CN1331345A - 集成式微阵列装置 - Google Patents

集成式微阵列装置 Download PDF

Info

Publication number
CN1331345A
CN1331345A CN00109792A CN00109792A CN1331345A CN 1331345 A CN1331345 A CN 1331345A CN 00109792 A CN00109792 A CN 00109792A CN 00109792 A CN00109792 A CN 00109792A CN 1331345 A CN1331345 A CN 1331345A
Authority
CN
China
Prior art keywords
reaction tank
microarray device
integrated microarray
micro
integrated
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN00109792A
Other languages
English (en)
Other versions
CN1137999C (zh
Inventor
邵威
许俊泉
邢婉丽
程京
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tsinghua University
CapitalBio Corp
Original Assignee
Tsinghua University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to CNB00109792XA priority Critical patent/CN1137999C/zh
Application filed by Tsinghua University filed Critical Tsinghua University
Priority to PCT/IB2001/001530 priority patent/WO2002002794A2/en
Priority to EP01958280A priority patent/EP1299564B1/en
Priority to JP2002508034A priority patent/JP3650615B2/ja
Priority to CA2412992A priority patent/CA2412992C/en
Priority to AT01958280T priority patent/ATE432361T1/de
Priority to ES01958280T priority patent/ES2327211T3/es
Priority to DE60138810T priority patent/DE60138810D1/de
Priority to US09/898,271 priority patent/US6703203B2/en
Priority to AU8000301A priority patent/AU8000301A/xx
Publication of CN1331345A publication Critical patent/CN1331345A/zh
Priority to US10/212,917 priority patent/US6998236B2/en
Application granted granted Critical
Publication of CN1137999C publication Critical patent/CN1137999C/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Images

Classifications

    • 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
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50851—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates specially adapted for heating or cooling samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • B01J2219/00315—Microtiter plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00495—Means for heating or cooling the reaction vessels
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00527—Sheets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00527—Sheets
    • B01J2219/00529—DNA chips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00585—Parallel processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00596—Solid-phase processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00608—DNA chips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/0061—The surface being organic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00612—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports the surface being inorganic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00614—Delimitation of the attachment areas
    • B01J2219/00621—Delimitation of the attachment areas by physical means, e.g. trenches, raised areas
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00623—Immobilisation or binding
    • B01J2219/00626—Covalent
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
    • B01J2219/00623—Immobilisation or binding
    • B01J2219/0063—Other, e.g. van der Waals forces, hydrogen bonding
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • B01J2219/00662—Two-dimensional arrays within two-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00722—Nucleotides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/0074—Biological products
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/0074—Biological products
    • B01J2219/00743—Cells
    • 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
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B7/00—Microstructural systems; Auxiliary parts of microstructural devices or systems
    • B81B7/04—Networks or arrays of similar microstructural devices
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • G01N2035/00099—Characterised by type of test elements
    • G01N2035/00158—Elements containing microarrays, i.e. "biochip"
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S977/00—Nanotechnology
    • Y10S977/902—Specified use of nanostructure
    • Y10S977/904—Specified use of nanostructure for medical, immunological, body treatment, or diagnosis
    • Y10S977/924—Specified use of nanostructure for medical, immunological, body treatment, or diagnosis using nanostructure as support of dna analysis

Abstract

一种用于临床诊断、药物筛选、动植物育种、食品卫生检验和司法鉴定等领域的集成式微阵列装置。该装置包括一基片,其上设置了多个反应池,每个反应池中装配了一微阵列芯片。每个反应池底部装配了一温控器,用于单独控制反应池的温度。该装置的规格与标准的96孔板、384孔板或1536孔板相吻合以便用机械手进行自动加样、清洗等操作。反应池之间做成镂空状以利于隔热。该装置可作为载体简便、高效、可靠地完成生化反应和检测。

