WO2012126292A1 - 一种用于生物芯片的接口装置 - Google Patents

一种用于生物芯片的接口装置 Download PDF

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Publication number
WO2012126292A1
WO2012126292A1 PCT/CN2012/070998 CN2012070998W WO2012126292A1 WO 2012126292 A1 WO2012126292 A1 WO 2012126292A1 CN 2012070998 W CN2012070998 W CN 2012070998W WO 2012126292 A1 WO2012126292 A1 WO 2012126292A1
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WIPO (PCT)
Prior art keywords
interface
sample
instrument
layer
biochip
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PCT/CN2012/070998
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English (en)
French (fr)
Inventor
叶嘉明
王品虹
王国青
邢婉丽
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博奥生物有限公司
清华大学
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Application filed by 博奥生物有限公司, 清华大学 filed Critical 博奥生物有限公司
Priority to US14/006,512 priority Critical patent/US9101924B2/en
Publication of WO2012126292A1 publication Critical patent/WO2012126292A1/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
    • 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
    • B01L3/502715—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 interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • 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
    • B01L3/502769—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 multiphase flow arrangements
    • B01L3/502784—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 multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • 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
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/141—Preventing contamination, tampering
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0874—Three dimensional network
    • 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
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics

Definitions

  • the present invention relates to an interface device for a biochip. Background technique
  • Biochip is a multidisciplinary integrated technology developed at the end of the 20th century. As a technology platform, biochip has been widely used in gene expression, functional genomics, disease diagnosis, drug screening and other fields, and gradually extended to biosynthesis, biochemistry. Other fields such as reaction and nanobiology.
  • Biochips need to be equipped with large instruments to operate and process the chips and samples. In order to avoid cross-contamination between different samples, most biochips are used in a single-use manner. However, the interface between the instruments and the chips is not one-time use. After each chip operation is completed, it is necessary to perform long-time cleaning and disinfection of the interface between the instrument and the chip to avoid contamination caused by residual chemical or biological molecules at the interface. Although the process of increasing the cleaning can reduce the occurrence of pollution to a certain extent, the cumbersome operation process, large-scale cleaning reagents, and incomplete cleaning and disinfection still plague the user, restricting the biological to some extent. The promotion and use of chip technology. Summary of the invention
  • biochip interface device that is structurally simple, easy to operate, and inexpensive.
  • the biochip interface device isolates the sample solution from the instrument interface to avoid sample contamination caused by direct contact of multiple sample solutions with the instrument interface.
  • the interface device for a biochip comprises at least one interface unit, the interface unit is formed by an instrument interface layer, a fluid channel layer and a sample interface layer, and the instrument interface layer is provided with at least one instrument interface, a fluid channel
  • the layer is provided with a hollow fluid channel
  • the sample interface layer is provided with at least one sample interface, and the two ends of the fluid channel are respectively connected to the sample interface and the instrument interface.
  • the interface unit for the interface device of the biochip provided by the invention may also be formed by two layers of the instrument interface layer and the sample interface layer, the instrument interface layer is provided with at least one instrument interface and a groove, and the sample interface layer is provided with at least one A sample interface, the two ends of the groove are respectively connected to the sample interface and the instrument interface as a fluid channel.
  • the interface unit for the interface device of the biochip provided by the invention may also be formed by two layers of the instrument interface layer and the sample interface layer, the instrument interface layer is provided with at least one instrument interface, and the sample interface layer is provided with at least one sample interface and one A groove, the two ends of which are respectively connected to the sample interface and the instrument interface as a fluid passage.
  • the shape of the interface device for a biochip provided by the present invention may be a plate shape or a disk shape, and may be designed according to actual needs.
  • a person skilled in the art can make modifications and alterations to the products described herein to implement and apply the techniques of the present invention. All such alternatives and modifications are considered to be included within the scope of the present invention.
  • the interface device for a biochip provided by the present invention, the material of the instrument interface layer, the fluid channel layer and the sample interface layer are independently selected from the group consisting of glass, high molecular polymer, silicon wafer, metal or metal oxide, preferably polycarbonate. , polypropylene, plexiglass, polystyrene, ABS, polyethylene, polyvinyl chloride, polyoxymethylene.
  • the sealing between the instrument interface layer, the fluid channel layer and the sample interface layer can be sealed by means of adhesive, welding, or sealing.
