WO2018214747A1 - 一种用于样品检测的芯片及其封装方法 - Google Patents

一种用于样品检测的芯片及其封装方法 Download PDF

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Publication number
WO2018214747A1
WO2018214747A1 PCT/CN2018/086363 CN2018086363W WO2018214747A1 WO 2018214747 A1 WO2018214747 A1 WO 2018214747A1 CN 2018086363 W CN2018086363 W CN 2018086363W WO 2018214747 A1 WO2018214747 A1 WO 2018214747A1
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Prior art keywords
chip
substrate
end surface
sample detection
lower cover
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PCT/CN2018/086363
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English (en)
French (fr)
Inventor
王战会
陈方璐
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天津微纳芯科技有限公司
微纳芯（苏州）科技有限公司
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Priority to EP18805747.5A priority Critical patent/EP3632563A4/en
Publication of WO2018214747A1 publication Critical patent/WO2018214747A1/zh
Priority to US16/691,541 priority patent/US20200086314A1/en

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0689—Sealing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—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
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials

Definitions

  • the invention relates to the technical field of sample detection, and in particular to a chip for sample detection and a packaging method thereof.
  • Microfluidic chip technology is a systematic science technology for precise manipulation of very small (generally microliter, nanoliter or picoliter) fluids in micron-scale flow channels, and is an important part of modern biological and chemical sciences.
  • Information collection and processing platform This technology can be used to integrate or basically integrate basic operations such as sample preparation, reaction, detection, separation or cell culture, sorting, and cleavage involved in the biochemical field onto a microchip, and a network formed by the microchannel can control the fluid.
  • This not only enables automated operations, detection and analysis in traditional biological and chemical experiments, but also successfully implements certain experiments that are difficult or impossible to accomplish under traditional biological and chemical means.
  • Microfluidic chip technology has been widely used in biology, chemistry and medicine for its flexible combination and scale integration of various unit technologies on a whole controllable micro platform.
  • the current microfluidic chip is mainly composed of a substrate 11 and a cover 12, and a micro flow channel 13 is formed on the substrate 11 , and the cover 12 encloses the substrate 11 on which the micro flow channel 13 is formed. Thereby, the micro flow path 13 is formed in a relatively sealed state.
  • the microfluidic chip When the microfluidic chip is applied to optical detection, the sample to be detected and the reagent are placed in the detection area to be reacted, and the substance generated after the detection reaction is detected by an optical method.
  • the chip has high transmittance for light (especially ultraviolet light, 340 nm wavelength), so the general substrate is selected such as plastic, glass or quartz, and the material itself is expensive, and the chip is expensive.
  • Many micro-channels, various chambers for optical detection, etc. are designed on the substrate, which have high processing requirements, which makes the production process cumbersome, and further leads to high production cost of the chip.
  • the embodiments of the present invention are directed to providing a chip for sample detection and a packaging method thereof, so as to solve the problem that when the chip in the prior art is applied to the field of optical detection, the material itself has high transmittance and production. The process is more complicated, and the like, resulting in high technical costs of chip fabrication.
  • One aspect of the present invention provides a chip for sample detection, comprising a substrate, an upper cover disposed above the substrate, and a lower cover disposed under the substrate, the upper end surface of the substrate and the upper cover are sealed, the substrate is The lower end surface is sealed with the lower cover plate, and the substrate is provided with through holes penetrating the upper end surface and the lower end surface.
  • the chip is a microfluidic chip and the via comprises one or more of a microchannel, a reaction chamber, and a detection chamber.
  • the upper end surface of the substrate and the upper cover and/or the lower end of the substrate are directly sealed from the lower cover.
  • the medium is sealed between the upper end surface of the substrate and the upper cover and/or between the lower end surface of the substrate and the lower cover.
  • the medium is a subbing layer.
  • the adhesive layer is a pressure sensitive double sided tape, a UV curable adhesive or an optical grade double sided tape.
  • the upper cover and/or the lower cover is a sheet or film material and is made of one of silicon, glass, and quartz.
  • the upper and/or lower cover is a sheet or film material made of a thermoplastic polymer.
  • thermoplastic polymer comprises one or more of polydimethyl methacrylate, polycarbonate, polystyrene, polyamide, and polyethylene terephthalate.
  • Another aspect of the present invention provides a method for packaging a chip for sample detection, comprising: sealing a surface between an upper end surface of a substrate and an upper cover; sealing the lower end surface of the substrate and the lower cover Wherein the substrate is disposed between the upper cover and the lower cover, and the substrate is provided with through holes penetrating the upper end surface and the lower end surface.
  • the sealing process between the upper end surface of the substrate and the upper cover plate comprises: bonding the adhesive layer to the upper cover; sealing the upper cover plate with the adhesive layer and the upper end surface of the substrate deal with.
  • the sealing process between the lower end surface of the substrate and the lower cover comprises: bonding the adhesive layer to the lower cover; sealing the lower cover to which the adhesive layer is attached and the lower end surface of the substrate deal with.
  • the adhesive layer is a pressure sensitive double sided tape, a UV curable adhesive or an optical grade double sided tape.
  • the upper and/or lower cover is a sheet or film material made of glass, quartz or a thermoplastic polymer.
