Abstract: A method and system for correlating characteristics (e.g., type of nucleotide) of biomolecules (e.g., DNA) to molecular tags with unique molecular weights that are associated with the biomolecule. In one embodiment. the molecular tags are applied to primers used when synthesizing the biomolecule. The system initially receives a mapping of each characteristic of the biomolecules to the corresponding molecular weight of the molecular tag. The system also receives an indication of the molecular weights detected when analyzing the biomolecules to which the molecular tags have been associated. For each molecular weight detected, the system determines based on the received mapping the characteristic corresponding to the detected molecular weight. The system then indicates that the analyzed biomolecule has the determined characteristic.

Abstract: Methods and compounds, including compositions therefrom, are provided for determining the sequence of nucleic acid molecules. The methods permit the determination of multiple nucleic acid sequences simultaneously. The compounds are used as tags to generate tagged nucleic acid fragments which are complementary to a selected target nucleic acid molecule. Each tag is correlative with a particular nucleotide and, in a preferred embodiment, is detectable by mass spectrometry. Following separation of the tagged fragments by sequential length, the tags are cleaved from the tagged fragments. In a preferred embodiment, the tags are detected by mass spectrometry and the sequence of the nucleic acid molecule is determined therefrom. The individual steps of the methods can be used in automated format, e.g., by the incorporation into systems.

Abstract: A novel human protein has been isolated which is encoded by a nucleic acid molecule comprising the polynucleotide sequence provided in SEQ ID NO:1 or a polynucleotide sequence that is completely complementary thereto. This novel protein binds to at least two members of the family of TGF-beta proteins, which are the human bone morphogenic protein-5 and human bone morphogenic protein-6.

Abstract: A method for depositing biomolecule onto a solid support, the method including the steps of: immersing a tip of a spring probe into a solution of biomolecule; removing said tip from said solution to provide biomolecule solution adhered to said tip; and contacting said biomolecule solution with a solid support to thereby transfer biomolecule solution from said tip to said solid support. The spring probe has a planar tip but it otherwise identical to commercial spring probes. The solution of biomolecule contains a thickening agent in addition to biomolecule, where oligonucleotide is a preferred biomolecule.

Abstract: The present invention provide methods and an apparatus for performing amplification and other enzymatic reactions on nucleic acid molecules that have been printed onto a solid substrate, such as a silicon wafer or glass slide.

Abstract: Compositions and methods are provided for increasing the specificity of a probe nucleic acid for a target nucleic acid in a hybridization solution. An abasic residue, deoxyNebularine residue, or a hybotrope is used to increase specificity. A method is provided for identifying useful hybotropes, including salts, water miscible organic solvents, aprotic solvents and organic solvents, on the basis of enthalpy considerations. Hybotropic hybridization and modified oligonucleotides may be used in amplification reactions, such as PCR, sequence analysis methods, and genomic screening methods.

Abstract: A method and system for correlating characteristics (e.g., type of nucleotide) of biomolecules (e.g., DNA) to molecular tags with unique molecular weights that are associated with the biomolecule. In one embodiment, the molecular tags are applied to primers used when synthesizing the biomolecule. The system initially receives a mapping of each characteristic of the biomolecules to the corresponding molecular weight of the molecular tag. The system also receives an indication of the molecular weights detected when analyzing the biomolecules to which the molecular tags have been associated. For each molecular weight detected, the system determines based on the received mapping the characteristic corresponding to the detected molecular weight. The system then indicates that the analyzed biomolecule has the determined characteristic.

Abstract: Methods and compounds, including compositions therefrom, are provided for determining the sequence of nucleic acid molecules. The methods permit the determination of multiple nucleic acid sequences simultaneously. The compounds are used as tags to generate tagged nucleic acid fragments which are complementary to a selected target nucleic acid molecule. Each tag is correlative with a particular nucleotide and, in a preferred embodiment, is detectable by mass spectrometry. Following separation of the tagged fragments by sequential length, the tags are cleaved from the tagged fragments. In a preferred embodiment, the tags are detected by mass spectrometry and the sequence of the nucleic acid molecule is determined therefrom. The individual steps of the methods can be used in automated format, e.g., by the incorporation into systems.

