JP2000146977A - Method and apparatus for determination of biologically specific reaction - Google Patents
Method and apparatus for determination of biologically specific reactionInfo
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- JP2000146977A JP2000146977A JP10332019A JP33201998A JP2000146977A JP 2000146977 A JP2000146977 A JP 2000146977A JP 10332019 A JP10332019 A JP 10332019A JP 33201998 A JP33201998 A JP 33201998A JP 2000146977 A JP2000146977 A JP 2000146977A
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- measured
- substance
- measurement
- antigen
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Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、生物学的特異反応
による試料中の物質の測定方法及び測定装置に関するも
のである。このような測定方法及び装置はとりわけ臨床
検査や食品検査等の分野に利用される。TECHNICAL FIELD The present invention relates to a method and an apparatus for measuring a substance in a sample by a biological specific reaction. Such a measuring method and apparatus are used especially in the fields of clinical inspection, food inspection and the like.
【０００２】[0002]
【従来の技術】被測定物質を特異的に捕獲できるリガン
ドを保持させた反応固相、例えば多孔質マトリックスを
用い、被測定物質をフロースルータイプで測定する生物
学的特異反応測定法は、特表昭６１−５０２２１４号、
特開平４−３１８４６２号、特開平６−５０９７３号等
に示されているように公知である。このような測定法に
使用される装置としては、通常、上部開口部を有するコ
ンテナーに吸収材を収容すると共に当該吸収材の上方に
被測定物質と特異的に反応するリガンドを固定化した多
孔質マトリックスを設けた装置が用いられる。係る装置
を用いた被測定物質の測定は、例えば被測定物質が抗原
の場合、上部開口部に被測定物質（即ち、抗原）液を加
えて、被測定物質と特異的に反応するリガンド（即ち、
抗体）を固定化した多孔質マトリックスを通過させ、抗
原を捕獲させる。次いで、上部開口部に、標識（例え
ば、酵素）を結合させた抗体液を添加することにより、
当該抗体をマトリックス上に捕獲された抗原と結合さ
せ、更に標識に基づくシグナル（例えば、発光、放射能
等）を測定することにより抗原の測定が行われる。な
お、多孔質マトリックスを通過した各液は、前記の吸収
材に吸収される。2. Description of the Related Art A biologically specific reaction measuring method for measuring a substance to be measured in a flow-through type using a reaction solid phase holding a ligand capable of specifically capturing the substance to be measured, for example, a porous matrix, is particularly known. No. 61-502214,
It is known as disclosed in JP-A-4-318462 and JP-A-6-50973. As a device used for such a measuring method, a porous material is generally used in which an absorbent is accommodated in a container having an upper opening and a ligand which specifically reacts with a substance to be measured is immobilized above the absorbent. A device provided with a matrix is used. In the measurement of a substance to be measured using such an apparatus, for example, when the substance to be measured is an antigen, a liquid to be measured (that is, an antigen) is added to the upper opening, and a ligand (that is, a ligand that specifically reacts with the substance to be measured) ,
Antibody) is passed through the immobilized porous matrix to capture the antigen. Next, by adding an antibody solution to which a label (for example, an enzyme) is bound,
The antigen is measured by binding the antibody to the antigen captured on the matrix and measuring a signal (for example, luminescence, radioactivity, etc.) based on the label. Each liquid that has passed through the porous matrix is absorbed by the absorbent.
【０００３】[0003]
【発明が解決しようとする課題】上述の被測定物質を特
異的に捕獲できるリガンドを保持させた反応固相（以
下、便宜上、反応マトリックスと称する）を用い、被測
定物質をフロースルータイプで測定する生物学的特異反
応測定法によれば、簡便に被測定物質の測定を行うこと
ができるという効果を奏する。しかし、コンテナー内の
吸収材においても標識に基づくシグナル（非特異的シグ
ナル）が発生する。そのため、反応マトリックスのシグ
ナルを測定する際に、吸収材からの非特異的シグナルの
影響を受けることになり、反応マトリックスのシグナル
を高精度で測定することができなくなるという問題があ
る。係る問題を解消するための手段として、例えば、吸
収材から透過してくる非特異的光シグナルを低減させる
ことを目的として、吸収材と反応マトリックスの間に透
過光低減要素を装着した装置が提案されている（特開平
８−５０６４２０号）。係る装置によれば、吸収材から
の透過光をある程度は低減することができるが、その影
響を完全に排除することは困難であった。The substance to be measured is measured by a flow-through type using a reaction solid phase (hereinafter, referred to as a reaction matrix for convenience) holding a ligand capable of specifically capturing the substance to be measured. According to the method for measuring a biologically specific reaction described above, there is an effect that the substance to be measured can be easily measured. However, a signal based on the label (a non-specific signal) is also generated in the absorbing material in the container. Therefore, when measuring the signal of the reaction matrix, it is affected by the non-specific signal from the absorbing material, and there is a problem that the signal of the reaction matrix cannot be measured with high accuracy. As a means for solving such a problem, for example, an apparatus in which a transmission light reducing element is mounted between the absorber and the reaction matrix for the purpose of reducing non-specific light signals transmitted from the absorber is proposed. (JP-A-8-506420). According to such an apparatus, transmitted light from the absorber can be reduced to some extent, but it has been difficult to completely eliminate the effect.