  • adhesive adhesive, welding, or sealing.
  • the material of each layer is glass, polymer, silicon wafer, metal or metal oxide, it is preferably sealed by a binder which is a calendering type binder, a hot melt type binder, and a reaction.
  • Type of adhesive, solvent type adhesive, emulsion type adhesive or solventless liquid adhesive when the material of each layer is metal or metal oxide, it can also be sealed by welding or the like.
  • the number of sample interfaces of the interface device for biochips provided by the present invention is 1-8, which not only avoids between samples and instruments. Contact contamination can also avoid cross-contamination between biological samples.
  • the number of instrument interfaces of the interface device for a biochip provided by the present invention is 1-8.
  • the interface device for a biochip provided by the present invention may be used independently or integrated on a biochip in the form of an anti-pollution functional unit.
  • the interface device for a biochip of the present invention can be used to prevent static hybrid biochip contamination. After the sample solution is added to the sample hole of the biochip, the interface device of the present invention and the biochip are sealed by means of adhesive or mechanical clamp, so that the sample interface of the interface device is connected with the sample hole of the biochip, and the interface is The instrument interface of the device is closed.
  • hybridization in a static water bath or an air bath can be performed to avoid contact contamination between the sample solution and the hybridization box, so as to avoid the washing step of the hybridization cassette, and the same hybridization cassette can be used to repeat the same Hybridization experiments of sub-biochips.
  • the interface device for a biochip of the present invention can also be used to prevent contamination of a reciprocating flow hybrid biochip.
  • the reciprocating flow type dynamic hybridization biochip comprises a sample introduction unit and a biochip, the sample introduction unit comprising at least one hybridization reaction chamber, two microfluidic channels and two through holes, the sample introduction unit being composed of a cover sheet layer and The microfluidic layer is formed by sealing, the cover sheet layer is provided with two through holes, and the microfluidic layer is provided with a hollow hybridization reaction chamber and two hollow microfluidic channels, and each microfluidic channel is hybridized at one end.
  • reaction chambers are connected, and the other end is respectively connected with a through hole of the cover sheet layer; the microfluidic layer of the sample introduction unit is sealed with the biochip, and the hybridization reaction chamber is connected with the bioprobe lattice region of the biochip.
  • the interface device of the present invention and the reciprocating flow hybrid biochip are sealed by means of sealing jaws, seals or mechanical clips, and the interface is made
  • the sample interface of the device is in communication with a through hole of the biochip, and the pump valve system gas outlet for providing reciprocating flow force is in communication with the instrument interface of the interface device.
  • the DNA sample is stopped when the hybridization reaction chamber is reached. Thereafter, the sample solution is driven to reflux by the negative pressure mode.
  • the sample solution reciprocates in the hybridization reaction chamber, the sample solution flows from the lower layer of the reciprocating flow hybrid biochip through the sample interface.
  • the fluid passage to the upper interface device is designed to be long enough to ensure that the sample solution does not touch the instrument interface during the reciprocating flow, thereby avoiding contamination problems caused by direct contact between the sample solution and the pump valve system interface.
  • the interface device of the biochip provided by the invention is used for preventing the contamination of the reciprocating flow hybrid biochip by separating the sample solution from the instrument interface through the fluid in the fluid channel, thereby avoiding direct contact between the sample solution and the instrument interface. And cause instrument pollution.
  • the fluid within the fluid passage is a gas or liquid that does not diffuse, dissolve, and react with the sample solution.
  • Chip sealing; gasket and sealing material can be metal or non-metallic materials, such as rubber, plastic, ceramic, graphite, etc. and composite materials, such as rubber-asbestos board, rubber elastomeric materials are currently the most used. .
  • the invention has the advantages that the interface device for the biochip of the invention can prevent the sample from contaminating the instrument, omitting the cumbersome cleaning process after the instrument is used, and has the characteristics of structural tube, operation tube, low cost, and the like, and is suitable for Many fields, such as chemical, biological and medical analysis, have foreseeable enormous economic and social value.
  • Figure 1 is a schematic diagram of an interface device for preventing contamination of a single sample from an instrument interface
  • (a) is a schematic plan view
  • (b) is a schematic view of a three-dimensional structure.
  • 1 is the instrument interface of the biochip interface device
  • 2 is the fluid channel
  • 3 is the sample interface of the biochip interface device.