Description

集成式微阵列装置
本发明涉及一种用于在临床诊断、药物筛选、动植物育种、食品卫生检验和司法鉴定等领域中对多种生物样品进行反应和检测的微阵列装置。
微阵列(microarray)自九十年代初出现以来[参见Fodor S.P.A.，ReadJ.L.，Pirning M.C.等的“光寻址并行化学合成(Light-directed spatiallyaddressable parallel chemical synthesis)”，科学(Science)，第251期，p767-773(1991)]发展非常迅猛，目前它作为生物芯片的一大类别在医学诊断、疾病机理研究、药物筛选、卫生监测、功能基因组学研究等方面具有广阔的应用前景[参见Hacia J.G.的文章，自然遗传学(Nature Genetics)，第14期，p441-447(1996)；Heller R A.等的文章，美国科学院院刊(Proc.Natl.Acad.Sci.USA)，第94期，p2150-2155(1997)]。其基本原理是在各种材料(如玻璃、硅、尼龙膜)表面固定一定密度的探针，如DNA、抗体或抗原、细胞、组织，这些探针包含着特定意义的信息，如对应于某些疾病的特定基因片段，药物待作用的特定细胞或组织，使用该微阵列时，将样品处理后与微阵列上的探针进行作用，样品中的待作用物质(可以是DNA、RNA、抗体或抗原等)可用荧光、化学发光试剂或同位素进行标记以便于检测作用结果。针对不同的标记方法，目前的检测手段有荧光共焦扫描仪、微弱发光测量仪、同位素成像仪等。
目前微阵列虽然应用广泛，但也存在一些问题，比如：目前的微阵列大多追求高密度，每个微阵列上的探针数量达几万至几十万，以求达到高通量并行分析的目的，但是对于特定目的来说，并不一定需要很高密度的探针，相应的微阵列制作成本也就无需那么高。而且，目前的高密度微阵列不能保证检测结果的高可靠性，因为微阵列上的众多探针各方面性质不尽相同，比如用DNA作为探针时，其碱基数或碱基组成并不一定完全相同，这样它们最适宜的杂交温度也就不同，而只有在最适宜的杂交温度下才能得到最严格的杂交特异性结果，也就是说，才能将错配的比例减小到最低，以得到最准确的分析检测结果。另外，目前的微阵列大多只能逐个检测，因此操作起来不方便，检测效率低。
本发明的目的是克服目前微阵列装置的上述不足，提供一种用于对多种生物样品进行反应和检测的高效、廉价、检测结果可靠的微阵列装置。
为实现上述目的，根据本发明的技术方案提出一种集成式微阵列装置，该装置包括一基片，所述基片上设置了多个反应池，每个所述反应池中装配了一个微阵列芯片。该微阵列芯片可以是低密度芯片。在优选的方案中，每个所述反应池底部还装配了一个温控器，这些温控器在计算机的控制下可以对各反应池的温度进行单独控制。使用该装置时，将众多的探针按其热熔点温度的相近程度分成不同的小组，然后将每个小组固定在一个反应池中的一个微阵列芯片上，这一小组所需的特定适宜的反应温度可以通过本装置每个反应池底部的温控器来单独控制。这样对探针进行精细的分组和单独控制温度便可以使操作者严格地控制诸如杂交反应的温度条件，使由于温度控制不适宜导致的检测误差减低到最小。另外，按照本发明优选方案的集成式微阵列装置的尺寸规格与标准的多孔板例如标准的96孔板、384孔板或1836孔板相对应，也就是说，反应池的数量及各反应池之间的距离是标准的，以利于用机械手进行加样、清洗等自动化操作，从而实现简便、高效的生化反应和检测目的。
通过下面结合附图对本发明优选实施例的详细描述，本发明的上述目的和优点将会更加清楚。附图中相同的参考数字表示相同的部件。
图1为根据本发明优选实施例的集成式微阵列装置的俯视图；
图2为根据本发明优选实施例的集成式微阵列装置中的一个单元的立体图；
图3为根据本发明的集成式微阵列装置中的温控器的连线示意图；
图4为可在根据本发明的集成式微阵列装置中用作温控器的一半导体双向温度控制器的结构示意图。
图1为根据本发明优选实施例的集成式微阵列装置的俯视图。该装置包括一个基片1。基片1的材料可以是塑料、玻璃、硅、陶瓷等，根据不同的用途，可以采用致密或非致密材料，刚性或弹性材料。
基片1上以例如蚀刻的方法形成了多个反应池2，每个反应池2中装配了一个微阵列芯片3。反应池的数量及各反应池之间的距离可以根据实际需要进行选择，但是最好与一个标准的多孔板，例如标准的96孔板、384孔板或1836孔板上孔的数量及孔间距相对应，以利于用机械手进行加样、清洗等自动化操作。图1中作为例子示出的集成式微阵列装置的尺寸规格与一标准的96孔板的尺寸相对应，也就是说，基片1上共有96个反应池2，各反应池2之间的距离为9毫米，与标准的96孔板的孔间距相同。
图2为根据本发明优选实施例的集成式微阵列装置中的一个单元的立体图，其中清楚地示出了一个反应池2和装配在其中的微阵列芯片3。反应池2的上端口的形状为长方形，其外接圆直径不大于标准的96孔板的孔径。装配在反应池2中的微阵列芯片3的形状也是长方形的。在本实施例中将反应池2与微阵列芯片3均制成长方形是为了便于正确地定位，但本领域技术人员可以理解，反应池2与微阵列芯片3也可以采用其他形状、例如圆形等，而不限于长方形。反应池2的深度可根据微阵列芯片3的厚度和加样量来决定，例如可在几百微米至几厘米之间变化。
