WO2022165751A1 - 微流控芯片 - Google Patents
微流控芯片 Download PDFInfo
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- WO2022165751A1 WO2022165751A1 PCT/CN2021/075518 CN2021075518W WO2022165751A1 WO 2022165751 A1 WO2022165751 A1 WO 2022165751A1 CN 2021075518 W CN2021075518 W CN 2021075518W WO 2022165751 A1 WO2022165751 A1 WO 2022165751A1
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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
- B01L3/502723—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 venting arrangements
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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
- B01L3/502746—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
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B1/00—Devices without movable or flexible elements, e.g. microcapillary devices
- B81B1/006—Microdevices formed as a single homogeneous piece, i.e. wherein the mechanical function is obtained by the use of the device, e.g. cutters
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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
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
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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
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
- B01L2300/0654—Lenses; Optical fibres
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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
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
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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
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/087—Multiple sequential chambers
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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
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0877—Flow chambers
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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
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0883—Serpentine channels
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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
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0887—Laminated structure
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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
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B2201/00—Specific applications of microelectromechanical systems
- B81B2201/05—Microfluidics
- B81B2201/051—Micromixers, microreactors
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B2203/00—Basic microelectromechanical structures
- B81B2203/03—Static structures
- B81B2203/0323—Grooves
- B81B2203/033—Trenches
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B2203/00—Basic microelectromechanical structures
- B81B2203/03—Static structures
- B81B2203/0323—Grooves
- B81B2203/0338—Channels
Definitions
- the present disclosure relates to the field of biological detection, in particular to a microfluidic chip.
- Microfluidics is a technology for precise control and manipulation of micro-scale fluids. Through this technology, basic operation units such as sample preparation, reaction, separation, and detection involved in the detection and analysis process can be integrated into a centimeter-scale chip. superior. Microfluidic technology is generally used in the analysis process of trace drugs in the fields of biology, chemistry, and medicine. Microfluidic devices have advantages such as low sample consumption, fast detection speed, easy operation, multi-functional integration, small size, and easy portability, and have great application potential in biology, chemistry, medicine and other fields.
- a microfluidic chip includes a first substrate including: a sample inlet; and a reaction zone, the reaction zone is located downstream of the sample inlet, the reaction zone includes at least one groove, each The orthographic projection of the groove on the first substrate is an axis-symmetric pattern, the width of the axis-symmetric pattern in the first direction is not less than the width of the axis-symmetric pattern in the second direction, and the first direction is vertical in the second direction.
- the reaction zone includes at least two grooves, and the orthographic shapes of the at least two grooves on the first substrate are different.
- the reaction zone includes at least two grooves, and the orthographic shapes of the at least two grooves on the first substrate are the same.
- the orthographic projection of the reaction zone on the first substrate includes a first axisymmetric figure and a second axisymmetric figure, and the width of the first axisymmetric figure in the first direction is smaller than the width of the first axisymmetric figure The width of the second axisymmetric figure in the first direction.
- the width of the first axisymmetric pattern in the second direction is greater than the width of the second axisymmetric pattern in the second direction.
- the axisymmetric figures include polygons and circles.
- the end of the axisymmetric pattern near the injection port includes a semi-circular ring shape.
- the first substrate further includes a mixing region downstream of the injection port, the mixing region including a serpentine flow channel.
- the reaction zone includes a first groove and a second groove
- the mixing zone includes a first mixing zone upstream of the first groove and a second mixing zone upstream of the second groove uniform area.
- the flow channel length of the second mixing zone is greater than the flow channel length of the first mixing zone.
- the first substrate further includes a waste region and a sample outlet, the waste region being located downstream of the reaction zone and upstream of the sample outlet.
- the orthographic projection of the waste region on the first substrate is a rectangle.
- the microfluidic chip further includes: a second substrate, the second substrate is disposed opposite to the first substrate, the second substrate is provided with an opening, and the opening penetrates the second substrate , the orthographic projection of the opening on the first substrate at least partially overlaps the orthographic projection of the reaction zone on the first substrate; and a cover plate, the orthographic projection of the opening on the first substrate is located in the orthographic projection of the cover plate on the first substrate.
- the orthographic projection of the reaction zone on the first substrate is within the orthographic projection of the opening on the first substrate.
- the orthographic projection of the opening on the first substrate is within the orthographic projection of the reaction zone on the first substrate.
- an orthographic projection of two opposite edges of the reaction zone in the second direction on the first substrate along the first direction and two opposite edges of the opening in the second direction coincide.
- a surface of the second substrate facing away from the first substrate is provided with a concave portion, and an orthographic projection of the opening on the first substrate is located at the position of the concave portion on the first substrate. in the orthographic projection, and the cover plate is located in the recess.
- the orthographic projection of the opening on the first substrate comprises a square.
- the material of the cover plate includes a chemically modified material.
- a surface of the second substrate facing the first substrate and a surface of the cover plate facing the first substrate are in the same plane.
- the surface of the second substrate facing the first substrate and the surface of the cover plate facing the first substrate are not in the same plane.
- the recessed portion of the second substrate includes arcuate edges on opposite sides of the opening.
- FIG. 1 schematically shows a top view of a first substrate according to an embodiment of the present disclosure
- FIG. 2 schematically shows a perspective structural view of a first substrate according to an embodiment of the present disclosure
- FIG. 3 schematically shows a sample injection simulation result diagram of a microfluidic chip according to an embodiment of the present disclosure
- FIG. 4 schematically shows a perspective structural view of a first substrate according to an embodiment of the present disclosure
- FIG. 5 schematically shows a three-dimensional structure diagram of a microfluidic chip according to an embodiment of the present disclosure
- FIG. 6 schematically shows a top view of a second substrate and a cover plate according to an embodiment of the present disclosure
- FIG. 7A schematically shows a cross-sectional view of the second substrate and the cover plate taken along the line AA in FIG. 6;
- FIG. 7B schematically shows another cross-sectional view of the second substrate and the cover plate taken along the line AA in FIG. 6;
- FIG. 8 schematically shows a top view of a second substrate and a cover plate according to an embodiment of the present disclosure
- FIG. 9 schematically shows a cross-sectional view of the second substrate and the cover plate taken along the line AA in FIG. 8;
- FIG. 10 schematically shows a perspective structural view of a second substrate according to an embodiment of the present disclosure
- FIG. 11 schematically shows a dimension drawing of a first substrate according to an embodiment of the present disclosure
- FIG. 12 schematically shows a dimension drawing of a second substrate according to an embodiment of the present disclosure
- FIG. 13 schematically illustrates a dimensional drawing of a first substrate according to an embodiment of the present disclosure.
- FIG. 14 schematically illustrates a dimensional view of a second substrate according to an embodiment of the present disclosure.
