Abstract: The invention provides modified nucleotide or nucleoside molecule comprising a purine or pyrimidine base and a ribose or deoxyribose sugar moiety having a removable 3?-OH blocking group covalently attached thereto, such that the 3? carbon atom has attached a group of the structure —O—Z wherein Z is any of —C(R?)2-O—R?, —C(R?)2-N(R?)2, —C(R?)2-N(H)R?, —C(R?)2-S—R? and —C(R?)2-F, wherein each R? is or is part of a removable protecting group; each R? is independently a hydrogen atom, an alkyl, substituted alkyl, arylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclic, acyl, cyano, alkoxy, aryloxy, heteroaryloxy or amido group, or a detectable label attached through a linking group; or (R?)2 represents an alkylidene group of formula ?C(R??)2 wherein each R?? may be the same or different and is selected from the group comprising hydrogen and halogen atoms and alkyl groups; and wherein said molecule may be reacted to yield an intermediate in which each R? is exchanged for H or, where Z is —C(R?)2-F, the F is ex

Abstract: Compounds relating to attachment chemistries for binding biomolecules to a substrate surface are described. These include compounds of the following structure: The biomolecule includes a single nucleic acid, oligonucleotides, polynucleotides, DNAs, RNAs, proteins, peptides, enzymes, antibodies, CNAs (cyclohexyl nucleic acids), p-MeNAs (methyl or methoxy phosphate nucleic acids), peptide nucleic acids (PNAs), and pyranosyl RNAs (p-RNAs).

Abstract: Methods are provided for amplification and monitoring of oligonucleotide amplification in which a primer has an overlap with one or more bases of a detection probe.

Abstract: The invention provides a novel array method for nucleic acid sequence detection with improved specificity which allows for detection of genetic variation, from simple SNPs (where the variation occurs at a fixed position and is of limited allelic number) to more complex sequence variation patterns (such as with multigene families or multiple genetic strains of an organism where the sequence variation between the individual members is neither fixed nor consistent). The array is comprised of short, synthetic oligonucleotide probes attached to a solid surface which are hybridized to single-stranded targets. Single stranded targets can be produced using a method that employs primers modified on the 5? end to prohibit degradation by a 5?-exonuclease that is introduced to degrade the unprotected strand. The invention further provides for printing buffers/solutions for the immobilization of oligonucleotide probes to an array surface.

Abstract: The invention relates to novel fluorescent compounds derived from non-fluorinated dipyrromethene-boron, to a method for preparing same and to the use thereof for the fluorescent marking of biological molecules. The invention also relates to biological molecules marked with said fluorescent compounds, and to the use thereof in detection methods such as medical diagnosis methods. More particularly, the detection methods of the invention are particularly useful for diagnosing neurodegenerative diseases such as Alzheimer's disease.

Abstract: A labeled compound is so designed that an aromatic tertiary amine compound is bondable with a biomolecule. One of S1 and S2 contains a group bound with a molecular chain 10 (e.g. an oligonucleotide) capable of binding with a biomolecule or a reactive group covalently binding with a reactive group present in the biomolecule, n is 0 or 1, R3 is a phenyl group or a naphthyl group, Ar1 is a phenylene group or a naphthylene group, and Ar2 is any of a phenylene group, a naphthylene group, an anthrylene group, and a phenanthrene group. The detection of a fluorescence emitted by excitation of the labeled compound bound to a biomolecule ensures the biomolecule being detected at high sensitivity and a high SN ratio.

Abstract: Nucleotide analogs that can sustain the enzymatic synthesis of double-stranded nucleic acid from a nucleic template are described. The nucleotide analogs include: (i) a base selected from the group consisting of adenine, guanine, cytosine, thymine, uracil and their analogs; (ii) a label attached to the base or analog of the base via a cleavable linker; (iii) a deoxyribose; and (iv) one or more phosphate groups. The linker and/or the label inhibits template directed polymerase incorporation of a further nucleotide substrate onto an extended primer strand. In addition, cleavage of the linker leaves a residue attached to the base which is not present in the natural nucleotide and which does not inhibit extension of the primer strand. The nucleotide analogs can therefore be used as reversible terminators in sequencing by synthesis methods without blocking the 3? hydroxyl group. Methods of sequencing DNA using the substrates are also described.