  • the chip is a microfluidic chip and the via comprises one or more of a microchannel, a reaction chamber, and a detection chamber.
  • the through hole designed on the substrate is penetrated, thereby reducing the requirement of the substrate material for the light transmittance, so that the selection of the substrate material is not limited.
  • the material cost is reduced, and on the other hand, the processing requirements are reduced in the chip production process, which simplifies the production process.
  • the chip structure proposed in this embodiment adds a cover structure, a material with excellent light transmittance is required, but the pure material cost of the upper/lower cover material is only about 1/10 of the cost of the substrate material, and has no function.
  • the flow channel and chamber structure will also have a relatively low manufacturing and processing cost. Therefore, the chip structure provided by the embodiment greatly reduces the overall cost of the chip while satisfying the light transmittance.
  • the packaging method for the chip for sample detection provided by the embodiment of the invention is such that the reaction chamber, the detection chamber and/or the functional flow channel penetrating on the substrate are packaged together by the upper and lower cover plates to form the inside of the chip.
  • the relatively sealed flow path system realizes the function of the chip and satisfies the requirement of the light transmittance of the chip, and the packaging program is simple and easy to operate.
  • FIG. 1 is a schematic structural view of a microfluidic chip in the prior art.
  • FIG. 2 is a schematic structural view of a chip for sample detection according to an embodiment of the present invention.
  • FIG. 3(a) is a schematic structural view of a chip for sample detection according to another embodiment of the present invention.
  • Fig. 3(b) is a schematic cross-sectional view showing the A1-A2 portion of the chip for sample detection shown in Fig. 3(a).
  • FIG. 4 is a flow chart showing a method for packaging a chip for sample detection according to an embodiment of the present invention.
  • FIG. 5 is a flow chart showing a method of packaging a chip for sample detection according to another embodiment of the present invention.
  • the chip includes a substrate 22a, an upper cover 21a disposed above the substrate 22a, and a lower cover 23a disposed under the substrate 22a.
  • the upper end surface of the substrate 22a is sealed between the upper cover 21a, and the lower end surface of the substrate 22a is sealed between the lower cover 23a.
  • a through hole 24a penetrating the upper end surface and the lower end surface is provided on the substrate 22a.
  • the upper cover 21a, the lower cover 23a and the substrate 22a have the same shape and shape, and the shape of the chip may be circular, elliptical, rectangular, square or any other polygonal shape.
  • a material of a plate material (generally having a thickness of 0.5 mm or more) or a film (generally having a thickness of 0.5 mm or less) may be selected.
  • the materials of the two materials may be the same or different, and may be selected from materials such as glass, quartz or thermoplastic polymers which have good light transmittance.
  • the processing methods of the upper cover 21a and the lower cover 23a can be selected from the same or different methods, and the processing techniques such as injection molding and die-cutting can be used, which is not limited in the present invention.
  • a material having a good light transmittance such as glass, quartz or a thermoplastic polymer may be selected, or a material such as a metal or an alloy may be selected as long as a through hole 24a may be formed thereon.
  • the invention is not limited thereto.
  • methods such as injection molding, engraving engraving or 3D printing may be selected, and the invention is not limited thereto.
  • the method of sealing between the upper end surface of the substrate 22a and the upper cover 21a and between the lower end surface of the substrate 22a and the lower cover 23a may be the same or different.
  • the sealing method mainly includes two types of direct sealing method and indirect sealing method.
  • the direct sealing method refers to a method in which the contact surface of the chip material is melted by heating, ultrasonic vibration, etc., and then the two layers of the chip structure are sealed together by heat, ultrasonic vibration, etc., specifically including a method of sealing the two layers of the chip structure together, specifically including Heat sealing method, laser welding method or ultrasonic welding method.
  • the indirect sealing method mainly seals the two-layer chip structure by curing a medium by attaching a layer of medium between the two layers of material.
  • the medium in the middle is generally a glue layer, and specifically may be a pressure sensitive double-sided tape, an ultraviolet light curing glue or an optical grade double-sided tape.
  • the upper end surface of the substrate 22a and the upper cover 21a and the lower end surface of the substrate 22a and the lower cover 23a are sealed by direct sealing.
  • one of the between the upper end surface of the substrate 22a and the upper cover 21a and between the lower end surface of the substrate 22a and the lower cover 23a may be selected to be indirectly sealed, and the other is directly sealed. Or both use indirect sealing.
  • the through hole 24a specifically includes a reaction chamber, a detection chamber, and/or a functional flow path for connecting the reaction chamber and the detection chamber, and the like.
  • the shape and number of the through holes 24a can be differently set according to specific needs or actual needs, for example, the shape can be selected from a circle, an ellipse, a square or other polygons, and the number can be 1-30 or more than 30, The shape and number of the through holes 24a are not limited in the invention.
  • the distribution position of the through holes 24a on the substrate 22a is also set according to the actual needs of those skilled in the art, and is generally distributed outwardly at the center of the chip.
  • the through hole designed on the substrate is penetrated, so that the requirement of the substrate material for the light transmittance is reduced, so that the selection of the material of the substrate is not limited, and the aspect is reduced.