在使用本发明的集成式微阵列装置进行生物或药物分子的检测时，可以将众多的探针按其性质如碱基数或碱基组成分为性质相近的小组，将每个小组的探针固定在一个反应池2中的微阵列芯片3上。探针的种类可以是cDNA、寡核苷酸、抗体或抗原、受体、多肽以及细胞、组织等。微阵列芯片3的基质可以用各种材料如硅、玻璃、尼龙膜等制成。探针与微阵列芯片3的基质之间的固定可以用各种方法，如被动吸附、共价键合、包埋等[参见Beattie W.G.等的文章，分子生物技术(Molecular Biotechnology)，第4期，p213-225(1995)；Subramanian A.等的文章，酶与微生物技术(Enzyme&Microbial Techno1.)，第24期，p26-34(1999)]。
由于对于特定的目的例如诊断或研究某种特定类型的疾病、筛选某种特定药物、进行特定类别的功能基因组研究来说不一定需要很高密度的探针，所以本发明装置中采用的微阵列芯片3可以是其上仅固定了例如数十至数百个探针的低密度微阵列芯片。因此，本发明的装置可以用成本较低的低密度微阵列芯片制成。另一方面，由于本发明的集成式微阵列装置中包括多个单元(例如可为96个、384个、1836个等等)，尽管每个单元中的探针数量可能较少，但整个集成式装置中固定的探针数量可以多达数万至数十万个，能够实现高通量分析的目的。
为了对位于各反应池2中性质各不相同的探针所需的特定的适宜反应温度进行控制，如图2所示，根据本发明的集成式微阵列装置在每个反应池2的底部装配了一个温控器6。图3示出了各温控器6的一种连线方式。其中，每个温控器6具有两根引线9、9’，分别连接至电源的正、负极(未示出)。通过用计算机控制各温控器6与电源接通/不接通，可以对各反应池2中的温度进行单独控制。
温控器6可以简单地为一用来对反应池2进行加热的电阻，该电阻可以以粘合的方式固定在反应池2的底部。如果基片1的材料是硅，可以直接用微加工技术在反应池2背面进行刻蚀，将适于用作加热元件的金属(如铜)沉积或蒸镀到硅材料上。反应池2的底部做得尽量薄以利于加热元件与微阵列芯片3之间的导热。
温控器6也可以是如图4所示的一个半导体双向温度控制器。该半导体双向温度控制器是一种公知的器件，它一方面可以对反应池2进行加热，另一方面当反应池2中的温度高于环境温度、例如为50℃时，可以用来降低反应池2中的温度。该半导体双向温度控制器可以以粘合的方式固定在反应池2的底部。
本领域的技术人员应该理解，可以采用任何合适的现有温控器件作为本发明中的温控器6，而不限于上述的电阻或半导体双向温度控制器。例如，可以采用陶瓷加热器作为温控器6，并将该陶瓷加热器以粘合的方式固定在反应池2的底部以对反应池直接加热。或者，可以采用红外加热器作为温控器6，以非接触式红外光照射的方式对反应池2进行加热。另外，为了对各温控器6进行单独选择和控制所采用的连线方式也不限于图3中所示的方式，而可以根据现有技术中对多个单元中的特定单元进行选择和控制的任何方法来设计。
另外如图1和图2中所示，在按照本发明优选实施例的装置中，各反应池2之间的隔离墙被做成由支撑壁4及其间的通孔5构成的镂空形状，以利于各反应池之间的隔热。镂空的尺寸根据基片材料的不同在保证牢固度的前提下尽量做得较大。举例来说，当基片1的材料为塑料时，每个镂空孔尺寸可以为3×2毫米。镂空的加工手段根据基片材料的不同可采用激光切除[参见Simpson P.C.等的文章，美国科学院院刊(Proc.Natl.Acad.Sci.USA)，第95期，p2256-2261(1998)]、铸模[参见Becker H.等的“Integratedcapillary electrophoresis for chemical analysis(用于化学分析的集成式毛细管电泳)”，传感器现代化(Sensors Update)，卷3，p208-238(1998)]、模压[参见Kopp M.U.等的文章，化学生物学新观点(Current Opinion inChem.Bio1.)，第1期，p410-419(1997)]、铸造[参见Delamarche E.等的文章，美国化学学会杂志(J.Am.Chem.Soc.)，第120期，p500-508(1998)]等。
使用本发明的装置进行生化反应时，在反应池2中的微阵列芯片3上加入样品后，为了防止样品挥发，可以用盖玻片来盖住样品，盖玻片的大小根据微阵列的大小来调节(不大于微阵列的大小)。也可以用高沸点的疏水有机试剂层8覆盖样品层7进行封闭，如图2中所示。有机试剂可以是辛烷烃等，加入的有机试剂量视样品量和微阵列芯片的面积而定，此方法简便、高效。
对本发明装置的各反应池2中的反应结果的检测可用CCD或同位素成像仪来进行，具体使用哪种方法视微阵列芯片3上的样品所使用的标记物质而定。检测时，将集成式微阵列装置置于可以固定尺寸移动的显微镜载物台上。CCD或同位素成像仪每次对一个微阵列芯片成像一次，然后承载集成式微阵列装置的载物台上的动力学装置移动一个反应池的距离，再对下一个微阵列芯片进行成像。这样的检测装置价格较低，操作简单，效率高，可以为一般小型医院和实验室接受。
以上结合优选实施例对根据本发明的集成式微阵列装置进行了描述。本领域的技术人员可以理解，上文中提到的参数例如数量、尺寸和温度等均是示例性的而不应视为对本发明的限制。本发明的范围由后附的权利要求书限定。

