FI93997B - Homogena fluorometriska bestämningsmetoder, vari man eliminerar den fluorescerande bakgrunden och använder såsom fluoroforer vattenlösliga kelater av sällsynta jordartsmetaller - Google Patents
Homogena fluorometriska bestämningsmetoder, vari man eliminerar den fluorescerande bakgrunden och använder såsom fluoroforer vattenlösliga kelater av sällsynta jordartsmetaller Download PDFInfo
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- FI93997B FI93997B FI880719A FI880719A FI93997B FI 93997 B FI93997 B FI 93997B FI 880719 A FI880719 A FI 880719A FI 880719 A FI880719 A FI 880719A FI 93997 B FI93997 B FI 93997B
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Classifications
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- 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
- G01N33/536—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase
- G01N33/542—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
-
- 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
- G01N33/531—Production of immunochemical test materials
- G01N33/532—Production of labelled immunochemicals
- G01N33/533—Production of labelled immunochemicals with fluorescent label
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2458/00—Labels used in chemical analysis of biological material
- G01N2458/40—Rare earth chelates
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- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
Claims (30)
1. Homogent förfarande för kvantitativ bestämning av en specifik bindningsreaktion i en vattenlösning, 5 kännetecknat av, att man a) blandar en vattenlöslig förening, vilken inne-häller en biospecifik grupp med en första märkessubstans, med en vattenlösning, vilken innehäller en biospecifik motdel av den biospecifika gruppen med den första märkes- 10 substansen, varigenom bildas en vattenlöslig produkt som innehäller ett specifikt bindningspar, vilket som ett re-sultat av en dylik specifik bindning innehäller en ny märkessubstans, vilken är olik den första märkessubstansen visavi fluorescensen, varvid ätminstone den ena av den 15 första märkessubstansen och den nya märkessubstansen om-fattar ett fluorescent kelat som innehäller en sällsynt jordmetall, varvid kelatet är vattenlösligt i vattenlös-ningen och har en metall-ligand-bindningskonstant som överstiger ca 1013ΜΧ och en avklingnings-livslängd som är 20 läng i jämförelse med den längsta avklingnings-livslängden hos omgivande substanser; b) exciterar den vattenlösliga produkten frän steg a) med ätminstone en elektromagnetisk strälningspuls, varvid nämnda puis har en varaktighet som är kort i jämförel- 25 se med avklingnings-livslängden hos den länglivade, fluo-rescenta emissionen; c) detekterar den fluorescenta emissionen frän den exciterade vattenlösliga produkten efter att fluorescensen hos nämnda omgivande substanser väsentligen avklingat, och 30 d) hänför den i c) detekterade fluorescensen tili : graden specifik bindningsreaktion som sker i lösningen.
2. Förfarande enligt patentkrav 1, kännetecknat av, att bäde den första märkessubstansen och den andra märkessubstansen bestär av kelatkomplex 35 som bildats av sällsynta jordmetaller, varvid den ena av • · 93997 60 ί dessa har släckt fluorescens som ett resultat av den spe-cifika bindningsreaktionen.
3. Förfarande enligt patentkrav 1, känne-t e c k n a t av, att bäde den första märkessubstansen 5 och den nya märkessubstansen bestär av kelatkomplex som bildats av sällsynta jordmetaller, varvid den ena har ökad fluorescens som ett resultat av den speciflka bindningsreaktionen.
4. Förfarande enligt patentkrav 2, känne- 10 tecknat av, att den släckta fluorescensen är ett resultat av energiöverföring frän den första märkessubstansen till en grupp, vilken bringats fram till omedelbar närhet av den första märkessubstansen genom den specifika bindningsreaktionen. 15
5. Förfarande enligt patentkrav 4, känne- tecknat av, att den omedelbara närheten är en dis-tans av ca 0,5 - 7,5 nm.
6. Förfarande enligt patentkrav 5, känne- tecknat av, att kelatet av sällsynt jordmetall om- 20 fattar terbium eller europium.
7. Förfarande enligt patentkrav 6, känne- tecknat av, att gruppen som bringas främ till omedelbar närhet av den första märkessubstansen genom den specifika bindningsreaktionen är den grupp som undergär 25 den specifika bindningsreaktionen.