  • the material cost on the other hand, the processing requirements in the chip production process are correspondingly reduced, simplifying the production process.
  • the chip structure proposed in this embodiment adds a cover structure, a material with excellent light transmittance is required, but the pure material cost of the upper/lower cover material is only about 1/10 of the cost of the substrate material, and has no function.
  • the flow channel and chamber structure will also have a relatively low manufacturing and processing cost. Therefore, the chip structure provided by the embodiment greatly reduces the overall cost of the chip while satisfying the light transmittance.
  • FIG. 3(a) is a schematic structural view of a chip for sample detection according to another embodiment of the present invention.
  • This embodiment is basically the same as the embodiment shown in FIG. 2, and the differences will be mainly described below, and the same portions will not be repeatedly described.
  • the chip for sample detection provided in this embodiment is a microfluidic chip, and includes a substrate 22b, an upper cover 21b disposed above the substrate 22b, and a substrate. Lower cover 23b below 22b.
  • the substrate 22b is provided with a detection chamber, a reaction chamber 25 and a microchannel 26, wherein the detection chamber is penetrating, and the reaction chamber 25 and the microchannel 26 are non-penetrating, that is, the through hole 24b includes only Detection chamber.
  • the microfluidic chip is used for detecting the index in the human body. As long as the detection chamber has high light transmittance, the reaction chamber 25 and the micro flow channel 26 have no special requirements for light transmittance, so it can be set to be non-penetrating. of.
  • one or more of the reaction chamber, the detection chamber and the micro flow channel may be designed as a through hole according to specific needs, which is not limited in the present invention.
  • the reaction chamber 25 and the micro flow path 26 are disposed in the intermediate portion of the chip, and the detection chamber (i.e., the through hole 24b) is disposed around the reaction chamber 25 and the micro flow path 26 at the edge of the chip. region.
  • the positions of the above three are not fixed, and the respective numbers thereof may be differently set according to the specific needs of those skilled in the art, and the present invention does not specifically limit this.
  • the size and shape of the plurality of through holes 24b on the same chip may be the same or different, and those skilled in the art may also make different selections according to specific needs, which is not limited by the present invention.
  • the upper cover 21b and/or the lower cover 23b in this embodiment are made of a transparent film material, and the thickness thereof is generally 0.05 mm to 0.5 mm.
  • the material can be selected from thermoplastic polymers, including PMMA (polymethyl methacrylate), PC (polycarbonate), PS (polystyrene), PA (polyamide) and PET (polyethylene terephthalate).
  • PMMA polymethyl methacrylate
  • PC polycarbonate
  • PS polystyrene
  • PA polyamide
  • PET polyethylene terephthalate
  • One or more of the alcohol esters are less expensive to process and process, and are more suitable for large-scale industrial production.
  • the substrate 22b may be made of ABS resin (acrylonitrile-butadiene-styrene copolymer) or PMMA, which has the characteristics of high strength, good toughness, low cost, and easy processing.
  • the upper end surface of the substrate 22b and the upper cover 21b and the lower end surface of the substrate 22b and the lower cover 23b are sealed by indirect sealing method.
  • the upper and lower layers of the chip structure are sealed by curing of the adhesive layer, and the adhesive layer is specifically One of pressure-sensitive double-sided adhesive, ultraviolet-curable adhesive and optical grade double-sided adhesive.
  • the chip for sample detection provided by the embodiment is substantially a microfluidic chip, and the reaction chamber, the detection chamber and the micro flow channel on the substrate are packaged by the upper and lower cover plates together to form a relatively sealed inner portion of the chip.
  • the micro flow path system realizes the function of the micro flow channel chip and reduces the requirement of the substrate material for the ultraviolet transmittance.
  • the upper cover and/or the lower cover are made of a thermoplastic polymer, which has lower cost and processing cost and is suitable for large-scale industrial production.
  • the indirect bonding method between the substrate and the upper cover and between the substrate and the lower cover can be performed at normal temperature, and does not require special supporting equipment for packaging, thereby improving the yield of the chip package and reducing the cost. Also suitable for large-scale industrial production.
  • the experimental instrument used in this experiment is the Celercare M1 automatic biochemical analyzer (detection wavelength 340nm/800nm) of Tianjin Micro-Nano Technology Co., Ltd.
  • the light transmittance of the 340nm ultraviolet light is mainly detected by this instrument.
  • the chip to be tested includes two groups.
  • the first group is the chip structure in the embodiment of the present invention, including two upper and lower cover plates, and the detection holes in the substrate are penetrated.
  • the substrate material is high-transparent PMMA, and the upper and lower cover materials are respectively made of high-transparency PC film, and the upper and lower cover plates and the substrate are respectively sealed by pressure-sensitive double-sided tape. .
  • the second group is a prior art chip structure comprising only the upper cover and the detection holes in the substrate are not penetrating.
  • the substrate material is high-transparent PMMA
  • the upper cover plate is made of high-transparency PC film
  • the upper cover plate and the substrate are sealed together by pressure-sensitive double-sided tape.
  • the two sets of chips are respectively subjected to light source exposure detection, and the light intensity values before and after passing through the upper PC film cover are counted, thereby calculating the absorbance and the transmittance.
