WO2020199125A1 - 生物信息检测基板和基因芯片 - Google Patents

生物信息检测基板和基因芯片 Download PDF

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Publication number
WO2020199125A1
WO2020199125A1 PCT/CN2019/081026 CN2019081026W WO2020199125A1 WO 2020199125 A1 WO2020199125 A1 WO 2020199125A1 CN 2019081026 W CN2019081026 W CN 2019081026W WO 2020199125 A1 WO2020199125 A1 WO 2020199125A1
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WIPO (PCT)
Prior art keywords
substrate
groove
sub
area
test area
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PCT/CN2019/081026
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English (en)
French (fr)
Inventor
吴申康
黄东升
董廷泽
尚建兴
李亦哲
耿越
李建
陈国伟
徐洪亮
王阔海
代昶
魏娜
李心
信霄
孙超
Original Assignee
京东方科技集团股份有限公司
北京京东方光电科技有限公司
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Application filed by 京东方科技集团股份有限公司, 北京京东方光电科技有限公司 filed Critical 京东方科技集团股份有限公司
Priority to CN201980000453.5A priority Critical patent/CN112105459B/zh
Priority to EP19861238.4A priority patent/EP3950131A4/en
Priority to PCT/CN2019/081026 priority patent/WO2020199125A1/zh
Priority to US16/643,457 priority patent/US11583856B2/en
Publication of WO2020199125A1 publication Critical patent/WO2020199125A1/zh

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—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 or forces applied to move the fluids
    • 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
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • 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
    • 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
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • 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
    • B01L2300/0803—Disc shape
    • 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
    • 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
    • B01L2300/0819—Microarrays; Biochips
    • 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
    • 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
    • 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

Definitions

  • At least one embodiment of the present disclosure relates to a biological information detection substrate and a gene chip.
  • a typical microfluidic chip generally refers to the integration of biological and chemical reactions, analysis, and detection processes into a chip with a micron-sized detection unit.
  • chip packaging is a very important part.
  • the current packaging methods still cannot meet the requirements in terms of flatness and sealing of the chip, which severely restricts the performance of the chip.
  • At least one embodiment of the present disclosure provides a substrate for biological information detection.
  • the substrate includes a first main surface, the first main surface includes a test area and a dummy area around the test area, at least one accommodating area is provided on the first main surface, and the accommodating area is located at the Description of the dummy area.
  • the accommodating area is provided as a first groove, and the first groove surrounds the test area.
  • the first groove includes at least one first sub-groove
  • the planar shape of the first sub-groove on the surface of the second substrate is a closed ring .
  • the centroid of the closed loop coincides with the centroid of the test area.
  • the distances from the opposite sides of the first sub-groove to the centroid of the test area are equal.
  • the first groove includes at least one second sub-groove
  • the planar shape of the second sub-groove on the surface of the second substrate is a line segment.
  • the second sub-groove is provided in multiples, and the centroid of the pattern formed by all the second sub-grooves coincides with the centroid of the test area .
  • the substrate provided by at least one embodiment of the present disclosure, there are two second sub-recesses, and the two second sub-recesses are symmetrical with respect to the centroid center of the test area; or There are no less than three second sub-grooves, and the second sub-grooves are equally spaced in a ring centered on the centroid of the test area.
  • At least one first via hole is provided in a region of the substrate where the first groove is provided, and the first via hole makes the first groove The surface opposite to the first main surface communicates.
  • the pattern formed by the first groove is symmetrical with respect to the centroid of the test area.
  • a plurality of the first grooves are arranged at intervals, and the edges of the test area are The first grooves and the edges of the substrate are distributed at equal intervals; or one of the first grooves is provided between the edge of the test area and the edge of the substrate, and the edges of the test area, the The first groove and the edge of the substrate are distributed at equal intervals.
  • the substrate provided by at least one embodiment of the present disclosure further includes at least one second groove.
  • the second groove is located in the test area and on the first main surface of the substrate.
  • the substrate includes second via holes located at both ends of the second groove, and the second via holes allow the second groove to communicate with a surface opposite to the first main surface.
  • the widths of the first groove and the second groove are equal.
  • At least one embodiment of the present disclosure provides a gene chip, which includes a first substrate, a second substrate and an encapsulating glue layer.
  • the first substrate is the substrate of any one of the foregoing embodiments
  • the second substrate is disposed opposite to the first substrate
  • the encapsulant layer is located between the first substrate and the second substrate, and at least Part of it is located in the dummy area, and the packaging glue layer surrounds the accommodating area.
  • the first substrate includes at least one second groove located in the test area and on the first main surface of the first substrate, and the At least two second via holes are provided at the position of the first substrate where the second groove is provided, and the second via holes penetrate the first substrate.
  • the second substrate further includes a modified layer, and the modified layer is located on a surface of the second substrate facing the first substrate.
  • the accommodating area and the second groove in a direction parallel to the first main surface, have the same width.
  • the second substrate includes at least one second groove located in the test area and on the surface of the second substrate facing the first substrate , And the second substrate includes second via holes located at both ends of the second groove, and the second via holes penetrate the second substrate.
  • the first substrate further includes a modified layer, and the modified layer is located on the first main surface of the first substrate.
  • the accommodating area and the second groove in a direction parallel to the first main surface, have the same width.
  • the packaging glue layer includes UV glue.
  • At least one embodiment of the present disclosure provides a method for preparing a substrate according to any one of the above embodiments, the method comprising: patterning the first main surface of the substrate to form at least one of the accommodating elements in the dummy area Area.
  • the preparation method provided by at least one embodiment of the present disclosure further includes: forming at least one second groove in the test area of the substrate; and forming a second pass through the substrate at both ends of the second groove. hole.
  • At least one embodiment of the present disclosure provides a method for preparing a gene chip according to any one of the above embodiments.
  • the method includes: providing the first substrate and patterning the first main surface of the first substrate to The dummy area forms at least one of the accommodating areas; the second substrate is provided; the first main surface of the first substrate or the surface of the second substrate facing the first main surface is coated Cover the encapsulation glue, the encapsulation glue is formed at least partly in the dummy area, the encapsulation glue surrounds the accommodating area; the first substrate and the second substrate are combined, and the first substrate The first main surface faces the second substrate; and curing the packaging glue to form the packaging glue layer.
  • the method of curing the encapsulant layer includes at least one of laser bonding and UV curing.
  • FIG. 1A is a plan view of a substrate provided by an embodiment of the disclosure.
  • Fig. 1B is a cross-sectional view of the substrate shown in Fig. 1A along M-N;
  • FIG. 2A is a schematic structural diagram of a gene chip provided by an embodiment of the disclosure.
  • Figure 2B is a cross-sectional view of the gene chip shown in Figure 2 along A-B;
  • FIG. 2C is a plan view of the first substrate of the gene chip shown in FIG. 2A;
  • 3A is a plan view of a first substrate of a gene chip provided by an embodiment of the present disclosure
  • 3B is a plan view of another first substrate of the gene chip provided by an embodiment of the disclosure.
  • 3C is a plan view of another first substrate of the gene chip provided by an embodiment of the disclosure.
  • FIG. 4A is a cross-sectional view of a structure of the gene chip shown in FIG. 2B;
  • FIG. 4B is a plan view of the first substrate of the gene chip shown in FIG. 4A;
  • FIG. 5A is a cross-sectional view of another structure of the gene chip shown in FIG. 2B.
  • Fig. 5B is a plan view of the second substrate of the gene chip shown in Fig. 5A.
  • Gene chips are usually formed by two substrates paired with cassettes, and multiple chambers for gene sequencing are formed between the two substrates. Therefore, the flatness and sealing degree of the two substrates after the cassette will affect the performance of the gene chip, thereby affecting the accuracy of the gene sequencing result.
  • the current gene chip there may be bubbles between the two substrates during the box matching process, and the bubbles are difficult to discharge after being squeezed, thus forming an internal and external communication channel between the two substrates, reducing the degree of sealing of the gene chip; in addition, Air bubbles will cause uneven distribution of forces on the two substrates when they are pressed together, thereby reducing the flatness of the gene chip. Therefore, the packaging yield of the gene chip is limited by applying the current box matching technology.
  • At least one embodiment of the present disclosure provides a substrate for biological information detection.
  • the substrate includes a first main surface.
  • the first main surface includes a test area and a dummy area around the test area.
  • At least one accommodating area is provided on the first main surface, and the accommodating area is located in the dummy area.
  • the accommodating area has an accommodating function.
  • the substrate can be used in a gene chip to improve the packaging yield of the gene chip.
  • At least one embodiment of the present disclosure provides a gene chip, which includes a first substrate, a second substrate and an encapsulating glue layer.
  • the first substrate is the substrate provided by the above-mentioned embodiment of the present disclosure
  • the second substrate is disposed opposite to the first substrate
  • the packaging glue layer is located between the first substrate and the second substrate and at least partly in the dummy area
  • the packaging glue layer surrounds the container. ⁇ .