Abstract: The present invention is in the field of nucleic acid binding compounds comprising 7-substituted 7-deaza-8aza-2,6-diamino-purine bases, compounds useful for the preparation of such compounds, various uses thereof and methods for the determination of nucleic acids using said compounds in the field of diagnostics.

Abstract: Labeled nucleotide analogs used in place of naturally occurring nucleoside triphosphates or other analogs in template directed nucleic acid synthesis reactions and other nucleic acid reactions, and various analyses based thereon, including DNA sequencing, single base identification, hybridization assays and others.

Abstract: Disclosed is a method for analyzing nucleic acids in a sample comprising the following steps: (i) adding a DNA binding dye containing a benzothiazolium or benzoxazolium group to the sample to be analyzed, (ii) carrying out a polymerase chain reaction, (iii) applying the sample to a gel matrix, (iv) separating the nucleic acid molecules according to their size by applying a voltage and (v) excitation with light of a suitable wavelength for the optical visualization of the nucleic acid/DNA binding dye complexes.

Abstract: The present invention provides compounds that have motifs that target the compounds to cells that express integrins. In particular, the compounds have peptides with one or more RD motifs conjugated to an agent selected from an imaging agent and a targeting agent. The compounds may be used to detect, monitor and treat a variety of disorders mediated by integrins.

Abstract: The present invention provides massively parallel oligonucleotide synthesis and purification for applications that utilize large collections of defined high-fidelity oligonucleotides (e.g., from about 101 to about 105 different sequences, generally between 25-160 bases in length).

Abstract: Disclosed are new acridone dye derivatives having characteristic fluorescence lifetimes. Also disclosed are methods for labelling target biological materials employing the acridone dyes and use of the labelled materials in biological assays.

Abstract: The present invention relates to a DNA sequencing method using a nucleoside triphosphate with a fluorescent blocking group on its 3?-OH end as a reversible terminator. Further, the present invention relates to sequencing-by-synthesis method using the mono-modified reversible terminator (MRT), the novel nucleotide monomer having a reversible fluorescent blocking group removable chemically or enzymatically at its 3?-OH end. The sequencing method of the present invention facilitates sequencing of bases inserted by terminating extension of a nucleotide chain by the nucleotide monomer and then detecting fluorescence signal from 3?-OH end. At this time, after analyzing the fluorescence signal, the blocking group conjugated to the 3?-OH end can be effectively removed, indicating that a free 3?-OH functional group can be successfully restored, so that the next monomer insertion is possible, making continuous sequencing possible.

Abstract: A compound having the general formula shown below: where R1-6 are independently selected from the group consisting of an electron withdrawing group, an alkyl group, an aryl group, hydrogen, a heteroaryl group, and a five or six member ring structure formed from the R1 and R2 pair, the R3 and R4 pair, the R4 and R5 pair, or the R5 and R6 pair; R7 is a substituted or unsubstituted aryl group; and Y is a nucleophile.

Abstract: The present invention provides novel, water-soluble, red-emitting fluorescent rhodamine dyes and red-emitting fluorescent energy-transfer dye pairs, as well as labeled conjugates comprising the same and methods for their use. The dyes, energy-transfer dye pairs and labeled conjugates are useful in a variety of aqueous-based applications, particularly in assays involving staining of cells, protein binding, and/or analysis of nucleic acids, such as hybridization assays and nucleic acid sequencing.