- the existing immunoassay microfluidic chips usually use polymer or glass substrates. Compared with glass substrates, polymer substrates are easier to prepare the flow channels and reaction areas required for immune reactions, but the disadvantage of polymers is that the surface Chemical modification is difficult to accomplish. If both substrates are made of polymer substrates, the antibodies need to be lyophilized and stored before thermocompression bonding of the two substrates. The thermocompression process will affect the antibodies. If the two substrates are a polymer substrate and a glass substrate, respectively, there will be a problem of difficulty in bonding. At the same time, during the use of the conventional microfluidic chip, when the liquid flows through the reaction zone, bubbles are easily generated, resulting in uneven or insufficient reaction, which affects the detection effect of the microfluidic chip.
- FIG. 1 schematically shows a top view of a first substrate 100 according to an embodiment of the present disclosure.
- the first substrate 100 may include: an injection port 101 , and a reaction zone 102 located downstream of the injection port 101 .
- the reaction zone 102 includes at least one groove, and the orthographic projection of each groove on the first substrate is an axisymmetric figure, and the width of the axisymmetric figure in the first direction D1 is not smaller than that of the axisymmetric figure in the first direction.
- the width in two directions D2, the first direction D1 is perpendicular to the second direction D2.
- the first direction refers to the direction in which the liquid flows through the reaction zone during the use of the microfluidic chip
- the second direction refers to the direction perpendicular to the flow direction of the liquid in the reaction zone.
- the reaction zone includes a first groove 1021 and a second groove 1022
- the orthographic projection of the first groove 1021 on the first substrate is a first axisymmetric figure, so The first axisymmetric figure has a first axis of symmetry (along the first direction D1 in FIG.
- the orthographic projection of the second groove 1022 on the first substrate is a second axisymmetric figure, and the second axis is symmetrical
- the figure has a second axis of symmetry (also in the first direction D1 in FIG. 1 ).
- the fact that the first axis of symmetry and the second axis of symmetry are in the same direction is only exemplary, and in some embodiments, there may be an included angle between the first axis of symmetry and the second axis of symmetry. More specifically, for the embodiment in which the reaction zone includes more grooves, the included angles between the axes of symmetry of each axisymmetric figure may be the same or different.
- the liquid can have a smaller advancing surface, which is beneficial to reduce air bubbles, facilitate the sample to pass through the reaction zone more uniformly, and improve the detection effect.
- the reaction zone may include at least two grooves, and the orthographic shapes of the at least two grooves on the first substrate may be different.
- the shape of the first groove 1021 and the shape of the second groove 1022 may be different.
- the orthographic projection of the first groove 1021 on the first substrate is a first axisymmetric figure
- the orthographic projection of the second groove 1022 on the first substrate is a second axisymmetric figure.
- the width of the first axis-symmetric pattern in the first direction D1 is smaller than the width of the second axis-symmetric pattern in the first direction D1.
- the width of the first axisymmetric figure in the second direction D2 is greater than the width of the second axisymmetric figure in the second direction D2.
- the reaction zone may include at least two grooves, and the orthographic shapes of the at least two grooves on the first substrate may be the same.
- the axisymmetric figures may include polygons, circles, spindles, etc. Those skilled in the art can reasonably design the shape and size of the reaction zone according to actual needs, which are not specifically limited in the present disclosure.
- FIG. 1 exemplarily shows a hexagonal-shaped reaction zone, such a reaction zone can effectively reduce the bubbles generated during the liquid flow and make the reactant flow more uniform.
- FIG. 2 schematically shows a perspective structural view of a first substrate according to an embodiment of the present disclosure.
- Fig. 3 shows a sample injection simulation result diagram of a microfluidic chip according to an embodiment of the present disclosure. The direction indicated by the arrow in the figure is the liquid flow direction. It can be seen from the simulation results that no bubbles are generated during the liquid advancing process, and the flow evenly.
- the end of the reaction zone close to the injection port may include a semi-circular shape.
- the end 1023 of the first groove 1021 for the reaction may be The end 1024 of the groove 1022 may be in the shape of a semi-circle. This design can further reduce the bubbles in the reaction zone, make the liquid advance surface nearly flush, make the liquid flow more uniform, and further improve the detection accuracy of the microfluidic chip.
- the first substrate 100 may further include a mixing area located downstream of the injection port 101 , for example, a first mixing area 103 located upstream of the first groove 1021 and an upstream area of the second groove 1022
- the second mixing zone 104 as shown in FIG. 1, the mixing zone may include a serpentine flow channel.
- the serpentine flow channel can make the design of the flow channel more compact, and provide a longer flow channel in the limited chip area, so that the reactants can be mixed more fully and uniformly.
- the length of the flow channel of the second mixing zone 104 is greater than the length of the flow channel of the first mixing zone 103 . After the sample reacts more fully, it enters the second groove 1022 of the reaction zone 102 for subsequent reactions.
- the first substrate 100 may further include a waste liquid area 105 and a sample outlet 106 , and the waste liquid area 105 is located downstream of the reaction area 102 and located at the outlet port 106 . upstream of sample port 106 .
- the buffer can be pumped from the injection port to wash off the unreacted antibodies.
- the waste liquid area is used to collect the waste liquid from the cleaning reaction area to avoid affecting the detection results.
- the waste liquid region may be rectangular in shape as shown in FIG. 1 .
- FIG. 5 schematically shows a three-dimensional structural view of the microfluidic chip 10 according to an embodiment of the present disclosure.
- the microfluidic chip 10 may further include: a second substrate 200 disposed opposite to the first substrate 100 , the second substrate 200 is provided with openings (eg, the first opening 201 and the second opening 202 ), so The opening penetrates through the second substrate, and the orthographic projection of the opening on the first substrate at least partially overlaps the orthographic projection of the reaction area on the first substrate (for example, the first opening 201 and the reaction area).
- the first groove 1021 of the reaction zone corresponds to the first groove 1021
- the second opening 202 corresponds to the second groove 1022 of the reaction zone
- the orthographic projection of the first opening 201 on the first substrate is the same as the first groove 1021 of the reaction zone on the first substrate.
- the orthographic projections at least partially overlap, and the orthographic projection of the first opening 202 on the first substrate at least partially overlaps the orthographic projection of the second groove 1022 of the reaction zone on the first substrate); and the cover plate 300 (eg, the first cover plate 301 and the second cover plate 302), the orthographic projection of the opening on the first substrate is located within the orthographic projection of the cover plate on the first substrate (for example, the first cover plate 301 covers the first opening 201, the second cover plate 302 covers the second opening 202, the orthographic projection of the first opening 201 on the first substrate is located within the orthographic projection of the first cover plate 301 on the first substrate, and the second opening 202 is on the first substrate is located within the orthographic projection of the second cover plate 302 on the first substrate).
- the cover plate 300 eg, the first cover plate 301 and the second cover plate 302
- the first substrate and the second substrate can be boxed together, and the second substrate can be covered after pretreatment of the cover plate.
- the opening of the substrate so that the substance of the cover plate is not affected by the first substrate and the second substrate to the cell process.