  • the second substrate faces the first main surface of the first substrate.
  • the structure of the accommodating area can be designed as required.
  • the accommodating area is configured as a groove (such as a first groove), for example, the first groove surrounds the test area.
  • the first groove can form a cavity, and the air bubbles in the packaging glue layer will enter the cavity under pressure.
  • the accommodating area may be configured as a concave-convex structure, so that the substrate has a concave-convex surface in the accommodating area.
  • the bump structure is distributed around the test area. In this way, after the first substrate and the second substrate are boxed together, the concave-convex structure makes a gap between the first substrate and the second substrate, and the air bubbles in the encapsulant layer will enter the gap under pressure.
  • the gene chip can be placed in an oil bath during use. If the encapsulating layer of the gene chip overflows, it will contaminate the oil medium (such as silicone oil) in the oil bath, which will adversely affect the test results.
  • the cavity formed by the first groove can provide a buffer space for the extension of the packaging glue layer. After the packaging glue layer is squeezed during the box aligning process, part of the packaging glue layer can extend to At the first groove, the risk of the packaging glue layer overflowing the gene chip is reduced, thereby improving the accuracy of the gene sequencing result.
  • FIG. 1A is a plan view of a substrate provided by an embodiment of the disclosure
  • FIG. 1B is a cross-sectional view of the substrate shown in FIG. 1A along M-N.
  • the substrate can be used for biological information detection, such as gene sequencing.
  • the substrate 100 includes a first main surface 111.
  • the first main surface 111 includes a test area 102 and a dummy area 101 located around the test area 102.
  • a main surface 111 includes an accommodation area 12 located in the dummy area 102, and the accommodation area 12 is configured as a first groove 120.
  • the bubbles located in the dummy area 102 may be squeezed into the first groove 120.
  • the packaging structure such as the packaging glue layer
  • the biological information detection substrate can be used to form a gene chip.
  • the biological information detection substrate taking the application of the biological information detection substrate as the first substrate of the gene chip as an example, the biological information detection substrate provided by at least one embodiment of the present disclosure and the same The preparation method, gene chip and preparation method thereof are described.
  • Fig. 2A is a schematic structural diagram of a gene chip provided by an embodiment of the present disclosure
  • Fig. 2B is a cross-sectional view of the gene chip shown in Fig. 2 along A-B
  • Fig. 2C is a plan view of the first substrate of the gene chip shown in Fig. 2A. 2A, 2B, and 2C only show a partial structure of the dummy area 101 of the gene chip.
  • the gene chip includes a first substrate 100, a second substrate 200, and an encapsulating glue layer 300.
  • the first main surface 111 of the first substrate 100 includes a test area 102 and a dummy area 101 located around the test area 102.
  • the first main surface 111 of the first substrate 100 is provided with at least one first groove 120. 120 is located in the dummy area 102.
  • the second substrate 200 is disposed opposite to the first substrate 100, and the first main surface 111 of the first substrate 100 faces the second substrate 200.
  • the packaging glue layer 300 is located between the first substrate 100 and the second substrate 200, and the packaging glue layer 300 is at least partially located in the dummy area 101.
  • the encapsulant layer 300 surrounds the first groove 120 and is broken at the first groove 120.
  • the bubbles will be squeezed into the first groove 120.
  • the packaging glue layer 300 After the first substrate 100 and the second substrate 200 are assembled, there will be no air bubbles in the packaging glue layer 300, so there will be no internal and external communication channels formed by the air bubbles in the packaging glue layer 300; and, the packaging glue layer 300 After there are no air bubbles, the pressure of the first substrate 100 and the second substrate 200 when the box is applied can be uniformly applied to the packaging glue layer 300, so that the thickness of the packaging glue layer 300 is uniform, thereby improving the flatness of the gene chip.
  • the first groove is disposed around the test area, and the first groove is spaced from the test area.
  • an encapsulation glue layer is arranged between the first groove and the test area to avoid the communication between the first groove and the test area, and there are air bubbles in the encapsulation glue layer during the process of aligning the first substrate and the second substrate. In this case, all bubbles around the test area can be squeezed into the first groove.
  • the first groove includes at least one first sub-groove, the planar shape of the first sub-groove on the surface of the second substrate is a closed ring, and the first sub-groove surrounds the test Area.
  • the first groove includes two first sub-grooves 121a, 121b. Both 121a and 121b are closed loops and surround the test area 102.
  • the air bubbles can enter the first groove 120 ( For example, in the cavity formed by the first groove 120), thereby improving the packaging yield of the gene chip.
  • 121a and 121b are arranged in a concentric ring shape, for example, the two first sub-grooves 121a and 121b are arranged in a "back" shape.
  • the first substrate and the second substrate will not contact. Therefore, in the box matching process, the gap between the first substrate and the second substrate is pressed to a predetermined thickness.
  • the pressure required for the area where the packaging glue is located is greater than the pressure required for the area where the first groove is pressed.
  • the planar shape of the first sub-groove is a closed ring
  • the centroid of the closed ring coincides with the centroid of the test area. In this way, the first sub-grooves can be evenly distributed with respect to the test area.
  • the force distribution of the first substrate and the second substrate when they are pressed is uniform as a whole, for example, for the relative relationship of the gene chip
  • the pressure required to press the two sides of the box technology is equal, so that the flatness of the gene chip is improved.
  • the centroid of the test area coincides with the centroid of the surface of the substrate provided with the first groove.
  • the shape of the test area is a regular pattern, such as rectangle, circle, ellipse, etc., for example, the shape of the side of the test area (the boundary line between the test area and the dummy area) can be a straight line, a smooth curve or a wave , Zigzag, etc.
  • the distances from the opposite sides of the first sub-groove to the centroid of the test area are equal.
  • the first sub-groove 121 a is rectangular, and the centroid of the rectangle coincides with the centroid of the test area 102.
  • the distance between the first substrate 100 and the second substrate 200 is pressed to a predetermined value (for example, the thickness of the encapsulation layer 300), and the amount of force that needs to be applied is related to the amount of the encapsulation layer 300.
  • first sub-grooves 121a, 121b are evenly distributed in the dummy area of the first substrate 100, so that the packaging glue layer 300 is evenly distributed in the dummy area of the first substrate 100. In this way, in the box matching process, The force distribution of the first substrate 100 and the second substrate 200 when they are pressed together can improve the flatness of the gene chip.
  • the centroids of the patterns formed by all the second sub-grooves coincide with the centroids of the test area.
  • the second sub-grooves can be evenly distributed relative to the test area.
  • the force distribution of the first substrate and the second substrate when they are pressed is uniform as a whole, for example, for the relative difference of the gene chip
  • the pressure required to press the two sides of the box technology is equal, so that the flatness of the gene chip is improved.
  • the plurality of first sub grooves may communicate with each other.
  • the two first sub-grooves 121a and 121b are in communication with each other.
  • the two chambers formed by 121a and 121b are also in communication with each other.
  • the pressure in the middle is equal.
  • the first groove includes at least one second sub-groove, and the planar shape of the second sub-groove on the surface of the second substrate is a line segment shape.
  • the first groove includes two line-segment-shaped second sub-grooves 122a, 122b. From the edge of the dummy area (not shown, for example, the area of the first substrate 100 excluding the test area 102) to the edge of the test area 102, 122a and 122b are sequentially arranged at intervals.
  • the first grooves can be arranged according to the areas where bubbles are easily generated and the important specific areas, and the first grooves in the shape of a line segment are formed on the first substrate 100, and the processing difficulty is low.
  • the line segment shape can be a straight line segment as shown in FIG. 3B, or it can be set as a curve segment or other types of line segments.
  • the planar shape of the first groove and the sub-groove (such as the first sub-groove, the second sub-groove, etc.) included in the first groove is based on the extended track (such as the length Direction), the first groove and the sub-grooves included therein have a certain width in the width direction perpendicular to the extending track.
  • the planar shape of the first sub-groove 121a, 121b is a "mouth" shape (ring).
  • the inner side of the "mouth” shape facing the test area 102
  • the separation distance (width) between the side (the side away from the test area 102) and the outside (the side away from the test area 102) is greater than zero.
  • the planar shapes of the second sub-groove 122a, 122b are all straight-line segments, and in a direction parallel to the XY plane, for the second sub-groove 122a, 122b that constitutes an "I" shape,
  • the length direction is parallel to the X axis
  • the width direction is parallel to the Y axis.
  • the length direction is parallel to the Y axis
  • the width direction is parallel to the X axis.
  • the width of the grooves 122a, 122b in the width direction thereof is greater than zero.
  • the two second sub-grooves there are two second sub-grooves, and the two second sub-grooves are symmetrical with respect to the centroid center of the test area; or, there are no less than three second sub-grooves.