Abstract: Compositions and methods of preparing carboranes and metallacarboranes, which can be used as a new type of electrochemically active label for biological compounds, are disclosed. Nucleic acid derivatives labelled with carborane or metallacarborane can be detected by electrochemical methods and can find several practical applications, such as materials for nanoconstruction, in DNA array technology or for the construction of biosensors, especially electrochemical biosensors. Other applications can include use as modified primers in amplification of RNA and DNA, antisense drugs, boron carriers for BNCT, radiopharmaceuticals bearing a range of isotopes useful in different types of radiotherapy, molecular probes, elements of biosensors, materials for nanotechnology and others.

Abstract: Methods of determining the presence or amount of a target polynucleotide in a sample are provided. A sample that contains a target polynucleotide, a polynucleotide that may include nucleic acid analogs and that is complementary to a target nucleic acid sequence of the target polynucleotide, and a dye for which the rate of change in an optical property is different in the presence and absence of a target polynucleotide/polynucleotide hybrid are combined to produce a reaction mixture. The rate of change in an optical property of the dye in the reaction mixture is compared to a reference value characteristic of the rate of change in the optical property of the dye in a similar reaction mixture containing a known amount of a polynucleotide/polynucleotide hybrid to determine a relative rate of change in the optical property. The relative rate of change in the optical property of dye in the reaction mixture is correlated with the presence or amount of the specified target polynucleotide in the sample.

Abstract: This disclosure provides novel reversibly terminated ribonucleotides which can be used as a reagent for DNA sequencing reactions. Methods of sequencing nucleic acids using the disclosed nucleotides are also provided.

Abstract: The present invention relates to carboxamide-substituted dyes, the production and use of such dyes as labeling groups in analytics.

Abstract: Compositions and methods for detecting 5-methylcytosine in a nucleic acid are disclosed. A 5-methylcytosine discriminator, which is a deoxyribonucleosidetriphosphate comprising a cytosine-pairing moiety such as a guanosine and a moiety which hinders hydrogen bonding between the cytosine-pairing moiety and a 5-methylcytosine is described. The discriminator is able to base pair with a cytosine but not a 5-methylcytosine. A 5-methylcytosine comprised by a target nucleotide can be detected in a reaction using a DNA polymerase and a primer hybridized immediately adjacent to the target nucleotide. In the reaction, pyrophosphate released upon incorporation of a dNTP complementary to a target nucleotide is detected. Lack of incorporation of the discriminator, but incorporation of a dGTP, can indicate that the target nucleotide is a 5-methylcytosine.

Abstract: Certain disclosed embodiments of the present invention concern the synthesis, derivatization, conjugation to immunoglobulins and signal amplification based on discrete, relatively short polymers having plural reactive functional groups that react with plural molecules of interest. Reactive functional groups, such as hydrazides, may be derivatized with a variety of detectable labels, particularly haptens. The remaining reactive functional groups may be conjugated directly to a specific binding molecule, such as to the oxidized carbohydrate of the Fc region of the antibody. Disclosed conjugates display large signal amplification as compared to those based on molecules derivatized with single haptens, and are useful for assay methods, particularly multiplexed assays.

Abstract: This invention provides a process for making 3?-O-allyl-dGTP-PC-Biodopy-FL-510, 3?-O-allyl-dATP-PC-ROX, 3?-O-allyl-dCTP-PC-Bodipy-650 and 3?-O-allyl-dUTP-PC-R6G, and related methods.

Abstract: The present invention provides methods for determining the presence of immobilized nucleic acid employing unsymmetrical cyanine dyes that are derivatives of thiazole orange, a staining solution and select fluorogenic compounds that are characterized as being essentially non-genotoxic. The methods comprise immobilizing nucleic acid, single or double stranded DNA, RNA or a combination thereof, on a solid or semi solid support, contacting the immobilized nucleic acid with an unsymmetrical cyanine dye compound and then illuminating the immobilized nucleic acid with an appropriate wavelength whereby the presence of the nucleic acid is determined. The cyanine dye compounds are typically present in an aqueous staining solution comprising the dye compound and a tris acetate or tris borate buffer wherein the solution facilitates the contact of the dye compound and the immobilized nucleic acid.

