水层140覆盖检测单元120的部分包括化学修饰基团141。例如，化学修饰基团141可以采用化学改性处理的方法得到，且可以和目标抗原或抗体结合。通过设置化学修饰基团141，可以使目标抗原或抗体稳固地附着在检测单元120上，在待检测溶液的流动 冲刷下，目标抗原或抗体不易脱落，从而可以提高免疫检测结果的准确度。
例如，如图2所示，在一些示例中，该检测芯片100还包括疏水层150。疏水层150设置在第一基板110上，检测单元120和导流坝130设置在疏水层150上。通过设置疏水层150，可以使待检测溶液在检测芯片100中更容易流动，并且可以使待检测溶液中的标志物不易附着在第一基板110上，以避免待检测溶液中的标志物被浪费。
例如，疏水层150的材料为树脂或硅氮化物。当然，疏水层150也可以采用其他合适的无机或有机材料制备，只要保证疏水层150远离第一基板110的一侧具有疏水性即可。例如，疏水层150可以采用疏水性材料直接制备。又例如，疏水层150可以采用不具有疏水性的材料制备，在这种情况下，需要在该疏水层150远离第一基板110的表面进行疏水化处理，从而使该疏水层150远离第一基板110的表面具有疏水性。
例如，如图2所示，在一些示例中，该检测芯片100还包括第二基板160。例如，第二基板160与第一基板110相对设置，且与第一基板110间隔开以提供检测空间(即液体流动空间)。第二基板160的材料可以与第一基板110的材料相同或不同，本公开的实施例对此不作限制。例如，第二基板160为透明基板(例如玻璃基板)，以使光线可以无损或损耗较低地穿过该透明基板，从而可以提高后续光学检测的准确性，降低对另行提供的光学检测设备的要求。
例如，如图1所示，在一些示例中，该检测芯片100还包括进样口171、出样口172和检测区域001。例如，多个检测单元120位于检测区域001中，多个检测单元120排列为多列，进样口171和出样口172沿列方向Z分布在检测区域001的两侧(例如位于图中的上下侧)。例如，待检测溶液可以通过微量注射泵或通过移液枪注射到进样口171，在沿着列方向Z流经多个检测单元120之后，从出样口172流出。例如，进样口171和出样口172沿列方向Z轴对称或中心对称分布在检测区域001的两侧，从而可以进一步提高流场的平行性和稳定性。当然，本公开的实施例不限于此，进样口171和出样口172也可以呈不对称分布，这可以根据流场的特性和实际需求而定。
例如，进样口171和出样口172设置在第二基板160上。例如，如图2所示，进样口171可以为贯穿第二基板160的通孔，该通孔在平行于第二基板160的截面上的形状可以为圆形、矩形、正方形等任意适用的形状。类似 地，出样口172也可以为贯穿第二基板160的通孔，且出样口172在平行于第二基板160的截面上的形状可以与进样口171的形状相同或不同。需要说明的是，图2仅示意性地示出进样口171在第二基板160上的设置方式，但进样口171和检测单元120的相对位置并不受图2所示的情形的限制。
例如，如图1和图2所示，在一些示例中，该检测芯片100还包括封框胶180，封框胶180位于第一基板110和第二基板160之间，且围绕导流坝130和多个检测单元120。例如，第一基板110、第二基板160和封框胶180共同限定待检测溶液的流动空间。例如，在一些示例中，可以在封框胶180中混合隔垫物，从而可以通过隔垫物控制第一基板110和第二基板160之间的间距，并且加强该检测芯片100的抗压强度。
例如，如图2所示，导流坝130沿垂直于第一基板110的方向的高度h1大于检测单元120沿垂直于第一基板110的方向的高度h2，从而可以更好地起到调节流场平行性的作用。例如，导流坝130的高度h1为第一基板110与第二基板160之间的距离h0的30％至60％，例如为40％或50％。例如，在一些示例中，第一基板110与第二基板160之间的距离h0为100微米，导流坝130的高度h1为50微米，检测单元120的高度h2为3微米，h1和h2的高度差异较大，可以更好地调节流场的平行性。例如，在一些示例中，当导流坝130在垂直于第一路径的方向(例如列方向Z)上的截面形状为半圆形时，该半圆形的半径可以大于或等于第一基板110与第二基板160之间的距离h0的一半。