Claims (13)

1、一种集成式微阵列装置，包括：
一基片(1)；
设置在所述基片(1)上的多个反应池(2)；和
装配在每个所述反应池(2)中的微阵列芯片(3)。
2、根据权利要求1所述的集成式微阵列装置，其特征在于：
每个所述反应池(2)底部还装配了一个温控器(6)，用于对该反应池的温度进行单独控制。
3、根据权利要求1或2所述的集成式微阵列装置，其特征在于：
设置在基片(1)上的所述反应池(2)的数量和各反应池之间的距离与一标准多孔板上的孔的数量和孔间距相对应。
4、根据权利要求3所述的集成式微阵列装置，其特征在于：
所述标准多孔板为标准的96孔板、384孔板和1836孔板之一。
5、根据权利要求3所述的集成式微阵列装置，其特征在于：
每个所述反应池(2)的上端口的形状为长方形，装配在其中的微阵列芯片(3)的形状也为长方形。
6、根据权利要求3所述的集成式微阵列装置，其特征在于：
每个所述反应池(2)的上端口的形状为圆形。
7、根据权利要求3所述的集成式微阵列装置，其特征在于：
设置在基片(1)上的各所述反应池(2)之间的隔离墙被做成镂空的形状，以利于各反应池之间的隔热。
8、根据权利要求3所述的集成式微阵列装置，其特征在于：
所述基片(1)的材料为塑料、玻璃、硅、陶瓷中的任意一种，基片(1)的表面是致密的或者非致密的。
9、根据权利要求3所述的集成式微阵列装置，其特征在于：
所述温控器(6)为一电阻，该电阻以粘合或蚀刻的方式固定在反应池(2)的底部。
10、根据权利要求3所述的集成式微阵列装置，其特征在于：
所述温控器(6)为一半导体双向温度控制器，该半导体双向温度控制器以粘合的方式固定在反应池(2)的底部。
11、根据权利要求3所述的集成式微阵列装置，其特征在于：
所述温控器(6)为一陶瓷加热器，该陶瓷加热器以粘合的方式固定在反应池(2)的底部。
12、根据权利要求3所述的集成式微阵列装置，其特征在于：
所述温控器(6)为一红外加热器，该红外加热器以非接触式红外光照射的方式对反应池(2)进行加热。
13、根据权利要求3所述的集成式微阵列装置，其特征在于：
所述微阵列芯片(3)为一低密度微阵列芯片。
CNB00109792XA 2000-07-04 2000-07-04 集成式微阵列装置 Expired - Fee Related CN1137999C (zh)

Priority Applications (11)

Application Number Priority Date Filing Date Title
CNB00109792XA CN1137999C (zh) 2000-07-04 2000-07-04 集成式微阵列装置
US09/898,271 US6703203B2 (en) 2000-07-04 2001-07-02 Integrated microarray devices
JP2002508034A JP3650615B2 (ja) 2000-07-04 2001-07-02 集積マイクロアレイデバイス
CA2412992A CA2412992C (en) 2000-07-04 2001-07-02 Integrated microarray devices
AT01958280T ATE432361T1 (de) 2000-07-04 2001-07-02 Vorrichtung mit integrierter mikromatrize
ES01958280T ES2327211T3 (es) 2000-07-04 2001-07-02 Dispositivos de micromatriz integrada.
PCT/IB2001/001530 WO2002002794A2 (en) 2000-07-04 2001-07-02 Integrated microarray devices
EP01958280A EP1299564B1 (en) 2000-07-04 2001-07-02 Integrated microarray devices
AU8000301A AU8000301A (en) 2000-07-04 2001-07-02 Integrated microarray devices
DE60138810T DE60138810D1 (de) 2000-07-04 2001-07-02 Vorrichtung mit integrierter mikromatrize
US10/212,917 US6998236B2 (en) 2000-07-04 2002-08-05 Methods for detecting interaction between a test moiety and a plurality of target moieties

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CNB00109792XA CN1137999C (zh) 2000-07-04 2000-07-04 集成式微阵列装置

Publications (2)

Publication Number Publication Date
CN1331345A true CN1331345A (zh) 2002-01-16
CN1137999C CN1137999C (zh) 2004-02-11

Family

ID=4579868

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB00109792XA Expired - Fee Related CN1137999C (zh) 2000-07-04 2000-07-04 集成式微阵列装置

Country Status (10)

