WO1992017782A1 - Dispositif d'analyse simple - Google Patents

Dispositif d'analyse simple Download PDF

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Publication number
WO1992017782A1
WO1992017782A1 PCT/JP1992/000394 JP9200394W WO9217782A1 WO 1992017782 A1 WO1992017782 A1 WO 1992017782A1 JP 9200394 W JP9200394 W JP 9200394W WO 9217782 A1 WO9217782 A1 WO 9217782A1
Authority
WO
WIPO (PCT)
Prior art keywords
container
antibody
analyte
liquid sample
porous member
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.)
Ceased
Application number
PCT/JP1992/000394
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
Fumio Kimura
Naohisa Koizumi
Kouichi Matsuo
Minoru Aoyagi
Kiyomi Harakawa
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.)
Meiji Seika Kaisha Ltd
Original Assignee
Meiji Seika Kaisha Ltd
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
Application filed by Meiji Seika Kaisha Ltd filed Critical Meiji Seika Kaisha Ltd
Priority to US07/949,624 priority Critical patent/US5418171A/en
Priority to DE69226916T priority patent/DE69226916T2/de
Priority to JP04506997A priority patent/JP3126383B2/ja
Priority to EP92907605A priority patent/EP0532762B1/en
Publication of WO1992017782A1 publication Critical patent/WO1992017782A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508Rigid containers without fluid transport within
    • B01L3/5085Rigid containers without fluid transport within for multiple samples, e.g. microtitration plates
    • B01L3/50853Rigid containers without fluid transport within for multiple samples, e.g. microtitration plates with covers or lids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302Apparatus specially adapted for immunological test procedures
    • G01N33/5304Reaction vessels, e.g. agglutination plates
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/04Closures and closing means
    • B01L2300/046Function or devices integrated in the closure
    • B01L2300/047Additional chamber, reservoir
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/069Absorbents; Gels to retain a fluid
    • YGENERAL 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
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00Chemistry: molecular biology and microbiology
    • Y10S435/81Packaged device or kit
    • YGENERAL 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
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00Chemistry: analytical and immunological testing
    • Y10S436/805Optical property
    • YGENERAL 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
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00Chemistry: analytical and immunological testing
    • Y10S436/807Apparatus included in process claim, e.g. physical support structures
    • YGENERAL 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
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00Chemistry: analytical and immunological testing
    • Y10S436/807Apparatus included in process claim, e.g. physical support structures
    • Y10S436/809Multifield plates or multicontainer arrays
    • YGENERAL 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
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00Chemistry: analytical and immunological testing
    • Y10S436/807Apparatus included in process claim, e.g. physical support structures
    • Y10S436/81Tube, bottle, or dipstick