- FIG. 6 schematically shows a top view of a second substrate and a cover plate according to an embodiment of the present disclosure. Viewed from the direction from the first substrate to the second substrate, the first opening 201 and the second opening 202 are covered by the first cover plate 301 and the second cover plate 302, respectively.
- 7A and 7B schematically illustrate cross-sectional views of the second substrate and the cover plate taken along line AA in FIG. 6 .
- the cover plate may be embedded in the opening.
- the first cover plate may be embedded in the first opening 201
- the second cover plate 302 may be embedded in the second opening 202 .
- the cover plate may be arranged on the surface of the second substrate 200 away from the first substrate. As shown in FIG.
- the first cover plate 301 and the second cover plate 302 are arranged on the surface of the second substrate 200 away from the first substrate. and the orthographic projection of the first cover plate 301 on the first substrate covers the first opening 201 , and the orthographic projection of the second cover plate 302 on the first substrate covers the second opening 202 .
- the orthographic projection of the reaction zone on the first substrate may be located within the orthographic projection of the opening on the first substrate, for example, the orthographic projection of the first groove of the reaction zone on the first substrate is located on the first substrate.
- the orthographic projection of an opening on the first substrate, the orthographic projection of the second groove of the reaction zone on the first substrate is located in the orthographic projection of the second opening on the first substrate, so that the The detection substance can sufficiently contact the substance on the cover plate.
- the orthographic projection of the opening on the first substrate may be located within the orthographic projection of the reaction zone on the first substrate, for example, the orthographic projection of the first opening on the first substrate is in the first groove of the reaction zone In the orthographic projection of the first substrate, the orthographic projection of the second opening on the first substrate is located in the orthographic projection of the second groove of the reaction zone on the first substrate, so that the substances on the cover plate can fully interact with the first substrate.
- the substance to be detected that flows through the reaction zone is contacted.
- Those skilled in the art can reasonably design the shape and size of the reaction zone and the opening according to actual needs.
- the width of the orthographic projection of the reaction zone on the first substrate and the orthographic projection of the opening on the first substrate in the second direction can be equal, and the two edges of the orthographic projection of the reaction zone on the first substrate perpendicular to the second direction and the two edges of the orthographic projection of the opening on the first substrate perpendicular to the second direction are coincident with each other. Further optionally, the orthographic projection of the reaction zone on the first substrate and the orthographic projection of the opening on the first substrate may completely coincide.
- FIG. 8 schematically shows a top view of a second substrate and a cover plate according to an embodiment of the present disclosure.
- the surface of the second substrate facing away from the first substrate is provided with a first recessed portion 203 and a second recessed portion 204, and the first opening 201 is located in the first recessed portion 203 (ie, the first opening 201 is located in the first recessed portion 203).
- the orthographic projection on the substrate is located in the orthographic projection of the first recessed portion 203 on the first substrate), and the second opening 112 is located in the second recessed portion 204 (that is, the orthographic projection of the second opening 202 on the first substrate is located in the first substrate).
- the two concave portions 204 are in the orthographic projection of the first substrate).
- FIG. 9 schematically shows a cross-sectional view of the second substrate and the cover plate taken along line AA in FIG. 8 .
- the first cover plate 301 is embedded in the first concave portion 203
- the second groove is embedded in the second concave portion 204 .
- FIG. 10 schematically shows a perspective structural view of the second substrate 200 .
- the inlay of the cover plate can be more convenient.
- UV-curable adhesive or die-cut double-sided adhesive can be coated on the recessed portion to encapsulate the cover plate and the second substrate.
- the encapsulation of the microfluidic chip is more convenient by designing the concave portion, and at the same time, the leakage of reactants can be effectively prevented.
- the height difference between the surface of the second substrate facing the first substrate and the surface of the cover plate facing the first substrate is reduced by designing the concave portion, thereby avoiding the inconsistency of sample flow in the reaction zone. uniformity. Therefore, by designing the concave portion, the packaging of the microfluidic chip is not only more convenient, but also the reliability and detection stability of the microfluidic chip are improved.
- the surface of the second substrate facing the first substrate and the surface of the cover plate facing the first substrate may be in the same plane.
- the surface of the second substrate facing the first substrate and the surface of the cover plate facing the first substrate may not be in the same plane.
- the first concave parts 203 may be located at the edges of opposite sides of the first opening 201 and the second concave parts 204 may be located at opposite sides of the second opening 202
- the edge is designed as a circular arc, such as a semi-circle, which makes the operation of the cover more convenient.
- the arcs at the four corners of the first concave portion 203 and the second concave portion 204 in FIGS. 8 and 10 are due to the inconvenience of machining dead corners due to machining, and such arc design can facilitate the machining of grooves make.
- the opening of the second substrate is designed to be square, also for the convenience of processing, and those skilled in the art can reasonably design the shape of the opening according to the actual processing technology.
- the surface of the second substrate 200 facing away from the first substrate and the surface of the cover plate (the first cover plate 301 and the second cover plate 302 ) facing away from the first substrate may be in the same plane , so that the bottom surface of the microfluidic chip is flush and easy to lay flat.
- the first substrate and the second substrate may employ polymeric materials such as polymethyl methacrylate (PMMA), polydimethylsiloxane, polycarbonate, polyethylene terephthalate Esters, cycloolefin copolymers, etc.
- PMMA polymethyl methacrylate
- Polydimethylsiloxane polydimethylsiloxane
- polycarbonate polyethylene terephthalate Esters
- cycloolefin copolymers etc.
- Polymer materials are easy to process, and it is easier to prepare the flow channels and various functional areas of microfluidic chips.
- the cover plate may be glass.
- the glass surface is easy to be chemically modified.
- antibodies can be grafted on the glass surface.
- a variety of capture antibodies can be pre-embedded on the glass by the spotter, and multi-index joint inspection can be carried out to improve the detection throughput.
- upstream of a certain region refers to the region through which the liquid has flowed before reaching the region during the operation of the microfluidic chip
- downstream of a certain region refers to the region during the operation of the microfluidic chip , the area to which the liquid will flow after flowing through the area.
- the first substrate and the second substrate can both be made of polymer materials, such as PMMA, and the cover plate can be made of glass.
- the antibody can be grafted on the modified glass and then stored lyophilized, and the cover plate can be attached to the second substrate after thermocompression bonding of the first and second substrates .
- thermocompression bonding can be performed separately, avoiding the effect of thermocompression bonding on antibody grafting and storage.
- the reaction flow of the microfluidic chip for immunofluorescence detection will be described with reference to FIG. 1 and FIG. 5 .
- the sample to be tested enters from the injection port 101, passes through the serpentine first mixing zone 103 and then enters the first groove 1021 of the reaction zone.
- the sample to be tested will be pre-buried on the cover plate 301 corresponding to the first groove 1021.
- the lyophilized fluorescent antibody reacts to redissolve the antibody, and the antigen and antibody are specifically combined.
- the antigen in the sample fully reacts with the fluorescent antibody.
- the capture antibody grafted on the cover plate 302 corresponding to the second groove 1022 reacts to form a double-antibody sandwich.