8. Förfarande enligt patentkrav 6, känne- tecknat av, att gruppen som bringas fram till omedelbar närhet av den första märkessubstansen genom den specifika bindningsreaktionen är en grupp, vilken är 30 fäst vid gruppen som undergär den specifika bindningsreak- .- tionen. • «
9. Förfarande enligt patentkrav 8, känne- tecknat av, att gruppen som bringas fram till omedelbar närhet är ett komplex av en övergängsmetall ur 35 gruppen IV. II 61 93997
10. Förfarande enligt patentkrav 8, känne-t e c k n a t av, att gruppen som brlngas fram tili ome-delbar närhet är rodamin.
11. Förfarande enligt patentkrav 10, känne-5 tecknat av, att den första märkessubstansen är ett europiumkelat av en aryl-substituerad 2,6-[N,N-bis(karb-oxylalkyl)aminoalkyl]pyridinligand.
12. Förfarande enligt patentkrav 10, känne-tecknat av, att den första märkessubstansen är ett 10 terbiumkelat av en aryl-substituerad 2,6-[N,N-bis(karb-oxylalkyl)aminoalkyl]pyridinligand.
13. Förfarande enligt patentkrav 3, känne-tecknat av, att den ökade fluorescensen är ett re-sultat av energiöverföring tili den första märkessubstan- 15 sen frän en grupp, vilken bringats fram tili omedelbar närhet av den första märkessubstansen genom den spedfikä bindningsreaktionen.
14. Förfarande enligt patentkrav 13, känne-tecknat av, att den omedelbara närheten är en dis- 20 tans av ca 0,5 - 7,5 nm.
15. Förfarande enligt patentkrav 14, känne-tecknat av, att kelatet av sällsynt jordmetall om-fattar terbium eller europium.
16. Förfarande enligt patentkrav 15, känne- 25 tecknat av, att gruppen som bringas fram tili omedelbar närhet av den första märkessubstansen genom den spedfikä bindningsreaktionen är gruppen som undergär spe-cifik bindningsreaktion.
17. Förfarande enligt patentkrav 16, känne- 30 tecknat av, att gruppen som bringas fram tili ome- . delbar närhet är en anti-teofyllinantikropp.
18. Förfarande enligt patentkrav 17, känne-tecknat av, att den första märkessubstansen är ett europiumkelat av en aryl-substituerad 2,6-[N,N-bis(karb- 35 oxylalkyl)aminoalkyl]pyridinligand. i 62 93997
19. Förfarande enligt patentkrav 17, känne-t e c k n a t av, att den första märkessubstansen är ett terbiumkelat av en aryl-substituerad 2,6-[N,N-bis(karb-oxialkyl)aminoalkyl]pyridinligand. 5
20. Förfarande enligt patentkrav 15, känne- t e c k n a t av, att gruppen som bringas fram tili ome-delbar närhet av den första märkessubstansen genom den specifika bindningsreaktionen är en grupp, vilken är fäst vid gruppen som undergär den specifika bindningsreak-10 tionen.
21. Förfarande enligt patentkrav 20, känne-t e c k n a t av, att energin överförs tili liganden, som omfattar det första kelatet av sällsynt jordmetall.
22. Förfarande enligt patentkrav 1, känne-15 tecknat av, att bäde den första och den nya märkessubstansen bestär av kelatkomplex av sällsynt jordmetall, varvid den ena bildats genom direkt överföring av sällsyn-ta jordmetalljoner mellan tvä ligander, vilka bringats i omedelbar närhet av den första märkessubstansen genom 20 den specifika bindningsreaktionen.
23. Förfarande enligt patentkrav 22, känne- tecknat av, att det första kelatkomplexet har en stabilitet av ätminstone en storleksklass under stabilite-ten hos det nya kelatkomplexet. '25
24. Förfarande enligt patentkrav 23, känne- tecknat av, att den sällsynta jordmetallen är europium eller terbium.
25. Förfarande enligt patentkrav 23, känne- tecknat av, att den nya märkessubstansen har ökad 30 fluorescens i jämförelse med den första märkessubstansen.
.* 26. Förfarande enligt patentkrav 25, känne- tecknat av, att den första märkessubstansen är ett europium- eller terbiumkelat av en alkylpolyaminpolykar-bonsyra. 35 • « 63 93997
27. Förfarande enligt patentkrav 26, känne-tecknat av, att den nya märkessubstansen omfattar ett europium- eller terbiumkelat av en aryl-substituerad 2,6-[N,N-bis(karboxylalkyl)aminoalky1]pyridinligand. 5
28. Förfarande enligt patentkrav 26, känne- tecknat av, att den nya märkessubstansen omfattar ett europium- eller terbiumkelat av en 2,6-[N,N-bis(karboxylalkyl )aminoalkyl]fenantrolinligand.
