WO2000039581A2 - Test system for detecting different markers, and production and use thereof - Google Patents
Test system for detecting different markers, and production and use thereof Download PDFInfo
- Publication number
- WO2000039581A2 WO2000039581A2 PCT/EP1999/010333 EP9910333W WO0039581A2 WO 2000039581 A2 WO2000039581 A2 WO 2000039581A2 EP 9910333 W EP9910333 W EP 9910333W WO 0039581 A2 WO0039581 A2 WO 0039581A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- natural
- nucleic acid
- stranded
- derivative
- antibody
- Prior art date
Links
Classifications
-
- 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
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6813—Hybridisation assays
- C12Q1/6816—Hybridisation assays characterised by the detection means
-
- 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
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54306—Solid-phase reaction mechanisms
-
- 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
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
Definitions
- the present invention relates to a test system containing at least two detection species. recognize the at least two different markers to form a complex. its manufacture and use in a suitable detection method.
- test systems such as. B. Diagnostics are in biology, biochemistry. Medicine and pharmacology widely used. Especially in medicine, a reliable and clear diagnosis of diseases, such as B. viral infections or cancer. of extraordinary importance for increasing the quality of life, because timely and effective treatment can only be achieved by early detection of an illness.
- disease-specific markers or ligands such as B. nucleic acid sequences, proteins or antigens
- the pathogen or the disease is detected in the biological sample. Diagnostic tests are widespread, in which a marker or a class of markers is detected, such as. B. in ELISA or amplification methods such as PCR, b-DNA, Southern, Western or Northern blotting.
- the types of detection used range from simple staining methods and calorimetric methods to fluorescence energy transfer (FRET) and fluorescence quenching to scintillation proximity assay (SPA).
- FRET fluorescence energy transfer
- SPA scintillation proximity assay
- a major disadvantage when using only one marker or one marker class is that positive test results are easily erroneously produced, which also lead to incorrect conclusions regarding a specific disease. Often, therefore, a second Test or other tests on the same or complementary analytes are carried out in order to be able to make a reliable statement regarding ill / healthy. This leads to several tests, the results of which can be compared with one another, which is at the same time complex and cost-intensive.
- the object of the present invention is therefore to develop qualitatively better, less complex and less expensive analytical tests than those already known.
- the invention therefore relates to a detection method comprising the following steps: (a) Treatment of a sample containing a first and a second marker with a first recognition species. that recognizes the first marker,
- the present invention furthermore relates to a detection method comprising the following steps:
- the detection method is carried out in a homogeneous, partially homogeneous (modular) or immobilized form.
- the binding events are generated step by step and the complex that may be formed is detected in a so-called proximity assay.
- the first and last components are preferably marked so that they can only generate a signal when they are close together.
- Preferred detection methods are e.g. B. LOCI (Ullmann, E. et al. (1994) Proc. Natl. Acad. Sci. USA 91, 5426), Fluorescence Energy Transfer (FRET) Cordullo. RA (1992) in Nonradioactive Labeling and Detection of Biomolecules' * , 414-423.
- the binding events are generated step by step and in solution and, once the complex has formed, are bound to a solid support via one of the components.
- the complex which is formed is detected by a label, in particular a non-radioactive label or radioactive label, preferably by means of fluorescent labeling, enzymatic labeling, redox labeling or spin labeling (Kessler, C. (Ed.) Nonradioactive Labeling and Detection of Biomolecules (1992 ), Springer Verlag, 414-423).
- a recognition species preferably the first recognition species, is bound to a solid support and the complex is subsequently built up by gradually adding the further components.
- the marking is preferably carried out according to the same or similar methods as in the partially homogeneous embodiment.
- Solid or gel-like material in particular chip material and / or thin layers of the material, preferably ceramic, metal, in particular noble metal, glasses, plastics, crystalline materials or (bio) molecular filaments, in particular cellulose or framework proteins, are particularly suitable as supports for the immobilization.
- the recognition species and / or markers used in the detection method according to the invention are in particular a synthetic substance, a natural product and / or a natural product derivative, preferably a peptide, peptoid, protein, saccharide or a nucleic acid.