  • Each group included 10 pcs test samples, and the test results are shown in Table 1.
  • the transmittance of the second group of chips (ie, the chips in the prior art) in the 340 nm band is only about 84%
  • the first group of chips ie, the chips in the embodiment of the present invention
  • the light transmittance is over 91%, which fully meets the requirements of the chip for the transmittance of the ultraviolet band. It can be seen that the chip structure provided by the embodiment of the invention reduces the overall cost and improves the production process flow when the transmittance of the chip itself is improved.
  • FIG. 4 is a flow chart showing a method for packaging a chip for sample detection according to an embodiment of the present invention. As shown in FIG. 4, the method includes:
  • Step 401 sealing the upper end surface of the substrate and the upper cover
  • Step 402 Perform a sealing process between the lower end surface of the substrate and the lower cover plate; wherein the substrate is disposed between the upper cover plate and the lower cover plate, and the substrate is provided with through holes penetrating the upper end surface and the lower end surface thereof.
  • the upper cover/lower cover has the same shape and shape as the substrate, and may be a plate material (generally having a thickness of 0.5 mm or more) or a film material (generally having a thickness of 0.5 mm or less).
  • the materials of the two materials may be the same or different, and may be selected from materials such as glass, quartz or thermoplastic polymers which have good light transmittance.
  • processing techniques such as injection molding and die cutting can be employed.
  • the material of the substrate is not limited, and a material having a good light transmittance such as glass, quartz or a thermoplastic polymer may be selected, and a material such as a metal or an alloy may be selected as long as a through hole can be formed therethrough.
  • the processing method can be selected such as injection molding, engraving engraving or 3D printing.
  • the through hole specifically includes a reaction chamber, a detection chamber, and/or a functional flow path for connecting the reaction chamber and the detection chamber, and the like.
  • the shape and number can be set differently according to specific needs or actual needs.
  • the shape can be selected from a circle, an ellipse, a square or other polygons, and the number can be 1-30 or more than 30.
  • the distribution position of the through holes on the substrate can also be set before the substrate processing is prepared according to actual needs of those skilled in the art.
  • the reaction chamber, the detection chamber and/or the functional flow channel penetrating on the substrate can be packaged by the upper and lower cover plates to form the inside of the chip.
  • the relatively sealed flow path system realizes the function of the chip and satisfies the requirement of the light transmittance of the chip, and the packaging program is simple and easy to operate.
  • FIG. 5 is a flow chart showing a method of packaging a chip for sample detection according to another embodiment of the present invention. As shown in FIG. 5, the encapsulation method provided by the embodiment of the present invention includes:
  • Step 501 laminating the adhesive layer with the upper cover
  • Step 502 sealing the upper cover plate to which the adhesive layer is attached and the upper end surface of the substrate;
  • Step 503 bonding the adhesive layer to the lower cover
  • Step 504 sealing the lower cover plate to which the adhesive layer is attached and the lower end surface of the substrate; wherein the substrate is disposed between the upper cover and the lower cover, and the substrate is provided with an upper end surface and a lower end surface. Through hole.
  • the above-mentioned through holes include one or more of a reaction chamber for various biochemical reactions, a detection chamber for biochemical detection, and a micro flow path for forming a connection channel, and the number and shape of the through holes can be as needed And to make different settings, the formed chip can be a microfluidic chip.
  • the upper cover and/or the lower cover may be made of a thermoplastic polymer, and specifically include PMMA (polydimethyl methacrylate), PC (polycarbonate), PS (polystyrene), and PA (polyamide). And one or more of PET (polyethylene terephthalate). Compared to conventional glass and quartz, thermoplastic polymers are less expensive to process and process, and are more suitable for large-scale industrial production.
  • the middle adhesive layer can be pressure sensitive double-sided adhesive, ultraviolet light-cured adhesive or optical grade double-sided adhesive.
  • the packaging method of the micro flow channel chip provided by the embodiment, the upper cover and the lower cover are respectively sealed with the substrate provided with the through hole through the adhesive layer to form a relatively micro-flow path system inside the chip, thereby realizing
  • the microfluidic chip function also meets the requirements for ultraviolet light transmittance.
  • the packaging process can be carried out at normal temperature, and does not require special supporting equipment for packaging, which improves the chip packaging yield rate and reduces the cost, and is suitable for large-scale industrial production.