29. Förfarande enligt patentkrav 23, känne-10 tecknat av, att den nya märkessubstansen har släckt fluorescens i jämförelse med den första märkessubstansen.
30. Förfarande enligt patentkrav 1, känne-tecknat av, att bäde den första och nya märkessubstansen bestär av kelatkomplex av sällsynt jordmetall, var- 15 vid den ena bildats genom tillsättning av en ytterligare ligand, vilken bringats fram tili omedelbar närhet av den första genom den specifikä bindningsreaktionen.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87528786A | 1986-06-17 | 1986-06-17 | |
| US87528786 | 1986-06-17 | ||
| US8701407 | 1987-06-15 | ||
| PCT/US1987/001407 WO1987007955A1 (en) | 1986-06-17 | 1987-06-15 | Homogeneous fluoroassay methods employing fluorescent background rejection and water-soluble rare earth metal chelate fluorophores |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI880719L FI880719L (sv) | 1988-02-16 |
| FI880719A0 FI880719A0 (sv) | 1988-02-16 |
| FI93997B true FI93997B (sv) | 1995-03-15 |
| FI93997C FI93997C (sv) | 1995-06-26 |
Family
ID=25365527
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI880719A FI93997C (sv) | 1986-06-17 | 1988-02-16 | Homogena fluorometriska bestämningsmetoder, vari man eliminerar den fluorescerande bakgrunden och använder såsom fluoroforer vattenlösliga kelater av sällsynta jordartsmetaller |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US6242268B1 (sv) |
| EP (1) | EP0272320B1 (sv) |
| JP (1) | JP2802921B2 (sv) |
| CA (1) | CA1309016C (sv) |
| DE (1) | DE3789430T2 (sv) |
| DK (1) | DK172464B1 (sv) |
| FI (1) | FI93997C (sv) |
| WO (1) | WO1987007955A1 (sv) |
Families Citing this family (66)
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| FI80801C (sv) * | 1987-01-14 | 1990-07-10 | Innofarm Oy | Konjugat av en monoklonal antikropp eller ett fragment därav och ett k elaterande ämne, dess framställning och användning |
| SE8702824L (sv) * | 1987-07-10 | 1989-01-11 | Wallac Oy | Metall-kelaterande 2,6-disubstituerade pyridinfoereningar och deras anvaendning |
| SE8703682L (sv) * | 1987-09-24 | 1989-03-25 | Wallac Oy | Homogen bestaemningsmetod som utnyttjar affinitetsreaktioner |
| SE8800613D0 (sv) * | 1988-02-23 | 1988-02-23 | Wallac Oy | A novel spectrofluorometric method and compounds that are of value for the method |
| US6127529A (en) * | 1988-06-29 | 2000-10-03 | Wallac Oy | Metal-chelating 2,6-disubstituted pyridine compounds and their use |
| US5998135A (en) * | 1989-02-24 | 1999-12-07 | Enzo Diagnostics, Inc. | Energy transfer hybridization assay using intercalators and lanthanide metals |
| GB9003593D0 (en) * | 1990-02-16 | 1990-04-11 | Pa Consulting Services | Improvements in or relating to fluorescence assays |
| FR2664699B1 (fr) * | 1990-07-13 | 1995-08-18 | Cis Bio Int | Procede d'amplification du signal d'emission d'un compose luminescent. |
| US5367080A (en) * | 1990-11-08 | 1994-11-22 | Sterling Winthrop Inc. | Complexing agents and targeting radioactive immunoreagents useful in therapeutic and diagnostic imaging compositions and methods |
| FI88654C (sv) * | 1991-03-15 | 1993-06-10 | Datacity Center Oy | Fluorescenshöjningsmetod |
| FI963989L (sv) * | 1996-10-04 | 1998-04-05 | Wallac Oy | Homogena bestämningsmetoder som baserar sig på överföring av luminescensenergi |
| US6087088A (en) * | 1997-01-31 | 2000-07-11 | Bayer Corporation | Binding assays using more than one label for determining analyte in the presence of interfering factors |
| AU757901B2 (en) * | 1998-03-11 | 2003-03-13 | Sensors For Medicine And Science, Inc. | Detection of analytes by fluorescent lanthanide chelates |