例如，如图2所示，导流坝130的宽度W1为50微米至200微米，例如为80微米、100微米或150微米。导流坝130与相邻的检测单元120的间距d大于或等于100微米。
例如，如图1所示，导流坝130的长度L大于或等于多个检测单元120在第一路径(例如列方向Z)上的长度之和。例如，在一些示例中，导流坝130的长度L为1厘米。
需要说明的是，本公开的实施例中，高度h1既可以指导流坝130自身的高度，又可以指导流坝130和亲水层140的高度之和，同样地，高度h2既可以指检测单元120自身的高度，又可以指检测单元120和亲水层140的高度之和。类似地，宽度W1和间距d也可以将亲水层140的厚度考虑在内。
在使用该检测芯片100时，首先在第一基板110和第二基板160对盒之 前，使目标抗原或抗体附着在检测单元120上。例如，可以将包含目标抗原或抗体的液体滴在检测单元120上，由于存在化学修饰基团141，因此目标抗原或抗体与化学修饰基团141结合，从而可以附着在检测单元120上。然后，采用封框胶180将第一基板110和第二基板160对盒。接着，从进样口171注入待检测溶液，使待检测溶液流过检测区域001，并从出样口172流出。待检测溶液中的标志物在流经检测单元120时，会与附着在检测单元120上的目标抗原或抗体结合或反应。然后，可以将例如牛血清白蛋白(BSA)溶液注入该检测芯片100，以对检测芯片100的内部空间进行清洗，从而减少检测芯片100的内部空间中除检测单元120之外的部分对待检测溶液的吸附，进而提高后续检测的准确性。最后，采用光学检测设备对该检测芯片100进行光学检测，从而得到免疫检测结果。
图3为本公开一些实施例提供的一种检测芯片的流场仿真示意图，该仿真结果例如为图1和图2所示的检测芯片100的仿真结果。由图3可知，由于设置了导流坝130，该检测芯片100内的不同区域的流场分布均匀性较好。并且，在该检测芯片100的检测区域001中，各个导流坝130之间的区域的流速较大，该流场具有很好的稳定性和平行性，从而有助于提高免疫检测结果的准确度。并且，由图3可知，与导流坝130紧邻且位于导流坝130两侧的区域内的流速较小，因此需要使导流坝130与检测单元120保持一定间距(例如为上述的间距d，且d大于或等于100微米)，从而使检测单元120避开该流速较小的区域。
图4为本公开一些实施例提供的另一种检测芯片的平面示意图，图5为图4所示的检测芯片的剖面示意图。如图4和图5所示，除了还进一步包括定位部件190外，该实施例的检测芯片200与图1和图2所示的检测芯片100基本相同。
在该实施例中，定位部件190用于与另行提供的光学检测设备配合以实现检测芯片200的定位，从而便于光学检测设备对检测芯片200进行光学检测。例如，定位部件190设置在第一基板110上，且被疏水层150覆盖。定位部件190可以采用金属材料制备，例如钼(Mo)，也可以采用不透光的绝缘材料制备，本公开的实施例对此不作限制。例如，在一些示例中，进行定位时，光学检测设备的光学定位器件发出用于定位的光，若检测芯片200位于预设的位置，由于定位部件190不透光，因此设置在相应位置的传感器检 测到的光强很小或者为零，从而可以判断该检测芯片200位于预设的位置，以实现定位。定位完成后，可以采用光学检测设备对特定位点进行光学检测及信号读取。例如，该特定位点为某个或某些检测单元120，其上附着有目标抗原或抗体。
例如，定位部件190位于检测区域001之外，例如进一步位于第一基板110、第二基板160和封框胶180形成的液体流动空间之外，以避免影响光学检测。例如，在一些示例中，如图4所示，多个定位部件190设置在检测芯片200的一侧且靠近检测芯片200的边缘。通过设置多个定位部件190，可以提高定位精度。当然，本公开的实施例不限于此，定位部件190的设置位置可以根据实际需求而定，例如可以设置在检测芯片200的任意一侧、任意两侧、四周或其他合适的位置，这可以根据与之配合的光学检测设备的定位方式而定。定位部件190的数量也不受限制，可以为任意数量，这可以根据实际需求而定。
本公开至少一实施例还提供一种检测芯片的制备方法，可用于制备本公开任一实施例所述的检测芯片。利用该制备方法，可以提高检测芯片内部的流场的稳定性和平行性，有助于提高免疫检测结果的准确度，且制备的检测芯片具有体积小、高通量等特点。