  • the second sub-grooves are equally spaced on a ring centered on the centroid of the test area.
  • the second sub-groove 122a is in the shape of a straight line segment.
  • the distance between the two second sub-groove 122a and the centroid of the test area 102 is equal.
  • the distances from the two second sub-grooves 122b to the centroid of the test area 102 are equal.
  • the distance between the first substrate 100 and the second substrate 200 is pressed to a predetermined thickness.
  • the amount of force that needs to be applied is related to the amount of the encapsulation layer 300, and the amount of the encapsulation layer 300 is larger. Areas require greater pressure, and the distribution of the first grooves (the second sub-grooves 122a, 122b) will affect the distribution of the encapsulant layer 300.
  • the second sub-grooves 122a and 122b can be evenly arranged in the dummy area of the first substrate 100, so that the encapsulant layer 300 is evenly distributed in the dummy area of the first substrate 100.
  • the force distribution of the first substrate 100 and the second substrate 200 when they are pressed is uniform, which can improve the flatness of the gene chip.
  • the thickness of the encapsulant layer may be set to be not greater than 40 ⁇ m, and further, for example, not greater than 20 ⁇ m.
  • the plurality of second sub grooves may communicate with each other.
  • the two second sub-grooves 122a and 122b are in communication with each other.
  • the two chambers formed by 122a and 122b are also in communication with each other.
  • the air pressure in the middle is equal.
  • the two second sub-grooves may be formed in the shape of "I", "H", or "U", as shown in FIG. 3B. "N" shape and so on.
  • the first groove may include at least one first sub-groove and at least one second sub-groove.
  • the second sub-groove 122c in the shape of a line segment is located between the test area 102 and the first sub-groove 121c in the closed ring shape.
  • the second sub-groove 122c may be provided in a dummy area with a larger area.
  • the second sub-groove 122c communicates with the first sub-groove 121c. In this way, the probability of bubbles in the packaging adhesive layer 300 entering the first groove can be increased, and the packaging yield of the gene chip after the box can be improved.
  • the structure of the first sub-groove 121c can refer to the related description of the first sub-groove 121a in the embodiment shown in FIG. 3A, and the second sub-groove 122c can refer to the second sub-groove 122a in the embodiment shown in FIG. 3B.
  • the region of the first substrate where the first groove is provided is provided with at least one first via hole, and the first via hole makes the first groove communicate with the surface opposite to the first main surface .
  • a first via 130 is provided in the first groove (the first sub-groove 121a, 121b, 121c, and the second sub-groove 122a, 122b, 122c).
  • the first via 130 makes the first groove communicate with the second main surface 112 of the first substrate 100 (as shown in FIG. 2B).
  • the pressure of the cavity formed by the first groove will not change, that is, the pressure of the cavity formed by each first groove is equal
  • the pressure distribution is uniform, which is beneficial to improve the flatness of the gene chip.
  • the pattern formed by the first groove is centered symmetric with the centroid of the test area as a reference.
  • the first grooves can be evenly distributed relative to the test area.
  • the force distribution of the first substrate and the second substrate when they are pressed is uniform as a whole, for example, for the relative difference of the gene chip
  • the pressure required by the box process to press the two sides of the area is equal, so that the flatness of the gene chip is improved.
  • a plurality of first grooves are arranged at intervals, and the edge of the test area, the plurality of first grooves, and the The edges are distributed at equal intervals; or a first groove is arranged between the edge of the test area and the edge of the first substrate, and the edges of the test area, the first groove, and the edge of the substrate are distributed at equal intervals.
  • the distance a between the edge of the first substrate 100 and the first sub-groove 121c is equal to that of the first sub-groove 121c and the second sub-groove 122c.
  • the distance b is equal to the distance c between the second sub-groove 122c and the edge of the test area 102.
  • the width s of the first sub-groove 121c and the second sub-groove 122c are equal. In this way, when the first substrate 100 and the second substrate 200 are pressed together, the pressure distribution is uniform, which is beneficial to improve the flatness of the gene chip.
  • the number of first grooves is not limited, and it can be based on the parameters of the packaging glue layer, the width of the dummy area, the width of the first groove, Design related equipment parameters.
  • the number of first grooves can be designed according to the formula N ⁇ L/( ⁇ d+s).
  • N is the number of first grooves
  • L is the distance from the test area 102 to the edge of the first substrate 100
  • ⁇ is the expansion coefficient of the material of the encapsulation layer under the process conditions of the box
  • d is the coating
  • s is the width of the first groove.
  • the first groove includes a first sub-groove 121c and a second sub-groove 122c, and N is 2.
  • FIG. 4A is a cross-sectional view of a structure of the gene chip shown in FIG. 2B
  • FIG. 4B is a plan view of the first substrate of the gene chip shown in FIG. 4A.
  • 4A and 4B show at least one structure of the test area of the gene chip.
  • the first substrate further includes at least one second groove.
  • the second groove is located in the test area and on the first main surface of the first substrate.
  • At least two second via holes are provided at the position of the first substrate where the second groove is provided, and the second via holes make the second groove communicate with the surface opposite to the first main surface.
  • both ends of the second groove are provided with second via holes penetrating the first substrate.
  • a plurality of second grooves 140 are provided on the first main surface 111 of the first substrate 100, and each second groove 140 is provided There are two second via holes 150, and the second via hole 150 communicates the second groove 140 with the second main surface 112 of the first substrate 100.
  • the second recess 140 forms a chamber, which can be used as a reaction chamber for gene sequencing.
  • the two second via holes 150 can be respectively used as an inflow port and an outflow port for the material to be tested.
  • the area of the first main surface 111 of the first substrate 100 where the second groove 140 is provided is coated with an encapsulating glue layer 300.
  • the packaging glue layer 300 can separate the chambers formed by the respective second grooves 140.
  • the second via 150 may be provided at both ends of each second groove 140, thereby increasing the circulation path of the test fluid and improving the test accuracy.
  • the second via hole 150 can be arranged at any position in the second groove according to actual needs, and the distance between the two via holes 150 can be set as needed.
  • the taper of the second via hole is not greater than 15°, and the edge chipping is not greater than 100 ⁇ m.
  • the diameter of one end of the second via located in the second groove may be set to be larger than the diameter of the other end. In this way, when the fluid enters the second groove through the second via hole, the flow rate of the fluid can be slowed down (for example, a laminar flow is formed), and the formation of turbulence can be avoided to facilitate gene sequencing.
  • the width of the first groove and the second groove are equal.
  • the widths of each first groove 120 and each second groove 140 are equal.
  • the pressure distribution is uniform, which is beneficial to improve the flatness of the gene chip.
  • the depth of the second groove may be 50-200 ⁇ m, such as 80 ⁇ m, 100 ⁇ m, 120 ⁇ m, 160 ⁇ m, etc.
  • the width of the second groove may be 1 to 3 mm, such as 1.2 mm, 1.8 mm, 2.4 mm, etc.
  • the distance between adjacent second grooves may be 0.5-2 mm, such as 0.8 mm, 1 mm, 1.2 mm, 1.6 mm, etc.
  • the second substrate when the first substrate is provided with the second groove, the second substrate may further include a modification layer, and the modification layer is located on the surface of the second substrate facing the first substrate.
  • the modification layer 400 can be used to match different gene fragments (or nucleotides), and different gene fragments can have different fluorescent labels (or isotope labels).
  • fluorescent labels or isotope labels
  • genes can be sequenced.
  • the modification layer 400 may cover the entire surface of the second substrate 200 as shown in FIG. 4A, or may be provided only in the area corresponding to the second groove 140.
  • the material of the modification layer may include epoxy silane.
  • a plurality of micro-reaction chambers in the reaction chamber formed by the second groove, can be provided to match different gene fragments, so that no modification layer is required.
  • a plurality of micro-reaction chambers such as micro-grooves
  • Different materials can be set in the chamber to match specific gene fragments.
  • FIG. 5A is a cross-sectional view of another structure of the gene chip shown in FIG. 2B
  • FIG. 5B is a plan view of the second substrate of the gene chip shown in FIG. 5A
  • 5A and 5B show at least another structure of the test area of the gene chip.
  • the second substrate includes at least one second groove, the second groove is located in the test area and on the surface of the second substrate facing the first substrate, and the second substrate is arranged At least two second via holes are provided where the second groove is located, and the second via holes penetrate the second substrate. Exemplarily, as shown in FIGS.
  • the surface of the second substrate 200 facing the first substrate 100 is provided with a plurality of second grooves 240, and each second groove 240 is Two second via holes 250 are provided, and the second via holes 250 penetrate the second substrate 200.
  • the second groove 240 forms a chamber, which can be used as a reaction chamber for gene sequencing.
  • two second via holes 250 can be respectively used as an inflow port and an outflow port for the material to be tested.
  • the packaging glue layer 300 can separate the chambers formed by the second grooves 240.