【０００４】係る問題点を解消するために、本発明者等
は、反応マトリックスを用いるフロースルータイプの生
物学的特異反応測定装置を用いて被測定物質を測定をす
る方法において、反応終了後、反応マトリックスとその
下部に設置されている吸収材を分離し、反応マトリック
スのみをシグナル測定に付すことにより感度の高い測定
ができることを見出し本発明を完成した。本発明は係る
知見に基づいてなされたもので、本発明は、臨床検査の
分野で通常行われる血清、血漿及びその他の体液中の成
分をフロースルータイプの生物学的特異反応測定方法及
びその装置において、吸収材からの非特異的シグナルの
影響を排除でき、測定精度を著しく高めることのできる
測定方法及び測定装置を提供する。[0004] In order to solve such a problem, the present inventors have proposed a method for measuring a substance to be measured using a flow-through type biologically specific reaction measuring device using a reaction matrix. The present inventors have found that a highly sensitive measurement can be performed by separating the reaction matrix from the absorbing material provided under the reaction matrix and subjecting only the reaction matrix to signal measurement, thereby completing the present invention. The present invention has been made based on such findings, and the present invention provides a method and apparatus for measuring a flow-through type biological specific reaction of components in serum, plasma, and other body fluids usually performed in the field of clinical testing. In the above, there is provided a measuring method and a measuring apparatus which can eliminate the influence of a non-specific signal from an absorbing material and can remarkably increase the measuring accuracy.
【０００５】[0005]
【課題を解決するための手段】上記の課題を解決するた
めになされた本発明の要旨は、被測定成分を捕獲できる
リガンドを保持させた反応固相（即ち、反応マトリック
ス）を用いるフロースルータイプの生物学的特異反応測
定において、反応マトリックスを装置本体から分離して
シグナルを測定することからなる生物学的特異反応測定
法及び反応マトリックスが装置本体から分離可能に形成
されていることからなる生物学的特異反応測定装置であ
る。The gist of the present invention to solve the above-mentioned problems is to provide a flow-through type using a reaction solid phase (ie, a reaction matrix) holding a ligand capable of capturing a component to be measured. In the biological specific reaction measurement, a biological specific reaction measuring method comprising separating a reaction matrix from an apparatus main body and measuring a signal, and an organism comprising a reaction matrix being formed separably from the apparatus main body. It is a biologically specific reaction measuring device.
【０００６】[0006]
【発明の実施の形態】本発明は上記の構成からなり、本
発明の測定法及び装置の基本的原理であるフロースルー
タイプの生物学的特異反応測定法及び装置は前述のよう
に公知であり、反応マトリックス、吸収材、コンテナー
等については前掲の文献を参照することができる。本発
明は、反応終了後、反応マトリックスのシグナル測定を
行う際に、反応マトリックスを装置本体から分離してシ
グナルを測定を行うことを特徴とするものであり、係る
測定に使用される装置の一例の概略図を図１に示す。図
１に示される反応装置は、プラスチック等からなる円筒
状のコンテナー１に、吸収材２（例えば、ガラス繊維
等）が収容されており、当該吸収材２の上方には反応マ
トリックス３が設けられており、更にコンテナー１は上
部に開口部４及びキャップ部材５を有する構成となって
いる。反応マトリックス３は、マトリックス保持部材６
により、コンテナー１と分離可能に保持されている。BEST MODE FOR CARRYING OUT THE INVENTION The present invention has the above constitution, and a flow-through type biological specific reaction measuring method and apparatus which are the basic principle of the measuring method and apparatus of the present invention are known as described above. For the reaction matrix, absorbent, container and the like, the above-mentioned documents can be referred to. The present invention is characterized in that, when a signal of a reaction matrix is measured after completion of a reaction, a signal is measured by separating the reaction matrix from an apparatus body, and an example of an apparatus used for such measurement Is schematically shown in FIG. In the reaction device shown in FIG. 1, an absorbent 2 (for example, glass fiber or the like) is contained in a cylindrical container 1 made of plastic or the like, and a reaction matrix 3 is provided above the absorbent 2. The container 1 further has an opening 4 and a cap member 5 at the top. The reaction matrix 3 includes a matrix holding member 6
, And is held so as to be separable from the container 1.