- a receptor or a functional part thereof in particular a functional part originating from the extracellular domain of a membrane-standing receptor, an antibody or a functional part thereof, in particular an Fv fragment (Skerra & Plückthun (1988 ), Science 240, 1038), a single chain Fv fragment (scFv; Bird et al. (1988), Science 242, 423; Huston et al. (1988), Proc. Natl. Acad. Sci.
- an aptamer for example a DNA or RNA aptamer or derivatives thereof, for example aptamers provided with protective groups customary in nucleic acid chemistry, a cell component, in particular a Lipid, glycoprotein, filament component, lectin, liposome, mitogen, antigen.
- a cell in particular a lymphoid cell, or a virus, in particular a virus component, in particular a capsid, or a viroid or a derivative, in particular an acetate, or its active parts, or a single-stranded or double-stranded nucleic acid , in particular DNA, RNA, p-RNA (Pitsch, S. et al., Helv. Chim. Acta. (1993), 76, 2161; Pitsch, S. et al., Helv. Chim. Acta. (1995), 78, 1621), p-DNA (DE 198 37 387.2), PNA (peptide nucleic acid (Nielsen, PE et al.
- aptamers count due to their binding properties to specific molecules other than nucleic acids, such as. B. proteins, not to the nucleic acids, but to antibody derivatives. DNA aptamers or RNA aptamers are preferred.
- nucleic acids according to the invention can also be modified.
- the methods known to the person skilled in the art from nucleic acid chemistry can be used for this purpose. Modifications which lead to stabilization of the nucleic acids are preferred (see, for example, Uhlmann, E. & Peyman, A. (1990) Chemical Reviews, 90, 543, No. 4).
- a marker is usually recognized by a recognition species via non-covalent interactions, in particular via hydrogen bridges, salt bridges. Stacking, metal lining, charge transfer complexes, Van der Waals forces or hydrophobic interactions.
- a nucleic acid is recognized as a marker by a completely or partially complementary nucleic acid or a synthetic substance, such as. B. a chemical, a natural product and / or a natural product derivative as antigenic substances are recognized by a corresponding antibody or antibody derivative.
- the markers can belong to any substance class, but preferably from at least two different ones.
- the marking can, depending on whether it is a homogeneous, partially homogeneous (modular) or immobilized embodiment, be non-radioactive or radioactive, preferably LOCI, FRET. Fluorescence quenching, SPA, a fluorescent label, enzymatic label, redox label or spin label.
- the marker and / or the signal can be amplified, which leads to an increase in the sensitivity of the detection method.
- Amplification of the marker relates in particular to the amplification of nucleic acids, for example by PCR, NASBA, LCR, SDA, Qß replication or RT-PCR (Kessler, C. (1992) supra).
- the signal amplification is achieved, for example, by so-called cross-linking of binding partners, antibody or nucleic acid trees (e.g. b-DNA), catalytic substrate conversion (e.g. alkaline phosphatase, peroxidase, ß-galactosidase) or signal cascades.
- in vivo amplification e.g. B. Detection of r-RNA, indirect detection of antigens possible.
- the markers can be divided into two classes. In the case of so-called positive markers, the absence of these markers is detected, e.g. B. about the lack of a signal. Positive markers generally refer to markers present in a healthy organism, e.g. m-RNA. Negative markers are generally the substances of a pathogen or a diseased organism which can be determined using the detection method according to the invention.
- either two or more negative, two or more positive or two or more positive and negative markers can be detected.
- Evidence is thus provided either about the occurrence or the absence of a signal.
- a displacement of a signal e.g. by displacing a molecule from a complex or from its binding conformation (e.g. Molecular Beacons, S. Tyaki, Kramer FR, Nature Biotechnology 14, 303-308, 1996; RP Ekins. Clinical Chemistry, 44/9, 2015-2030 , 1998) in a competitive assay.
- a substance is added to the test system which displaces one of the markers to be detected, whereby the molecular complex built up from markers and recognition species and thus also the signal associated therewith disappears.
- the concentration of the displaced marker can thus be determined in a simple manner via a titration.