  • the second via hole 250 may be provided at both ends of each second groove 240, thereby increasing the circulation path of the test fluid and improving the test accuracy.
  • the second via hole 250 can be arranged at any position in the second groove according to actual needs, and the distance between the two via holes 150 can be set as needed.
  • the first substrate when the second substrate is provided with the second groove, the first substrate further includes a modification layer, and the modification layer is located on the first main surface of the first substrate.
  • the modified layer 400 can be used to match different gene fragments (or nucleotides), and different gene fragments can have different fluorescent labels.
  • the gene can be sequenced.
  • the modification layer 400 may cover the first main surface 111 in the test area 102 as shown in FIG. 5A, or may be provided only in the area corresponding to the second groove 140.
  • the type of the material of the encapsulant layer is not limited, and the selection of the material can be selected according to the curing method of the encapsulant layer.
  • the curing method of the encapsulation adhesive layer may be UV curing, and the material of the encapsulation adhesive layer may include UV adhesive.
  • UV glue Before being cured, UV glue has certain fluidity and is easy to deform under the action of external force. In this way, when aligning the first substrate and the second substrate of the box, even if the thickness distribution of the UV glue in each area is not uniform, by squeezing the UV glue to flow, the thickness of the UV glue in each area can be made uniform; in addition, UV The glue has fluidity, and when it is squeezed, it can also facilitate the gas in the bubbles to enter the first groove.
  • the curing method of the UV glue can be UV light irradiation or thermal curing. UV curing has simple operation, good sealing performance and short curing time, which can improve the production efficiency of gene chips and reduce production costs.
  • a certain pressure for example, a pressure equivalent to 0.01-1 MPa, for example a pressure of 0.05 MPa, 0.1 MPa or 0.5 MPa
  • a certain period of time For example, 5-30s, and further, for example, 10s
  • the UV light intensity of the UV curing may be 1000 mJ to 3000 mJ, for example, further 2000 mJ.
  • the curing method of the encapsulant layer may be laser bonding.
  • the material of the encapsulant layer can be pure metal chromium, silicon powder, and the like.
  • At least one embodiment of the present disclosure provides a method for preparing a substrate according to any one of the above-mentioned embodiments.
  • the method includes: patterning a first main surface of the substrate to form at least one accommodating area in a dummy area of the substrate.
  • the bubbles located in the dummy area can be squeezed into the containing area.
  • the packaging structure such as the packaging glue layer
  • the patterning can be a photolithography patterning process or mechanical processing.
  • the accommodating area refer to the relevant description in the foregoing embodiment.
  • the accommodating area is set as a first groove, and the first groove surrounds the test area.
  • the formed first groove may include at least one first sub-groove, and the planar shape of the first sub-groove on the surface of the second substrate is a closed ring.
  • the first sub-groove surrounds the test area. In this way, at least for air bubbles generated at any position of the dummy area, the air bubbles can enter the first groove during box alignment, thereby improving the packaging yield of products obtained from the substrate, such as gene chips.
  • the formed first groove may include at least one second sub-groove, and the planar shape of the second sub-groove on the surface of the second substrate is a line segment. .
  • the first grooves can be laid out according to the areas where bubbles are easily generated and the important specific areas, and the first grooves in the shape of line segments are formed on the substrate, so the processing difficulty is low.
  • the first groove may include at least one first sub-groove and at least one second sub-groove.
  • the planar shape of the first sub-groove on the surface of the second substrate is a closed ring and surrounds the test area
  • the planar shape of the second sub-groove on the surface of the second substrate is a line segment shape.