Abstract: The present invention provide methods and an apparatus for performing amplification and other enzymatic reactions on nucleic acid molecules that have been printed onto a solid substrate, such as a silicon wafer or glass slide.

Abstract: An array of biomolecules is formed from a solid substrate comprising a surface, where said surface is at least partially covered with a layer of poly(ethylenimine) (PEI), and the layer is divided among a plurality of discrete first regions abutted and surrounded by a contiguous second region. The first regions are defined by the presence of a biomolecule and PEI. The second region is defined by the presence of PEI and the substantial absence of the biomolecule. The array may be prepared by a process including the steps of providing a solid substrate having a surface, wherein a layer of poly(ethylenimine) (PEI) covers at least a portion of the surface. The layer contains a plurality of discrete first regions abutted and surrounded by a contiguous second region. The process includes the step of depositing a biomolecule into the first regions while maintaining the second region substantially free of the biomolecule.

Abstract: Methods are provided for detecting the binding of a first member to a second member of a ligand pair, comprising the steps of (a) combining a set of first tagged members with a biological sample which may contain one or more second members, under conditions, and for a time sufficient to permit binding of a first member to a second member, wherein said tag is correlative with a particular first member and detectable by non-fluorescent spectrometry, or potentiometry, (b) separating bound first and second members from unbound members, (c) cleaving the tag from the tagged first member, and (d) detecting the tag by non-fluorescent spectrometry, or potentiometry, and therefrom detecting the binding of the first member to the second member.

Abstract: Methods related to solid supports for binding reactions are disclosed. The present invention provides procedures for prepaing solid supports, and their use in binding assays, such that non-specific background on the solid supports is reduced. The reduction of non-specific background permits the detection of low levels of specific binding which normally would be masked by the non-specific binding. The methods are applicable to a variety of target ligands and probes, including nucleic acids such as oligonucleotides.

Abstract: Compositions and methods for covalently immobilizing an oligonucleotide onto a polymer-coated solid support or similar structure are provided. Specifically, the polymer-coated support, such as a bead, possesses a large number of activatable moieties, preferably primary and secondary amines. An oligonucleotide is activated with a monofunctional or multifunctional reagent, preferably the homotrifunctional reagent cyanuric chloride. The resultant covalently immobilized oligonucleotides on the support serve as nucleic acid probes, and hybridization assays can be conducted wherein specific target nucleic acids are detected in complex biological samples. The beads or similar structures can be employed free in solution, such as in a microtiter well format; in a flow-through format, such as in a column; or in a dipstick. Additionally, dichlorotriazine oligonucleotides and processes for activating oligonucleotides by treatment with cyanuric chloride and derivatives are included in the present invention.

Abstract: Compounds that selectively modulate the remodeling pathway of platelet activating factor (PAF) are described. Related pharmaceutical compositions and methods are also disclosed. These compounds, pharmaceutical compositions and methods are useful for reducing or eliminating inflammation.

Abstract: Compositions and methods for covalently immobilizing an oligonucleotide onto a polymer-coated bead or similar structure are described. Specifically, the polymer-coated bead or similar structure possesses a large number of activatable moieties, preferably primary and secondary amines. An oligonucleotide is activated with a monofunctional or multifunctional reagent, preferably the homotrifunctional reagent cyanuric chloride. The resultant covalently immobilized oligonucleotides on the beads or similar structures can serve as nucleic acid probes on solid supports, and hybridization assays can be conducted wherein specific target nucleic acids are detected in complex biological samples.

