Abstract: The present invention provides a useful system for assays that comprises a solid support, a plurality of capture oligonucleotides immobilized onto the solid support, and complementary oligonucleotides attached to capture ligands. A detectable label can be directly attached to the capture oligonucleotides or the complementary oligonucleotides. The labeled oligonucleotides can be detected, and used to determine the quality of the assay. A labeled detector ligand corresponding to a target ligand can also be independently detected apart from the labeled oligonucleotide.

Abstract: The present invention provides a useful system for assays that comprises a solid support, a plurality of capture oligonucleotides immobilized onto the solid support, and complementary oligonucleotides attached to capture ligands. A detectable label can be directly attached to the capture oligonucleotides or the complementary oligonucleotides. The labeled oligonucleotides can be detected, and used to determine the quality of the assay. A labeled detector ligand corresponding to a target ligand can also be independently detected apart from the labeled oligonucleotide.

Abstract: This invention provides dye phosphoramidites, particularly phosphoramidites of substituted cyclic bridged cyanine and related dyes, of the general formula: In this formula, each dotted line represents carbon atoms necessary to form a fused substituted or unsubstituted aromatic ring; m is an integer from 1 to 18; Y and Z are independently selected from the group consisting of S, O, N, CH2 and C(CH3)2; R1 is an alkyl; (PAM) is a phosphoramidite group; X{circle around (?)} is a negative ion; and Q is L-W, wherein L is a conjugated cyclic moiety and W is OR2, wherein R2 is a second alkyl. Methods of making and using the dye phosphoramidites are also provided.

Abstract: The invention is an oligonucleotide-based assay system and kit useful for sorting, detecting, and identifying analytes. The system utilizes complementary oligonucleotide pairs in which one oligonucleotide of each pair is immobilized to a solid substrate and the other oligonucleotide has an analyte binding agent attached to it. The different oligonucleotide pairs hybridize at substantially the same rate, have substantially the same Tm, have nucleotide sequences designed to minimize cross-hybridization between different pairs, and hybridize together relatively rapidly at ambient temperatures without detectable cross-hybridization.

Abstract: This invention provides dye phosphoramidites, particularly phosphoramidites of substituted cyclic bridged cyanine and related dyes, of the general formula: In this formula, each dotted line represents carbon atoms necessary to form a fused substituted or unsubstituted aromatic ring; m is an integer from 1 to 18; Y and Z are independently selected from the group consisting of S, O, N, CH2 and C(CH3)2; R1 is an alkyl; (PAM) is a phosphoramidite group; X is a n{circle around (?)}egative ion; and Q is L-W, wherein L is a conjugated cyclic moiety and W is OR2, wherein R2 is a second alkyl. Methods of making and using the dye phosphoramidites are also provided.

Abstract: The present invention relates to an improved method for forming a protein-oligonucleotide conjugate. The method is particularly amenable for forming antibody-oligonucleotide conjugates. The invention further concerns the conjugate molecules produced using such improved methods.

Abstract: The present invention relates to an improved method for forming a protein-oligonucleotide conjugate. The method is particularly amenable for forming antibody-oligonucleotide conjugates. The invention further concerns the conjugate molecules produced using such improved methods.

Abstract: The present invention provides a system using internal reference spots to reduce microarray assay variation. A microarray device for quantifying a plurality of target ligands in a sample includes a solid support having a plurality of test areas; a plurality of different target capture ligands immobilized onto the test areas; and at least one reference capture ligand immobilized onto the test areas. The reference capture ligand captures a reference ligand not normally present in the sample.

Abstract: The present invention provides a useful system for assays that comprises a solid support, a plurality of capture oligonucleotides immobilized onto the solid support, and complementary oligonucleotides attached to capture ligands. A detectable label can be directly attached to the capture oligonucleotides or the complementary oligonucleotides. The labeled oligonucleotides can be detected, and used to determine the quality of the assay. A labeled detector ligand corresponding to a target ligand can also be independently detected apart from the labeled oligonucleotide.

Abstract: The invention is an oligonucleotide-based assay system and kit useful for sorting, detecting, and identifying analytes. The system utilizes complementary oligonucleotide pairs in which one oligonucleotide of each pair is immobilized to a solid substrate and the other oligonucleotide has an analyte binding agent attached to it. The different oligonucleotide pairs hybridize at substantially the same rate, have substantially the same Tm, have nucleotide sequences designed to minimize cross-hybridization between different pairs, and hybridize together relatively rapidly at ambient temperatures without detectable cross-hybridization.

Abstract: Processes for the solid state phase formation synthesis of biomolecule conjugates, particularly protein-oligonucleotide conjugates are shown. One of the protein or oligonucleotide is reversibly bound to a solid substrate phase. At least one portion of each of the protein and the oligonucleotide molecules is activated with complementary activation groups. The activated protein and the activated oligonucleotide are then reacted, in a buffered solution resulting in the formation of the desired conjugate which remains reversibly bound to the substrate. The nature of the buffered solution is then modified causing the conjugate to be released from the substrate solid phase.