  • the second sub-groove may be located in a dummy area with a larger area. In this way, the probability of bubbles entering the first groove can be increased, and the packaging yield of products obtained from the substrate, such as gene chips, can be improved.
  • the method for preparing a substrate provided by at least one embodiment of the present disclosure further includes: forming at least one second groove in the test area of the substrate, and forming second via holes penetrating the substrate at both ends of the second groove.
  • the structure of the substrate obtained according to this method reference may be made to the related description of the first substrate 100 in the embodiment shown in FIG. 4B.
  • At least one embodiment of the present disclosure provides a method for preparing a gene chip according to any one of the above embodiments.
  • the method includes: providing a first substrate, and patterning a first main surface of the first substrate to form at least one accommodating area; providing A second substrate; coating the encapsulant on the first main surface of the first substrate or the surface of the second substrate facing the first main surface, the encapsulant is at least partially formed in the dummy area, and the encapsulant surrounds the accommodating area;
  • the first substrate and the second substrate are boxed, the second substrate is located on the first main surface of the first substrate; and the packaging glue is cured to form the packaging glue layer.
  • the accommodating area is set as a first groove, and the first groove surrounds the test area.
  • the method of curing the encapsulant layer includes at least one of laser bonding and UV curing.
  • the material type, curing method, etc. of the encapsulant layer reference may be made to the relevant description in the foregoing embodiment, which is not repeated here.

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Abstract

一种生物信息检测基板和包括该基板的基因芯片，其中，该基板包括第一主表面(111)，第一主表面(111)包括测试区(102)以及位于测试区(102)周围的虚设区(101)，第一主表面(111)上设置有至少一个容置区(12)，容置区(12)位于虚设区(101)。在该基板用于对盒时，容置区(12)可以用于消除气泡，提高对盒后的产品良率。

Description

生物信息检测基板和基因芯片 技术领域
本公开至少一个实施例涉及一种生物信息检测基板和基因芯片。
背景技术
近年来，生物芯片或者微流体芯片的研究引起了越来越广泛的关注。典型的微流体芯片一般是指把生物、化学方面的反应、分析、检测等过程集成到一块具备微米尺寸检测单元的芯片上去。在上述芯片的生产工艺中，芯片封装是很重要的部分。但是，当前的封装方式在芯片的平面度、密封程度方面，仍不能满足要求，严重制约芯片的性能。
发明内容
本公开至少一个实施例提供一种用于生物信息检测的基板。该基板包括第一主表面，所述第一主表面包括测试区以及位于所述测试区周围的虚设区，所述第一主表面上设置有至少一个容置区，所述容置区位于所述虚设区。
例如，在本公开至少一个实施例提供的基板中，所述容置区设置为第一凹槽，所述第一凹槽环绕所述测试区。
例如，在本公开至少一个实施例提供的基板中，所述第一凹槽包括至少一个第一子凹槽，所述第一子凹槽在所述第二基板表面上的平面形状为闭合环形。
例如，在本公开至少一个实施例提供的基板中，所述闭合环形的形心与所述测试区的形心重合。
例如，在本公开至少一个实施例提供的基板中，所述第一子凹槽的彼此相对的两边至所述测试区的形心的距离相等。
例如，在本公开至少一个实施例提供的基板中，所述第一凹槽包括至少一个第二子凹槽，所述第二子凹槽在所述第二基板表面上的平面形状为线段形。
例如，在本公开至少一个实施例提供的基板中，所述第二子凹槽设置 为多个，并且所有所述第二子凹槽构成的图形的形心与所述测试区的形心重合。
例如，在本公开至少一个实施例提供的基板中，所述第二子凹槽为两个，并且两个所述第二子凹槽相对于所述测试区的形心中心对称；或者所述第二子凹槽不少于三个，并且所述第二子凹槽在以所述测试区的形心为中心的环形上等间距分布。
例如，在本公开至少一个实施例提供的基板中，所述基板的设置有所述第一凹槽的区域设置有至少一个第一过孔，所述第一过孔使得所述第一凹槽与所述第一主表面相对的表面连通。
例如，在本公开至少一个实施例提供的基板中，所述第一凹槽构成的图形以所述测试区的形心为基准中心对称。
例如，在本公开至少一个实施例提供的基板中，所述测试区的边缘至所述基板的边缘之间，间隔排布多个所述第一凹槽，所述测试区的边缘、多个所述第一凹槽、所述基板的边缘为等间距分布；或者所述测试区的边缘至所述基板的边缘之间设置一个所述第一凹槽，所述测试区的边缘、所述第一凹槽、所述基板的边缘为等间距分布。
例如，本公开至少一个实施例提供的基板还包括至少一个第二凹槽。所述第二凹槽位于所述测试区且位于所述基板的第一主表面上。所述基板包括位于所述第二凹槽两端的第二过孔，所述第二过孔使得所述第二凹槽与所述第一主表面相对的表面连通。
例如，在本公开至少一个实施例提供的基板中，在平行于所述第一主表面的方向上，所述第一凹槽和所述第二凹槽的宽度相等。
本公开至少一个实施例提供一种基因芯片，该基因芯片包括第一基板、第二基板和封装胶层。所述第一基板为前述任一实施例的基板，所述第二基板与所述第一基板相对设置，所述封装胶层位于所述第一基板和所述第二基板之间，并至少部分位于所述虚设区内，所述封装胶层环绕所述容置区。
例如，在本公开至少一个实施例提供的基因芯片中，所述第一基板包括至少一个第二凹槽，位于所述测试区且位于所述第一基板的第一主表面上，以及所述第一基板的设置有所述第二凹槽的位置设置有至少两个第二过孔，所述第二过孔贯穿所述第一基板。
例如，在本公开至少一个实施例提供的基因芯片中，所述第二基板还包括修饰层，以及所述修饰层位于所述第二基板的面向所述第一基板的表面。
例如，在本公开至少一个实施例提供的基因芯片中，在平行于所述第一主表面的方向上，所述容置区和所述第二凹槽的宽度相等。
例如，在本公开至少一个实施例提供的基因芯片中，所述第二基板包括至少一个第二凹槽，位于所述测试区且位于所述第二基板的面向所述第一基板的表面上，以及所述第二基板包括位于所述第二凹槽两端的第二过孔，所述第二过孔贯穿所述第二基板。
例如，在本公开至少一个实施例提供的基因芯片中，所述第一基板还包括修饰层，以及所述修饰层位于所述第一基板的第一主表面上。
例如，在本公开至少一个实施例提供的基因芯片中，在平行于所述第一主表面的方向上，所述容置区和所述第二凹槽的宽度相等。
例如，在本公开至少一个实施例提供的基因芯片中，所述封装胶层包括UV胶。
本公开至少一个实施例提供一种根据上述任一实施例的基板的制备方法，该方法包括：构图所述基板的所述第一主表面，以在所述虚设区形成至少一个所述容置区。
例如，本公开至少一个实施例提供的制备方法还包括：在所述基板的测试区形成至少一个第二凹槽；以及在所述第二凹槽的两端形成贯穿所述基板的第二过孔。
本公开至少一个实施例提供一种根据上述任一实施例的基因芯片的制备方法，该方法包括：提供所述第一基板，构图所述第一基板的所述第一主表面以在所述虚设区形成至少一个所述容置区；提供所述第二基板；在所述第一基板的所述第一主表面或所述第二基板的面对所述第一主表面的表面上涂覆封装胶，所述封装胶至少部分形成在所述虚设区内，所述封装胶环绕所述容置区；对盒所述第一基板和所述第二基板，所述第一基板的所述第一主表面面向所述第二基板；以及固化所述封装胶以形成所述封装胶层。
例如，在本公开至少一个实施例提供的制备方法中，固化所述封装胶层的方法包括激光键合和UV固化中的至少一种。
附图说明