Abstract: This invention relates to novel methods for the release of nucleic acids from cells in complex biological samples or specimens to prepare and make available the nucleic acid material present for a hybridization assay or for extraction. Novel methods for hybridization of nucleic acids are also presented. In particular methods are described for isolating nucleic acid from a sample containing a complex biological mixture of nucleic acid and non-nucleic acids wherein the sample is combined with a hybridization medium comprising a lactam which promotes and enables nucleic acid pairing when complementary nucleic acid is introduced. The lactam is preferably about 5 to about 70% of the hybridization medium and is most preferably 2-pyrrolidone, N-ethyl-2-pyrrolidone, N-cyclohexyl-2-pyrrolidone, N-dodecyl-2-pyrrolidone, N-methyl-2-pyrrolidone, N-hydroxyethyl-2-pyrrolidone, N-methyl-2-piperidone, 2-.epsilon.-caprolactam, N-methyl-2-caprolactam, 2-piperidone or N-(4-hydroxybenzyl)pyrrolidone.

Abstract: Novel methods and compositions for detecting a member of a ligand pair on solid supports having intrinsic fluorescence are disclosed. A target member of a ligand pair is contacted with a capture member of a ligand pair, wherein the capture member is immobilized on a solid support having intrinsic fluorescence, and the contacted pair is in association with a colorimetric reporter, then the solid support is irradiated the solid support, and the resultant fluorescence is determined. Preferably, methods include hybridization assays of nucleic acid sequences on such solid supports. The extent of detecting a member of a ligand pair, preferably a nucleic acid sequence, is determined using a method or technique described throughout this document as fluorescent quenching. Methods and compositions pertaining to solid supports having their intrinsic or natural fluorescence quenched or masked are also described herein. The present invention has utility in detection assays for a member of a ligand pair.

Abstract: This invention relates to safe and effective methods for the extraction of nucleic acids. In particular, methods are described for isolating nucleic acid from a sample containing a biological mixture of nucleic acids and other biological compounds wherein the sample is combined with an extraction solution containing at least one organic compound such as benzyl alcohol or a benzyl alcohol derivative to form an aqueous and non-aqueous phase. The nucleic acid is isolated from the aqueous phase. Preferably, the resulting combined solution also contains bentonite, as defined below. Typically, the sample will first be combined with a lysing agent before extraction. The lysing agents preferred are chaotropic salts such as guanidinium hydrochloride and guanidinium isothiocyanate.

Abstract: This invention relates to novel methods for the extraction of nucleic acid. In particular methods are described for isolating nucleic acid from a sample containing a complex biological mixture of nucleic acid and non-nucleic acids wherein the sample is combined with an extraction solution comprising a lactam and then the nucleic acid material is isolated from the resulting combined solution. The resulting combined solution is mixed and becomes biphasic and the nucleic acid material is isolated from the aqueous phase by precipitation with ethanol. The lactam is preferably about 5 to about 70% of the extraction solution and is most preferably 2-pyrrolidone, N-ethyl-2-pyrrolidone, N-cyclohexyl-2-pyrrolidone, N-dodecyl-2-pyrrolidone, N-methyl-2-pyrrolidone, N-hydroxyethyl-2-pyrrolidone, N-methyl-2-piperidone, 2-.epsilon.-caprolactam, N-methyl-2-caprolactam, 2-piperidone or N-(4-hydroxybenzyl)pyrrolidone. Methods for selectively isolating DNA, ribosomal RNA and plasmid DNA are also disclosed.

Abstract: This invention relates to novel methods for the release of nucleic acids from cells in complex biological samples or specimens to prepare and make available the nucleic acid material present for a hybridization assay or for extraction. Novel methods for hybridization of nucleic acids are also presented. In particular methods are described for isolating nucleic acid from a sample containing a complex biological mixture of nucleic acid and non-nucleic acids wherein the sample is combined with a hybridization medium comprising a lactam which promotes and enables nucleic acid pairing when complementary nucleic acid is introduced. The lactam is preferably about 5 to about 70% of the hybridization medium and is most preferably 2-pyrrolidone, N-ethyl-2-pyrrolidone, N-cyclohexyl-2-pyrrolidone, N-dodecyl-2-pyrrolidone, N-methyl-2-pyrrolidone, N-hydroxyethyl-2-pyrrolidone, N-methyl-2-piperidone, 2-.epsilon.-caprolactam, N-methyl-2-caprolactam, 2-piperidone or N-(4-hydroxybenzyl)pyrrolidone.