- the buffer is pumped from the injection port 101 of the chip, and the reaction area is Rinsing is performed to remove the uncaptured fluorescent antibodies, and the waste liquid flows into the waste liquid area 106 .
- the chip is placed under a fluorescence microscope for optical signal detection to determine the antigen content in the sample.
- the immunomicrofluidic chip has the advantages of high throughput, rapidity, simple operation, and high degree of automation.
- FIG. 11 schematically shows a dimensional view of a first substrate according to an embodiment of the present disclosure.
- Fig. 12 schematically shows a dimension drawing of a second substrate corresponding to the first substrate shown in Fig. 11 .
- the length of the first substrate and the second substrate can be 76mm
- the width can be 26mm
- the sample inlet and outlet can be through holes with a diameter of 2mm
- the first mixing area and the second The width of the flow channel in the mixing zone can be 0.8mm
- the gap between adjacent flow channels can be 0.4mm
- each corner of the hexagonal reaction zone can have a chamfered arc with a radius of 0.80mm.
- the width of the groove at the widest point in the second direction may be 8 mm
- the width of the second groove of the reaction zone at the widest position in the second direction may be 6 mm
- the depth of the reaction zone may be 0.2 mm.
- the first opening of the first substrate may be a square with a side length of 8 mm
- the second opening may be a square with a side length of 6 mm
- the distance between the edge of the first recess without the arc and the edge of the first opening may be 1 mm
- the second opening may be a square with a side length of 6 mm.
- the distance between the edge of the recessed part without the arc and the edge of the second opening may be 2 mm, and the depth of the first recessed part and the second recessed part may be 1 mm.
- the orthographic projection of the two opposite edges of the first groove of the reaction zone in the second direction on the first substrate along the first direction and the first opening in the second direction coincide, and the two opposite edges of the second groove of the reaction zone in the second direction are along the first substrate.
- the orthographic projection in the first direction coincides with the orthographic projection of two opposite edges of the second opening in the second direction on the first substrate along the first direction.
- the two edges of the reaction zone in the second direction and the two edges of the opening in the second direction are coincident with each other, so as to ensure that the substance to be tested and the substance on the cover plate are not identical under the condition that the shapes of the reaction zone and the opening are inconsistent Full contact, but also to ensure the uniformity of the flow of the substance to be tested.
- FIG. 13 schematically shows a dimension drawing of the first substrate of the embodiment shown in FIG. 4 .
- FIG. 14 schematically shows a dimension drawing of a second substrate corresponding to the first substrate shown in FIG. 13 .
- both the first opening and the second opening may be squares with a side length of 6 mm, and the edges of the first recess and the second recess without arcs are separated from the edges of the first opening and the second opening.
- the distance can be 2mm.