为了更清楚地说明本发明实施例的技术方案，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发明的一些实施例，而非对本发明的限制。
图1A为本公开一实施例提供的一种基板的平面图；
图1B为图1A所示基板沿M-N的截面图；
图2A为本公开一实施例提供的一种基因芯片的结构示意图；
图2B为图2所示基因芯片沿A-B的截面图；
图2C为图2A所示基因芯片的第一基板的平面图；
图3A为本公开一实施例提供的基因芯片的一种第一基板的平面图；
图3B为本公开一实施例提供的基因芯片的另一种第一基板的平面图；
图3C为本公开一实施例提供的基因芯片的另一种第一基板的平面图；
图4A为图2B所示的基因芯片的一种结构的截面图；
图4B为图4A所示的基因芯片的第一基板的平面图；
图5A为图2B所示的基因芯片的另一种结构的截面图；以及
图5B为图5A所示的基因芯片的第二基板的平面图。
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚，下面将结合本发明实施例的附图，对本发明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发明的一部分实施例，而不是全部的实施例。基于所描述的本发明的实施例，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，都属于本发明保护的范围。
除非另外定义，本公开使用的技术术语或者科学术语应当为本发明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。“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。
基因芯片通常由两个基板对盒形成，两个基板之间形成多个用于基因测序的腔室。因此，两个基板对盒后的平面度、密封程度等参数会影响基因芯片的性能，从而影响基因测序结果的准确度。对于当前的基因芯片，在对盒过程中，两个基板之间可能存在气泡，气泡受到挤压后难以排出从而在两个基板之间形成内外连通的通道，降低基因芯片的密封程度；此外，气泡会使得两个基板在压合时的受力分布不均匀，从而降低基因芯片的平面度。因此，应用当前的对盒工艺，基因芯片的封装良率有限。
本公开至少一个实施例提供一种用于生物信息检测的基板。该基板包括第一主表面，第一主表面包括测试区以及位于测试区周围的虚设区，第一主表面上设置有至少一个容置区，容置区位于虚设区。容置区具有容纳功能，如此，在利用封装胶层将该基板与另一基板对盒时，封装胶层的气泡受压后会导入该容置区，从而提高该封装胶层的封装效果。例如，该基板可以用于基因芯片中，以提高基因芯片的封装良率。
本公开至少一个实施例提供一种基因芯片，该基因芯片包括第一基板、第二基板和封装胶层。第一基板为本公开上述实施例提供的基板，第二基板与第一基板相对设置，封装胶层位于第一基板和第二基板之间，并至少部分位于虚设区内，封装胶层环绕容置区。第二基板面对第一基板的第一主表面。在将第一基板和第二基板对盒以形成基因芯片的工艺中，在封装胶层中存在气泡的情况下，气泡受压会进入容置区中而不会残留在封装胶层中。如此，封装胶层中不会因气泡而产生使得基因芯片内外连通的通道；气泡进入容置区后也不会影响第一基板和第二基板在压合时的受力分布，从而提高基因芯片的平面度。相对于当前的基因芯片，本公开实施例中的基因芯片的封装良率提高，成本降低。
需要说明的是，在本公开的实施例中，只要容置区设置为具有容纳功能即可，基于此，容置区的结构可以根据需要进行设计。例如，在一些实施例中，容置区设置为凹槽(例如第一凹槽)，例如，第一凹槽环绕测试区。如此，在第一基板和第二基板对盒后，第一凹槽可以形成腔室，封装胶层中的气泡受压会进入该腔室中。例如，在另一些实施例中，容置区可以设置为凹凸结构，以使得基板在容置区具有凹凸表面。例如，凹凸结构的环 绕测试区分布。如此，在第一基板和第二基板对盒后，凹凸结构使得第一基板和第二基板之间存在缝隙，封装胶层中的气泡受压会进入该缝隙中。
下面，以容置区设置为第一凹槽为例，对本公开下述至少一个实施例中的技术方案进行说明。
基因芯片在使用过程中，可以放置在油浴锅中，如果基因芯片的封装胶层溢出，会污染油浴锅中的油体介质(例如硅油)，从而对测试结果产生不良影响。在本公开至少一个实施例中，第一凹槽形成的腔室可以为封装胶层的延伸提供缓冲的空间，在对盒过程中，封装胶层受到挤压后，部分封装胶层可以延伸至第一凹槽处，降低封装胶层溢出基因芯片的风险，从而可以提高基因测序结果的准确度。
下面，结合附图对根据本公开至少一个实施例的生物信息检测基板及其制备方法、基因芯片及其制备方法进行说明。
图1A为本公开一实施例提供的一种基板的平面图，图1B为图1A所示基板沿M-N的截面图，该基板可以用于生物信息检测，例如基因测序。
本公开至少一个实施例提供一种基板，如图1A和图1B所示，基板100包括第一主表面111，第一主表面111包括测试区102以及位于测试区102周围的虚设区101，第一主表面111包括位于虚设区102的容置区12，并且容置区12设置为第一凹槽120。在基板100用于对盒的封装工艺中，位于虚设区102的气泡可以被挤压至第一凹槽120中。如此，在利用基板100完成对盒工艺之后，封装结构(例如封装胶层)中不会存在气泡，使得利用基板100形成的产品例如基因芯片的封装良率得到保证。
生物信息检测基板可以用于构成基因芯片，在本公开至少一个实施例中，以生物信息检测基板应用为基因芯片的第一基板为例，对本公开至少一个实施例提供的生物信息检测基板及其制备方法、基因芯片及其制备方法进行说明。
图2A为本公开一实施例提供的一种基因芯片的结构示意图；图2B为图2所示基因芯片沿A-B的截面图；图2C为图2A所示基因芯片的第一基板的平面图。图2A、图2B和图2C仅示出基因芯片的虚设区101的部分结构。
本公开至少一个实施例提供一种基因芯片，如图2A、图2B和图2C所示，该基因芯片包括第一基板100、第二基板200和封装胶层300。第一 基板100的第一主表面111包括测试区102以及位于测试区102周围的虚设区101，第一基板100的第一主表面111上设置有至少一个第一凹槽120，第一凹槽120位于虚设区102中。第二基板200与第一基板100相对设置，并且第一基板100的第一主表面111面向第二基板200上。封装胶层300位于第一基板100和第二基板200之间，并且封装胶层300至少部分位于虚设区101内。封装胶层300环绕第一凹槽120并且在第一凹槽120处断开。在第一基板100和第二基板200对盒的过程中，在封装胶层300中具有气泡的情况下，该气泡会被挤压至第一凹槽120中。如此，第一基板100和第二基板200对盒之后，封装胶层300中不会存在气泡，从而封装胶层300中也不会存在因气泡形成的内外连通的通道；并且，封装胶层300中没有气泡后，第一基板100和第二基板200对盒时的压力都能均匀施加至封装胶层300，使得封装胶层300的厚度均匀，从而提高基因芯片的平面度。
例如，在本公开至少一个实施例中，第一凹槽环绕测试区设置，并且第一凹槽与测试区间隔。如此，第一凹槽和测试区之间设置封装胶层，避免第一凹槽的和测试区连通，而且在第一基板和第二基板对盒的过程中，在封装胶层中具有气泡的情况下，测试区周围的气泡都可以被挤压至第一凹槽中。
在本公开至少一个实施例中，对第一凹槽的形状以及在虚设区的分布等设计不做限制，只要该设计有利于封装胶层的气泡进入该凹槽中即可。
例如，在本公开至少一个实施例中，第一凹槽包括至少一个第一子凹槽，第一子凹槽在第二基板表面上的平面形状为闭合环形，以及第一子凹槽环绕测试区。示例性的，如图3A所示，第一凹槽包括两个第一子凹槽121a、121b。121a和121b皆为闭合环形且环绕测试区102。如此，至少对于虚设区(未示出，例如，第一基板100的除测试区102之外的区域)的任意位置产生的气泡，在对盒时，该气泡都可以进入第一凹槽120(例如由该第一凹槽120形成的腔室)中，从而提高基因芯片的封装良率。例如，121a和121b为同心环形排布，例如两个第一子凹槽121a、121b排布为“回”字形。
在基因芯片的第一凹槽所在的区域，第一基板和第二基板不会接触，因而在对盒工艺中，将第一基板和第二基板的间隙压合至预定厚度的情况 下，压合封装胶所在的区域所需要的压力要大于压合第一凹槽所在的区域所需要的压力。例如，在本公开至少一个实施例中，在第一子凹槽的平面形状为闭合环形的情况下，该闭合环形的形心与测试区的形心重合。如此，第一子凹槽相对于测试区可以均匀分布，在对盒工艺中，第一基板和第二基板在被压合时的受力分布整体上是均匀的，例如，对于基因芯片的相对的两侧区域，对盒工艺压合该两侧区域所需要的压力相等，从而使得基因芯片的平面度提高。例如，在本公开至少一个实施例中，测试区的形心与基板的设置有第一凹槽的表面的形心重合。例如，测试区的形状为规则图形，例如矩形、圆形、椭圆形等，例如，测试区的边(测试区和虚设区的交界线)的形状可以为直线形、平滑的曲线形或者波浪形、锯齿形等。
例如，在本公开至少一个实施例中，第一子凹槽的彼此相对的两边至测试区的形心的距离相等。示例性的，如图3A所示，第一子凹槽121a为矩形，该矩形的形心和测试区102的形心重合。在对盒工艺中，将第一基板100和第二基板200之间的间距压合至预定值(例如封装胶层300的厚度)，需要施加的力的大小与封装胶层300的量有关，在封装胶层300的量多的区域，需要更大的压力，第一凹槽(第一子凹槽121a、121b)的分布会影响封装胶层300的分布。根据上述设计，第一子凹槽121a、121b在第一基板100的虚设区中分布均匀，从而使得封装胶层300在第一基板100的虚设区中分布均匀，如此，在对盒工艺中，第一基板100和第二基板200在被压合时的受力分布均匀，可以提高基因芯片的平面度。
例如，在本公开至少一个实施例中，第二子凹槽设置为多个，并且所有第二子凹槽构成的图形的形心与测试区的形心重合。如此，第二子凹槽相对于测试区可以均匀分布，在对盒工艺中，第一基板和第二基板在被压合时的受力分布整体上是均匀的，例如，对于基因芯片的相对的两侧区域，对盒工艺压合该两侧区域所需要的压力相等，从而使得基因芯片的平面度提高。