【０００７】係る構成からなる反応装置を使用して被測
定物質を測定する本発明の方法の一例として、被測定物
質である抗原を測定する例の概略を説明する。まず、コ
ンテナー１にキャップ部材５を嵌合させた後、被測定物
質である抗原を含有する試料液を開口部４に供給する。
開口部４に供給された試料液は、抗体（モノクローナル
抗体又はポリクローナル抗体）を保持（感作）させた反
応マトリックス３を通過し、抗原は当該反応マトリック
ス３に捕獲されると共に通過した試料液は吸収材２に吸
収される。次いで、標識化された抗体を開口部４を介し
て供給し、標識化された抗体を反応マトリックス３に捕
獲された抗原と結合させる。その後、開口部４から適当
な洗浄液を供給し、反応マトリックス３を洗浄する。洗
浄された反応マトリックス３は、反応マトリックス保持
部材６をコンテナー１から取り外すことにより装置から
分離し、反応マトリックス３をシグナル測定装置に移
し、常法に準じて標識に基づくシグナルを測定すること
により抗原（被測定物質）を測定（定量又は定性）する
ことができる。[0007] As an example of the method of the present invention for measuring a substance to be measured using a reaction apparatus having such a configuration, an example of measuring an antigen as a substance to be measured will be described briefly. First, after the cap member 5 is fitted to the container 1, a sample liquid containing an antigen which is a substance to be measured is supplied to the opening 4.
The sample liquid supplied to the opening 4 passes through the reaction matrix 3 holding (sensitizing) an antibody (monoclonal antibody or polyclonal antibody), and the antigen is captured by the reaction matrix 3 and the sample liquid passed therethrough is Absorbed by the absorbent 2. Next, the labeled antibody is supplied through the opening 4, and the labeled antibody is bound to the antigen captured by the reaction matrix 3. Thereafter, an appropriate cleaning liquid is supplied from the opening 4 to wash the reaction matrix 3. The washed reaction matrix 3 is separated from the apparatus by removing the reaction matrix holding member 6 from the container 1, and the reaction matrix 3 is transferred to a signal measuring apparatus, and the signal based on the label is measured according to a conventional method to measure the antigen. (Determined substance) can be measured (quantitatively or qualitatively).
【０００８】上記のシグナル測定としては、例えば、化
学発光測定、蛍光測定、比色測定、放射能測定等が例示
される。なお、当該測定は、測定法に応じて計器的測
定、目視的測定の何れであってもよい。また、標識とし
て酵素、蛍光物質、放射性物質等が利用できること；化
学発光基質、蛍光源物質、色原物質等により標識に基づ
く光シグナルを発生させること及びその光学的測定法；
放射性物質に基づく放射能の測定法等はこの分野で周知
である。[0008] Examples of the above signal measurement include chemiluminescence measurement, fluorescence measurement, colorimetric measurement, and radioactivity measurement. The measurement may be either instrumental measurement or visual measurement depending on the measurement method. In addition, an enzyme, a fluorescent substance, a radioactive substance, etc. can be used as a label; a light signal based on the label is generated by a chemiluminescent substrate, a fluorescent substance, a chromogen, etc., and an optical measurement method thereof;
Methods for measuring radioactivity based on radioactive materials are well known in the art.
【０００９】本発明の測定法は、生物学的特異反応に基
づいて被測定物質を測定する方法であれば何れの方法に
も適用でき、このような例として、抗原−抗体反応、核
酸のハイブリダイゼーション、糖鎖−レクチンの反応、
酵素−基質又は阻害剤との反応、生理活性物質−受容体
反応、ビオチン−アビジン反応等が挙げられる。従っ
て、本発明の方法及び装置の測定対象となる物質として
は、例えば、抗原、抗体、ＤＮＡ、ｃＤＮＡ、ＲＮＡ、
糖類、酵素及びその阻害剤、生理活性物質及びその受容
体、ビオチン化物質、アビジン化物質等が例示できる。The measurement method of the present invention can be applied to any method for measuring a substance to be measured based on a biological specific reaction. Examples of such a method include an antigen-antibody reaction and a nucleic acid hybridization method. Hybridization, sugar chain-lectin reaction,
Examples include a reaction with an enzyme-substrate or an inhibitor, a physiologically active substance-receptor reaction, a biotin-avidin reaction, and the like. Therefore, as a substance to be measured by the method and the device of the present invention, for example, antigen, antibody, DNA, cDNA, RNA,
Examples include saccharides, enzymes and their inhibitors, physiologically active substances and their receptors, biotinylated substances, avidinated substances and the like.