Definitions

  • the present invention relates to an analyzer capable of easily knowing whether or not an object to be analyzed is present in a sample by means of an immunoassay or the like.
  • the presence or absence of an analyte in a sample is brought into contact with a substance that has the property of specifically binding to the analyte, and determination is made based on the presence or absence of a binding reaction between the two substances. Is being done.
  • the presence or absence of the target sequence can be determined by an immunological method using an antigen-antibody reaction or by a hybridization reaction with an oligonucleotide.
  • Immunological methods include antigen and specific ⁇ fc8
  • Japanese Patent Application Laid-Open No. 63-127160 discloses that a membrane in which an antibody is applied in the form of a spot is placed on the upper surface of a cylindrical upper valley and moisture is absorbed under the membrane. Devices buried with highly volatile materials are disclosed. First, a liquid sample was added to the device, followed by gold color. Drop the antibody labeled with the particle. If the antigen is present in the liquid sample at a concentration above the detectable concentration, red-purple spots will be observed. -Similar devices are disclosed in, for example, Japanese Patent Publication No. 61502214 and Japanese Patent Publication No. Sho 633-25551.
  • the present invention aims to provide a simple analyzer.
  • the present invention also provides a device that is hygienic and easy to carry, in which the membrane surface does not easily dry after the reaction, so that the reaction result has little change with time. It is intended.
  • an analyzer is a device for detecting the presence or absence of an analyte in a sample.
  • a porous member having a front surface and a back surface, and carrying on its surface a substance that binds favorably to an analyte
  • the surface of the porous member is observable from outside the container through a transparent portion of the container, and the liquid is An insertion member which is supported in the insertion member so that the sample is absorbed by the absorbent through the porous member;
  • the power is the power.
  • the reaction between the analyte and the substance that specifically binds to the analyte can be easily observed from the outside of the apparatus. be able to .
  • FIG. 1 is a cross-sectional view of a preferred embodiment of the analyzer according to the present invention.
  • FIG. 2 is a cross-sectional view of still another preferred embodiment of the analyzer according to the present invention.
  • FIG. 3 is a perspective view of a preferred embodiment of the analyzer according to the present invention.
  • FIG. 4 and FIG. 5 are diagrams of an embodiment in which a plurality of analyzers according to the present invention are connected.
  • FIG. 6 is a diagram of an embodiment in which a plurality of analyzers according to the present invention are connected to each other and can be easily separated one by one.
  • FIG. 1 shows a preferred embodiment of a diffraction apparatus according to the present invention.
  • FIG. 1 is a cross-sectional view of an analyzer according to the present invention, wherein a container 1 is made of a transparent material, for example, resin, and is a cylindrical container made of a transparent material. It consists of the end 12 provided in the section. This container 1 may be transparent as a whole, or only the bottom 11 may be transparent.
  • the insertion member 2 that can be inserted into the container 1 has a cylindrical shape having an open portion 26 provided on a support member 22 that is also a body of the insertion member 2.
  • the insertion member 2 can be inserted into the container 1, and a projection 27 is provided on the insertion member 2 for stably fixing the two when the insertion member 2 is inserted into the container 1. ing .
  • the projection 27 engages with the end 12 of the container 1 when the insertion member 2 is inserted into the container 1.
  • Fig. 2 shows another preferred embodiment of the analyzer according to the present invention.
  • the support member 22 of the insertion member 2 has a cylindrical tube portion 28 and a flat plate portion 29 connected to the opening thereof.
  • an opening 26 is provided at the bottom of the cylindrical tube, and a ventilation hole 25 is provided at the side of the cylindrical tube.
  • the membrane 21 is inserted into the bottom of the cylindrical portion 28, and the absorbent 23 physically contacted with the membrane 21 is inserted into the membrane 21.
  • the membrane 21 and the absorbing material 23 are cylindrical portions of the supporting member 22.
  • the fixing plate 24 is fixed by being bonded to the flat plate portion of the support member 22.
  • the membrane is made of a porous material.
  • the term “porous” means that the membrane 21 has such a water permeability that water can permeate through the membrane 21 and easily reach the absorbent 23. It is used for its meaning.
  • Preferred examples of the material of the membrane 21 include nitrocellulose, cellulose mixed ester, polyvinylidene fluoride, and nadrolide.
  • Absorbing material 23 is a material capable of absorbing water permeated through membrane 21, such as zero, which can be raised such as iron 66.
  • Preferable examples are filter paper, filter paper powder, ⁇ -star paper, chip ball paper, flute, non-woven cloth, absorbent cotton, and polyacryl. Examples include sodium, linoleic acid, rubber, and polymers ⁇
  • the surface of the membrane 21 on the side of the opening 26 has a specific t ⁇ with respect to the analyte to be examined for the presence or absence thereof. Substance is carried.
  • the analytes whose presence or absence can be examined by the analyzer according to the present invention are substances that are specifically u-ported to the analytes.
  • the analyte and The type is not limited, provided that it is possible to examine the presence or absence of a bond with a substance that specifically binds thereto.
  • a preferred example of a combination of an analyte and a substance that specifically binds to the analyte is an antigen and an antibody, and two hybridizable antibodies. Examples include nucleotide sequences.
  • the presence of the labeling substance on the membrane 21 It is possible to know whether or not the object to be analyzed is present in the object.
  • the container 21 is transparent. The signal generated by the labeling substance can be easily observed from the outside of the container 1.
  • the analyzer according to the present invention can prevent the container 1 from covering the membranes 21... And prevent the membranes 21 from drying out. Therefore, it is possible to judge the test result even after the lapse of time.