Abstract: Embodiments of the present disclosure relate generally to reporter compositions which are synthetic nucleotides that comprise nucleotides with a high charge mass moiety attached thereto via a linker molecule. The linker molecules can vary in length in part to enable the high charge mass moiety to extend out from a DNA polymerase complex so that polymerization may not be influenced.

Abstract: Disclosed is a method for the purification and collection of a nucleic acid comprising a specific nucleotide sequence, which can be carried out within an extremely short period and can achieve both high sequence-specificity and a high collection rate. Specifically disclosed is a method for the purification of a target nucleic acid comprising a specific nucleotide sequence and contained in a nucleic acid mixture. The method comprises the steps of: hybridizing a photo-ligating nucleic acid having a group represented by formula (I) as abase moiety with the target nucleic acid to form a hybrid; irradiating the hybrid of the photo-ligating nucleic acid and the target nucleic acid with light to cause the photo-ligation of the hybrid; removing any un-photo-ligated nucleic acid by washing; and irradiating the hybrid of the photo-ligating nucleic acid and the target nucleic acid with light to cause the photo-cleavage of the hybrid.

Abstract: Engineered nucleotide compositions, having polymerase interacting components that improve the interactivity of the polymerase and the nucleotide, particularly for nucleic acid sequencing applications. Compositions include the interactive polymerases along with the nucleotide analogs. Kits, methods and systems are provided for analysis of nucleic acid synthesis reactions.

Abstract: The present disclosure provides compounds that may be used as chromogens, fluorochromes, or as both. Said compounds may further be used as substrate for at least one enzyme, wherein said enzyme is capable of processing an aromatic amine group (—NH2), an aromatic hydroxyl group (—OH), or an aromatic phosphate group (—PO4). Furthermore, the present disclosure also provides methods for precipitating said compounds as well as methods for detecting a target using said compounds. Even further, kits comprising said compounds are disclosed. Said compounds may be used in any method utilizing a fluorochrome, a chromogen, or both.

Abstract: Labeled reactant compositions, and particularly labeled nucleic acid reaction compositions, that include structural components that maintain potentially damaging labeling components sufficiently distal from the reactant portion of the molecule such that damaging effects of the label group on other reaction components, such as enzymes, are reduced, minimized and/or eliminated.

Abstract: The present invention is directed to a self-quenching primer comprising; a fluorophore that can be quenched by guanine; an oligonucleotide sequence that forms a hairpin; an oligonucleotide that is a target specific sequence and; use in amplification reactions, particularly in polymerase chain reactions, during which the fluorophore is released thereby emitting fluorescence.

Abstract: The object of the present invention is to provide a nucleoside or nucleotide having a 5-substituted-2-oxo(1H)pyridin-3-yl group as a base, as well as a method using the same. In one embodiment, the nucleoside or nucleotide of the present invention has a fluorescent dye selected from the group consisting of 5-FAM, 6-FAM, 5-TAMRA, 6-TAMRA, DANSYL, 5-HEX, 6-HEX, 5-TET, 6-TET, 5-ROX and 6-ROX or a quencher dye selected from the group consisting of DABCYL, BHQ1 and BHQ2, which is attached either directly or through a linker to the 5-position of the above base.

Abstract: The disclosure provides nucleotide analogs and methods of their use. Analogs of the invention comprise a reporter molecule (label) attached via the N4, N6, O4, or O6 position of the nitrogenous base portion of the analog. In a preferred embodiment, nucleotide analogs of the invention comprise a label attached to the nitrogenous base portion of the analog via a cleavable linker at the N4, O4, N6 or O6 position.