Country Link
US (2) US6703203B2 (zh)
EP (1) EP1299564B1 (zh)
JP (1) JP3650615B2 (zh)
CN (1) CN1137999C (zh)
AT (1) ATE432361T1 (zh)
AU (1) AU8000301A (zh)
CA (1) CA2412992C (zh)
DE (1) DE60138810D1 (zh)
ES (1) ES2327211T3 (zh)
WO (1) WO2002002794A2 (zh)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100405625C (zh) * 2005-07-18 2008-07-23 财团法人工业技术研究院 制作微型热电元件的方法及其整合热电元件的结构
CN101405410A (zh) * 2006-03-21 2009-04-08 皇家飞利浦电子股份有限公司 具有传感器阵列的微电子传感器装置
CN101952720A (zh) * 2007-11-02 2011-01-19 屯特大学 用于分析具有不同拓扑图的表面与环境之间相互作用的高通量筛选方法和设备
CN102998297A (zh) * 2012-12-11 2013-03-27 东南大学 用于表面增强拉曼散射光谱分析的多孔微量反应板
CN111220429A (zh) * 2018-11-23 2020-06-02 中国科学院大连化学物理研究所 一种阵列高通量蛋白质样品预处理装置
CN112108195A (zh) * 2020-09-26 2020-12-22 绍兴市高砚智生物科技有限公司 Pcr装置及控制方法