- the inner diameter of the semi-circle may be 2.2mm and the outer diameter may be 3mm.
- the depth D 1 of the reaction zone can be 0.3mm, and the depth D 2 of the semi-circle can be 0.2mm.
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Abstract
一种微流控芯片,包括第一基板(100),第一基板(100)包括:进样口(101);以及反应区(102),反应区(102)位于进样口(101)的下游,反应区(102)包括至少一个凹槽(1021,1022),每个凹槽(1021,1022)在第一基板(100)上的正投影为轴对称图形,轴对称图形在第一方向(D1)上的宽度不小于轴对称图形在第二方向(D2)上的宽度,第一方向(D1)垂直于第二方向(D2)。
Description
本公开涉及生物检测领域,具体涉及一种微流控芯片。
微流控技术(Microfluidics)是一种精确控制和操控微尺度流体的技术,通过该技术,可以把检测分析过程中涉及的样品制备、反应、分离、检测等基本操作单元集成到一块厘米级芯片上。微流控技术一般应用于生物、化学、医药等领域的微量药品的分析过程。微流控装置具有诸如样品消耗少、检测速度快、操作简便、多功能集成、体积小和便于携带等优点,在生物、化学、医药等领域有着巨大的应用潜力。
公开内容
根据本公开的一方面,提供了一种微流控芯片。该微流控芯片包括第一基板,所述第一基板包括:进样口;以及反应区,所述反应区位于所述进样口的下游,所述反应区包括至少一个凹槽,每个凹槽在所述第一基板上的正投影为轴对称图形,所述轴对称图形在第一方向上的宽度不小于所述轴对称图形在第二方向上的宽度,所述第一方向垂直于所述第二方向。
在一些实施例中,所述反应区包括至少两个凹槽,所述至少两个凹槽在所述第一基板上的正投影形状不相同。
在一些实施例中,所述反应区包括至少两个凹槽,所述至少两个凹槽在所述第一基板上的正投影形状相同。
在一些实施例中,所述反应区在所述第一基板上的正投影包括第一轴对称图形和第二轴对称图形,所述第一轴对称图形在第一方向上的宽度小于所述第二轴对称图形在第一方向上的宽度。
在一些实施例中,所述第一轴对称图形在第二方向上的宽度大于所述第二轴对称图形在第二方向上的宽度。
在一些实施例中,所述轴对称图形包括多边形和圆形。
在一些实施例中,所述轴对称图形的靠近进样口的端部包括半圆 环形状。
在一些实施例中,所述第一基板还包括位于所述进样口下游的混匀区,所述混匀区包括蛇形流道。
在一些实施例中,所述反应区包括第一凹槽和第二凹槽,所述混匀区包括位于第一凹槽上游的第一混匀区和位于第二凹槽上游的第二混匀区。
在一些实施例中,所述第二混匀区的流道长度大于所述第一混匀区的流道长度。
在一些实施例中,所述第一基板还包括废液区和出样口,所述废液区位于所述反应区的下游并且位于所述出样口的上游。
在一些实施例中,所述废液区在第一基板上的正投影为矩形。
在一些实施例中所述微流控芯片还包括:第二基板,所述第二基板与所述第一基板相对设置,所述第二基板设置有开口,所述开口贯穿所述第二基板,所述开口在所述第一基板上的正投影与所述反应区在所述第一基板上的正投影至少部分重叠;以及盖板,所述开口在所述第一基板上的正投影位于所述盖板在所述第一基板上的正投影内。
在一些实施例中,所述反应区在所述第一基板上的正投影位于所述开口在所述第一基板上的正投影内。
在一些实施例中,所述开口在所述第一基板上的正投影位于所述反应区在所述第一基板上的正投影内。
在一些实施例中,所述反应区在第二方向相对的两个边缘在所述第一基板上的沿第一方向上的正投影与所述开口在第二方向上的相对的两个边缘在所述第一基板上的沿第一方向上的正投影重合。。
在一些实施例中,所述第二基板背离所述第一基板的表面设置有凹陷部,所述开口在所述第一基板上的正投影位于所述凹陷部在所述第一基板上的正投影内,并且所述盖板位于所述凹陷部内。
在一些实施例中,所述开口在所述第一基板上的正投影包括正方形。
在一些实施例中,所述盖板的材料包括经化学修饰的材料。
在一些实施例中,所述第二基板面向所述第一基板的表面与所述盖板面向所述第一基板的表面在同一平面内。
在一些实施例中,所述第二基板面向所述第一基板的表面与所述 盖板面向所述第一基板的表面不在同一平面内。
在一些实施例中,所述第二基板的凹陷部包括位于所述开口的相对的两侧的圆弧形边缘。
为了更清楚地说明本公开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,下面描述中的附图仅仅是本公开的一些实施例,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。
图1示意性地示出了根据本公开实施例的第一基板的俯视图;
图2示意性地示出了根据本公开实施例的第一基板的立体结构图;
图3示意性地示出了根据本公开实施例的微流控芯片的进样仿真结果图;
图4示意性地示出了根据本公开实施例的第一基板的立体结构图;
图5示意性地示出了根据本公开实施例的微流控芯片的立体结构图;
图6示意性地示出了根据本公开实施例的第二基板和盖板的俯视图;
图7A示意性地示出了沿图6中的AA线截取的第二基板和盖板的一种截面图;
图7B示意性地示出了沿图6中的AA线截取的第二基板和盖板的另一种一种截面图;
图8示意性地示出了根据本公开实施例的第二基板和盖板的俯视图;
图9示意性地示出了沿图8中的AA线截取的第二基板和盖板的截面图;
图10示意性地示出了根据本公开实施例的第二基板的立体结构图;
图11示意性地示出了根据本公开实施例的第一基板的尺寸图;
图12示意性地示出了根据本公开实施例的第二基板的尺寸图;
图13示意性地示出了根据本公开实施例的第一基板的尺寸图;以及
图14示意性地示出了根据本公开实施例的第二基板的尺寸图。
附图中各部分的形状和大小不反映各部分的真实比例,只是示意性地说明本公开内容。
下面将结合本公开实施例中的附图,对本公开实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本公开一部分实施例,而不是全部的实施例。基于本公开中的实施例,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,都属于本公开保护的范围。
发明人发现,现有的免疫分析微流控芯片通常采用聚合物或玻璃基板,聚合物基板相较于玻璃基板更容易制备免疫反应所需要的流道和反应区域,但聚合物的缺点是表面化学修饰很难完成。如果两个基板均采用聚合物基板,需要将抗体先冻干存储再将两个基板热压键合,热压过程会对抗体产生影响。如果两个基板分别采用聚合物基板和玻璃基板,将存在难以键合的问题。同时,在常规微流控芯片的使用过程中,液体流经反应区时,容易产生气泡,造成反应不均匀或不充分,影响微流控芯片的检测效果。
本公开提供了一种微流控芯片,包括第一基板。图1示意性地示出了根据本公开实施例的第一基板100的俯视图。如图1所示,第一基板100可以包括:进样口101,以及位于进样口101下游的反应区102。反应区102包括至少一个凹槽,每个凹槽在所述第一基板上的正投影为轴对称图形,所述轴对称图形在第一方向D1上的宽度不小于所述轴对称图形在第二方向D2上的宽度,所述第一方向D1垂直于所述第二方向D2。需要说明的是,本公开中第一方向是指微流控芯片使用过程中液体经过反应区时流动的方向,所述第二方向是指垂直于反应区中液体流动方向的方向。在一些实施例中,如图1所示,反应区包括第一凹槽1021和第二凹槽1022,所述第一凹槽1021在第一基板上的正投影为第一轴对称图形,所述第一轴对称图形具有第一对称轴(图1中沿第一方向D1),所述第二凹槽1022在第一基板上的正投影为第二轴对称图形,所述第二轴对称图形具有第二对称轴(图1中也沿第一方向D1)。需要说明的是,第一对称轴与第二对称轴沿相同方向仅 是示例性的,在一些实施例中,第一对称轴和第二对称轴之间可以具有夹角。更具体地,对于反应区包括更多个凹槽的实施例,各个轴对称图形的对称轴彼此之间的夹角可以相同,也可以不同。