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Abstract

一种用于样品检测的芯片及其封装方法，该芯片包括基板（22a）、设置于基板（22a）上方的上盖板（21a）以及设置于基板（22a）下方的下盖板（23a），基板（22a）的上端面与上盖板（21a）之间密封，基板（22a）的下端面与下盖板（23a）之间密封，基板（22a）上设置有贯穿于上端面和下端面的通孔（24a）。

Description

一种用于样品检测的芯片及其封装方法 技术领域
本发明涉及样品检测技术领域，具体涉及一种用于样品检测的芯片及其封装方法。
发明背景
微流控芯片技术是一种在微米尺度的流道中对极小量(一般为微升、纳升或皮升量级)流体进行精确操控的系统科学技术，是现代生物和化学科学的一个重要的信息采集和处理平台。应用此技术可以将生化领域中涉及的样品制备、反应、检测、分离或细胞培养、分选、裂解等基本操作集成或基本集成到一块微型芯片上，由微流道形成网络，从而可以控制流体贯穿整个系统。这样不仅能够完成传统生物和化学实验中的自动化操作、检测与分析，还可顺利实现传统生物学和化学手段下很难完成或不能完成的某些实验。微流控芯片技术以其将各种单元技术在整体可控的微小平台上灵活组合、规模集成等优势，在生物、化学及医学等领域已得到了广泛的应用。
如图1所示，目前的微流控芯片主要由基板11和盖板12两部分组成，基板11上制作有微流道13，盖板12将制作有微流道13的基板11封装起来，从而使微流道13形成相对密封的状态。
当微流控芯片应用于光学检测时，将待检测样本与试剂放在检测区域内使其反应，通过光学方法对检测反应后生成物质进行检测。这就要求芯片材质本身对光线的吸收程度特别小，以尽可能地减小材料本身对光学检测的影响。该芯片对光线(特别是紫外波段光线，340nm波长)的透过率要求较高，故一般基板选择如塑料、玻璃或石英等透光性优良的材料，材料本身的价格就比较昂贵，而且芯片基板上会设计很多微流道、用于光学检测的各种腔室等，对加工要求较高，使得生产工艺比较繁琐，进一步导致了芯片的制作成本居高不下。
发明内容
有鉴于此，本发明实施例致力于提供一种用于样品检测的芯片及其封装方法，以解决现有技术中的芯片应用于光学检测领域时，由于材质本身对透光率要求高、生产工艺较复杂等原因，从而导致的芯片制作成本高的技术问题。
本发明一方面提供了一种用于样品检测的芯片，包括基板、设置于基板上方的上盖板以及设置于基板下方的下盖板，基板的上端面与上盖板之间密封，基板 的下端面与下盖板之间密封，基板上设置有贯穿于上端面和下端面的通孔。
在一个实施例中，芯片为微流控芯片，通孔包括微流道、反应腔室和检测腔室中的一种或多种。
在一个实施例中，基板的上端面与上盖板之间和/或基板的下端面与下盖板之间直接密封。
在一个实施例中，基板的上端面与上盖板之间和/或基板的下端面与下盖板之间通过介质密封。
在一个实施例中，介质为胶层。
在一个实施例中，胶层为压敏双面胶、紫外光固化胶或光学级双面胶。
在一个实施例中，上盖板和/或下盖板为板材或薄膜材料，材质为硅、玻璃、石英中的一种。
在一个实施例中，上盖板和/或下盖板为板材或薄膜材料，材质为热塑性聚合物。
在一个实施例中，热塑性聚合物包括聚二甲基丙烯酸甲酯、聚碳酸酯、聚苯乙烯、聚酰胺和聚对苯二甲酸乙二醇酯中的一种或多种。
本发明另一方面提供了一种用于样品检测的芯片的封装方法，包括：将基板的上端面与上盖板之间进行密封处理；将基板的下端面与下盖板之间进行密封处理；其中，基板设置于上盖板和下盖板之间，基板上设置有贯穿于上端面和下端面的通孔。
在一个实施例中，将基板的上端面与上盖板之间进行密封处理包括：将胶层与上盖板进行贴合；将贴合有胶层的上盖板与基板的上端面进行密封处理。
在一个实施例中，将基板的下端面与下盖板之间进行密封处理包括：将胶层与下盖板进行贴合；将贴合有胶层的下盖板与基板的下端面进行密封处理。
在一个实施例中，胶层为压敏双面胶、紫外光固化胶或光学级双面胶。
在一个实施例中，上盖板和/或下盖板为板材或薄膜材料，材质为玻璃、石英或热塑性聚合物。
在一个实施例中，芯片为微流控芯片，通孔包括微流道、反应腔室和检测腔室中的一种或多种。
在本发明实施例提供的用于样品检测的芯片中，其基板上设计的通孔是贯穿的，故降低了基板材质对于透光率的要求，使得对于基板材质的选择不受限制，一方面降低了材料成本，另一方面在芯片生产过程中对加工要求也相应降低，简化了生产工艺流程。虽然本实施例提出的芯片结构增加了一层盖板结构，需选用透光性优良的材质，但是由于上/下盖板材质的纯物料成本只有基板材料成本的1/10左右，且没有功能性流道及腔室结构，制作加工成本也会相应较低。所以本实施例提供的芯片结构在满足透光率的同时，极大地降低了芯片的总体成本。