Families Citing this family (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10112387B4 (de) * 2001-03-15 2004-03-25 Bruker Daltonik Gmbh Massenspektrometrische Genotypisierung
US7504364B2 (en) * 2002-03-01 2009-03-17 Receptors Llc Methods of making arrays and artificial receptors
CA2484681A1 (en) * 2002-04-16 2003-10-23 Dot Diagnostics B.V. Human papilloma virus detection with dna microarray
AU2003256814A1 (en) * 2002-07-26 2004-02-16 Alfa Wasserman, Inc. Macromolecular protection assay
US6870185B2 (en) 2002-08-02 2005-03-22 Amersham Biosciences (Sv) Corp Integrated microchip design
US7469076B2 (en) * 2003-09-03 2008-12-23 Receptors Llc Sensors employing combinatorial artificial receptors
US20050170385A1 (en) * 2002-09-16 2005-08-04 Receptors Llc Artificial receptors including gradients
US20050136483A1 (en) * 2003-09-03 2005-06-23 Receptors Llc Nanodevices employing combinatorial artificial receptors
US20040137481A1 (en) * 2002-09-16 2004-07-15 Receptors Llc Artificial receptor building blocks, components, and kits
US20050037381A1 (en) * 2002-09-16 2005-02-17 Receptors Llc Artificial receptors, building blocks, and methods
US20050037429A1 (en) * 2003-03-28 2005-02-17 Receptors Llc Artificial receptors including reversibly immobilized building blocks and methods
US20060057625A1 (en) * 2002-09-16 2006-03-16 Carlson Robert E Scaffold-based artificial receptors and methods
US20050037428A1 (en) * 2002-09-16 2005-02-17 Receptors Llc Artificial receptors including reversibly immobilized building blocks, the building blocks, and methods
US9453251B2 (en) 2002-10-08 2016-09-27 Pfenex Inc. Expression of mammalian proteins in Pseudomonas fluorescens
EP1613737A4 (en) * 2003-03-28 2008-12-03 Receptors Llc ARTIFICIAL RECEPTORS COMPRISING REVERSIBLE IMMOBILIZED CONSTRUCTION BLOCKS AND METHODS
JP2004313181A (ja) 2003-04-02 2004-11-11 Canon Inc 感染症起炎菌検出用プローブ及びプローブセット、ならびに担体及び遺伝子検査方法
US7384781B2 (en) * 2003-04-30 2008-06-10 Moyle William R Sensors for biomolecular detection and cell classification
US7381440B2 (en) * 2003-06-06 2008-06-03 The United States Of America As Represented By The Secretary Of The Navy Biological laser printing for tissue microdissection via indirect photon-biomaterial interactions
US20050037424A1 (en) * 2003-08-13 2005-02-17 Schembri Carol T. Selectable length linear microarrays
CN100514065C (zh) * 2003-08-27 2009-07-15 松下电器产业株式会社 微芯片及其制造方法以及使用微芯片的检查方法
JP2005069973A (ja) * 2003-08-27 2005-03-17 Kyocera Corp 遺伝子反応管および遺伝子検出装置
CA2537264A1 (en) * 2003-09-03 2005-03-17 Receptors Llc Building blocks for artificial receptors
FR2860641B1 (fr) * 2003-10-03 2006-10-13 Commissariat Energie Atomique Matrice de resistances adressables independamment, et son procede de realisation
US20050084867A1 (en) * 2003-10-15 2005-04-21 Caren Michael P. Hybridization and scanning apparatus
US20050084866A1 (en) * 2003-10-15 2005-04-21 Caren Michael P. Methods and apparatus for sample mixing
NL1024578C2 (nl) * 2003-10-21 2005-04-22 Univ Delft Tech Inrichting voor het uitvoeren van een reactie.
WO2005047454A1 (ja) * 2003-11-13 2005-05-26 Ajinomoto Co., Inc. アミノ酸培地を含有するプレート及びアミノ酸培地を含有するプレートを用いたスクリーニング方法
US20050112588A1 (en) * 2003-11-25 2005-05-26 Caren Michael P. Methods and apparatus for analyzing arrays
US7499166B2 (en) * 2004-05-20 2009-03-03 The Regents Of The University Of California Wide field imager for quantitative analysis of microarrays
US8210119B2 (en) * 2004-07-06 2012-07-03 University Of Utah Research Foundation Spotting device and method for high concentration spot deposition on microarrays and other microscale devices
EP1789797A1 (en) 2004-09-03 2007-05-30 Receptors LLC Combinatorial artifical receptors including tether building blocks
WO2006029383A2 (en) * 2004-09-11 2006-03-16 Receptors Llc Combinatorial artificial receptors including peptide building blocks
DE102004056735A1 (de) * 2004-11-09 2006-07-20 Clondiag Chip Technologies Gmbh Vorrichtung für die Durchführung und Analyse von Mikroarray-Experimenten
US20060106548A1 (en) * 2004-11-12 2006-05-18 Wilson William H Apparatus and method for facilitating molecular interaction measurements
US7879764B2 (en) * 2004-12-28 2011-02-01 Intel Corporation Electrically active combinatorial chemical (EACC) chip for biochemical analyte detection
US8252775B2 (en) * 2005-07-21 2012-08-28 The Board Of Trustees Of The Leland Stanford Junior University Method of treating multiple sclerosis with phosphocholine containing lipids
JP2007078393A (ja) * 2005-09-12 2007-03-29 Yamaha Corp マイクロチップ
US7741106B2 (en) * 2005-09-21 2010-06-22 Moyle William R Sensors for biomolecular detection and cell classification
WO2007034374A2 (en) * 2005-09-23 2007-03-29 Koninklijke Philips Electronics N.V. A micro-fluidic device based upon active matrix principles
US20070090166A1 (en) * 2005-10-18 2007-04-26 Shuichi Takayama Microfluidic cell culture device
US20070084706A1 (en) * 2005-10-18 2007-04-19 Shuichi Takayama Microfluidic cell culture device and method for using same
US20070134784A1 (en) * 2005-12-09 2007-06-14 Halverson Kurt J Microreplicated microarrays
CN101365996B (zh) * 2005-12-19 2011-06-15 皇家飞利浦电子股份有限公司 有源矩阵温度控制器阵列
US20070155020A1 (en) * 2005-12-19 2007-07-05 Intel Corporation Detection of chemical analytes by array of surface enhanced Raman scattering reactions
US20090305238A1 (en) * 2006-01-23 2009-12-10 Applera Corporation Microarray Microcard
US7951572B2 (en) * 2006-02-27 2011-05-31 Korea Advanced Institute Of Science And Technology Construction of gold nanoparticle-based peptide chip, and assaying enzyme activity and inhibitor effect using secondary ion mass spectrometric analysis thereof
WO2007107892A1 (en) 2006-03-21 2007-09-27 Koninklijke Philips Electronics N.V. Microelectronic sensor device with sensor array
BRPI0712655A2 (pt) 2006-06-08 2012-11-20 Koninkl Philips Electronics Nv dispositivo de sensor microeletrânico, mÉtodo para investigaÇço de pelo menos uma substÂncia alvo biolàgica, e, uso do dispositivo de sensor microeletrânico
WO2008064304A2 (en) * 2006-11-22 2008-05-29 Trana Discovery, Inc. Compositions and methods for the identification of inhibitors of protein synthesis
US7796510B2 (en) * 2007-03-12 2010-09-14 Citrix Systems, Inc. Systems and methods for providing virtual fair queueing of network traffic
CA2697357A1 (en) * 2007-04-16 2008-10-30 John T. Mcdevitt Cardibioindex/cardibioscore and utility of salivary proteome in cardiovascular diagnostics
BRPI0810120A2 (pt) 2007-04-27 2014-11-11 Dow Global Technologies Inc Processo para selecionar rapidamente hospedeiros microbianos para a identificação de certas cepas com maior rendimento e/ou qualidade na expressão de proteínas heterólogas
US9580719B2 (en) 2007-04-27 2017-02-28 Pfenex, Inc. Method for rapidly screening microbial hosts to identify certain strains with improved yield and/or quality in the expression of heterologous proteins
EP2167635A4 (en) * 2007-06-15 2010-06-30 Glaxosmithkline Llc ANTIBODY FORMULATIONS
EP2197455A4 (en) * 2007-09-14 2010-10-20 Univ North Carolina State COMPOSITIONS AND METHODS FOR IDENTIFYING INHIBITORS OF RETROVIRAL INFECTIONS
KR20090119187A (ko) * 2008-05-15 2009-11-19 삼성전자주식회사 연료전지를 포함하는 패키지, 그 제조 방법, 및 패키지를포함하는 카드 및 시스템
WO2010027003A1 (ja) 2008-09-02 2010-03-11 独立行政法人産業技術総合研究所 細胞検出方法及び該方法に用いるマイクロアレイチップ
CA2776044A1 (en) * 2008-09-29 2010-04-01 Trana Discovery, Inc. Screening methods for identifying specific staphylococcus aureus inhibitors
SG194413A1 (en) * 2008-10-06 2013-11-29 Univ Singapore Bio-assay using liquid crystals
EP2506973A2 (en) * 2009-12-02 2012-10-10 Roche Diagniostics GmbH Multiplexed microarray and method of fabricating thereof
US8753873B2 (en) 2011-04-15 2014-06-17 Roche Nimblegen, Inc. Multiplexed microarray assembly and method for fabricating a multiplexed microarray
TW201243287A (en) * 2011-04-28 2012-11-01 Hon Hai Prec Ind Co Ltd Laser range finder
US10300450B2 (en) 2012-09-14 2019-05-28 Carterra, Inc. Method and device for depositing a substance on a submerged surface
CN103949292B (zh) * 2014-04-04 2016-05-04 北京贝泰科技有限公司 多靶标微阵列芯片全自动杂交清洗染色系统
CN105170208B (zh) * 2015-10-15 2017-05-10 华中科技大学 一种微阵列芯片的制备方法及其产品
EP3901634A1 (en) * 2016-01-20 2021-10-27 Brooks Automation, Inc. Microplate with sub-optimal storage density comprising tube holding receptacles , and method