通过设计细长形状的反应区,能够使液体具有较小的前进面,有利于减少气泡,便于样品更均匀地经过反应区,提高检测效果。
在一些实施例中,反应区可以包括至少两个凹槽,所述至少两个凹槽在所述第一基板上的正投影形状可以不相同。例如,如图1中示意性示出的第一凹槽1021和第二凹槽1022,第一凹槽1021的形状与第二凹槽1022的形状可以不同。第一凹槽1021在第一基板上的正投影为第一轴对称图形,第二凹槽1022在第一基板上的正投影为第二轴对称图形。在一些实施例中,所述第一轴对称图形在第一方向D1上的宽度小于所述第二轴对称图形在第一方向D1上的宽度。在一些实施例中,所述第一轴对称图形在第二方向D2上的宽度大于所述第二轴对称图形在第二方向D2上的宽度。
在一些实施例中,反应区可以包括至少两个凹槽,所述至少两个凹槽在所述第一基板上的正投影形状可以相同。
在一些实施例中,轴对称图形可以包括多边形、圆形、纺锤形等,本领技术人员可以根据实际需要合理地设计反应区的形状和大小,本公开对此不作具体限定。
图1中示例性地示出了六边形形状的反应区,这样的反应区能够有效减少液体流动过程中产生的气泡,使反应物流动更加均匀。图2示意性地示出了根据本公开实施例的第一基板的立体结构图。图3示出了根据本公开实施例的微流控芯片的进样仿真结果图,图中箭头所指示的方向为液体流动方向,从仿真结果可以看出,液体前进过程中没有气泡产生,流动均匀。
在一些实施例中,反应区靠近进样口的端部可以包括半圆环形状,如图4所示,反应的第一凹槽1021的端部1023可以为半圆环形状,反应的第一凹槽1022的端部1024可以为半圆环形状。这种设计能够进一步减少反应区的气泡,使液体前进面接近平齐,使液体流动更加均匀,进一步提高微流控芯片的检测精度。
返回参考图1,所述第一基板100还可以包括位于所述进样口101下游的混匀区,例如位于第一凹槽1021上游的第一混匀区103和位于 第二凹槽1022上游的第二混匀区104,如图1所示,混匀区可以包括蛇形流道。蛇形流道可以使流道的设计更加紧凑,在有限的芯片面积上提供更长的流道,使得反应物更加充分地混合均匀。
在一些实施例中,如图1所示,第二混匀区104的流道长度大于所述第一混匀区103的流道长度,这可以使在反应区102的第一凹槽1021中的样品反应更加充分之后再进入反应区102的第二凹槽1022进行后续反应。
在一些实施例中,如图1所示,所述第一基板100还可以包括废液区105和出样口106,所述废液区105位于所述反应区102的下游并且位于所述出样口106的上游。微流控芯片中的反应完成后,可以从进样口泵入缓冲液,清洗掉没有反应的抗体,废液区用于收集清洗反应区的废液,避免对检测结果的影响。示例性地,废液区可以为如图1所示的矩形形状。
图5示意性地示出了根据本公开实施例的微流控芯片10的立体结构图。如图5所示,微流控芯片10还可以包括:与第一基板100相对设置的第二基板200,第二基板200设置有开口(例如,第一开口201和第二开口202),所述开口贯穿所述第二基板,所述开口在所述第一基板上的正投影与所述反应区在所述第一基板上的正投影至少部分重叠(例如,第一开口201与反应区的第一凹槽1021对应,第二开口202与反应区的第二凹槽1022对应,第一开口201在第一基板上的正投影与反应区的第一凹槽1021在第一基板上的正投影至少部分重叠,第一开口202在第一基板上的正投影与反应区的第二凹槽1022在第一基板上的正投影至少部分重叠);以及盖板300(例如第一盖板301和第二盖板302),所述开口在所述第一基板上的正投影位于所述盖板在所述第一基板上的正投影内(例如,第一盖板301覆盖第一开口201,第二盖板302覆盖第二开口202,第一开口201在第一基板上的正投影位于第一盖板301在第一基板上的正投影内,第二开口202在第一基板上的正投影位于第二盖板302在第一基板上的正投影内)。
通过对第二基板进行镂空设计,即在第二基板上设置开口以及提供覆盖开口的盖板,可以先将第一基板与第二基板对盒,在对盖板进行预处理之后再覆盖第二基板的开口,从而使得盖板的物质不受第一基板与第二基板对盒工艺的影响。
需要理解的是,本公开的实施例以微流控芯片反应区包括两个凹槽为例进行说明,本领域技术人员可以根据实际需要设计反应区的凹槽数量和第二基板的开口数量,本公开对此不作限定。
图6示意性地示出了根据本公开实施例的第二基板和盖板的俯视图。从第一基板指向第二基板的方向观看,第一开口201和第二开口202分别被第一盖板301和第二盖板302覆盖。图7A和图7B示意性地示出了沿图6中的AA线截取的第二基板和盖板的截面图。在一些实施例中,盖板可以镶嵌在开口中,如图7A所示,第一盖板可以镶嵌在第一开口201中,第二盖板302可以镶嵌在第二开口202中。在一些实施例中,盖板可以布置在第二基板200背离第一基板的表面,如图7B所示,第一盖板301和第二盖板302布置在第二基板200远离第一基板表面上,并且第一盖板301在第一基板的正投影覆盖第一开口201,第二盖板302在第一基板的的正投影覆盖第二开口202。
在一些实施例中,反应区在第一基板上的正投影可以位于开口在所述第一基板上的正投影内,例如,反应区的第一凹槽在第一基板上的正投影位于第一开口在第一基板上的正投影内,反应区的第二凹槽在第一基板上的正投影位于第二开口在第一基板上的正投影内,这样可以使流经反应区的待检测物质能够充分与盖板上的物质充分接触。在一些实施例中,开口在第一基板上的正投影可以位于反应区在第一基板上的正投影内,例如,第一开口在第一基板上的正投影位于反应区的第一凹槽在第一基板上的正投影内,第二开口在第一基板上的正投影位于反应区的第二凹槽在第一基板上的正投影内,这样可以使盖板上的物质能够充分与流经反应区的待检测物质接触。本领域技术人员可以根据实际需要合理设计反应区与开口的形状和大小,可选地,反应区在第一基板上的正投影与开口在第一基板上的正投影在第二方向上的宽度可以相等,并且反应区在第一基板上的正投影在垂直于第二方向上的两个边缘与开口在第一基板上的正投影在垂直于第二方向上的两个边缘都互相重合。进一步可选地,反应区在第一基板上的正投影与开口在第一基板上的正投影可以完全重合。
图8示意性地示出了根据本公开实施例的第二基板和盖板的俯视图。在该实施例中,第二基板背离第一基板的表面设置有第一凹陷部203和第二凹陷部204,第一开口201位于第一凹陷部203中(即,第 一开口201在第一基板上的正投影位于第一凹陷部203在第一基板上的正投影内),第二开口112位于第二凹陷部204中(即,第二开口202在第一基板上的正投影位于第二凹陷部204在第一基板上的正投影内)。图9示意性地示出了沿图8中的AA线截取的第二基板和盖板的截面图。如图9所示,第一盖板301镶嵌在第一凹陷部203中,第二凹槽镶嵌在第二凹陷部204中。图10示意性地示出了第二基板200的立体结构图。
通过在第二基板上设置凹陷部,可以使盖板的镶嵌更加方便。例如,可以在凹陷部上涂覆紫外固化胶或模切双面胶,将盖板与第二基板封装。相比于图7A所示的实施例,通过设计凹陷部使得微流控芯片的封装更加方便,同时能够有效地防止反应物渗出。相比于图7B所示的实施例,通过设计凹陷部使得第二基板面向第一基板的表面与盖板面向第一基板的表面之间的高度差减小,避免了反应区样品流动的不均匀性。因此,通过设计凹陷部,不仅使微流控芯片的封装更加便捷,同时提高了微流控芯片的可靠性和检测稳定度。
在一些实施例中,如图7A所示,第二基板面向第一基板的表面与盖板面向所述第一基板的表面可以在在同一平面内。
在一些实施例中如图7B和图9所示,第二基板面向第一基板的表面与盖板面向第一基板的表面可以不在同一平面内。