图6为本公开一些实施例提供的一种检测芯片的制备方法的流程示意图。例如，在一些示例中，如图6所示，该制备方法包括以下操作。
步骤S300：在第一基板110上形成多个检测单元120和至少一个导流坝130，该导流坝130沿第一路径延伸且位于相邻的检测单元120之间。
例如，可以采用光刻胶，并通过曝光、显影、刻蚀等工艺形成检测单元120和导流坝130。
需要说明的是，本公开的实施例中，该制备方法还可以包括更多的步骤，各个步骤之间的顺序不受限制，可以根据实际需求而定。关于该制备方法的详细说明和技术效果可以参考上文中关于检测芯片100/200的描述，此处不再赘述。
有以下几点需要说明：
(1)本公开实施例附图只涉及到本公开实施例涉及到的结构，其他结构可参考通常设计。
(2)在不冲突的情况下，本公开的实施例及实施例中的特征可以相互组 合以得到新的实施例。
以上所述，仅为本公开的具体实施方式，但本公开的保护范围并不局限于此，本公开的保护范围应以所述权利要求的保护范围为准。

Claims (21)

  1. 一种检测芯片，包括：
    第一基板；
    多个检测单元，位于所述第一基板上；
    至少一个导流坝，位于所述第一基板上，所述导流坝沿第一路径延伸且位于相邻的检测单元之间。
  2. 根据权利要求1所述的检测芯片，其中，所述多个检测单元排列为多列，所述第一路径沿列方向延伸。
  3. 根据权利要求2所述的检测芯片，其中，每列检测单元的两侧均设置有所述导流坝。
  4. 根据权利要求1-3任一所述的检测芯片，其中，所述至少一个导流坝包括多个导流坝，所述多个导流坝彼此平行。
  5. 根据权利要求1-4任一所述的检测芯片，其中，所述导流坝沿垂直于所述第一基板的方向的高度大于所述检测单元沿垂直于所述第一基板的方向的高度。
  6. 根据权利要求1-5任一所述的检测芯片，还包括亲水层，其中，所述亲水层覆盖所述检测单元和所述导流坝。
  7. 根据权利要求6所述的检测芯片，其中，所述亲水层覆盖所述检测单元的部分包括化学修饰基团。
  8. 根据权利要求1-5任一所述的检测芯片，还包括疏水层，其中，所述疏水层设置在所述第一基板上，所述检测单元和所述导流坝设置在所述疏水层上。
  9. 根据权利要求1-5任一所述的检测芯片，还包括第二基板，其中，所述第二基板与所述第一基板相对设置，且与所述第一基板间隔开以提供检测空间。
  10. 根据权利要求9所述的检测芯片，还包括进样口和出样口，其中，所述进样口和所述出样口设置在所述第二基板上。
  11. 根据权利要求10所述的检测芯片，还包括检测区域，其中，所述多个检测单元位于所述检测区域中，
    所述多个检测单元排列为多列，所述进样口和所述出样口沿列方向分布 在所述检测区域的两侧。
  12. 根据权利要求11所述的检测芯片，其中，所述进样口和所述出样口沿所述列方向轴对称或中心对称分布在所述检测区域的两侧。
  13. 根据权利要求9-12任一所述的检测芯片，其中，所述第一基板和/或所述第二基板为玻璃基板。
  14. 根据权利要求9-13任一所述的检测芯片，还包括封框胶，其中，所述封框胶位于所述第一基板和所述第二基板之间，且围绕所述导流坝和所述多个检测单元。
  15. 根据权利要求9-14任一所述的检测芯片，其中，所述导流坝的高度为所述第一基板与所述第二基板之间的距离的30％至60％。
  16. 根据权利要求1-15任一所述的检测芯片，其中，所述导流坝的宽度为50微米至200微米，所述导流坝与相邻的检测单元的间距大于或等于100微米。
  17. 根据权利要求1-16任一所述的检测芯片，其中，所述导流坝的长度大于或等于所述多个检测单元在所述第一路径上的长度之和。
  18. 根据权利要求1-17任一所述的检测芯片，其中，所述导流坝在垂直于所述第一路径的方向上的截面形状为矩形、正方形、梯形或半圆形。
  19. 根据权利要求1-18任一所述的检测芯片，其中，所述导流坝的材料包括光刻胶。
  20. 根据权利要求8所述的检测芯片，还包括定位部件，其中，所述定位部件位于所述第一基板上，所述疏水层设置在所述定位部件上。
  21. 一种如权利要求1-20任一所述的检测芯片的制备方法，包括：
    在第一基板上形成多个检测单元和至少一个导流坝；