- At least one marker is a natural or non-natural, single-stranded or double-stranded nucleic acid and each further marker is a synthetic substance, natural product or derivative of a natural substance, preferably an antigen, which is different from a nucleic acid.
- the first marker and each additional marker is a natural or non-natural, single-stranded or double-stranded nucleic acid or alternatively a synthetic substance other than a nucleic acid, a natural product or a natural product derivative, preferably an antigen.
- a natural or non-natural, single-stranded or double-stranded nucleic acid as a marker is recognized by a natural or non-natural, single-stranded or double-stranded nucleic acid as a recognition species.
- a synthetic substance, a natural product or a natural product derivative is recognized as a recognition species by a synthetic substance, a natural product or a natural product derivative, preferably by an antibody or an antibody derivative.
- At least one recognition species is a natural or non-natural, single-stranded or double-stranded nucleic acid and each further recognition species is a synthetic substance, different natural product or different natural product derivative different from a nucleic acid, preferably an antibody or an antibody derivative.
- the first recognition species and each further recognition species is a natural or non-natural, single-stranded or double-stranded nucleic acid or alternatively a synthetic substance, different natural product or different natural product derivative different from a nucleic acid, preferably an antibody or an antibody derivative.
- At least one recognition species is a hybrid of a natural or unnatural, single-stranded or double-stranded nucleic acid and another natural or unnatural, single-stranded or double-stranded nucleic acid.
- At least one recognition species is a hybrid of a synthetic substance, a natural substance or a natural substance derivative and another synthetic substance, another natural substance or another natural substance derivative.
- At least one recognition species is a hybrid of a natural or unnatural, single-stranded or double-stranded nucleic acid and a synthetic substance different from a nucleic acid, a different natural product or a different natural product derivative, preferably an antibody or antibody derivative.
- a first recognition species is a natural or non-natural, single-stranded or double-stranded nucleic acid
- a second recognition species is a hybrid of a natural or non-natural, single-stranded or double-stranded nucleic acid and a synthetic substance, a natural product or a natural product derivative, preferably an antibody or antibody derivative.
- a first recognition species is a natural or non-natural, single-stranded or double-stranded nucleic acid
- a second recognition species is a hybrid of a natural or non-natural, single-stranded or double-stranded nucleic acid and another natural or non-natural single-stranded or double-stranded Nucleic acid
- the third recognition species is another natural or non-natural, single-stranded or double-stranded nucleic acid.
- a first recognition species is a synthetic substance, a natural product or a natural product derivative, preferably an antibody or antibody derivative, a second
- the recognition species is a hybrid of a synthetic substance, a natural substance or a natural product derivative, preferably an antibody or antibody derivative, and another synthetic substance another natural product or another natural product derivative, preferably another antibody or antibody derivative, and a third recognition species is another synthetic substance, another natural product or another different natural product derivative, preferably another antibody or another antibody derivative.
- Another object of the present invention is a test system containing at least two recognition species that recognize at least two different markers to form a complex, preferably the recognition species or markers already described above.
- at least one recognition species is immobilized on a support, as preferably described above.
- At least one recognition species is a natural or non-natural, single-stranded or double-stranded nucleic acid and at least one other recognition species is another natural or non-natural, single-stranded or double-stranded nucleic acid.
- At least one recognition species is a synthetic substance, a different natural product or a different natural product derivative different from a nucleic acid, preferably an antibody or antibody derivative, and at least one other recognition species is another synthetic substance, different natural product or different from a nucleic acid various natural product derivative, preferably an antibody or antibody derivative.
- At least one recognition species is a hybrid of a natural or unnatural, single-stranded or double-stranded nucleic acid and one of one Nucleic acid different synthetic substance, different natural product or different natural product derivative, preferably an antibody or antibody derivative.
- At least one recognition species is a hybrid of a natural or unnatural, single-stranded or double-stranded nucleic acid and another natural or unnatural single-stranded or double-stranded nucleic acid.
- At least one recognition species is a hybrid of a synthetic substance different from a nucleic acid, different natural product or different
- Natural product derivative preferably an antibody or antibody derivative and another synthetic substance different from a nucleic acid, different natural product or different natural product derivative, preferably an antibody or antibody derivative.