利用本发明实施例提供的用于样品检测的芯片的封装方法，使基板上贯穿的反应腔室、检测腔室和/或功能性流道由上下两层盖板封装在一起，形成了芯片内部相对密封的流路系统，实现了芯片功能的同时，也满足了芯片对于透光率的要求，封装程序简单、易操作。
附图简要说明
图1所示为现有技术中一种微流控芯片的结构示意图。
图2所示为本发明一实施例提供的一种用于样品检测的芯片的结构示意图。
图3(a)所示为本发明另一实施例提供的一种用于样品检测的芯片的结构示意图。
图3(b)为图3(a)所示的用于样品检测的芯片的A1-A2部分的截面示意图。
图4所示为本发明一实施例提供的一种用于样品检测的芯片的封装方法的流程图。
图5所示为本发明另一实施例提供的一种用于样品检测的芯片的封装方法的流程图。
实施本发明的方式
为使本发明的目的、技术手段和优点更加清楚明白，以下结合附图对本发明作进一步详细说明。
图2所示为本发明一实施例提供的一种用于样品检测的芯片的结构示意图。如图2所示，该芯片包括基板22a、设置于基板22a上方的上盖板21a以及设置于基板22a下方的下盖板23a。基板22a的上端面与上盖板21a之间密封，基板22a的下端面与下盖板23a之间密封。基板22a上设置有贯穿于上端面和下端面的通孔24a。
上盖板21a、下盖板23a与基板22a的形状大小相同，芯片的形状可为圆形、椭圆形、长方形、正方形或其他任意多边形。
对于上盖板21a和下盖板23a，可选择板材(一般厚度在0.5mm以上)或薄膜(一般厚度在0.5mm以下)材料。二者的材质既可以相同，也可不同，具体可选择为透光性较好的如玻璃、石英或热塑性聚合物等材质。同样，对于上盖板21a和下盖板23a的加工方式，既可选择相同也可选择不同的方法，可采用如注塑成型、模切成型等加工工艺，本发明对此不做限定。
对于基板22a的材质，其既可选择如玻璃、石英或热塑性聚合物等透光性较好的材质，也可选择如金属或合金等材料，只要可以在其上形成贯穿的通孔24a 即可，本发明对此不做限定。对于其加工方式，可选择如注塑成型、精雕雕刻或3D打印等方法，本发明对此也不做限定。
基板22a的上端面与上盖板21a之间以及基板22a的下端面与下盖板23a之间密封的方法可以相同，也可不同。密封方法主要包括直接封接法和间接封接法两类。直接封接法是指两层材料之间不需要其他介质，通过加热、超声波振动等手段使芯片材质的接触面达到熔融的状态，然后固化将两层芯片结构封接在一起的方法，具体包括热封法、激光焊接法或超声波焊接法等。间接封接法主要通过在两层材料之间贴附一层介质，通过介质的固化将两层芯片结构密封起来。中间的介质一般为胶层，具体可为压敏双面胶、紫外光固化胶或光学级双面胶等。
在本实施例中，如图2所示，基板22a的上端面与上盖板21a之间以及基板22a的下端面与下盖板23a之间采用直接封接法进行密封。在其他实施例中，也可以选择基板22a的上端面和上盖板21a之间和基板22a的下端面和下盖板23a之间中的一个采用间接封接法，另一个采用直接封接法；或者两个都采用间接封接法。
通孔24a具体包括反应腔室、检测腔室和/或用于连接反应腔室和检测腔室的功能性流道等。通孔24a的形状和数目可根据特定需求或实际需要而进行不同的设定，例如，形状可选择圆形、椭圆形、正方形或其他多边形，数目可以为1-30，也可以大于30，本发明对通孔24a的形状和数目不做限定。通孔24a在基板22a上的分布位置也根据本领域的技术人员的实际需求进行设定，一般以芯片的中心向外扩散分布。
在本实施例提供的用于样品检测的芯片中，其基板上设计的通孔是贯穿的，故降低了基板材质对于透光率的要求，使得对于基板材质的选择不受限制，一方面降低了材料成本，另一方面在芯片生产过程中对加工要求也相应降低，简化了生产工艺流程。虽然本实施例提出的芯片结构增加了一层盖板结构，需选用透光性优良的材质，但是由于上/下盖板材质的纯物料成本只有基板材料成本的1/10左右，且没有功能性流道及腔室结构，制作加工成本也会相应较低。所以本实施例提供的芯片结构在满足透光率的同时，极大地降低了芯片的总体成本。
图3(a)所示为本发明另一实施例提供的一种用于样品检测的芯片的结构示意图。本实施例与图2所示实施例基本相同，在下文中将主要描述不同之处，相同的部分将不再重复描述。如图3(a)和图3(b)所示，本实施例提供的用于样品检测的芯片为微流控芯片，包括基板22b、设置于基板22b上方的上盖板21b以及设置于基板22b下方的下盖板23b。基板22b上设置有检测腔室、反应腔室25和微流道26，其中检测腔室是贯穿的，而反应腔室25和微流道26是非贯穿的，也就是说，通孔24b只包括检测腔室。该微流控芯片用于检测人体内指标，只要检测腔室具有较高的透光性即可，反应腔室25和微流道26对透光性没有特别的 要求，所以可以设置成非贯穿的。而在其他实施例的微流控芯片中，可以根据具体的需要将反应腔室、检测腔室和微流道中的一种或多种设计成通孔的形式，本发明对此不做限定。