    其中，所述导流坝沿第一路径延伸且位于相邻的检测单元之间。
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20140067421A (ko) * 2012-11-26 2014-06-05 한국전기연구원 마이크로 채널의 수동형 펌프 구현을 위한 친수성 필라 제작 방법
CN207102625U (zh) * 2017-06-29 2018-03-16 宁波奥丞生物科技有限公司 一种微流体分析盒
CN108816300A (zh) * 2018-07-02 2018-11-16 京东方科技集团股份有限公司 一种微流控芯片、功能装置及其制作方法
CN109283231A (zh) * 2017-07-20 2019-01-29 京东方科技集团股份有限公司 一种医用检测基板、医用检测芯片及医用检测系统

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004008142A1 (ja) * 2002-07-12 2004-01-22 Mitsubishi Chemical Corporation 分析用チップ、分析用チップユニット、分析装置及びそれを用いた分析方法並びに分析用チップの作製方法
CN1858593B (zh) * 2006-03-23 2010-04-21 厦门大学 生物芯片专用亲疏水模式片基
US20100304501A1 (en) * 2007-11-09 2010-12-02 Electronics And Telecommunicaations Research Insti Bio lab-on-a-chip and method of fabricating and operating the same
EP2419216A1 (en) * 2009-04-15 2012-02-22 Koninklijke Philips Electronics N.V. Microfluidic device comprising sensor
TWI418858B (zh) * 2009-09-23 2013-12-11 Prime View Int Co Ltd 彩色濾光基板及彩色顯示裝置
WO2015054546A1 (en) * 2013-10-10 2015-04-16 Song Diagnostic Research Llc. Improved lateral flow assays
EP3792921A1 (en) * 2013-12-11 2021-03-17 Genapsys, Inc. Systems and methods for biological analysis and computation
CN105689029B (zh) * 2016-01-29 2018-01-05 深圳市国赛生物技术有限公司 一种微流控芯片及其使用方法
CN109590039B (zh) * 2019-01-18 2020-12-15 京东方科技集团股份有限公司 一种微流控组件、微流控芯片及其制备方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20140067421A (ko) * 2012-11-26 2014-06-05 한국전기연구원 마이크로 채널의 수동형 펌프 구현을 위한 친수성 필라 제작 방법
CN207102625U (zh) * 2017-06-29 2018-03-16 宁波奥丞生物科技有限公司 一种微流体分析盒
CN109283231A (zh) * 2017-07-20 2019-01-29 京东方科技集团股份有限公司 一种医用检测基板、医用检测芯片及医用检测系统
CN108816300A (zh) * 2018-07-02 2018-11-16 京东方科技集团股份有限公司 一种微流控芯片、功能装置及其制作方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP3984639A4 *

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