- test system according to the invention can be produced, for example, by assembling the recognition species necessary for the individual embodiments. or that at least one recognition species is immobilized on a support, as already preferably described above, according to methods generally known to the person skilled in the art.
- the test system according to the invention can be used in the detection method according to the invention. as described in more detail above.
- it serves to detect the presence and / or absence of at least two different markers in a sample.
- It is preferably in the form of a diagnostic agent or an analyte. It is therefore used in particular for the detection of diseases or for environmental analysis, in particular for the detection of toxins and / or allergens.
- FIG. 1 schematically shows the detection of two analytes (A and B) in an assay in the immobilized embodiment.
- FIG 2 schematically shows the detection of two analytes (antigens A and B) in an assay in the immobilized embodiment.
- FIG 3 schematically shows the detection of two analytes (nucleic acid A and B) in an assay in the immobilized embodiment.
- Example 4 schematically shows the complex of markers and recognition species according to Example 1.
- the reagents required for the example such as Texas-Red® labeled oligonucleotide conjugate (24-mer DNA; from Interactiva; DNA 1), a biotinylated oligonucleotide conjugate (24-mer DNA; from Interactiva; DNA 3); a synthetic oligonucleotide (57-mer DNA; Interepteptavidin-conjugated anti-human IgG F (ab ') 2 (goat; Rockland) and a fluorescein labeled human IgG F (ab ') 2 fragment (Rockland) as antigen, are all commercially available
- DNA 2 5'-ATT-GTC-ATA-ATC-ATC-TTG-AGA-CGC-TTT-TTT-TTT- TTT-ACA-TCA-CGA-CGA-CAT-GCA-TTT-3 '
- the supernatant solution was pipetted off and the carrier was washed 5 times with 500 ⁇ l 0.9% NaCl solution.
- 200 ⁇ l of a solution of 200 ⁇ l streptavidin-anti-human-IgG F (ab ') 2 (goat) solution (1.6 mg / ml) and 40 ⁇ l of the fluorescein-labeled solution, preincubated at RT for 2 h, were then added IgG F (ab ') 2 - fragment solution (5.0 mg / ml) and allowed to incubate for 1-2 h at RT.
- the supernatant solution was again pipetted off and the carrier was washed 5 times with 500 ⁇ l 0.9% NaCl solution.
- the formation of the complex was verified by measuring the fluorescence of the fluorescein ( ⁇ ma v 494 nm, ⁇ max E : 525 nm).
- DNA 2 5'-ATT-GTC-ATA-ATC-ATC-TTG-AGA-CGC-TTT-TTT-TTT- TTT-ACA-TCA-CGA-CGA-CAT-GCA-TTT-3 ' (marker 1)
- Antibody streptavidin-conjugated anti-human IgG F (ab ') (goat)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP99968373A EP1141725A2 (en) | 1998-12-23 | 1999-12-22 | Test system for detecting different analytes |
AU25390/00A AU773046B2 (en) | 1998-12-23 | 1999-12-22 | Test system for detecting different markers, and production and use thereof |
CA002353920A CA2353920A1 (en) | 1998-12-23 | 1999-12-22 | Test system for detecting different markers, and production and use thereof |
JP2000591429A JP2002533724A (en) | 1998-12-23 | 1999-12-22 | Test system for the recognition of different markers, its preparation and use |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19859912.9 | 1998-12-23 | ||
DE19859912A DE19859912C2 (en) | 1998-12-23 | 1998-12-23 | Test system for the detection of different markers, its production and use |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2000039581A2 true WO2000039581A2 (en) | 2000-07-06 |
WO2000039581A3 WO2000039581A3 (en) | 2000-11-23 |
Family
ID=7892569
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1999/010333 WO2000039581A2 (en) | 1998-12-23 | 1999-12-22 | Test system for detecting different markers, and production and use thereof |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP1141725A2 (en) |
JP (1) | JP2002533724A (en) |
AU (1) | AU773046B2 (en) |
CA (1) | CA2353920A1 (en) |
DE (1) | DE19859912C2 (en) |