  • FIG. 2 is a schematic diagram of an interface device for preventing cross-contamination between multiple samples and contamination of the sample interface with the instrument.
  • 1 is the instrument interface of the biochip interface device
  • 3 is the sample interface of the biochip interface device
  • 2-1 is used to prevent The fluid channel contaminated by the sample interface with the instrument
  • 2-2 is the fluid channel used to prevent cross-contamination between different samples.
  • 3 is a schematic diagram of the use effect of the biochip interface device for preventing static hybrid biochip contamination according to the present invention; wherein: 1 is an instrument interface of the biochip interface device, 3 is a sample interface of the biochip interface device, and 4 is an interface device. 5 is a static hybrid biochip.
  • FIG. 4 is a schematic flow chart showing the use of the interface device of the present invention for preventing contamination of a reciprocating flow hybrid biochip
  • Figure 4a 1 is the instrument interface of the biochip interface device, 2 is the fluid channel, 3 is the sample interface of the biochip interface device, 4 is the interface device, and 5 is the reciprocating flow hybrid biochip;
  • Figure 4b and Figure 4c show that the gas pressure pushes the solution to reciprocate in the fluid passage
  • 4d is a schematic structural view of a reciprocating flow hybrid biochip, wherein 11 is a cover sheet layer, 12 is a microfluidic layer, 13 is a microarray chip, and may be a DNA chip or a protein chip, and the specification is 25 X 75 mm, 14 is a pass. Hole, 15 is a microfluidic channel, 16 is a hybridization reaction chamber, 17 is a biological probe point Array. detailed description
  • the invention discloses an interface device for a biochip, and those skilled in the art can learn from the contents of the text and appropriately improve the implementation of the process parameters. It is to be understood that all such alternatives and modifications are obvious to those skilled in the art and are considered to be included in the present invention.
  • the products and applications of the present invention have been described in terms of preferred embodiments, and it is obvious that those skilled in the art can make modifications and/or changes and combinations of the methods and applications described herein without departing from the scope of the invention. The technique of the present invention is applied.
  • FIG. 1 A schematic diagram of an interface device for preventing contamination of a single sample from an instrument interface is shown in Fig. 1, (a) is a plan view, and (b) is a schematic view of a three-dimensional structure. Among them: 1 is the instrument interface of the interface device, 2 is the fluid channel, and 3 is the sample interface of the interface device.
  • Example 2
  • FIG. 2 A schematic diagram of a biochip interface device for preventing cross-contamination between multiple samples and contamination of the sample interface with the instrument is shown in Figure 2, wherein: 1 is the instrument interface of the interface device, 3 is the sample interface of the interface device, and 2-1 is used to prevent Cross-contaminated fluid channels between different samples, 2-2 are fluid channels used to prevent contamination of the sample interface with the instrument.
  • 1 is the instrument interface of the interface device
  • 3 is the sample interface of the interface device
  • 2-1 is used to prevent Cross-contaminated fluid channels between different samples
  • 2-2 are fluid channels used to prevent contamination of the sample interface with the instrument.
  • FIG. 1 A schematic diagram of the use of the interface device for a biochip of the present invention for preventing contamination of a static hybrid biochip is shown in FIG.
  • the hybrid chip is a commonly used microarray hybrid chip, which can be a DNA chip or a protein chip, and is composed of a closed cavity and two sample wells.
  • the sample interface of the interface device of the present invention is connected to the sample well of the biochip, and Sealing is carried out by means of adhesive or mechanical clamp clamping and the instrument interface of the interface device is closed.
  • the interface device for biochip of the present invention prevents the pollution effect of the reciprocating flow hybrid biochip from being shown in Fig. 4.
  • Fig. 4a 1 is the instrument interface of the biochip interface device
  • 2 is the fluid channel
  • 3 is the sample interface of the biochip interface device
  • 4 is the interface device
  • 5 is the reciprocating flow hybrid biochip, and its structure is shown in Fig. 4 (d
  • 11 is a cover sheet layer
  • 12 is a microfluidic layer
  • 13 is a microarray chip, which can be a DNA chip or a protein chip, and has a specification of 25 x 75 mm
  • 14 is a through hole
  • 15 is a microfluidic channel
  • 16 is a hybrid
  • the reaction chamber, 17 is a bioprobe lattice
  • the microfluidic layer is made of a silicon wafer, which is sealed with the microarray chip by an emulsion type adhesive to form a plate-like structure having a microfluidic channel inside
  • the hybridization reaction chamber Communicating with the bioprobe lattice region of the microarray chip, the shape and area of which correspond to the biopro
  • the sample interface of the interface device of the present invention is connected to the through hole, and the sample interface and the through hole can be clamped by means of adhesive or mechanical clamp. Sealed.