【００１０】[0010]
【発明の効果】本発明方法及び装置によれば、吸収材か
らの非特異的シグナルの影響を完全に排除することがで
きるので、分析感度・測定精度を著しく高めることがで
きるという効果を奏する。According to the method and apparatus of the present invention, the effect of non-specific signals from the absorbing material can be completely eliminated, so that there is an effect that the analytical sensitivity and the measurement accuracy can be significantly increased.
【００１１】[0011]
【実施例】以下、具体的な例を挙げて本発明を説明する
が、本発明は実施例に限定されるものではない。 実施例１反応装置の作製 図１に示すように、０．４５μｍの孔径を持つニトロセ
ルロースメンブラン上に抗ＨＢｓ抗原モノクローナル抗
体を感作させた感作メンブラン（反応マトリックス）を
反応マトリックス保持部材６に保持し、その下方に吸収
材２を備えた反応装置を作製した。ＨＢｓ抗原の測定 上記の装置を用いてＨＢｓ抗原の免疫測定を行った。即
ち、当該装置の開口部にＰＢＳ緩衝液１００μｌを添加
した後、３倍希釈調製した試料２００μｌを添加し、３
分後にペルオキシダーゼ標識した抗ＨＢｓ抗原モノクロ
ーナル抗体液１００μｌを添加した。ＰＢＳ緩衝液を主
成分とする洗浄液２００μｌを２回添加して洗浄した
後、化学発光基質液５０μｌを２回添加して発光測定器
にて発光シグナルを測定することにより免疫測定を行っ
た。なお、上記の測定において、試料として、ＨＢｓ抗
原を５ ＩＵ／ｍｌとなるように１％ＢＳＡ−ＰＢＳ緩
衝液中に調製した陽性コントロール試料（ＰＣ）と、Ｈ
Ｂｓ抗原を含まない１％ＢＳＡ−ＰＢＳ緩衝液のみの陰
性コントロール試料（ＮＣ）を用いて実施した。発光の
測定は、反応マトリックスを吸収材から分離して測定す
る本発明の方法（分離型）と分離しない一体型で測定す
る方法（一体型）を比較した。その結果を表１に示し
た。表１に示されるように、分離型で得られる陽性コン
トロール（ＰＣ）と陰性コントロール（ＮＣ）のシグナ
ルの比（Ｓ／Ｎ比）を比較すると、明らかに分離型の方
が比が大きく、分離型での測定の方が高感度であること
がわかった。Hereinafter, the present invention will be described with reference to specific examples, but the present invention is not limited to the examples. Example 1 Preparation of Reaction Apparatus As shown in FIG. 1, a sensitized membrane (reaction matrix) obtained by sensitizing an anti-HBs antigen monoclonal antibody on a nitrocellulose membrane having a pore diameter of 0.45 μm was used as a reaction matrix holding member 6. The reactor was held, and a reaction apparatus provided with the absorbing material 2 therebelow was produced. Measurement of HBs antigen Immunoassay for HBs antigen was performed using the above apparatus. That is, 100 μl of PBS buffer was added to the opening of the apparatus, and 200 μl of a three-fold diluted sample was added.
One minute later, 100 μl of a peroxidase-labeled anti-HBs antigen monoclonal antibody solution was added. After washing twice by adding 200 μl of a washing solution containing a PBS buffer as a main component, 50 μl of a chemiluminescent substrate solution was added twice, and an immunoassay was performed by measuring a luminescence signal with a luminometer. In the above measurement, as a sample, a positive control sample (PC) prepared in a 1% BSA-PBS buffer so that HBs antigen was 5 IU / ml, and H
This was performed using a negative control sample (NC) containing only 1% BSA-PBS buffer without Bs antigen. The luminescence was measured by comparing the method of the present invention, in which the reaction matrix was separated from the absorbent, and the measurement (separate type) of the present invention, and the method of integral measurement without separation (integral type). The results are shown in Table 1. As shown in Table 1, when the signal ratio (S / N ratio) of the positive control (PC) and the negative control (NC) obtained in the separated type was compared, the ratio of the separated type was clearly larger, It was found that measurement with a mold was more sensitive.
