JP2002511770A - 簡素化された連続的化学発光検出 - Google Patents
簡素化された連続的化学発光検出Info
- Publication number
- JP2002511770A JP2002511770A JP55298599A JP55298599A JP2002511770A JP 2002511770 A JP2002511770 A JP 2002511770A JP 55298599 A JP55298599 A JP 55298599A JP 55298599 A JP55298599 A JP 55298599A JP 2002511770 A JP2002511770 A JP 2002511770A
- Authority
- JP
- Japan
- Prior art keywords
- enzyme
- group
- peroxidase
- chemiluminescent
- target species
- 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
Links
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- 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
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
- G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/26—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase
- C12Q1/28—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving oxidoreductase involving peroxidase
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- 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
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/973—Simultaneous determination of more than one analyte
Landscapes
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- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Golf Clubs (AREA)
- Reinforced Plastic Materials (AREA)
- Ink Jet (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. 固相支持体上に第一および第二の標的種を固定化すること; 固定化された第一および第二の標的種と、第一標的腫に対して特異的に結合す る第一のパートナーおよび第二の標的種に対して特異的に結合する第二のパート ナーとを接触させ、第一の結合対と第二の結合対を形成すること; 第一の結合パートナーに対するラベルとしてペルオキシダーゼ酵素を付与し、 第二の結合パートナーに対するラベルとして第二の酵素を付与すること; 第一の化学発光シグナルを生じるために、第一の結合対を、化学発光ペルオキ シダーゼ基質および過酸化化合物と反応させること; 第一の化学発光シグナルを検出することによって、第一の標的種を検出するこ と; 第二の結合対を、第二の酵素に対する化学発光基質とペルオキシダーゼ酵素の インヒビターを含む組成物と反応させて、第一の化学発光シグナルを停止させて 、第二の化学発光シグナルを生じること;および 第二の化学発光シグナルを検出することによって第二の標的種を検出すること 、を含む二つの連続的な化学発光反応による第一および第二の標的種を含むと思 われるサンプル中の第一および第二の標的種を連続的に検出するための方法。 2. 第一の特異的結合パートナーが第一のハプテンを用いてラベルされ、第二 の特異的結合パートナーが、第一のハプテンと異なる第二のハプテンを用いてラ ベルされ、ペルオキシダーゼ酵素が第一のハプテンに結合する第三の特異的結合 パートナーとの共役体として供給され、第二の酵素が、第二のハプテンに結合す る第四の特異的結合パートナーとの共役体として提供される、請求項1記載の方 法。 3. 第一および第二のハプテンが、ビオチン、フルオレセインおよびジゴキシ ゲニンからなる群から独立に選択される、請求項2記載の方法。 4. 第一の特異的結合パートナーが、ペルオキシダーゼ酵素で直接的にラベル されている、請求項1記載の方法。 5. 第二の特異的結合パートナーが、第二の酵素で直接的にラベルされている 、請求項1記載の方法。 6. 第二の酵素が加水分解酵素である、請求項1記載の方法。 7. 加水分解酵素が、アルカリホスファターゼ、β-ガラクトシダーゼおよび グルクロニダーゼから選択される、請求項6記載の方法。 8. 加水分解酵素がアルカリホスファターゼである、請求項6記載の方法。 9. ペルオキシダーゼ酵素がホースラディッシュペルオキシダーゼである、請 求項1記載の方法。 10. 第一および第二の標的種が、核酸の第一の領域、およびその核酸の第二 の領域を含み、第一の特異的結合パートナーがその核酸の第一領域に相補的な第 一オリゴヌクレオチドプローブであり、第二の特異的結合パートナーが、核酸の 第二領域に相補的な第二オリゴヌクレオチドプローブである、請求項1記載の方 法。 11. 遺伝的変異の存在を調べるために用いられる請求項10記載の方法。 12. 第一および第二標的種は、正常遺伝子の第一ヌクレオチド配列およびそ の遺伝子の変異を含む第二ヌクレオチド配列を含み、第一の特異的結合パートナ ーは、第一のヌクレオチド配列に相補的なオリゴヌクレオチドプローブであり、 第二の特異的結合パートナーは、第二のヌクレオチド配列に相補的なオリゴヌク レオチドプローブである、請求項11記載の方法。 