在一些实施例中,如图8和图10所示,可以将第一凹陷部203位于第一开口201的相对的两侧的边缘以及第二凹陷部204位于第二开口202的相对的两侧的边缘设计为圆弧形,例如半圆环,这种设计使得对盖板的操作更加方便。
需要注意的是,图8和图10中第一凹陷部203和第二凹陷部204的四个角处的圆弧是由于机械加工不便于加工死角,这样的圆弧设计能够便于凹槽的加工制作。同样,将第二基板的开口设计为正方形,也是为了便于加工制作,本领域技术人员可以根据实际采用的加工工艺合理设计开口的形状。
在一些实施例中,如图9所示,第二基板200背离第一基板的表面与盖板(第一盖板301和第二盖板302)背离第一基板的表面可以在在同一平面内,这样微流控芯片的底面平齐,便于平放。
在一些实施例中,第一基板和第二基板可以采用聚合物材料,例 如聚甲基丙烯酸甲酯(PMMA)、聚二甲基硅氧烷、聚碳酸酯、聚对苯二甲酸乙二醇酯、环烯烃类共聚物等。聚合物材料便于加工,更容易制备微流控芯片的流道以及各个功能区域。
在一些实施例中,盖板可以采用玻璃。玻璃表面易于进行化学修饰,在免疫分析应用中,对玻璃表面进行化学修饰后,可以在玻璃表面接枝抗体。通过点样仪在玻璃上可以预埋多种捕获抗体,进行多指标联检,提高检测通量。
需要理解的是本公开实施例中反应区的形状和比例是示例性地,本领域技术人员可以根据实际芯片的尺寸和所针对的应用需求合理设计反应区的长宽比例。
在本公开中,“某区域的上游”是指在微流控芯片操作过程中,液体在到达该区域之前已经流过的区域,“某区域的下游”是指在微流控芯片操作过程中,液体流经该区域后将要流向的区域。
以用于免疫荧光检测的微流控芯片为例,第一基板和第二基板可以均采用聚合物材料,例如PMMA,盖板可以采用玻璃。在这种情况下,可以在修饰后的玻璃上接枝抗体,然后冻干存储,可以在将第一基板和第二基板热压键合后,再将盖板附接到到第二基板上。通过这种方式,抗体冻干和基板的热压键合可以分开进行,避免了热压键合对抗体接枝和存储的影响。
参考图1和图5说明免疫荧光检测的微流控芯片的反应流程。待检测样本从进样口101进入,经过蛇形的第一混匀区103后进入反应区的第一凹槽1021,待检测样本会与第一凹槽1021对应的盖板301上预埋的冻干荧光抗体反应,使抗体复溶,抗原与抗体特异性结合,经过蛇形的第二混匀区104后,样本中的抗原与荧光抗体充分反应,当此抗原抗体对到达反应区的第二凹槽1022时,与第二凹槽1022对应的盖板302上接枝的捕获抗体反应,形成双抗夹心,反应完成后从芯片的进样口101泵入缓冲液,对反应后的区域进行冲洗,清洗掉没有被捕获的荧光抗体,废液流入废液区106。将芯片放置于荧光显微镜下进行光学信号检测,以此来判断样本中抗原的含量。此免疫微流控芯片具有通量高、快速、操作简便、自动化程度高等优点。
图11示意性地示出了根据本公开实施例的第一基板的尺寸图。图12示意性地示出了与图11所示的第一基板相对应的第二基板的尺寸 图。如图11和图12所示,第一基板和第二基板的长度可以为76mm,宽度可以为26mm,进样口和出样口可以为直径2mm的通孔,第一混匀区和第二混匀区的流道宽度可以为0.8mm,相邻流道之间的间隙可以为0.4mm,六边形反应区的各个拐角可以具有半径为0.80mm的倒角圆弧,反应区的第一凹槽在第二方向上最宽处的宽度可以为8mm,反应区的第二凹槽在第二方向上最宽处的宽度可以为6mm,反应区的深度可以为0.2mm。第一基板的第一开口可以为边长8mm的正方形,第二开口可以为边长6mm的正方形,第一凹陷部的没有圆弧的边缘距第一开口的边缘的距离可以为1mm,第二凹陷部的没有圆弧的边缘距第二开口的边缘的距离可以为2mm,第一凹陷部和第二凹陷部的深度可以为1mm。当图11所示的第一基板与图2所示的第二基板对盒时,可以将反应区的第一凹槽在第二方向上的两个边缘(1021′,1021″)与第一开口在第二方向上的两个边缘(201′,201″)对准,同时将反应区的第二凹槽在第二方向上的两个边缘(1022′,1022″)与第二开口在第二方向上的两个边缘(202′,202″)对准。这样对盒后,所述反应区的第一凹槽在第二方向相对的两个边缘在所述第一基板上的沿第一方向上的正投影与所述第一开口在第二方向上的相对的两个边缘在所述第一基板上的沿第一方向上的正投影重合,并且反应区的第二凹槽在第二方向相对的两个边缘在所述第一基板上的沿第一方向上的正投影与所述第二开口在第二方向上的相对的两个边缘在所述第一基板上的沿第一方向上的正投影重合。使反应区在第二方向上的两个边缘与开口在第二方向上的两个边缘都互相重合,能够在反应区与开口形状不一致的情况下,既保证待测试物质与盖板上的物质充分接触,又保证待测试物质流动的均匀性。
图13示意性地示出了图4所示实施例的第一基板的尺寸图。图14示意性地示出了与图13所示的第一基板相对应的第二基板的尺寸图。如图13和图14所示,第一开口和第二开口都可以为边长6mm的正方形,第一凹陷部和第二凹陷部的没有圆弧的边缘距第一开口和第二开口的边缘的距离都可以为2mm。半圆环的内径可以为2.2mm,外径可以为3mm。反应区的深度D
1可以为0.3mm,而半圆环的深度D
2可以为0.2mm,通过这种设计,可以更进一步减少反应区的气泡,使液体前进面接近平齐,使液体流动更加均匀,更进一步提高微流控芯片的 检测精度。
在本公开的描述中,术语“上”、“下”、“左”、“右”等指示的方位或位置关系为基于附图所示的方位或位置关系,仅是为了便于描述本公开而不是要求本公开必须以特定的方位构造和操作,因此不能理解为对本公开的限制。
在本说明书的描述中,参考术语“一个实施例”、“另一个实施例”等的描述意指结合该实施例描述的具体特征、结构、材料或者特点包含于本公开的至少一个实施例中。在本说明书中,对上述术语的示意性表述不必须针对的是相同的实施例或示例。而且,描述的具体特征、结构、材料或者特点可以在任一个或多个实施例或示例中以合适的方式结合。此外,在不相互矛盾的情况下,本领域的技术人员可以将本说明书中描述的不同实施例或示例以及不同实施例或示例的特征进行结合和组合。另外,需要说明的是,本说明书中,术语“第一”、“第二”等仅用于描述目的,而不能理解为指示或暗示相对重要性或者隐含指明所指示的技术特征的数量。
如本领域技术人员将理解的,尽管在附图中以特定顺序描述了本公开中方法的各个步骤,但是这并非要求或者暗示必须按照该特定顺序来执行这些步骤,除非上下文另有明确说明。附加的或可替换的,可以将多个步骤合并为一个步骤执行,以及/或者将一个步骤分解为多个步骤执行。此外,在步骤之间可以插入其他方法步骤。插入的步骤可以表示诸如本文所描述的方法的改进,或者可以与该方法无关。此外,在下一步骤开始之前,给定步骤可能尚未完全完成。
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,任何熟悉本技术领域的技术人员在本公开揭露的技术范围内,可轻易想到变化或替换,都应涵盖在本公开的保护范围之内。因此,本公开的保护范围应以所述权利要求的保护范围为准。通过研究附图、公开内容和所附权利要求,本领域技术人员在实践所要求保护的发明时,可以理解和达成对所公开实施例的其它变型。权利要求中,词语“包括”不排除其它元素或步骤,单数形式的“一”“一个”“该”等术语不排除复数。在互不相同的从属权利要求中列举某些措施的纯粹事实并不表示这些措施的组合不能用于获利。权利要求中的任何附图标记不应解释为限制范围。
Claims (22)
- 一种微流控芯片,包括第一基板,所述第一基板包括:进样口;以及反应区,所述反应区位于所述进样口的下游,所述反应区包括至少一个凹槽,每个凹槽在所述第一基板上的正投影为轴对称图形,所述轴对称图形在第一方向上的宽度不小于所述轴对称图形在第二方向上的宽度,所述第一方向垂直于所述第二方向。
- 根据权利要求1所述的微流控芯片,其中,所述反应区包括至少两个凹槽,所述至少两个凹槽在所述第一基板上的正投影形状不相同。
- 根据权利要求1所述的微流控芯片,其中,所述反应区包括至少两个凹槽,所述至少两个凹槽在所述第一基板上的正投影形状相同。