如图3(a)所示，反应腔室25和微流道26设置于芯片的中间区域，而检测腔室(即通孔24b)围绕反应腔室25和微流道26设置于芯片的边缘区域。实际上上述三者的位置并没有固定的关系，它们各自的数量也可根据本领域技术人员的具体需要而做不同设定，本发明对此不做具体限定。另外，同一芯片上的多个通孔24b的大小和形状可以相同或不同，本领域的技术人员也可根据具体需求进行不同选择，本发明对此不做限定。
本实施例中的上盖板21b和/或下盖板23b采用透明的薄膜材料，其厚度一般为0.05mm～0.5mm。材质可选择热塑性聚合物，具体可包括PMMA(聚二甲基丙烯酸甲酯)、PC(聚碳酸酯)、PS(聚苯乙烯)、PA(聚酰胺)和PET(聚对苯二甲酸乙二醇酯)中的一种或多种。与传统的玻璃和石英相比，热塑性聚合物的成本和加工制作费用更低，且更适于大规模的工业生产。
基板22b可选择ABS树脂(丙烯腈-丁二烯-苯乙烯共聚物)或PMMA材质，其具有强度高、韧性好、成本低、易于加工成型等特点。
基板22b的上端面与上盖板21b之间以及基板22b的下端面与下盖板23b采用间接封接法密封，具体通过胶层的固化将上下两层芯片结构密封起来，其胶层具体为压敏双面胶、紫外光固化胶和光学级双面胶中的一种。
本实施例提供的用于样品检测的芯片实质为微流控芯片，基板上的反应腔室、检测腔室以及贯穿的微流道由上下两层盖板封装在一起，形成芯片内部相对密封的微流路系统，实现了微流道芯片功能的同时，也降低了基板材质对于紫外波段透光率的要求。另外，上盖板和/或下盖板的材质采用热塑性聚合物，其成本和加工制作费用更低，适于大规模的工业生产。基板与上盖板之间及基板与下盖板之间采用的间接密接法在常温下即可进行，不需要专门的配套设备进行封装，提高了芯片封装良品率的同时也降低了成本，同样也适于大规模的工业生产。
下面将对本实施例提供的具体芯片结构与现有技术中的芯片结构的透光性进行对比，这将有助于对本发明的理解。但是，应该理解，本发明并不局限于下述所用的具体材料及封装方法。
本实验所采用的实验仪器为天津微纳芯科技有限公司CelecareM1全自动生化分析仪(检测波长为340nm/800nm)，在本实验中，通过本仪器主要检测芯片对于340nm紫外波段光线的透光率。待测芯片包括两组，第一组为本发明实施例中的芯片结构，包括上、下两层盖板且基板中的检测孔是贯穿的。基板材质为高透光性的PMMA，上、下两层盖板材料分别采用高透光性的PC薄膜，上、下两层盖板与基板之间分别通过压敏双面胶封接在一起。第二组为现有技术中的芯片 结构，只包括上层盖板且基板中的检测孔不是贯穿的。基板材质为高透光性的PMMA，上层盖板采用高透光性的PC薄膜，上层盖板与基板之间通过压敏双面胶封接在一起。
将上述两组芯片分别进行光源曝光检测，统计透过上层PC薄膜盖板前后的光强数值，从而计算出吸光度和透射比。每组包括10pcs测试样品，其测试结果如表1所示。
表1透光性实验的对比数据
Figure PCTCN2018086363-appb-000001
通过上述对比实验发现，第二组芯片(即现有技术中的芯片)在340nm波段的透光率只有84％左右，而第一组芯片(即本发明实施例中的芯片)在340nm波段的透光率达到91％以上，完全符合芯片对于紫外波段透光率的要求。可以看出，本发明实施例提供的芯片结构在提高了芯片本身透光率的情况下，降低了总体成本，简化了生产工艺流程。
图4所示为本发明一实施例提供的一种用于样品检测的芯片的封装方法的流程图。如图4所示，该方法包括：
步骤401：将基板的上端面与上盖板之间进行密封处理；
步骤402：将基板的下端面与下盖板之间进行密封处理；其中，基板设置于上盖板和下盖板之间，基板上设置有贯穿于其上端面和下端面的通孔。
上述上盖板/下盖板与基板的形状大小相同，其既可为板材(一般厚度在0.5mm以上)也可为薄膜材料(一般厚度在0.5mm以下)。二者的材质既可以相同，也可不同，具体可选择为透光性较好的如玻璃、石英或热塑性聚合物等材质。对于其加工方式，可采用如注塑成型、模切成型等加工工艺。
对于基板的材质没有限制，既可选择如玻璃、石英或热塑性聚合物等透光性较好的材质，也可选择金属或合金等材料，只要能够在其上形成贯穿的通孔即可。其加工方式可选择如注塑成型、精雕雕刻或3D打印等方法。
通孔具体包括反应腔室、检测腔室和/或用于连接反应腔室和检测腔室的功能性流道等。其形状和数目可根据特定需求或实际需要而进行不同的设定，例如，形状可选择圆形、椭圆形、正方形或其他多边形，数目可以为1-30，也可以大于30。通孔在基板上的分布位置也可根据本领域的技术人员的实际需求在准备基板加工前进行设定。
利用本实施例提供的用于样品检测的芯片的封装方法，可使基板上贯穿的反应腔室、检测腔室和/或功能性流道由上下两层盖板封装在一起，形成了芯片内部相对密封的流路系统，实现了芯片功能的同时，也满足了芯片对于透光率的要求，封装程序简单、易操作。