| US5998146A (en) * | 1998-07-17 | 1999-12-07 | Wallac Oy | Homogeneous luminescence assay method based on energy transfer |
| WO2000063422A2 (en) * | 1999-04-19 | 2000-10-26 | Iit Research Institute | Detection of biological warfare agents |
| US6645733B1 (en) * | 1999-06-25 | 2003-11-11 | Ingeneus Corporation | Fluorescent intensity method for assaying binding between proteins or peptides |
| EP1412749A4 (en) * | 2001-06-28 | 2006-12-13 | Ia Inc | OPTICAL FIBER SENSOR ARRAY |
| DE10153829A1 (de) | 2001-11-05 | 2003-05-28 | Bayer Ag | Assay basierend auf dotierten Nanoteilchen |
| WO2003067211A2 (en) * | 2001-11-30 | 2003-08-14 | California Institute Of Technology | An improvement in a method bacterial endospore quantification using lanthanide dipicolinate luminescence |
| US8367013B2 (en) | 2001-12-24 | 2013-02-05 | Kimberly-Clark Worldwide, Inc. | Reading device, method, and system for conducting lateral flow assays |
| US20030119203A1 (en) | 2001-12-24 | 2003-06-26 | Kimberly-Clark Worldwide, Inc. | Lateral flow assay devices and methods for conducting assays |
| JP2005516213A (ja) * | 2002-02-01 | 2005-06-02 | カリフォルニア インスティチュート オブ テクノロジー | 細菌胞子の分析方法および装置 |
| US7314763B2 (en) * | 2002-08-27 | 2008-01-01 | Kimberly-Clark Worldwide, Inc. | Fluidics-based assay devices |
| US7432105B2 (en) | 2002-08-27 | 2008-10-07 | Kimberly-Clark Worldwide, Inc. | Self-calibration system for a magnetic binding assay |
| US7285424B2 (en) | 2002-08-27 | 2007-10-23 | Kimberly-Clark Worldwide, Inc. | Membrane-based assay devices |
| US7781172B2 (en) | 2003-11-21 | 2010-08-24 | Kimberly-Clark Worldwide, Inc. | Method for extending the dynamic detection range of assay devices |
| US7563615B2 (en) * | 2005-04-15 | 2009-07-21 | California Institute Of Technology | Apparatus and method for automated monitoring of airborne bacterial spores |
| US7611862B2 (en) | 2004-11-12 | 2009-11-03 | California Institute Of Technology | Method and apparatus for detecting and quantifying bacterial spores on a surface |
| US7608419B2 (en) * | 2003-11-13 | 2009-10-27 | California Institute Of Technology | Method and apparatus for detecting and quantifying bacterial spores on a surface |
| US7247500B2 (en) | 2002-12-19 | 2007-07-24 | Kimberly-Clark Worldwide, Inc. | Reduction of the hook effect in membrane-based assay devices |
| US7851209B2 (en) * | 2003-04-03 | 2010-12-14 | Kimberly-Clark Worldwide, Inc. | Reduction of the hook effect in assay devices |
| US20040197819A1 (en) | 2003-04-03 | 2004-10-07 | Kimberly-Clark Worldwide, Inc. | Assay devices that utilize hollow particles |
| CA2694876A1 (en) | 2003-07-01 | 2005-03-24 | Eric R. Diebold | Electrochemical affinity biosensor system and methods |
| US7943395B2 (en) | 2003-11-21 | 2011-05-17 | Kimberly-Clark Worldwide, Inc. | Extension of the dynamic detection range of assay devices |
| US20050112703A1 (en) | 2003-11-21 | 2005-05-26 | Kimberly-Clark Worldwide, Inc. | Membrane-based lateral flow assay devices that utilize phosphorescent detection |
| US7713748B2 (en) | 2003-11-21 | 2010-05-11 | Kimberly-Clark Worldwide, Inc. | Method of reducing the sensitivity of assay devices |
| US7943089B2 (en) | 2003-12-19 | 2011-05-17 | Kimberly-Clark Worldwide, Inc. | Laminated assay devices |
| US20050244953A1 (en) * | 2004-04-30 | 2005-11-03 | Kimberly-Clark Worldwide, Inc. | Techniques for controlling the optical properties of assay devices |
| US7796266B2 (en) * | 2004-04-30 | 2010-09-14 | Kimberly-Clark Worldwide, Inc. | Optical detection system using electromagnetic radiation to detect presence or quantity of analyte |