Abstract: Oligonucleotide probes, kits, and methods useful for detecting a polynucleotide target in a sample are provided. The method, a mixture is formed by combining a polynucleotide target sample, a first probe that is complementary to the polynucleotide target and having a first fluorescent donor or fluorescent acceptor; and a second probe that is partially complementary to the first probe and having a second fluorescent donor or fluorescent acceptor. The second probe competes with the polynucleotide target for binding to the first probe and the first probe preferentially binds to the polynucleotide target rather than to the second probe. The-first fluorescent donor or acceptor and second fluorescent donor or acceptor form a donor/acceptor pair capable of fluorescence resonance energy transfer (FRET) with each other in response to activation of the fluorescent donor by light of a predetermined wavelength or band of wavelengths.

Abstract: Oligonucleotide probes, kits, and methods useful for detecting a polynucleotide target in a sample are provided. The method, a mixture is formed by combining a polynucleotide target sample, a first probe that is complementary to the polynucleotide target and having a first fluorescent donor or fluorescent acceptor; and a second probe that is partially complementary to the first probe and having a second fluorescent donor or fluorescent acceptor. The second probe competes with the polynucleotide target for binding to the first probe, and the first probe preferentially binds to the polynucleotide target rather than to the second probe. The first fluorescent donor or acceptor and second fluorescent donor or acceptor form a donor/acceptor pair capable of fluorescence resonance energy transfer (FRET) with each other in response to activation of the fluorescent donor by light of a predetermined wavelength or band of wavelengths.

Abstract: This invention provides a system for immobilizing biological molecules onto a solid support having an available amino group that uses two steps. In a first step, a nucleophilic substitution reaction occurs so that the available amino group displaces a first leaving group of an activating compound to form an activated support.

Abstract: The present invention relates to an improved method for forming a protein-oligonucleotide conjugate. The method is particularly amenable for forming antibody-oligonucleotide conjugates. The invention further concerns the conjugate molecules produced using such improved methods.

Abstract: This invention provides cyclic-bridged dyes, particularly cyclic-bridged cyanine dyes, of the general formula: In this formula, each dotted line represents carbon atoms necessary to form a fused substituted or unsubstituted aromatic ring; n=1-18; m=1-18, selected independently from n. X and Y are selected independently from the group consisting of S, O, N, CH2 and C(CH3)2; at least one of said R1 and R2 comprises a sulfonic acid or sulfonate group attached to the aromatic ring; and R3 and R4 are independently selected from the group consisting of carboxyl, activated carboxyl and methyl, wherein at least one of said R3 and R4 groups is carboxylate or activated carboxylate. Methods of making and using the cyclic-bridged dyes are also provided.

Abstract: This invention provides dye phosphoramidites, particularly phosphoramidites of cyanine and related dyes, of the general formula: In this formula, each dotted line represents carbon atoms necessary to form a fused substituted or unsubstituted aromatic ring; m is an integer from 1 to 18; Y and Z are independently selected from the group consisting of S, O, N, CH2 and C(CH3)2; R1 is an alkyl; (PAM) is a phosphoramidite group; X⊖ is a negative ion; and Q is or wherein n is 1, 2 or 3. Methods of making and using the dye phosphoramidites are also provided.

Abstract: Activating groups based on N-hydroxynaphthalimide, are disclosed herein. The activating groups can mediate the coupling of labeling moieties, such as biotin or cyanine dyes, to a variety of components, including chain terminators, nucleoside triphosphates, and oligonucleotides, which are used in nucleotide sequencing. From these activating groups, activated esters of the labeling moieties can be prepared. The activated esters react with a component, for example a derivatized nucleotide chain terminator, to give a labeled component. In additions, methods of the present invention provide for labeling a nucleoside triphosphate in organic media. The activating groups and methods of the present invention allow the activation and coupling reactions to occur at a much higher yield, compared with the prior art.

Abstract: Universal solid support oligonucleotide synthesis reagents, oligonucleotide synthesis processes, and reagents for cleaving oligonucleotides from solid supports are disclosed. Oligonucleotide synthesis reagents have the following general formula:SS--R.sup.6 --O--R.sup.3 Iwherein SS is a solid support; R.sup.6 is ##STR1## where R.sup.5 is hydrogen or alkyl and R.sup.4 is a phosphate protecting group; and R.sup.3 is a ring moiety having vicinal groups --XR.sup.1 and --YR.sup.2 wherein each of X and Y is independently selected from the group consisting of O, S and NH and one of R.sup.1 and R.sup.2 is a blocking moiety and the other is hydrogen or a hydroxy protecting group. Oligonucleotide cleaving reagents include methylamine and/or ammonium hydroxide and trimethylamine.

Abstract: A compound of the general formula ##STR1## wherein R is alkyl of 1 to about 10 carbons and R' is selected from the group consisting of trityl and pixyl, for use in the synthesis of 2'-OMe RNA sequences. Fast cleavage and deprotection of oligonucleotides is facilitated by the use of a reagent comprising methylamine as active component in place of the traditional reagent ammonium hydroxide.