WO (1) | WO2000039581A2 (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6893822B2 (en) | 2001-07-19 | 2005-05-17 | Nanogen Recognomics Gmbh | Enzymatic modification of a nucleic acid-synthetic binding unit conjugate |
EP1386164B1 (en) * | 2000-08-24 | 2007-08-08 | Spectral Diagnostics Inc. | Differential immunoassay for myoglobin |
EP1947459A3 (en) * | 2000-08-24 | 2008-09-24 | Nanogen, Inc. | Differential immunoassay |
US9816984B2 (en) | 2009-07-31 | 2017-11-14 | Invisible Sentinel, Inc. | Device for detection of target molecules and uses thereof |
US9823240B2 (en) | 2012-03-09 | 2017-11-21 | Invisible Sentinel, Inc. | Methods and compositions for detecting multiple analytes with a single signal |
US10495638B2 (en) | 2009-10-09 | 2019-12-03 | Invisible Sentinel, Inc. | Device for detection of analytes and uses thereof |
US10705084B2 (en) | 2009-07-31 | 2020-07-07 | Invisible Sentinel, Inc. | Analyte detection devices, multiplex and tabletop devices for detection of analytes, and uses thereof |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11604186B2 (en) | 2018-10-17 | 2023-03-14 | Molecular Devices (Austria) GmbH | Real time western blot assays utilizing fluorescence resonance energy transfer (FRET) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992018866A1 (en) * | 1991-04-10 | 1992-10-29 | Biosite Diagnostics Incorporated | Novel conjugates and assays for simultaneous detection of multiple ligands |
WO1998023956A1 (en) * | 1996-11-28 | 1998-06-04 | University College London | Capture assays |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4320109A (en) * | 1979-06-29 | 1982-03-16 | The University Of Southern California | Immunoradiometric assay employing terminal radionuclide labeling and synthesis of conjugates for such assay |
JPH081438B2 (en) * | 1986-05-13 | 1996-01-10 | 三洋化成工業株式会社 | Enzyme immunoassay |
US5296347A (en) * | 1991-02-08 | 1994-03-22 | Ciba Corning Diagnostics Corp. | Bridge immunoassay |
-
1998
- 1998-12-23 DE DE19859912A patent/DE19859912C2/en not_active Expired - Fee Related
-
1999
- 1999-12-22 JP JP2000591429A patent/JP2002533724A/en active Pending
- 1999-12-22 AU AU25390/00A patent/AU773046B2/en not_active Ceased
- 1999-12-22 CA CA002353920A patent/CA2353920A1/en not_active Abandoned
- 1999-12-22 EP EP99968373A patent/EP1141725A2/en not_active Withdrawn
- 1999-12-22 WO PCT/EP1999/010333 patent/WO2000039581A2/en not_active Application Discontinuation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992018866A1 (en) * | 1991-04-10 | 1992-10-29 | Biosite Diagnostics Incorporated | Novel conjugates and assays for simultaneous detection of multiple ligands |
WO1998023956A1 (en) * | 1996-11-28 | 1998-06-04 | University College London | Capture assays |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1386164B1 (en) * | 2000-08-24 | 2007-08-08 | Spectral Diagnostics Inc. | Differential immunoassay for myoglobin |
EP1947459A3 (en) * | 2000-08-24 | 2008-09-24 | Nanogen, Inc. | Differential immunoassay |
US6893822B2 (en) | 2001-07-19 | 2005-05-17 | Nanogen Recognomics Gmbh | Enzymatic modification of a nucleic acid-synthetic binding unit conjugate |
US9816984B2 (en) | 2009-07-31 | 2017-11-14 | Invisible Sentinel, Inc. | Device for detection of target molecules and uses thereof |
US10705084B2 (en) | 2009-07-31 | 2020-07-07 | Invisible Sentinel, Inc. | Analyte detection devices, multiplex and tabletop devices for detection of analytes, and uses thereof |
US10495638B2 (en) | 2009-10-09 | 2019-12-03 | Invisible Sentinel, Inc. | Device for detection of analytes and uses thereof |
US9823240B2 (en) | 2012-03-09 | 2017-11-21 | Invisible Sentinel, Inc. | Methods and compositions for detecting multiple analytes with a single signal |
US10018626B2 (en) | 2012-03-09 | 2018-07-10 | Invisible Sentinel, Inc. | Methods and compositions for detecting multiple analytes with a single signal |