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6017696A (en) * 1993-11-01 2000-01-25 Nanogen, Inc. Methods for electronic stringency control for molecular biological analysis and diagnostics
CA2143365A1 (en) * 1994-03-14 1995-09-15 Hugh V. Cottingham Nucleic acid amplification method and apparatus
DE69527585T2 (de) * 1994-06-08 2003-04-03 Affymetrix Inc Verfahren und Vorrichtung zum Verpacken von Chips
US6403367B1 (en) * 1994-07-07 2002-06-11 Nanogen, Inc. Integrated portable biological detection system
US5928437A (en) 1995-02-09 1999-07-27 The Boeing Company Microarray for efficient energy generation for satellites
US5545531A (en) * 1995-06-07 1996-08-13 Affymax Technologies N.V. Methods for making a device for concurrently processing multiple biological chip assays
US5716459A (en) 1995-12-13 1998-02-10 Hughes Aircraft Company Monolithically integrated solar cell microarray and fabrication method
US5930117A (en) 1996-05-07 1999-07-27 Sheldahl, Inc. Heat sink structure comprising a microarray of thermal metal heat channels or vias in a polymeric or film layer
US6101946A (en) 1997-11-21 2000-08-15 Telechem International Inc. Microarray printing device including printing pins with flat tips and exterior channel and method of manufacture
US6232066B1 (en) * 1997-12-19 2001-05-15 Neogen, Inc. High throughput assay system
WO2000037684A1 (en) * 1998-12-22 2000-06-29 Kris Richard M High throughput assay system using mass spectrometry
US6004755A (en) 1998-04-07 1999-12-21 Incyte Pharmaceuticals, Inc. Quantitative microarray hybridizaton assays
US6093370A (en) * 1998-06-11 2000-07-25 Hitachi, Ltd. Polynucleotide separation method and apparatus therefor
CN1255552A (zh) * 1998-12-01 2000-06-07 宋克 通用微方阵
US6142681A (en) 1999-02-22 2000-11-07 Vialogy Corporation Method and apparatus for interpreting hybridized bioelectronic DNA microarray patterns using self-scaling convergent reverberant dynamics
US6245511B1 (en) 1999-02-22 2001-06-12 Vialogy Corp Method and apparatus for exponentially convergent therapy effectiveness monitoring using DNA microarray based viral load measurements
US6215894B1 (en) 1999-02-26 2001-04-10 General Scanning, Incorporated Automatic imaging and analysis of microarray biochips
CN1185492C (zh) * 1999-03-15 2005-01-19 清华大学 可单点选通式微电磁单元阵列芯片、电磁生物芯片及应用
US6309833B1 (en) 1999-04-12 2001-10-30 Nanogen/Becton Dickinson Partnership Multiplex amplification and separation of nucleic acid sequences on a bioelectronic microchip using asymmetric structures
US6258593B1 (en) * 1999-06-30 2001-07-10 Agilent Technologies Inc. Apparatus for conducting chemical or biochemical reactions on a solid surface within an enclosed chamber
CN1117282C (zh) * 1999-09-03 2003-08-06 何农跃 聚合酶链式反应微阵列探针循环检测型生物芯片
CN1096627C (zh) * 1999-09-10 2002-12-18 朱纪军 基于电子网板和丝网印刷的化合物微阵列芯片制备方法