| US7815854B2 (en) * | 2004-04-30 | 2010-10-19 | Kimberly-Clark Worldwide, Inc. | Electroluminescent illumination source for optical detection systems |
| US20060019265A1 (en) * | 2004-04-30 | 2006-01-26 | Kimberly-Clark Worldwide, Inc. | Transmission-based luminescent detection systems |
| US7521226B2 (en) | 2004-06-30 | 2009-04-21 | Kimberly-Clark Worldwide, Inc. | One-step enzymatic and amine detection technique |
| US7094528B2 (en) * | 2004-06-30 | 2006-08-22 | Kimberly-Clark Worldwide, Inc. | Magnetic enzyme detection techniques |
| US7906276B2 (en) * | 2004-06-30 | 2011-03-15 | Kimberly-Clark Worldwide, Inc. | Enzymatic detection techniques |
| US20070121113A1 (en) * | 2004-12-22 | 2007-05-31 | Cohen David S | Transmission-based optical detection systems |
| US7939342B2 (en) | 2005-03-30 | 2011-05-10 | Kimberly-Clark Worldwide, Inc. | Diagnostic test kits employing an internal calibration system |
| US7803319B2 (en) * | 2005-04-29 | 2010-09-28 | Kimberly-Clark Worldwide, Inc. | Metering technique for lateral flow assay devices |
| US7858384B2 (en) * | 2005-04-29 | 2010-12-28 | Kimberly-Clark Worldwide, Inc. | Flow control technique for assay devices |
| US7439079B2 (en) * | 2005-04-29 | 2008-10-21 | Kimberly-Clark Worldwide, Inc. | Assay devices having detection capabilities within the hook effect region |
| WO2007084180A2 (en) * | 2005-06-17 | 2007-07-26 | California Institute Of Technology | Airborne bacterial spores as an indicator of biomass in an indoor enviroment |
| US7504235B2 (en) * | 2005-08-31 | 2009-03-17 | Kimberly-Clark Worldwide, Inc. | Enzyme detection technique |
| US7829347B2 (en) * | 2005-08-31 | 2010-11-09 | Kimberly-Clark Worldwide, Inc. | Diagnostic test kits with improved detection accuracy |
| US7279136B2 (en) * | 2005-12-13 | 2007-10-09 | Takeuchi James M | Metering technique for lateral flow assay devices |
| US7745158B2 (en) * | 2005-12-14 | 2010-06-29 | Kimberly-Clark Worldwide, Inc. | Detection of secreted aspartyl proteases from Candida species |
| US7645583B2 (en) * | 2005-12-14 | 2010-01-12 | Kimberly-Clark Worldwide, Inc. | Identification of compounds for inhibiting complexation of C-reactive protein with fibronectin |
| US7618810B2 (en) | 2005-12-14 | 2009-11-17 | Kimberly-Clark Worldwide, Inc. | Metering strip and method for lateral flow assay devices |
| US8758989B2 (en) * | 2006-04-06 | 2014-06-24 | Kimberly-Clark Worldwide, Inc. | Enzymatic detection techniques |
| US7897360B2 (en) | 2006-12-15 | 2011-03-01 | Kimberly-Clark Worldwide, Inc. | Enzyme detection techniques |
| US7998414B2 (en) * | 2007-02-28 | 2011-08-16 | Corning Incorporated | System for high throughput GPCR functional assay |
| US8535617B2 (en) * | 2007-11-30 | 2013-09-17 | Kimberly-Clark Worldwide, Inc. | Blood cell barrier for a lateral flow device |
| FI20095302A0 (sv) | 2009-03-24 | 2009-03-24 | Arctic Partners Oy Ab | Luminiscensbestämningsmetod |
| JP6310575B2 (ja) | 2014-05-02 | 2018-04-11 | ラジオメーター・トゥルク・オサケユキチュア | ランタニドキレートのための新規発色団構造 |
| US11112409B2 (en) | 2016-02-12 | 2021-09-07 | The Regents Of The University Of California | Systems and compositions for diagnosing pathogenic fungal infection and methods of using the same |
| JP6924780B2 (ja) * | 2016-06-09 | 2021-08-25 | ラジオメーター・トゥルク・オサケユキチュア | 結合アッセイのバックグラウンド遮断剤 |
| US11726091B2 (en) | 2017-04-03 | 2023-08-15 | The Regents Of The University Of California | Compositions and methods of diagnosing pancreatic cancer |
| FI130554B (sv) | 2020-01-20 | 2023-11-16 | Oy Arctic Partners Ab | Luminescens hybridisering bestämningsmetod |