图5所示为本发明另一实施例提供的一种用于样品检测的芯片的封装方法的流程图。如图5所示，本发明实施例提供的封装方法包括：
步骤501：将胶层与上盖板进行贴合；
步骤502：将贴合有胶层的上盖板与基板的上端面进行密封处理；
步骤503：将胶层与下盖板进行贴合；
步骤504：将贴合有胶层的下盖板与基板的下端面进行密封处理；其中，基板设置于上盖板和下盖板之间，基板上设置有贯穿于其上端面和下端面的通孔。
上述的通孔包括用于各种生化反应的反应腔室、用于生化检测的检测腔室以及用于形成连接通道的微流道中的一种或多种，通孔的数量及形状可根据需要而做不同设定，形成的芯片可为微流控芯片。
上盖板和/或下盖板的材质可采用热塑性聚合物，其具体包括PMMA(聚二甲基丙烯酸甲酯)、PC(聚碳酸酯)、PS(聚苯乙烯)、PA(聚酰胺)和PET(聚对苯二甲酸乙二醇酯)中的一种或多种。与传统的玻璃和石英相比，热塑性聚合物的成本和加工制作费用更低，且更适于大规模的工业生产。
中间的胶层可为压敏双面胶、紫外光固化胶或光学级双面胶。
利用本实施例提供的微流道芯片的封装方法，使上盖板和下盖板分别与设置有贯穿的通孔的基板通过胶层进行密封，形成芯片内部相对密封的微流路系统，实现了微流控芯片功能的同时，也满足了其对紫外线透光率的要求。其封装过程在常温下即可进行，而且不需要专门的配套设备进行封装，提高了芯片封装良品率的同时，也降低了成本，适于大规模的工业生产。
以上仅为本发明的较佳实施例而已，并非用于限定本发明的保护范围。凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。

Claims (15)

  1. 一种用于样品检测的芯片，其特征在于，包括基板、设置于所述基板上方的上盖板以及设置于所述基板下方的下盖板，所述基板的上端面与所述上盖板之间密封，所述基板的下端面与所述下盖板之间密封，所述基板上设置有贯穿于所述上端面和所述下端面的通孔。
  2. 根据权利要求1所述的用于样品检测的芯片，其特征在于，所述芯片为微流控芯片，所述通孔包括微流道、反应腔室和检测腔室中的一种或多种。
  3. 根据权利要求1或2所述的用于样品检测的芯片，其特征在于，所述基板的上端面与所述上盖板之间和/或所述基板的下端面与所述下盖板之间直接密封。
  4. 根据权利要求1或2所述的用于样品检测的芯片，其特征在于，所述基板的上端面与所述上盖板之间和/或所述基板的下端面与所述下盖板之间通过介质密封。
  5. 根据权利要求4所述的用于样品检测的芯片，其特征在于，所述介质为胶层。
  6. 根据权利要求5所述的用于样品检测的芯片，其特征在于，所述胶层为压敏双面胶、紫外光固化胶或光学级双面胶。
  7. 根据权利要求1至6任意一项所述的用于样品检测的芯片，其特征在于，所述上盖板和/或所述下盖板为板材或薄膜材料，材质为玻璃或石英。
  8. 根据权利要求1至6任意一项所述的用于样品检测的芯片，其特征在于，所述上盖板和/或所述下盖板为板材或薄膜材料，材质为热塑性聚合物。
  9. 根据权利要求8所述的用于样品检测的芯片，其特征在于，所述热塑性聚合物包括聚二甲基丙烯酸甲酯、聚碳酸酯、聚苯乙烯、聚酰胺和聚对苯二甲酸乙二醇酯中的一种或多种。
  10. 一种用于样品检测的芯片的封装方法，其特征在于，包括：
    将基板的上端面与上盖板之间进行密封处理；
    将基板的下端面与下盖板之间进行密封处理；其中，
    所述基板设置于所述上盖板和所述下盖板之间，所述基板上设置有贯穿于所述上端面和所述下端面的通孔。
  11. 根据权利要求10所述的用于样品检测的芯片的封装方法，其特征在于，所述将基板的上端面与上盖板之间进行密封处理包括：
    将胶层与所述上盖板进行贴合；
    将贴合有所述胶层的上盖板与所述基板的上端面进行密封处理。
  12. 根据权利要求10所述的用于样品检测的芯片的封装方法，其特征在于， 所述将基板的下端面与下盖板之间进行密封处理包括：
    将胶层与所述下盖板进行贴合；
    将贴合有所述胶层的下盖板与所述基板的下端面进行密封处理。
  13. 根据权利要求11或12所述的用于样品检测的芯片的封装方法，其特征在于，所述胶层为压敏双面胶、紫外光固化胶或光学级双面胶。
  14. 根据权利要求10至13任意一项所述的用于样品检测的芯片的封装方法，其特征在于，所述上盖板和/或所述下盖板为板材或薄膜材料，材质为玻璃、石英或热塑性聚合物。
  15. 根据权利要求10至14任意一项所述的用于样品检测的芯片的封装方法，其特征在于，所述芯片为微流控芯片，所述通孔包括微流道、反应腔室和检测腔室中的一种或多种。
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