US10732177B2 (en) | 2012-03-09 | 2020-08-04 | Invisible Sentinel, Inc. | Methods and compositions for detecting multiple analytes with a single signal |
Also Published As
Publication number | Publication date |
---|---|
AU2539000A (en) | 2000-07-31 |
WO2000039581A3 (en) | 2000-11-23 |
EP1141725A2 (en) | 2001-10-10 |
DE19859912A1 (en) | 2000-07-06 |
JP2002533724A (en) | 2002-10-08 |
DE19859912C2 (en) | 2001-06-21 |
CA2353920A1 (en) | 2000-07-06 |
AU773046B2 (en) | 2004-05-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE69735532T2 (en) | DETERMINATION OF ANTIGENS BY OLIGONUCLEOTIDE ANTIBODY CONJUGATES | |
DE60014762T2 (en) | Method for the detection of ribonucleic acids | |
DE2915082C3 (en) | Method and use of a reagent set for the detection and characterization of nucleic acids and their sequences | |
DE69828502T2 (en) | Method for detecting biological molecules in biological samples by means of bacteriophages | |
DE69535428T2 (en) | Method for finding differentially expressed genes | |
DE69824099T2 (en) | ANALYTICAL PROCEDURE, TEST SET AND DEVICE | |
DE60029092T2 (en) | METHOD FOR DETECTING NUCLEIC ACIDS REFERRING TO CANCER INSTRUCTIONS | |
EP2376650B1 (en) | Detection conjugate and method for polychromatic analysis | |
DE60317315T2 (en) | DETECTION OF DNA BINDING PROTEINS | |
EP1565569A2 (en) | Method for the detection of mutations | |
DE19859912C2 (en) | Test system for the detection of different markers, its production and use | |
EP1364068B1 (en) | Method and kit for animal species-specific dna identification of a sample | |
DE10038237A1 (en) | Procedure for the detection of mutations in nucleotide sequences | |
DE60038029T2 (en) | METHODS AND REAGENTS FOR SITU AMPLIFICATION | |
DE60029607T2 (en) | Electrochemiluminescence HELIKASETEST | |
DE102005056639A1 (en) | Method, device and kit for the study of macromolecules in a sample | |
DE202021004362U1 (en) | Controls for proximity detection assays | |
WO1994026928A2 (en) | Complex diagnostic agent of genetic expression and medical diagnosis and gene isolation process using said diagnostic agent | |
DE102004043870B4 (en) | Method for expanding the dynamic detection range in microarrays | |
DE102020103958A1 (en) | Oligonucleotide probe for the specific detection of microorganisms, corresponding method and use | |
WO2002083941A2 (en) | Highly specific detection system for detecting nucleotide sequences coding for lambda and kappa light chains | |
DE102004023439B4 (en) | Detection of RNA via microarrays | |
DE69834208T2 (en) | BLOCKED POLYMERASE POLYNUCLEOTIDE IMMUNOASSAY AND KIT | |
AT412649B (en) | Method for detecting nucleic acid by hybridization, useful particularly for detecting Salmonella strains, comprises using two separate labeling components, one conjugated to a detection probe and the other having a marker | |
DE60120118T2 (en) | TEST AND PROOF METHOD FOR A MICROARRAY |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AU CA JP US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
AK | Designated states |
Kind code of ref document: A3 Designated state(s): AU CA JP US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A3 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
ENP | Entry into the national phase |
Ref document number: 2353920 Country of ref document: CA Ref country code: CA Ref document number: 2353920 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 25390/00 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1999968373 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 2000 591429 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 09868824 Country of ref document: US |
|
WWP | Wipo information: published in national office |
Ref document number: 1999968373 Country of ref document: EP |
|
WWG | Wipo information: grant in national office |
Ref document number: 25390/00 Country of ref document: AU |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1999968373 Country of ref document: EP |