例如，在本公开至少一个实施例中，在第一凹槽包括多个第一子凹槽的情况下，该多个第一子凹槽可以彼此连通。示例性的，如图3A所示，两个第一子凹槽121a、121b彼此连通，如此，在对盒时，由121a和121b形成的两个腔室也是彼此连通的，该两个腔室中的压强相等，在压合第一基板100和第二基板200时，压力分布均匀，有利于提高基因芯片的平面 度。
例如，在本公开至少一个实施例中，第一凹槽包括至少一个第二子凹槽，第二子凹槽在第二基板表面上的平面形状为线段形。示例性的，如图3B所示，第一凹槽包括两个线段形的第二子凹槽122a、122b。从虚设区(未示出，例如，第一基板100的除测试区102之外的区域)的边缘至测试区102的边缘，122a和122b依次间隔排布。如此，可以根据气泡容易产生的区域以及重要的特定区域布局第一凹槽，而且在第一基板100上形成线段形的第一凹槽，加工难度低。例如，该线段形可以为如图3B所示的直线段，也可以设置为曲线段或其它类型的线段。
需要说明的是，在本公开的实施例中，第一凹槽及其包括的子凹槽(例如第一子凹槽、第二子凹槽等)的平面形状是基于延伸的轨迹(例如长度方向)的形状，第一凹槽及其包括的子凹槽在垂直于延伸的轨迹的宽度方向上具有一定的宽度。例如，如图3A所示，第一子凹槽121a、121b的平面形状都为“口”字形(环形)，在平行于X-Y平面的方向上，该“口”字形的内侧(面向测试区102的一侧)和外侧(背离测试区102的一侧)的间隔距离(宽度)大于零。例如，如图3B所示，第二子凹槽122a、122b的平面形状都为直线段形，在平行于X-Y平面的方向上，对于构成“工”字形的第二子凹槽122a、122b，长度方向平行于X轴，宽度方向平行于Y轴，对于构成“H”形的第二子凹槽122a、122b，长度方向平行于Y轴，宽度方向平行于X轴，且所有第二子凹槽122a、122b在其宽度方向上的宽度大于零。
例如，在本公开至少一个实施例中，第二子凹槽为两个，并且两个第二子凹槽相对于测试区的形心中心对称；或者，第二子凹槽不少于三个，并且第二子凹槽在以测试区的形心为中心的环形上等间距分布。示例性的，如图3B所示，第二子凹槽122a为直线段形，在测试区102的相对的两侧，两个第二子凹槽122a至测试区102的形心的距离相等，两个第二子凹槽122b至测试区102的形心的距离相等。在对盒工艺中，将第一基板100和第二基板200之间的间距压合至预定厚度，需要施加的力的大小与封装胶层300的量有关，在封装胶层300的量多的区域，需要更大的压力，第一凹槽(第二子凹槽122a、122b)的分布会影响封装胶层300的分布。根据上述设计，第二子凹槽122a、122b可以在第一基板100的虚设区中均匀排 布，从而使得封装胶层300在第一基板100的虚设区中分布均匀，如此，在对盒工艺中，第一基板100和第二基板200在被压合时的受力分布均匀，可以提高基因芯片的平面度。
例如，在本公开至少一个实施例中，封装胶层的厚度可以设置为不大于40μm，进一步例如不大于20μm。
例如，在本公开至少一个实施例中，在第一凹槽包括多个第二子凹槽的情况下，该多个第二子凹槽可以彼此连通。示例性的，如图3B所示，两个第二子凹槽122a、122b彼此连通，如此，在对盒时，由122a和122b形成的两个腔室也是彼此连通的，该两个腔室中的气压相等，在压合第一基板100和第二基板200时，压力分布均匀，有利于提高基因芯片的平面度。例如，在两个第二子凹槽彼此连通的情况下，该两个第二子凹槽可以形成为图3B所示的“工”字形、“H”形，也可以为“U”形、“N”形等。
例如，在本公开至少一个实施例中，第一凹槽可以包括至少一个第一子凹槽和至少一个第二子凹槽。示例性的，如图3C所示，线段形的第二子凹槽122c位于测试区102和闭合环形的第一子凹槽121c之间。例如，第二子凹槽122c可以设置在面积较大的虚设区中。例如，第二子凹槽122c和第一子凹槽121c连通。如此，可以提高封装胶层300中的气泡进入第一凹槽的几率，提高对盒后的基因芯片的封装良率。第一子凹槽121c的结构可以参考图3A所示实施例中的第一子凹槽121a的相关说明，第二子凹槽122c可以参考图3B所示实施例中的第二子凹槽122a的相关说明。
例如，在本公开至少一个实施例中，第一基板的设置有第一凹槽的区域设置有至少一个第一过孔，第一过孔使得第一凹槽与第一主表面相对的表面连通。示例性的，如图3A、图3B和图3C所示，第一凹槽(第一子凹槽121a、121b、121c，第二子凹槽122a、122b、122c)处设置第一过孔130。第一过孔130使得第一凹槽与第一基板100的第二主表面112(如图2B所示)连通。如此，在对盒工艺中，即使气泡中的气体进入第一凹槽中，第一凹槽形成的腔室的压强也不会发生变化，即，各个第一凹槽形成的腔室的压强相等，在压合第一基板100和第二基板200时，压力分布均匀，有利于提高基因芯片的平面度。
例如，在本公开至少一个实施例中，第一凹槽构成的图形以测试区的形心为基准中心对称。如此，第一凹槽相对于测试区可以均匀分布，在对 盒工艺中，第一基板和第二基板在被压合时的受力分布整体上是均匀的，例如，对于基因芯片的相对的两侧区域，对盒工艺压合该两侧区域所需要的压力相等，从而使得基因芯片的平面度提高。
例如，在本公开至少一个实施例中，测试区的边缘至第一基板的边缘之间，间隔排布多个第一凹槽，测试区的边缘、多个第一凹槽、第一基板的边缘为等间距分布；或者测试区的边缘至第一基板的边缘之间设置一个第一凹槽，测试区的边缘、第一凹槽、基板的边缘为等间距分布。示例性的，如图3C所示，在测试区102的同一侧，第一基板100的边缘与第一子凹槽121c的间距a，等于第一子凹槽121c和第二子凹槽122c的间距b，且等于第二子凹槽122c和测试区102的边缘的间距c。例如，第一子凹槽121c、第二子凹槽122c的宽度s相等。如此，在压合第一基板100和第二基板200时，压力分布均匀，有利于提高基因芯片的平面度。
在本公开至少一个实施例提供的基板中，在测试区的同一侧，对第一凹槽的数量不做限制，可以根据封装胶层的参数、虚设区的宽度、第一凹槽的宽度、相关设备的参数进行设计。例如，如图3C所示，可以根据公式N≥L/(δ×d+s)来设计第一凹槽的设置数量。在该公式中，N为第一凹槽的设置数量，L为测试区102至第一基板100的边缘的距离；δ为封装胶层的材料在对盒工艺条件下的膨胀系数；d为涂覆设备涂覆封装胶时的胶宽；以及s为第一凹槽的宽度。图3C中，在测试区102的同一侧，第一凹槽包括第一子凹槽121c和第二子凹槽122c，N为2。
图4A为图2B所示的基因芯片的一种结构的截面图，图4B为图4A所示的基因芯片的第一基板的平面图。图4A和图4B至少示出基因芯片的测试区的一种结构。
例如，本公开一些实施例中，第一基板还包括至少一个第二凹槽。第二凹槽位于测试区且位于第一基板的第一主表面上。第一基板的设置有第二凹槽的位置设置有至少两个第二过孔，第二过孔使得第二凹槽与第一主表面相对的表面连通。例如，第二凹槽的两端设置贯穿第一基板的第二过孔。示例性的，如图4A和图4B所示，在测试区102中，第一基板100的第一主表面111上设置有多个第二凹槽140，每个第二凹槽140处都设置有两个第二过孔150，第二过孔150将第二凹槽140与第一基板100的第二主表面112连通。在第一基板100和第二基板200对盒之后，第二凹 槽140形成腔室，该腔室可以作为反应室以用于基因测序。在每个反应室中，两个第二过孔150可以分别作为待测试材料的流入口和流出口。例如，在基因芯片的测试区102中，在第一基板100的第一主表面111的设置有第二凹槽140的区域涂覆有封装胶层300。对盒之后，封装胶层300可以将各个第二凹槽140形成的腔室间隔开。
例如，第二过孔150可以设置在每个第二凹槽140的两端处，从而增加测试流体的流通路径，提高测试精度。备选地，可以根据实际需要而将第二过孔150设置在第二凹槽中的任意位置处，两个过孔150之间的间距可以根据需要而设定。
例如，第二过孔的锥度不大于15°，崩边不大于100μm。例如，第二过孔具有锥度的情况下，对于作为流入口的第二过孔，该第二过孔的位于第二凹槽中的一端的直径可以设置为大于其另一端的直径。如此，流体通过第二过孔进入第二凹槽时，可以减缓流体的流速(例如形成层流)，避免形成紊流，以便于进行基因测序。
例如，在本公开一些实施例中，在平行于第一主表面的方向上，第一凹槽和第二凹槽的宽度相等。例如，如图4A和图4B所示，每个第一凹槽120和每个第二凹槽140的宽度相等。如此，可以简化第一基板100的加工难度，降低成本。例如，在压合第一基板100和第二基板200时，压力分布均匀，有利于提高基因芯片的平面度。
例如，在本公开至少一个实施例中，第二凹槽设置为多个的情况下，可以设置为5～20条，例如8、10、16、18条等。第二凹槽的深度可以为50～200μm，例如80μm、100μm、120μm、160μm等。第二凹槽的宽度可以为1～3mm，例如1.2mm、1.8mm、2.4mm等。相邻第二凹槽的间距可以为0.5～2mm，例如0.8mm、1mm、1.2mm、1.6mm等。
例如，在本公开至少一个实施例中，在第一基板上设置有第二凹槽的情况下，第二基板还可以包括修饰层，以及修饰层位于第二基板的面向第一基板的表面。示例性的，如图4A所示，修饰层400可以用于匹配不同的基因片段(或者核苷酸)，不同的基因片段上可以具有不同的荧光标记(或者同位素标记)，如此，根据荧光标记沿修饰层400的分布，可以对基因进行测序。例如，修饰层400可以如图4A所示一样覆盖第二基板200的整个表面，也可以仅在与第二凹槽140对应的区域设置。
例如，修饰层的材料可以包括环氧硅烷。
例如，在本公开至少一个实施例中，第二凹槽形成的反应室中，可以设置多个微反应室以匹配不同的基因片段，如此，可以不需要设置修饰层。例如，在与第二凹槽形成的反应室对应的位置，在第一基板的表面或者第二基板的表面设置多个阵列排布的微反应室(例如微型的凹槽)，不同的微反应室中可以设置不同的材料(例如已知序列的靶核苷酸)以与特定的基因片段匹配。
图5A为图2B所示的基因芯片的另一种结构的截面图，图5B为图5A所示的基因芯片的第二基板的平面图。图5A和图5B至少示出基因芯片的测试区的另一种结构。例如，在本公开另一些实施例提供中，第二基板包括至少一个第二凹槽，第二凹槽位于测试区且位于第二基板的面向第一基板的表面上，以及第二基板的设置有第二凹槽的位置设置有至少两个第二过孔，第二过孔贯穿第二基板。示例性的，如图5A和图5B所示，在测试区102中，第二基板200的面向第一基板100的表面设置有多个第二凹槽240，每个第二凹槽240处都设置有两个第二过孔250，第二过孔250将第二基板200贯穿。在第一基板100和第二基板200对盒之后，第二凹槽240形成腔室，该腔室可以作为反应室以用于基因测序。在每个反应室中，两个第二过孔250可以分别作为待测试材料的流入口和流出口。例如，在基因芯片的测试区102中，在第二基板200的面向第一基板100的表面上，没有设置有第二凹槽240的区域涂覆有封装胶层300。对盒之后，封装胶层300可以将各个第二凹槽240形成的腔室间隔开。