Abstract: Novel technologies are provided to determine the structure of and produce a functional substance that has a high affinity to a target. Candidates for a substance having an affinity to a target (functional substance) are synthesized; a functional substance that has an affinity to the target is selected from among the functional substance candidates; a specific substituent group is eliminated from the selected functional substance; the functional substance from which the specific substituent group has been eliminated is amplified; the structure of the amplified functional substance is determined; and the functional substance is produced, based on the structure.

Abstract: Method for the synthesis of nucleotide derivatives wherein molecules of interest are grafted on the oligonucleotide with the help of a “click chemistry” reaction between an azide function on the molecule of interest and an alkyne function on the oligonucleotide, or between an alkyne function on the molecule of interest and an azide function on the oligonucleotide. Intermediate molecules, notably alkyne functionalized oligonucleotides, grafted oligonucleotides, azide functionalized oligonucleotides, oligonucleotide micro arrays containing them and the use of those grafted oligonucleotides for biological investigation and for cell targeting.

Abstract: The present invention relates to novel unsymmetrical cyanine dyes and to methods of performing nucleic acid analysis in the presence of such dyes. More specifically, the present invention relates to novel unsymmetrical cyanine dyes that have high affinity to double-stranded nucleic acids and that do not inhibit amplification reactions, particularly the polymerase chain reaction (PCR).

Abstract: Provided are a method of forming a signal probe-polymer which makes it possible to form a polymer efficiently and quantitatively, a signal probe-polymer formed by the method, oligonucleotide probes for use in the method, and a method of detecting target analyte having high sensitivity and excellent quantitative capability. The method of forming a signal probe-polymer comprises reacting a plurality of pairs of oligonucleotide probes with each other to form a polymer, a first probe of the pair of oligonucleotide probes comprising three nucleic acid regions of X, Y, and Z regions, located in the stated order from the 5?-terminal and a second probe comprising three nucleic acid regions of X?, Y?, and Z? regions, located in the stated order from the 5?-terminal, wherein each region of the oligonucleotide probes has a length of from 13 to 15 bases.

Abstract: The invention generally relates to nucleotide analogs and methods of their use in sequencing-by-synthesis reactions. In certain embodiments, the invention provides a nucleotide analog including a detectable label attached to a nitrogenous base portion of a nucleotide analog by a cleavable linker, in which contact of the analog with at least one activating agent results in cleavage of the label and elimination of the linker, thereby producing a natural nucleotide, a 9-deaza-G, 9-deaza-A, or ?-uridine.

Abstract: The present invention provides novel, water-soluble, red-emitting fluorescent rhodamine dyes and red-emitting fluorescent energy-transfer dye pairs, as well as labeled conjugates comprising the same and methods for their use. The dyes, energy-transfer dye pairs and labeled conjugates are useful in a variety of aqueous-based applications, particularly in assays involving staining of cells, protein binding, and/or analysis of nucleic acids, such as hybridization assays and nucleic acid sequencing.

Abstract: The invention relates to a method for isolating and/or identifying known or unknown, nucleic acid sequences (target sequences) which are marked, optionally, with reporter groups, by base specific hybridisation with, essentially, complementary sequences, which belong to a library or sequences. The sample sequences are characterised in that they support, on one of the termini thereof (5?-ends or 3?-ends, preferably on 5?-ends), a single double or multi-chained lipid part, which spreads in a monomolecular layer on a liquid gas or liquid-liquid phase boundary layer. The invention also relates to a system for detecting or isolating nucleic acids.

Abstract: The present invention is directed in part to a method for detecting a target nucleic acid using detector oligonucleotides detectable by mass spectrometry. This method takes advantage of the 5? to 3? nuclease activity of a nucleic acid polymerase to cleave annealed oligonucleotide probes from hybridized duplexes and releases labels for detection by mass spectrometry. This process is easily incorporated into a polymerase chain reaction (PCR) amplification assay. The method also includes embodiments directed to quantitative analysis of target nucleic acids.

Abstract: Oligonucleotide probes containing two labels are provided and are useful in hybridization assays. The probes can also contain a minor groove binding group.