- 根据权利要求1或2所述的微流控芯片,其中,所述反应区在所述第一基板上的正投影包括第一轴对称图形和第二轴对称图形,所述第一轴对称图形在第一方向上的宽度小于所述第二轴对称图形在第一方向上的宽度。
- 根据权利要求4所述的微流控芯片,其中,所述第一轴对称图形在第二方向上的宽度大于所述第二轴对称图形在第二方向上的宽度。
- 根据前述权利要求中的任一项所述的微流控芯片,其中,所述轴对称图形包括多边形和圆形。
- 根据权利要求1-5中任一项所述的微流控芯片,其中,所述轴对称图形的靠近进样口的端部包括半圆环形状。
- 根据前述权利要求中的任一项所述的微流控芯片,其中,所述第一基板还包括位于所述进样口下游的混匀区,所述混匀区包括蛇形流道。
- 根据权利要求8所述的微流控芯片,其中,所述反应区包括第一凹槽和第二凹槽,所述混匀区包括位于第一凹槽上游的第一混匀区和位于第二凹槽上游的第二混匀区。
- 根据权利要求9所述的微流控芯片,其中,所述第二混匀区的流道长度大于所述第一混匀区的流道长度。
- 根据前述权利要求中的任一项所述的微流控芯片,其中,所述第一基板还包括废液区和出样口,所述废液区位于所述反应区的下游并且位于所述出样口的上游。
- 根据权利要求9所述的微流控芯片,其中,所述废液区在第一基板上的正投影为矩形。
- 根据前述权利要求中任一项所述的微流控芯片,还包括:第二基板,所述第二基板与所述第一基板相对设置,所述第二基板设置有开口,所述开口贯穿所述第二基板,所述开口在所述第一基板上的正投影与所述反应区在所述第一基板上的正投影至少部分重叠;以及盖板,所述开口在所述第一基板上的正投影位于所述盖板在所述第一基板上的正投影内。
- 根据权利要求13所述的微流控芯片,其中,所述反应区在所述第一基板上的正投影位于所述开口在所述第一基板上的正投影内。
- 根据权利要求13所述的微流控芯片,其中,所述开口在所述第一基板上的正投影位于所述反应区在所述第一基板上的正投影内。
- 根据权利要求13-15中任一项所述的微流控芯片,其中,所述反应区在第二方向相对的两个边缘在所述第一基板上的沿第一方向上的正投影与所述开口在第二方向上的相对的两个边缘在所述第一基板上的沿第一方向上的正投影重合。
- 根据权利要求13-16中任一项所述的微流控芯片,其中,所述第二基板背离所述第一基板的表面设置有凹陷部,所述开口在所述第一基板上的正投影位于所述凹陷部在所述第一基板上的正投影内,并且所述盖板位于所述凹陷部内。
- 根据权利要求13-17中任一项所述的微流控芯片,其中,所述开口在所述第一基板上的正投影包括正方形。
- 根据权利要求13-18中任一项所述的微流控芯片,其中,所述盖板的材料包括经化学修饰的材料。
- 根据权利要求13-19中任一项所述的微流控芯片,其中,所述第二基板面向所述第一基板的表面与所述盖板面向所述第一基板的表面在同一平面内。
- 根据权利要求13-19中任一项所述的微流控芯片,其中,所述 第二基板面向所述第一基板的表面与所述盖板面向所述第一基板的表面不在同一平面内。
- 根据权利要求17-21中任一项所述的微流控芯片,其中,所述第二基板的凹陷部包括位于所述开口的相对的两侧的圆弧形边缘。
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Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20150202626A1 (en) * | 2011-11-08 | 2015-07-23 | Jung-Tang Huang | Biochip Device |
CN205157567U (zh) * | 2015-08-12 | 2016-04-13 | 中国科学院电子学研究所 | 基于磁微粒子的具有通道的光学微流控芯片 |
CN108398559A (zh) * | 2018-02-26 | 2018-08-14 | 北京华科泰生物技术有限公司 | 一种用于诊断冠心病的联合检测微流控芯片及其制备方法和用途 |
CN108786940A (zh) * | 2018-05-11 | 2018-11-13 | 南京岚煜生物科技有限公司 | 基于磁珠的化学发光微流控芯片 |
CN108956558A (zh) * | 2018-05-24 | 2018-12-07 | 深圳市帝迈生物技术有限公司 | 一种微流控芯片和免疫荧光分析仪 |
CN109870567A (zh) * | 2019-02-20 | 2019-06-11 | 广州睿辰生物科技有限公司 | 基于免疫法分选ApoE蛋白的微流控芯片及其分选方法 |
CN110343604A (zh) * | 2019-07-15 | 2019-10-18 | 浙江大学 | 一种微流控农残检测芯片及应用 |
CN110632168A (zh) * | 2019-09-17 | 2019-12-31 | 西安交通大学 | 一种基于磁阻生物传感器的微流控磁敏免疫装置及其使用方法 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
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FR3071925B1 (fr) * | 2017-09-29 | 2020-06-12 | Commissariat A L'energie Atomique Et Aux Energies Alternatives | Dispositif micro-fluidique employe dans l'analyse d'un echantillon liquide par voie optique |
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Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20150202626A1 (en) * | 2011-11-08 | 2015-07-23 | Jung-Tang Huang | Biochip Device |
CN205157567U (zh) * | 2015-08-12 | 2016-04-13 | 中国科学院电子学研究所 | 基于磁微粒子的具有通道的光学微流控芯片 |
CN108398559A (zh) * | 2018-02-26 | 2018-08-14 | 北京华科泰生物技术有限公司 | 一种用于诊断冠心病的联合检测微流控芯片及其制备方法和用途 |
CN108786940A (zh) * | 2018-05-11 | 2018-11-13 | 南京岚煜生物科技有限公司 | 基于磁珠的化学发光微流控芯片 |
CN108956558A (zh) * | 2018-05-24 | 2018-12-07 | 深圳市帝迈生物技术有限公司 | 一种微流控芯片和免疫荧光分析仪 |
CN109870567A (zh) * | 2019-02-20 | 2019-06-11 | 广州睿辰生物科技有限公司 | 基于免疫法分选ApoE蛋白的微流控芯片及其分选方法 |
CN110343604A (zh) * | 2019-07-15 | 2019-10-18 | 浙江大学 | 一种微流控农残检测芯片及应用 |
CN110632168A (zh) * | 2019-09-17 | 2019-12-31 | 西安交通大学 | 一种基于磁阻生物传感器的微流控磁敏免疫装置及其使用方法 |
Non-Patent Citations (1)
Title |
---|
See also references of EP4140584A4 * |
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CN115427148A (zh) | 2022-12-02 |
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