  • the pump valve system gas outlet for providing reciprocating flow force communicates with the instrument interface of the interface device, and can be tightly connected by a sealing port and a seal.
  • the sample solution is first pushed in a positive pressure manner until the DNA sample reaches the hybridization reaction chamber, and then the sample is driven by the negative pressure mode.
  • the sample solution flows from the lower biochip through the sample interface to the fluid channel of the upper interface device. Since the fluid channel is designed to be long enough, the sample solution is in the reciprocating flow process. The instrument interface is not touched, so direct contamination of the interface between the sample solution and the pump valve system can be avoided.
  • the biochip interface device is a single-use chip, the cleaning step of the catheter or the interface of the pump valve can be avoided, and the same pump valve is utilized.
  • the system repeats multiple chip hybridization experiments.

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Description

一种用于生物芯片的接口装置 本申请要求于 2011 年 3 月 22 日提交中国专利局、 申请号为 201110068678.x , 发明名称为"一种用于生物芯片的接口装置"的中国专利申请 的优先权， 其全部内容通过引用结合在本申请中。 技术领域
本发明涉及一种用于生物芯片的接口装置。 背景技术
生物芯片是 20世纪末发展起来的一门多学科综合技术， 生物芯片作为一 个技术平台已广泛应用于基因表达、 功能基因组学、 疾病诊断、 药物筛选等多 个领域， 并逐步扩展到生物合成， 生化反应及纳米生物学等其他领域。
生物芯片需要配套大型仪器对芯片及样品进行操作和处理，为了避免不同 样品间的交叉污染， 目前大多数的生物芯片采用一次性使用的方式， 然而， 仪 器与芯片的接口却不是一次性使用的，每张芯片操作完成后，都需要对仪器和 芯片的接口进行长时间的清洗和消毒等操作，以避免化学或生物分子在接口的 残留造成的污染。 虽然， 增加清洗的流程可以在一定程度上减少污染的发生， 但是繁瑣的操作流程、大体积的清洗试剂以及清洗和消毒的不彻底性等问题仍 然困扰着使用者， 在一定程度上制约了生物芯片技术的推广和使用。 发明内容
本发明的目的提供一种结构筒单、操作筒便、成本低廉的生物芯片接口装 置。该生物芯片接口装置将样品溶液与仪器接口隔离，避免多个样品溶液与仪 器接口的直接接触而导致的样品污染。