Abstract: The present invention relates generally to nucleobase polymer functionalizing reagents, to mobility-modified sequence-specific nucleobase polymers, to compositions comprising a plurality of mobility-modified sequence-specific nucleobase polymers, and to the use of such polymers and compositions in a variety of assays, such as, for example, for the detection of a plurality of selected nucleotide sequences within one or more target nucleic acids. The mobility-modifying polymers of the present invention include phosphoramidite reagents which can be joined to other mobility-modifying monomers and to sequence-specific oligonucleobase polymers via uncharged phosphate triester linkages. Addition of the mobility-modifying phosphoramidite reagents of the present invention to oligonucleobase polymers results in unexpectedly large effects the mobility of those modified oligonucleobase polymers, especially upon capillary electrophoresis in non-sieving media.

Abstract: The present invention relates to PNA derivatives which carry, at the C terminus, or at both the C and N termini of the PNA backbone, one or more phosphoryl radicals. The phosphoryl radicals carry, where appropriate, one or more labeling groups, groups for crosslinking, groups which promote intracellular uptake, or groups which increase the binding affinity of the PNA derivative for nucleic acids. The invention furthermore relates to a process for preparing the above-mentioned PNA derivatives and to their use as pharmaceuticals or diagnostic agents.

Abstract: This invention is related to methods, kits and compositions pertaining to stability modulation of PNA oligomer/nucleic acid complexes.

Abstract: The present invention provides compounds, methods and systems for sequencing nucleic acid using single molecule detection. Using labeled NPs that exhibit charge-switching behavior, single-molecule DNA sequencing in a microchannel sorting system is realized. In operation, sequencing products are detected enabling real-time sequencing as successive detectable moieties flow through a detection channel. By electrically sorting charged molecules, the cleaved product molecules are detected in isolation without interference from unincorporated NPs and without illuminating the polymerase-DNA complex.

Abstract: Embodiments of the present invention provide methods and nucleic acid reporter molecules for the detection of nucleic acid in a sample. The nucleic acid reporter molecule comprises two unsymmetrical cyanine monomer moieties, which may be the same or different, that are covalently attached by a linker comprising at least one aromatic, heteroaromatic, cyclic or heterocyclic moiety comprising 3-20 non-hydrogen atoms selected from the group consisting of O, N, S, P and C. The linker may be rigid, relatively flexible or some degree thereof. The unsymmetrical cyanine monomer moieties comprise a substituted or unsubstituted benzazolium moiety and a substituted or unsubstituted pyridinium or quinolinium moiety that is connected by a methine bridge that is monomethine, trimethine or pentamethine. The linkers form the cyanine dimer compounds by attaching to the pyridinium or quinolinium moiety of the monomer moieties.

Abstract: This invention pertains to the field of combination oligomers, including the block synthesis of combination oligomers in the absence of a template, as well as related methods, kits, libraries and other compositions.

Abstract: This invention provides a process for sequencing single-stranded DNA by employing a nanopore and modified nucleotides.

Abstract: The present disclosure provides methods and compositions for conducting an assay to detect a polynucleotide. In particular, ruthenium complexes having reduction potentials that do not coincide with the reduction potential of molecular oxygen are disclosed and amperometric techniques for their use are described. In preferred embodiments, the ruthenium complex is ruthenium (III) pentaamine pyridine and the polynucleotide that is detected is DNA. Further, techniques for enhancing detectable contrast between hybridized and unhybridized nucleic acids are disclosed. In particular, the use of elongated target strands as well as the use of uncharged probe strands are discussed.

Abstract: This invention provides for labeling reagents, labeled targets and processes for preparing labeling reagents. The labeling reagents can take the form of cyanine dyes, xanthene dyes, porphyrin dyes, coumarin dyes or composite dyes. These labeling reagents are useful for labeling probes or targets, including nucleic acids and proteins. These reagents can be usefully applied to protein and nucleic acid probe based assays. They are also applicable to real-time detection processes.