例如，第二过孔250可以设置在每个第二凹槽240的两端处，从而增加测试流体的流通路径，提高测试精度。备选地，可以根据实际需要而将第二过孔250设置在第二凹槽中的任意位置处，两个过孔150之间的间距可以根据需要而设定。
例如，在本公开至少一个实施例中，在第二基板上设置有第二凹槽的情况下，第一基板还包括修饰层，以及修饰层位于第一基板的第一主表面上。示例性的，如图5A所示，修饰层400可以用于匹配不同的基因片段(或者核苷酸)，不同的基因片段上可以具有不同的荧光标记，如此，根据荧光标记沿修饰层400的分布，可以对基因进行测序。例如，在第一主表面上，修饰层400可以如图5A所示一样覆盖测试区102中的第一主表面 111，也可以仅在与第二凹槽140对应的区域设置。
在本公开至少一个实施例中，对封装胶层的材料的类型不做限制，材料的选择可以根据封装胶层的固化方式进行选择。
例如，在本公开一些实施例提供中，封装胶层的固化方式可以为UV固化，封装胶层的材料可以包括UV胶。UV胶在未固化前，具有一定的流动性，在外力作用下容易变形。如此，在对盒第一基板和第二基板时，即使各区域的UV胶的厚度分布不均匀，通过挤压UV胶使其流动，也可以使得各区域的UV胶的厚度均匀；此外，UV胶具有流动性，在受到挤压的情况下，也可以便于气泡中的气体进入第一凹槽中。例如，UV胶的固化方式可以为UV光照射，也可以包括热固化。UV固化的操作简单，密封性好且固化时间短，可以提高基因芯片的生产效率，降低生产成本。
例如，在对盒过程中，可以向第一基板和第二基板施加一定的压力(例如相当于0.01～1MPa的压强，例如进一步为0.05MPa、0.1MPa或0.5MPa的压强)，保持一定时间(例如5～30s，进一步例如为10s)，然后UV固化封装胶层。例如，该UV固化的UV光强可以为1000mJ～3000mJ，例如进一步为2000mJ。
例如，在本公开另一些实施例提供中，封装胶层的固化方式可以为激光键合。例如，该封装胶层的材料可以为纯金属铬、硅粉等。
本公开至少一个实施例提供一种根据上述任一实施例的基板的制备方法，该方法包括：构图基板的第一主表面，以在基板的虚设区形成至少一个容置区。对于由该方法获得的基板，当该基板用于对盒的封装工艺中，位于虚设区的气泡可以被挤压至容置区中。如此，在利用该基板完成对盒工艺之后，封装结构(例如封装胶层)中不会存在气泡，使得利用基板100形成的产品例如基因芯片的封装良率得到保证。利用上述方法获得的基板的结构，可以参考图2A～图2C所示实施例中对第一基板100的相关说明。例如，该构图可以为光刻构图工艺，也可以为机械加工。容置区的设置方式可以参考前述实施例中的相关说明，例如，容置区设置为第一凹槽，第一凹槽环绕测试区。
例如，在本公开至少一个实施例提供的基板的制备方法中，形成的第一凹槽可以包括至少一个第一子凹槽，第一子凹槽在第二基板表面上的平面形状为闭合环形，第一子凹槽环绕测试区。如此，至少对于虚设区的任 意位置产生的气泡，在对盒时，该气泡都可以进入第一凹槽中，从而提高由该基板获得的产品例如基因芯片的封装良率。根据该方法获得的基板的结构可以参考图3A所示实施例的对第一基板100的相关说明，在此不做赘述。
例如，在本公开至少一个实施例提供的基板的制备方法中，形成的第一凹槽可以包括至少一个第二子凹槽，第二子凹槽在第二基板表面上的平面形状为线段形。如此，可以根据气泡容易产生的区域以及重要的特定区域布局第一凹槽，而且在基板上形成线段形的第一凹槽，加工难度低。根据该方法获得的基板的结构可以参考图3B所示实施例的对第一基板100的相关说明，在此不做赘述。
例如，在本公开至少一个实施例中，第一凹槽可以包括至少一个第一子凹槽和至少一个第二子凹槽。第一子凹槽在第二基板表面上的平面形状为闭合环形且环绕测试区，第二子凹槽在第二基板表面上的平面形状为线段形。例如，第二子凹槽可以位于面积较大的虚设区中。如此，可以提高气泡进入第一凹槽的几率，提高由该基板获得的产品例如基因芯片的封装良率。根据该方法获得的基板的结构可以参考图3C所示实施例的对第一基板100的相关说明，在此不做赘述。
例如，本公开至少一个实施例提供的基板的制备方法，还包括：在基板的测试区形成至少一个第二凹槽，并且在该第二凹槽的两端形成贯穿基板的第二过孔。根据该方法获得的基板的结构可以参考图4B所示实施例的对第一基板100的相关说明。
本公开至少一个实施例提供一种根据上述任一实施例的基因芯片的制备方法，该方法包括：提供第一基板，构图第一基板的第一主表面，以形成至少一个容置区；提供第二基板；在第一基板的第一主表面或第二基板的面对第一主表面的表面上涂覆封装胶，封装胶至少部分形成在虚设区内，封装胶环绕容置区；对盒第一基板和第二基板，第二基板位于第一基板的第一主表面上；以及固化封装胶以形成封装胶层。例如，容置区设置为第一凹槽，第一凹槽环绕测试区。利用上述方法获得的基因芯片的结构，可以参考图2A～图2C所示的实施例的相关说明。
例如，在本公开至少一个实施例提供的制备方法中，固化封装胶层的方法包括激光键合和UV固化中的至少一种。关于封装胶层的材料类型、 固化方式等可以参考前述实施例中的相关说明，在此不做赘述。
对于本公开，还有以下几点需要说明：
(1)本公开实施例附图只涉及到与本公开实施例涉及到的结构，其他结构可参考通常设计。
(2)为了清晰起见，在用于描述本公开的实施例的附图中，层或区域的厚度被放大或缩小，即这些附图并非按照实际的比例绘制。
(3)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，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权利要求的保护范围为准。

Claims (20)

  1. 一种用于生物信息检测的基板，包括第一主表面，所述第一主表面包括测试区和位于所述测试区周围的虚设区，
    其中，所述第一主表面上设置有至少一个容置区，所述容置区位于所述虚设区。
  2. 根据权利要求1所述的基板，其中，
    所述容置区设置为第一凹槽，所述第一凹槽环绕所述测试区。
  3. 根据权利要求2所述的基板，其中，
    所述第一凹槽包括至少一个第一子凹槽，所述第一子凹槽在所述第二基板表面上的平面形状为闭合环形。
  4. 根据权利要求3所述的基板，其中，
    所述闭合环形的形心与所述测试区的形心重合。
  5. 根据权利要求4所述的基板，其中，
    所述第一子凹槽的彼此相对的两边至所述测试区的形心的距离相等。
  6. 根据权利要求2所述的基板，其中，
    所述第一凹槽包括至少一个第二子凹槽，所述第二子凹槽在所述第二基板表面上的平面形状为线段形。
  7. 根据权利要求4所述的基板，其中，
    所述第二子凹槽设置为多个，并且所有所述第二子凹槽构成的图形的形心与所述测试区的形心重合。
  8. 根据权利要求7所述的基板，其中，
    所述第二子凹槽为两个，并且两个所述第二子凹槽相对于所述测试区的形心中心对称；或者
    所述第二子凹槽不少于三个，并且所述第二子凹槽在以所述测试区的形心为中心的环形上等间距分布。
  9. 根据权利要求2-8任一所述的基板，其中，
    所述基板的设置有所述第一凹槽的区域设置有至少一个第一过孔，所述第一过孔使得所述第一凹槽与所述第一主表面相对的表面连通。
  10. 根据权利要求2-9中任一项所述的基板，其中，
    所述第一凹槽构成的图形以所述测试区的形心为基准中心对称。
  11. 根据权利要求10所述的基板，其中，
    所述测试区的边缘至所述基板的边缘之间，间隔排布多个所述第一凹槽，所述测试区的边缘、多个所述第一凹槽、所述基板的边缘为等间距分布；或者
    所述测试区的边缘至所述基板的边缘之间设置一个所述第一凹槽，所述测试区的边缘、所述第一凹槽、所述基板的边缘为等间距分布。
  12. 根据权利要求2-11中任一项所述的基板，还包括：
    至少一个第二凹槽，位于所述测试区且位于所述基板的第一主表面；
    其中，所述基板包括位于所述第二凹槽两端的第二过孔，所述第二过孔使得所述第二凹槽与所述第一主表面相对的表面连通。
  13. 根据权利要求12所述的基板，其中，
    在平行于所述第一主表面的方向上，所述第一凹槽和所述第二凹槽的宽度相等。
  14. 一种基因芯片，包括：
    第一基板，所述第一基板为权利要求1-11中任一项所述的基板；
    第二基板，与所述第一基板相对设置；以及
    封装胶层，位于所述第一基板和所述第二基板之间，并至少部分位于所述虚设区内；
    其中，所述封装胶层环绕所述容置区。
  15. 根据权利要求14所述的基因芯片，其中，
    所述第一基板包括至少一个第二凹槽，位于所述测试区且位于所述第一基板的第一主表面上，以及
    所述第一基板的设置有所述第二凹槽的位置设置有至少两个第二过孔，所述第二过孔贯穿所述第一基板。
  16. 根据权利要求15所述的基因芯片，其中，所述第二基板还包括修饰层，以及
    所述修饰层位于所述第二基板的面向所述第一基板的表面。
  17. 根据权利要求15或16所述的基因芯片，其中，
    在平行于所述第一主表面的方向上，所述容置区和所述第二凹槽的宽度相等。
  18. 根据权利要求14所述的基因芯片，其中，所述第二基板包括至 少一个第二凹槽，位于所述测试区且位于所述第二基板的面向所述第一基板的表面上，以及
    所述第二基板包括位于所述第二凹槽两端的第二过孔，所述第二过孔贯穿所述第二基板。
  19. 根据权利要求18所述的基因芯片，其中，所述第一基板还包括修饰层，以及
    所述修饰层位于所述第一基板的第一主表面上。
  20. 根据权利要求18或19所述的基因芯片，其中，
    在平行于所述第一主表面的方向上，所述容置区和所述第二凹槽的宽度相等。
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