本发明提供的用于生物芯片的接口装置， 至少含有一个接口单元， 所述接 口单元由仪器接口层、 流体通道层、 样品接口层封固形成， 仪器接口层设置有 至少一个仪器接口， 流体通道层设置有一条镂空的流体通道，样品接口层设置 至少一个样品接口， 所述流体通道两端分别与样品接口和仪器接口连通。 本发明提供的用于生物芯片的接口装置的接口单元也可以由仪器接口层 与样品接口层两层封固形成， 仪器接口层设置有至少一个仪器接口和一凹槽， 样品接口层设置至少一个样品接口，所述凹槽两端分别与样品接口和仪器接口 连通， 作为流体通道。
本发明提供的用于生物芯片的接口装置的接口单元也可以由仪器接口层 与样品接口层两层封固形成，仪器接口层设置至少一个仪器接口，样品接口层 设置有至少一个样品接口和一凹槽，所述凹槽两端分别与样品接口和仪器接口 连通， 作为流体通道。
本发明提供的用于生物芯片的接口装置的形状可以是板状， 也可以是盘 状， 可以按照实际需要设计。相关人员可以对本文所述的产品进行改动或适当 变更， 来实现和应用本发明技术， 所有类似的替换和改动都被视为包括在本发 明的保护范围之内。
本发明提供的用于生物芯片的接口装置， 所述仪器接口层、 流体通道层、 样品接口层的材料独立选自玻璃、 高分子聚合物、 硅片、 金属或金属氧化物， 优选聚碳酸酯、 聚丙烯、 有机玻璃、 聚苯乙烯、 ABS、 聚乙烯、 聚氯乙烯、 聚 甲醛。
本发明提供的用于生物芯片的接口装置， 所述仪器接口层、 流体通道层、 样品接口层之间的封固可以通过粘合剂、焊接、或者加密封件的方式进行封固。 各层材料为玻璃、 高分子聚合物、 硅片、 金属或金属氧化物时， 优选通过粘合 剂进行封固， 所述粘合剂为压延型粘合剂、 热熔型粘合剂、 反应型粘合剂、 溶 剂型粘合剂、乳液型粘合剂或无溶剂液体粘合剂； 各层材料为金属或金属氧化 物时， 还可以通过焊接等方式进行封固。
为了达到同时对多个生物芯片样品进行处理并且避免样品间相互污染的 目的， 本发明提供的用于生物芯片的接口装置的样品接口的数目为 1-8个， 不 仅可避免样品与仪器之间的接触污染， 还可避免生物样品之间的交叉污染。
作为优选，本发明提供的用于生物芯片的接口装置所述仪器接口的数目为 1-8个。
本发明提供的用于生物芯片的接口装置， 可以独立使用，也可以是以防污 染功能单元的形式集成于生物芯片之上。 本发明所述用于生物芯片的接口装置可用于防止静态杂交生物芯片污 染。在生物芯片的样品孔加入样品溶液后，将本发明所述接口装置与生物芯片 采用胶粘剂或机械夹子夹紧的方式进行封接，使接口装置的样品接口与生物芯 片的样品孔连通，将接口装置的仪器接口封闭。将接口装置与生物芯片置于杂 交盒后， 进行静态水浴或空气浴杂交， 可以避免样品溶液和杂交盒之间的接触 污染， 以避免杂交盒的清洗步骤， 可利用同一个杂交盒重复进行多次生物芯片 的杂交实验。
本发明所述用于生物芯片的接口装置还可用于防止往复流式杂交生物芯 片的污染。往复流式动态杂交的生物芯片包含进样单元和生物芯片， 所述进样 单元至少含有一个杂交反应腔室、 两个微流体通道和两个通孔， 所述进样单元 由盖片层和微流体层封固形成， 所述盖片层设置有两个通孔， 所述微流体层设 置有一个镂空的杂交反应腔室和两个镂空的微流体通道，每个微流体通道一端 与杂交反应腔室连通， 另一端分别与盖片层的一个通孔连通； 所述进样单元的 微流体层与生物芯片封固， 其杂交反应腔室与生物芯片的生物探针点阵区连 通。
在往复流式杂交生物芯片的通孔处加入样品溶液后， 将本发明所述接口 装置与往复流式杂交生物芯片采用密封圏、密封件或机械夹子夹紧的方式进行 封接，且使接口装置的样品接口与生物芯片的一个通孔连通， 用于提供往复流 动力的泵阀系统气体出口与接口装置的仪器接口连通。
当提供气体压强泵阀系统开始工作， 先以正压方式推动样品溶液， 直至
DNA样品 4氏达杂交反应腔室时停止， 此后， 改用负压方式驱动样品溶液回流， 样品溶液在杂交反应腔室往复运动时，样品溶液从下层的往复流式杂交生物芯 片通过样品接口流往上层接口装置的流体通道， 由于流体通道设计得足够长， 保证了样品溶液在往复流过程中不会触及仪器接口，因此可以避免样品溶液与 泵阀系统接口的直接接触而导致的污染问题。