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100405625C (zh) * 2005-07-18 2008-07-23 财团法人工业技术研究院 制作微型热电元件的方法及其整合热电元件的结构
CN101405410A (zh) * 2006-03-21 2009-04-08 皇家飞利浦电子股份有限公司 具有传感器阵列的微电子传感器装置
CN101405076B (zh) * 2006-03-21 2013-05-08 皇家飞利浦电子股份有限公司 具有加热阵列的微电子装置
CN101405410B (zh) * 2006-03-21 2013-06-19 皇家飞利浦电子股份有限公司 具有传感器阵列的微电子传感器装置
CN101952720A (zh) * 2007-11-02 2011-01-19 屯特大学 用于分析具有不同拓扑图的表面与环境之间相互作用的高通量筛选方法和设备
CN102998297A (zh) * 2012-12-11 2013-03-27 东南大学 用于表面增强拉曼散射光谱分析的多孔微量反应板
CN111220429A (zh) * 2018-11-23 2020-06-02 中国科学院大连化学物理研究所 一种阵列高通量蛋白质样品预处理装置
CN112108195A (zh) * 2020-09-26 2020-12-22 绍兴市高砚智生物科技有限公司 Pcr装置及控制方法

Also Published As

Publication number Publication date
CA2412992A1 (en) 2002-01-10
DE60138810D1 (de) 2009-07-09
US20020048765A1 (en) 2002-04-25
WO2002002794A3 (en) 2002-08-15
WO2002002794A2 (en) 2002-01-10
JP2004502929A (ja) 2004-01-29
ES2327211T3 (es) 2009-10-27
AU8000301A (en) 2002-01-14
US6998236B2 (en) 2006-02-14
US6703203B2 (en) 2004-03-09
JP3650615B2 (ja) 2005-05-25
EP1299564B1 (en) 2009-05-27
EP1299564A4 (en) 2006-03-08
US20020187509A1 (en) 2002-12-12
CA2412992C (en) 2011-03-15
ATE432361T1 (de) 2009-06-15
CN1137999C (zh) 2004-02-11
EP1299564A2 (en) 2003-04-09

Similar Documents

Publication Publication Date Title
CN1137999C (zh) 集成式微阵列装置
EP1322413B1 (en) Method and apparatus for processing biomolecule arrays
US7097974B1 (en) Support for a method for determining an analyte and a method for producing the support
US6756223B2 (en) Electro-chemical analysis device with integrated thermal sensor and method for monitoring a sample using the device
EP1246698B1 (en) Ultra high throughput sampling and analysis systems and methods
JP5185335B2 (ja) 生物学的サンプル材料のアーカイブ及び臨床分析用のバイオチップ
Cuzin DNA chips: a new tool for genetic analysis and diagnostics
WO2007145206A1 (ja) 担体封入変形容器、担体封入変形容器処理装置、および担体封入変形容器処理方法
CN1117284C (zh) 微流体生物芯片检测分析板及其应用方法
EP1718411B1 (en) A device for analysing an interaction between target and probe molecules
US20040043494A1 (en) Apparatus for studying arrays
CN2390207Y (zh) 微流体生物芯片检测分析板
US20030152957A1 (en) Probe-immobilized reaction arrays
US20030044320A1 (en) High throughput screening micro array platform
JP2004512514A (ja) 再スポット機能を有する高精度知能型バイオチップアレイヤー
US20070141576A1 (en) Biological chip and use thereof
JPWO2004104584A1 (ja) 生体関連物質の検査方法と、そのための流体移送装置と流体移送方法
CN100439514C (zh) 一种细胞差异表达与基因测试复合微流芯片
JP4079808B2 (ja) 核酸増幅およびハイブリダイゼーション検出が可能なプローブ固相化反応アレイ
CN2751028Y (zh) 一种悬浮式生物芯片
JP2005517411A (ja) バイオ−セルチップ
Eickhoff et al. Eckhard Nordhoff, Lajos Nyarsik, Günther Zehetner, Wilfried Nietfeld, and Hans Lehrach
Steel et al. The Flow-Thru Chip
US20050112623A1 (en) Bio-cell chip

Legal Events

Date Code Title Description
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C06 Publication
PB01 Publication
ASS Succession or assignment of patent right

Owner name: CAPITALBIO CORPORATION

Free format text: FORMER OWNER: NONE

Effective date: 20021010

C41 Transfer of patent application or patent right or utility model
TA01 Transfer of patent application right

Effective date of registration: 20021010

Address after: 100084 Tsinghua Yuan, Beijing, Haidian District

Applicant after: Tsinghua University

Co-applicant after: Boao Biochip Co., Ltd., Beijing

Address before: 100084 Tsinghua Yuan, Beijing, Haidian District

Applicant before: Tsinghua University

C14 Grant of patent or utility model
GR01 Patent grant
C56 Change in the name or address of the patentee

Owner name: QINGHUA UNIVERSITY; BOAO BIOLOGICAL CO., LTD.

Free format text: FORMER NAME OR ADDRESS: QINGHUA UNIVERSITY; CAPITALBIO CORPORATION

CP03 Change of name, title or address

Address after: 100084 Tsinghua Yuan, Beijing, Haidian District

Co-patentee after: Capitalbio Corporation

Patentee after: Tsinghua University

Address before: 100084 Tsinghua Yuan, Beijing, Haidian District

Co-patentee before: Boao Biochip Co., Ltd., Beijing

Patentee before: Tsinghua University

CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20040211

Termination date: 20190704