【００１２】[0012]
【表１】 [Table 1]
【００１３】実施例２ＨＢｅ抗原の測定 抗ＨＢｓ抗原モノクローナル抗体の代わりに抗ＨＢｅ抗
原モノクローナル抗体を用い、ＨＢｓ抗原の代わりにＨ
Ｂｅ抗原を用いた他は実施例１と同様に操作して、ＨＢ
ｅ抗原の測定を行った。その結果を表２に示した。ＨＢ
ｅ抗原の場合にも分離型の方がＳ／Ｎ比が大きく、分離
型での測定の方が高感度であることがわかった。Example 2 Measurement of HBe Antigen An anti-HBe antigen monoclonal antibody was used in place of the anti-HBs antigen monoclonal antibody, and H was used instead of the HBs antigen.
Except for using the Be antigen, the same operation as in Example 1 was carried out to obtain HB
e antigen was measured. The results are shown in Table 2. HB
Also in the case of e antigen, it was found that the S / N ratio of the separation type was higher than that of the e antigen, and that the measurement of the separation type had higher sensitivity.
【００１４】[0014]
【表２】 [Table 2]
【図１】本発明の装置の一例を示す概略図である。FIG. 1 is a schematic view showing an example of the apparatus of the present invention.
１ コンテナー ２ 吸収材 ３ 反応マトリックス ４ 開口部 ５ キャップ部材 ６ 反応マトリックス保持部材 DESCRIPTION OF SYMBOLS 1 Container 2 Absorbent material 3 Reaction matrix 4 Opening 5 Cap member 6 Reaction matrix holding member
───────────────────────────────────────────────────── フロントページの続き (72)発明者 一口 毅 神戸市西区室谷１丁目１−２ 国際試薬株 式会社研究開発センター内 (72)発明者 小田原 卓哉 神戸市西区室谷１丁目１−２ 国際試薬株 式会社研究開発センター内 (72)発明者 斉藤 吉広 神戸市西区室谷１丁目１−２ 国際試薬株 式会社研究開発センター内 (72)発明者 元津 和典 神戸市西区室谷１丁目１−２ 国際試薬株 式会社研究開発センター内 ──────────────────────────────────────────────────続 き Continuing from the front page (72) Inventor Takeshi Ichiguchi 1-2-1 Muroya, Nishi-ku, Kobe International Reagent Co., Ltd. R & D Center (72) Inventor Takuya Odawara 1-2-1-2 Muroya, Nishi-ku, Kobe-shi International Reagent (72) Inventor Yoshihiro Saito 1-1-2 Muroya, Nishi-ku, Kobe International Reagent Co., Ltd. (72) Inventor Kazunori Mototsu 1-2-1-2 Muroya, Nishi-ku, Kobe International Reagent Co., Ltd. R & D Center
Claims (2)
保持させた反応固相を用いるフロースルータイプの生物
学的特異反応測定法において、当該反応固相を分離して
シグナルを測定することを特徴とする生物学的特異反応
測定法。1. A flow-through type biological specific reaction measuring method using a reaction solid phase holding a ligand capable of capturing an analyte, characterized in that the reaction solid phase is separated and a signal is measured. Biospecific reaction assay.
保持させた反応固相を用いるフロースルータイプの生物
学的特異反応装置において、当該反応固相が分離可能に
形成されていることを特徴とする生物学的特異反応測定
装置。2. A flow-through type biologically specific reaction apparatus using a reaction solid phase holding a ligand capable of capturing a substance to be measured, wherein the reaction solid phase is formed so as to be separable. Biological specific reaction measurement device.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10332019A JP2000146977A (en) | 1998-11-06 | 1998-11-06 | Method and apparatus for determination of biologically specific reaction |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10332019A JP2000146977A (en) | 1998-11-06 | 1998-11-06 | Method and apparatus for determination of biologically specific reaction |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2000146977A true JP2000146977A (en) | 2000-05-26 |
Family
ID=18250241
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10332019A Pending JP2000146977A (en) | 1998-11-06 | 1998-11-06 | Method and apparatus for determination of biologically specific reaction |
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| Country | Link |
|---|---|
| JP (1) | JP2000146977A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012047747A (en) * | 2011-09-02 | 2012-03-08 | Central Res Inst Of Electric Power Ind | Biosensor apparatus, and concentration measuring method employing the same |
-
1998
- 1998-11-06 JP JP10332019A patent/JP2000146977A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012047747A (en) * | 2011-09-02 | 2012-03-08 | Central Res Inst Of Electric Power Ind | Biosensor apparatus, and concentration measuring method employing the same |
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