本发明提供的一种生物芯片的接口装置在用于防止往复流式杂交生物芯 片的污染时，是通过流体通道内的流体将样品溶液与仪器接口隔离，从而避免 样品溶液与仪器接口的直接接触而导致仪器污染。所述流体通道内的流体为不 与样品溶液发生扩散、 溶解和反应的气体或液体。 本发明提供的用于生物芯片的接口装置在使用时，样品接口、仪器接口与 相应的生物芯片的样品孔或仪器连通后，再通过密封垫和密封圏等起密封功能 的部件使其与生物芯片封接； 密封垫和密封圏材料可为金属材料，也可以是非 金属材料， 如橡胶、 塑料、 陶瓷、 石墨等和复合材料， 如橡胶-石棉板， 目前 使用最多的是橡胶类弹性体材料。
本发明的优点在于：使用本发明所述用于生物芯片的接口装置可防止样品 污染仪器， 省略仪器使用后的繁瑣的清洗流程， 具有结构筒单、 操作筒便、 成 本低廉等特点， 适用于化学、 生物和医学分析等多个领域， 具有可预见的巨大 的经济价值和社会价值。 附图说明
图 1为一种防止单个样品与仪器接口污染的接口装置示意图；
( a ) 为平面示意图， （b ) 为立体结构示意图。 其中： 1 为生物芯片接口 装置的仪器接口， 2为流体通道， 3为生物芯片接口装置的样品接口。
图 2 为一种防止多个样品间交叉污染以及样品与仪器接口污染的接口装 置示意图， 1为生物芯片接口装置的仪器接口， 3为生物芯片接口装置的样品 接口， 2-1 为用于防止样品与仪器接口污染的流体通道， 2-2 为用于防止不同 多个样品间交叉污染的流体通道。
图 3 为本发明所述生物芯片接口装置用于防止静态杂交生物芯片污染的 使用效果示意图； 其中： 1为生物芯片接口装置的仪器接口， 3为生物芯片接 口装置的样品接口， 4为接口装置， 5为静态杂交生物芯片。
图 4 为本发明所述接口装置用于防止往复流式杂交生物芯片污染的使用 流程示意图；
图 4a: 1为生物芯片接口装置的仪器接口， 2为流体通道， 3为生物芯片 接口装置的样品接口， 4为接口装置， 5为往复流式杂交生物芯片；
图 4b与图 4c显示气体压强推动溶液在流体通道往复流动；
图 4d为往复流式杂交生物芯片的结构示意图， 其中 11为盖片层， 12为 微流体层， 13为微阵列芯片， 可为 DNA芯片或蛋白质芯片， 其规格为 25 X 75mm, 14为通孔， 15为微流体通道， 16为杂交反应腔室， 17为生物探针点 阵。 具体实施方式
本发明公开了一种用于生物芯片的接口装置，本领域技术人员可以借鉴本 文内容， 适当改进工艺参数实现。 特别需要指出的是， 所有类似的替换和改动 对本领域技术人员来说是显而易见的， 它们都被视为包括在本发明。本发明的 产品及应用已经通过较佳实施例进行了描述，相关人员明显能在不脱离本发明 内容、精神和范围内对本文所述的方法和应用进行改动或适当变更与组合， 来 实现和应用本发明技术。
为了使本领域的技术人员更好地理解本发明的技术方案， 下面结合具体 实施例对本发明作进一步的详细说明。 实施例 1
防止单个样品与仪器接口污染的接口装置示意图如图 1所示，（a )为平面 示意图， （b ) 为立体结构示意图。 其中： 1为接口装置的仪器接口， 2为流体 通道， 3为接口装置的样品接口。 实施例 2
防止多个样品间交叉污染以及样品与仪器接口污染的生物芯片接口装置 示意图如图 2所示， 其中： 1为接口装置的仪器接口， 3为接口装置的样品接 口， 2-1 为用于防止不同多个样品间交叉污染的流体通道， 2-2 为用于防止样 品与仪器接口污染的流体通道。 实施例 3
本发明所述用于生物芯片的接口装置用于防止静态杂交生物芯片污染的 使用效果示意图见图 3。
如图所示， 杂交芯片为目前常见的一种微阵列杂交芯片， 可为 DNA芯片 或蛋白质芯片， 由一个密闭腔体和两个样品孔构成。在生物芯片的样品孔加入 样品溶液后，将本发明所述接口装置的样品接口与生物芯片的样品孔连通， 并 采用胶粘剂或机械夹子夹紧的方式进行封接，并将所述接口装置的仪器接口封 闭。
将接口装置与生物芯片置于杂交盒后， 进行静态水浴或空气浴杂交， 可 以避免样品溶液和杂交盒之间的接触污染， 该接口装置为一次性使用， 因此可 以避免杂交盒的清洗步骤，利用同一个杂交盒重复进行多个生物芯片的杂交实 验。 实施例 4
本发明所述用于生物芯片的接口装置防止往复流式杂交生物芯片的污染 效果示意图见图 4。