  • the liquid sample is absorbed by the absorbing material 23 and the container 1 and the input member 2 are connected stably, and the liquid sample leaks out. It is sanitary without rubbing, and it is also possible to easily carry the analyzer.
  • the analyte to be detected for its presence may be either an antigen or an antibody.
  • the analyte include hemoglobin, HCG, anti-HIV antibody, anti-HCV antibody, HBV antibody, HIV antigen, HCV antigen, HBV antigen, LH, and the like.
  • the so-called Sandwich method is used to determine whether an antigen is present in a sample derived from a living body (eg, blood, saliva, urine, stool, etc.).
  • a sample derived from a living body eg, blood, saliva, urine, stool, etc.
  • the membrane 21 on which the first antibody against the antigen is to be carried is to be examined.
  • the loading of the antibody on the membrane 21 may be carried out by physical adsorption or chemical bonding, and the loading method may vary depending on the material of the membrane 21. You may choose it.
  • a second antibody that binds to the antigen is provided.
  • This second antibody may be labeled directly or indirectly.
  • the method of labeling the second antibody is not particularly limited, but the antibody may be, for example, metal particles, colored latex particles, blue dextrin, bacterial cells, or the like. Preferably, they are labeled by particles, dyes, liposomes, enzymes and the like.
  • a method of labeling an antibody with a gold alloy in particular, is disclosed. (Llori sberger and ossert-J. Histochera. Cytochem. 25, 295-305 (1877)), It is preferable to use Japanese Patent Application Laid-Open No. 635-152553 and Japanese Patent Application Laid-Open No. 63432169.
  • the first antibody and the second antibody described above may be the same antibody, or may be different antibodies.
  • the operation for examining the presence or absence of the antigen ft in the sample by the analyzer shown in FIG. 1 is performed as follows. First, a liquid sample is prepared by appropriately diluting a sample derived from a living body, and the second antibody described above is added to this solution. The liquid sample containing the antibody thus obtained is placed in container 1. In the container 1 containing the liquid sample containing the antibody, the first antibody described above is placed. The insertion member 2 provided with the membrane 21 supporting the body is inserted. If the target sample is present in the liquid sample, the analyte of the liquid sample probe will be the first antibody on the membrane 21 ⁇ ⁇ Also binds to the second antibody.
  • the labeled substance emits a signal on the membrane 2].
  • the signal can be observed from the outside of the container 1 through the transparent part of the container 1 to the volume ⁇ .
  • the membrane 21 will be colored reddish purple. This coloring can be easily observed through the transparent part of the container 1.
  • washing of the unreacted antigen which is usually performed by the Sandwich method, is performed.
  • the operation is omitted.
  • the membrane 21 and the liquid sample are brought into contact with each other without first mixing the second antibody in the liquid sample, the membrane 21 is contacted with washing water for washing.
  • the solution containing the second body may be brought into contact with the membrane 21.
  • the specificity of the second antibody is made more selective, the analysis of the analyte can be performed even if such a washing operation is not performed. It is possible to examine the presence or absence of the antigen, and it is also preferable to omit the washing operation from the viewpoint of simplifying the inspection process.
  • a more preferable example of the analysis using the analyzer according to the present invention is the analysis of hemoglobin in feces. 5 C for feces!
  • the liquid suspended at a concentration of ⁇ 1000-fold is referred to as the liquid sample.
  • a polyclonal antibody against hemoglobin is used as the first antibody, which is supported on the membrane 2.1, and the second antibody is used as the second antibody.
  • Ffl Hemoglobin Monoclonal Monoclonal Antibody Labeled with Gold Colloid This second antibody is combined with the liquid sample described above and the same procedure described above is used to determine the presence of hemoglobin in feces. Wear .
  • the folding device according to the present invention is obtained by integrating a plurality of containers 1 and a plurality of insertion members 2 respectively. It is also possible to configure it.
  • an analyzer according to the present invention in which a plurality of containers 1 and a plurality of insertion members 2 are connected in two rows.
  • FIG. 2 is a cross-sectional view and a plan view of FIG.
  • FIGS. 5 (a) and 5 (b) show an embodiment in which a plurality of containers 1 and insertion members 2 are connected in a row.
  • FIG. 6 it is possible to easily separate one or more of the connected containers 1 and the insertion members 2 as shown in FIG. You may have cuts or bows.
  • a mog-mouth bin solution 601 and the gold-colloid-labeled anti-human hemoglobin monoclonal antibody prepared in the above (2) 6 01 was added to the container 1 as shown in FIG.
  • the antibody-binding membrane prepared in the above (3) was prepared by supporting it as an import member as shown in FIG. 1, and this import member was used as a container. And then overlapped. Three minutes after the superposition, the bonded container and the input member were inverted, and the reaction results on the surface of the antibody-binding membrane were observed for another 60 minutes. . The results are as shown in Table 1.
  • Soil Slightly colored.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Analytical Chemistry (AREA)
  • Molecular Biology (AREA)
  • Clinical Laboratory Science (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Cell Biology (AREA)
  • General Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
  • Steroid Compounds (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
  • Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
PCT/JP1992/000394 1991-03-28 1992-03-30 Dispositif d'analyse simple Ceased WO1992017782A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US07/949,624 US5418171A (en) 1991-03-28 1992-03-30 Method for detecting a target analyte in a sample
DE69226916T DE69226916T2 (de) 1991-03-28 1992-03-30 Einfache analysenvorrichtung
JP04506997A JP3126383B2 (ja) 1991-03-28 1992-03-30 簡易な分析装置
EP92907605A EP0532762B1 (en) 1991-03-28 1992-03-30 Simple analyzing device