13. DNA配列分析に用いられる請求項1記載の方法。 14. 第一および第二標的種が、第一および第二タンパクであり、ウェスタン ブロットアッセイにおいて用いられる、請求項1記載の方法。 15. 第二酵素の化学発光基質が、酵素的引き金を引くジオキセタンである、 請求項1記載の方法。 16. ジオキセタンが、以下の式: [式中、A1およびA2は、ジオキセタンに安定性を付与する基であり、A3は直 鎖、分枝鎖または環状アルキル状の、置換されたアルキル、アリールおよび置換 されたアリール基から選択され、A4はジオキセタン環と共役しない位置を占め るOX置換基で置換された芳香環基であり、O−X結合を切断する酵素とOX置 換基との反応が、化学発光を生じる引き金をひくものであり、A1、A2、A3お よびA4基から選択されるあらゆる対が、ジオキセタン環に融合した環を形成す るように連結されうる。]を有する、請求項15記載の方法。 17. A1およびA2は、6ないし10の炭素原子を有する置換または非置換の ポリシクロアルキル基として結合され、A3は、1ないし10の炭素原子を有す る置換または非置換アルキル基であり、A4は、置換または非置換のフェニル基 であり、XはPO3 2-基、ガラクトシド基またはグルクロニド基から選択される 、請求項16記載の方法。 18. OX基がホスファート基である、請求項17記載の方法。 19. ジオキセタンが以下の式を有する、請求項18記載の方法。 20. 化学発光ペルオキシダーゼ基質が、以下の一般式: [式中、Rは、アルキル、ヘテロアルキルおよびアラルキル基から選択され、R1 からR8は、発光を妨げない基から独立に選択され、基R1からR8の隣接対が、 CH=CH−CH=CHを構成して、ベンゾ融合環を形成し、基C(=O)−Y はエステル、チオエステルまたはスルホンアミド基である。]を有するN-アル キルアクリダン-9-カルボキシラート誘導体から選択された、請求項1記載の方 法。 21. N-アルキルアクリダン-9-カルボキシラート誘導体が、以下の一般式 : [式中、R3は、H、Clまたはメトキシ基から選択される。]を有する、請求 項20記載の方法。 22. Yが、2,3,6-トリフルオロフェノキシ基である、請求項21記載の 方法。 23. R3がH原子である、請求項22記載の方法。 24. 固相支持体が、試験片、ブロッティング膜、フイルター、ガラススライ ド、プラスチックスライド、マイクロウェル、試験管およびビーズからなる群か ら選択される、請求項1記載の方法。 25. 固相支持体がブロッティング膜である、請求項24記載の方法。 26. 過酸化物が、過酸化水素、過酸化尿素および過ホウ酸塩からなる群から 選択される、請求項1記載の方法。 27. 化学発光ペルオキシダーゼ基質および過酸化物が、フェノールエンハン サーをさらに含む水性試薬組成物中に供給されている、請求項1記載の方法。 28. ペルオキシダーゼ基質を含む組成物が、さらに界面活性剤を含む、請求 項27記載の方法。 29. ペルオキシダーゼインヒビターが、過酸化水素を単独またはアジドイオ ン、シアニドイオン、フッ素イオン、イミダゾール、フェニルヒドラジンおよび 過ヨウ素酸塩と組み合わせたものから選択される、請求項1記載の方法。 30. ペルオキシダーゼインヒビターが過酸化水素である、請求項1記載の方 法。
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US09/064,451 US6068979A (en) | 1998-04-22 | 1998-04-22 | Simplified sequential chemiluminescent detection |
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PCT/US1999/006531 WO1999054503A1 (en) | 1998-04-22 | 1999-04-16 | Simplified sequential chemiluminescent detection |
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JP (1) | JP4156677B2 (ja) |
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AU (1) | AU747976C (ja) |
CA (1) | CA2294436C (ja) |
DE (1) | DE69936284T2 (ja) |
WO (1) | WO1999054503A1 (ja) |
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WO1999054503B1 (en) | 1999-11-25 |
WO1999054503A1 (en) | 1999-10-28 |
AU3546299A (en) | 1999-11-08 |
CA2294436A1 (en) | 1999-10-28 |
EP1015641B1 (en) | 2007-06-13 |
AU747976C (en) | 2002-12-05 |
DE69936284D1 (de) | 2007-07-26 |
ATE364719T1 (de) | 2007-07-15 |
EP1015641A4 (en) | 2003-04-16 |
CA2294436C (en) | 2009-04-14 |
US6068979A (en) | 2000-05-30 |
DE69936284T2 (de) | 2008-03-06 |
AU747976B2 (en) | 2002-05-30 |
EP1015641A1 (en) | 2000-07-05 |
JP4156677B2 (ja) | 2008-09-24 |
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