图 4a中 1为生物芯片接口装置的仪器接口， 2为流体通道， 3为生物芯片 接口装置的样品接口， 4为接口装置， 5为往复流式杂交生物芯片， 其结构图 见图 4 ( d ), 其中 11为盖片层， 12为微流体层， 13为微阵列芯片， 可为 DNA 芯片或蛋白质芯片， 其规格为 25 x 75mm, 14为通孔， 15为微流体通道， 16 为杂交反应腔室， 17为生物探针点阵， 微流体层材质为硅片， 通过乳液型粘 合剂与微阵列芯片封接， 形成内部具有微流体通道的板状结构， 所述杂交反应 腔室与所述微阵列芯片的生物探针点阵区连通，其形状与面积与所述微阵列芯 片的生物探针点阵区相对应。
当在往复流式杂交生物芯片的通孔处加入样品溶液后， 将本发明所述接 口装置的样品接口与通孔连通，样品接口与通孔之间可以采用胶粘剂或机械夹 子夹紧的方式进行封接。用于提供往复流动力的泵阀系统气体出口与所述接口 装置的仪器接口连通， 可以采用密封圏、 密封件进行紧密连接。
如图 4b与图 4c所示， 当提供气体压强泵阀系统开始工作，先以正压方式 推动样品溶液， 直至 DNA样品 4氏达杂交反应腔室时停止， 此后， 改用负压方 式驱动样品溶液回流，样品溶液在杂交反应腔室往复运动时，样品溶液会从下 层的生物芯片通过样品接口流往上层接口装置的流体通道，由于流体通道设计 得足够长，保证了样品溶液在往复流过程中不会触及仪器接口， 因此可以避免 样品溶液与泵阀系统接口的直接接触污染问题。由于该生物芯片接口装置为一 次性使用芯片， 因此可以避免泵阀的导管或接口的清洗步骤， 利用同一套泵阀 系统重复进行多次芯片杂交实验。 以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通 技术人员来说， 在不脱离本发明原理的前提下， 还可以做出若干改进和润饰， 这些改进和润饰也应视为本发明的保护范围。

Claims

权 利 要 求
1、 一种用于生物芯片的接口装置， 其特征在于， 至少含有一个接口单元， 所述接口单元由仪器接口层、 流体通道层、 样品接口层封固形成， 仪器接口层 设置有至少一个仪器接口， 流体通道层设置有一条镂空的流体通道，样品接口 层设置至少一个样品接口， 所述流体通道两端分别与样品接口和仪器接口连 通。
2、 一种用于生物芯片的接口装置， 其特征在于， 至少含有一个接口单元， 所述接口单元由仪器接口层与样品接口层封固形成，仪器接口层设置有至少一 个仪器接口和一凹槽，样品接口层设置至少一个样品接口， 所述凹槽两端分别 与样品接口和仪器接口连通。
3、 一种用于生物芯片的接口装置， 其特征在于， 至少含有一个接口单元， 所述接口单元由仪器接口层与样品接口层封固形成，仪器接口层设置至少一个 仪器接口，样品接口层设置有至少一个样品接口和一凹槽， 所述凹槽两端分别 与样品接口和仪器接口连通。
4、 根据权利要求 1-3任一项所述接口装置， 其特征在于： 所述仪器接口 层的材料选自玻璃、 高分子聚合物、 硅片、 金属或金属氧化物。
5、 根据权利要求 1所述接口装置， 其特征在于： 所述流体通道层的材料 选自玻璃、 高分子聚合物、 硅片、 金属或金属氧化物。
6、 根据权利要求 1-3任一项所述接口装置， 其特征在于： 所述样品接口 层的材料选自玻璃、 高分子聚合物、 硅片、 金属或金属氧化物。
7、 根据权利要求 1所述的接口装置， 其特征在于： 所述封固为用粘合剂 进行封固。
8、 根据权利要求 7所述接口装置， 其特征在于： 所述粘合剂为压延型粘 合剂、 热熔型粘合剂、 反应型粘合剂、 溶剂型粘合剂、 乳液型粘合剂或无溶剂 液体粘合剂。
9、 根据权利要求 1所述接口装置， 其特征在于： 所述封固为焊接。
10、 根据权利要求 1所述接口装置， 其特征在于： 所述封固为加密封件封 固。
11、 根据权利要求 1所述接口装置， 其特征在于： 所述样品接口的数目为 -8个。
12、 根据权利要求 1所述接口装置， 其特征在于： 所述仪器接口的数目为-8个。
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