Family Cites Families (16)
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| US3901654A (en) | 1971-06-21 | 1975-08-26 | Biological Developments | Receptor assays of biologically active compounds employing biologically specific receptors |
| US3998943A (en) | 1973-10-02 | 1976-12-21 | Syva Company | Double receptor fluorescent immunoassay |
| US3939350A (en) | 1974-04-29 | 1976-02-17 | Board Of Trustees Of The Leland Stanford Junior University | Fluorescent immunoassay employing total reflection for activation |
| US4341957A (en) * | 1975-11-26 | 1982-07-27 | Analytical Radiation Corporation | Fluorescent antibody composition for immunofluorometric assay |
| US4058732A (en) * | 1975-06-30 | 1977-11-15 | Analytical Radiation Corporation | Method and apparatus for improved analytical fluorescent spectroscopy |
| US4020151A (en) | 1976-02-17 | 1977-04-26 | International Diagnostic Technology, Inc. | Method for quantitation of antigens or antibodies on a solid surface |
| US4283382A (en) | 1977-12-28 | 1981-08-11 | Eastman Kodak Company | Fluorescent labels comprising rare earth chelates |
| US4220450A (en) | 1978-04-05 | 1980-09-02 | Syva Company | Chemically induced fluorescence immunoassay |
| SE428332B (sv) | 1979-03-08 | 1983-06-20 | Wallac Oy | Forfarande for fluorescensspektroskopisk bestemning av biologiskt aktivt emne, sasom hapten, antikropp eller antigen |
| US4352751A (en) * | 1979-09-10 | 1982-10-05 | Analytical Radiation Corporation | Species-linked diamine triacetic acids and their chelates |
| SE425439B (sv) | 1981-04-30 | 1982-09-27 | Wallac Oy | Immunologisk analys med lantanidkelatkomplex som markor |
| CA1205028A (en) * | 1981-07-01 | 1986-05-27 | Jerald C. Hinshaw | Fluorescent chelates and labeled specific binding reagents prepared therefrom |
| SE454115B (sv) * | 1982-09-13 | 1988-03-28 | Wallac Oy | Homogenfasanalys med lantanidkelat som merksubstans |
| US5830769A (en) * | 1985-03-18 | 1998-11-03 | Wieder; Irwin | Homogeneous fluorassay methods employing fluorescent background rejection and water-soluble rare earth metal chelates |
| US4761481A (en) | 1985-03-18 | 1988-08-02 | Baxter Travenol Laboratories, Inc. | Substituted pyridine derivatives |
| US4925804A (en) | 1986-06-17 | 1990-05-15 | Baxter International Inc. | Interligand metal transfer assay |
-
1987
- 1987-06-15 EP EP87905011A patent/EP0272320B1/en not_active Expired - Lifetime
- 1987-06-15 DE DE3789430T patent/DE3789430T2/de not_active Expired - Lifetime
- 1987-06-15 WO PCT/US1987/001407 patent/WO1987007955A1/en active IP Right Grant
- 1987-06-15 JP JP62504676A patent/JP2802921B2/ja not_active Expired - Lifetime
- 1987-06-16 CA CA000539778A patent/CA1309016C/en not_active Expired - Lifetime
-
1988
- 1988-02-16 FI FI880719A patent/FI93997C/sv not_active IP Right Cessation
- 1988-02-16 DK DK198800798A patent/DK172464B1/da not_active IP Right Cessation
-
1998
- 1998-11-02 US US09/184,330 patent/US6242268B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA1309016C (en) | 1992-10-20 |
| JP2802921B2 (ja) | 1998-09-24 |
| DE3789430T2 (de) | 1994-10-27 |
| FI93997C (sv) | 1995-06-26 |
| DE3789430D1 (de) | 1994-04-28 |
| US6242268B1 (en) | 2001-06-05 |
| DK79888A (da) | 1988-02-16 |
| DK172464B1 (da) | 1998-08-31 |
| FI880719L (sv) | 1988-02-16 |
| EP0272320B1 (en) | 1994-03-23 |
| EP0272320A4 (en) | 1989-08-09 |
| WO1987007955A1 (en) | 1987-12-30 |
| DK79888D0 (da) | 1988-02-16 |
| EP0272320A1 (en) | 1988-06-29 |
| JPH01500458A (ja) | 1989-02-16 |
| FI880719A0 (sv) | 1988-02-16 |
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