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP3/64433 1991-03-28
JP6443391 1991-03-28

Publications (1)

Publication Number Publication Date
WO1992017782A1 true WO1992017782A1 (fr) 1992-10-15

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1992/000394 Ceased WO1992017782A1 (fr) 1991-03-28 1992-03-30 Dispositif d'analyse simple

Country Status (6)

Country Link
US (1) US5418171A (enExample)
EP (1) EP0532762B1 (enExample)
JP (1) JP3126383B2 (enExample)
AT (1) ATE170981T1 (enExample)
DE (1) DE69226916T2 (enExample)
WO (1) WO1992017782A1 (enExample)

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EP1915447A4 (en) * 2005-08-19 2008-07-30 Bioventures Inc METHOD AND DEVICE FOR COLLECTING AND ISOLATING NUCLEIC ACIDS
WO2009145333A1 (ja) * 2008-05-29 2009-12-03 東洋鋼鈑株式会社 生体関連分子の相互作用を検出するための方法およびユニット
JP2016512597A (ja) * 2012-11-09 2016-04-28 オーション・バイオシステムズ・インコーポレイテッドAushon BioSystems,Inc. 検定の検出感度を向上させる方法とシステム
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WO2016138338A1 (en) * 2015-02-27 2016-09-01 Corning Incorporated Fitted lid for multi-well plate
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EP1915447A4 (en) * 2005-08-19 2008-07-30 Bioventures Inc METHOD AND DEVICE FOR COLLECTING AND ISOLATING NUCLEIC ACIDS
WO2009145333A1 (ja) * 2008-05-29 2009-12-03 東洋鋼鈑株式会社 生体関連分子の相互作用を検出するための方法およびユニット
JP4950336B2 (ja) * 2008-05-29 2012-06-13 東洋鋼鈑株式会社 生体関連分子の相互作用を検出するための方法及びユニット
JP2012123012A (ja) * 2008-05-29 2012-06-28 Toyo Kohan Co Ltd 生体関連分子の相互作用を検出するための方法及びユニット
US8778667B2 (en) 2008-05-29 2014-07-15 Toyo Kohan Co., Ltd. Method and unit for detection of interactions of biologically relevant molecules
JP2016512597A (ja) * 2012-11-09 2016-04-28 オーション・バイオシステムズ・インコーポレイテッドAushon BioSystems,Inc. 検定の検出感度を向上させる方法とシステム
US10191037B2 (en) 2012-11-09 2019-01-29 Aushon Biosystems, Inc. Methods of and systems for improved detection sensitivity of assays
JP2018537652A (ja) * 2016-09-19 2018-12-20 ソン シク バック 生化学検査と免疫反応検査を行うマルチユニット、及びこれを用いた検査方法

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EP0532762A1 (en) 1993-03-24
DE69226916T2 (de) 1999-05-12
DE69226916D1 (de) 1998-10-15
JP3126383B2 (ja) 2001-01-22
EP0532762A4 (enExample) 1994-04-13

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