Abstract: The invention provides uncharged water-soluble silica-adsorbing polymers for suppressing electroendoosmotic flow and to reduce analyte-wall interactions in capillary electrophoresis. In one aspect of the invention, one or more of such polymers are employed as components of a separation medium for the separation of biomolecules, such as polynucleotides, polysaccharides, proteins, and the like, by capillary electrophoresis. Generally, such polymers are characterized by (i) water solubility over the temperature range between about 20° C. to about 50° C., (ii) concentration in a separation medium in the range between about 0.001% to about 10% (weight/volume), (iii) molecular weight in the range of about 5×103 to about 1×106 daltons, and (iv) absence of charged groups in an aqueous medium having pH in the range of about 6 to about 9.

Abstract: Long wavelength, narrow emission bandwidth fluorecein dyes are provided for detecting spacially overlapping target substances. The dyes comprise 4,7-dichlorofluoresceins, and particularly 2?,4?,5?,7?-tetrachloro-4,7-dichloro-5- (and 6-)carboxyfluoresceins. Methods and kits for using the dyes in DNA analysis are provided.

Abstract: Dark quencher constructs, termed “multi-chromophoric quenchers” are described herein that comprise at least two dark quenching moieties, which can be the same or different, linked together by at least one multivalent linking moiety. The structure of the multi-chromophoric quenchers can be varied to selectively enhance quenching within a specific range of reporter emission wavelengths. This can be accomplished by linking together, into a single molecule, two or more identical quenchers, by reacting the quenchers with a multivalent linker. The structure of the multi-chromophoric quencher can also be varied to quench a broader range of reporter emission wavelengths than previously possible. This can be accomplished by linking together, into a single molecule, two or more different quenchers, by reacting the quenchers with a multivalent linker.

Abstract: Dibenzorhodamine compounds having the structure are disclosed, including nitrogen- and aryl-substituted forms thereof. In addition, two intermediates useful for synthesizing such compounds are disclosed, a first intermediate having the structure including nitrogen- and aryl-substituted forms thereof, and a second intermediate having the structure including nitrogen- and aryl-substituted forms thereof, wherein substituents at positions C-14 to C18 taken separately are selected from the group consisting of hydrogen, chlorine, fluorine, lower alkyl, carboxylic acid, sulfonic acid, —CH2OH, alkoxy, phenoxy, linking group, and substituted forms thereof. The invention further includes energy transfer dyes comprising the dibenzorhodamine compounds, nucleosides labeled with the dibenzorhodamine compounds, and nucleic acid analysis methods employing the dibenzorhodamine compounds.

Abstract: Ligation-based methods and kits are disclosed for determining the degree of methylation of one or more target nucleotides. In certain embodiments, the methylation status of one or more target nucleotides is determined by generating misligation products. In certain embodiments, at least one target nucleotide is amplified prior to the ligation reaction. In certain embodiments, at least one ligation product, at least one ligation product surrogate, at least one misligation product, at least one misligation product surrogate, or combinations thereof are amplified. In certain embodiments, one or more ligation probes comprise at least one nucleotide analog, at least one Modification, at least one mismatched nucleotide, or combinations thereof.

Abstract: Provided are nucleotide-dye conjugates and related compounds in which a dye is linked to a nucleobase directly or indirectly by an anionic linker. The anionic character of the linker is provided by one or more anionic moieties which are present in the linker, such as phosphate, phosphonate, sulfonate, and carboxylate groups. When the dye is a provided as a donor/acceptor dye pair, the anionic linker can be located between the donor and the acceptor, or between the nucleobase and either the donor or acceptor, or both. In one embodiment, conjugates of the invention provide enhanced electrophoretic mobility characteristics to sequencing fragments, e.g., for dideoxy sequencing using labeled terminators.

Abstract: Beads coded with phosphor particles and methods of making and using them are provided.

Abstract: Method and composition for detecting one or more selected polynucleotide regions in a target polynucleotide. In the method, a mixture of sequence-specific probes are reacted with the target polynucleotide under hybridization conditions, and the hybridized probes are treated to selectively modify those probes which are bound to the target polynucleotide in a base-specific manner. The resulting labeled probes include a polymer chain which imparts to each different-sequence probe, a distinctive ratio of charge/translational frictional drag, and a detectable label. The labeled probes are fractionated by electrophoresis in a non-sieving matrix, and the presence of one or more selected sequences in the target polynucleotide are detected according to the observed electrophoretic migration rates of the labeled probes in a non-sieving medium.

Abstract: Method and composition for detecting one or more selected polynucleotide regions in a target polynucleotide. In one embodiment of the invention, a plurality of different-sequence probe pairs are added to a target polynucleotide, where each probe pair includes two polynucleotide probe elements which are complementary in sequence to adjacent portions of a selected one of the target sequences in the target polynucleotide. In each probe pair, one of the probe elements contains a non-polynucleotide polymer chain which imparts a distinctive mobility to the associated probe pair, when the elements in the pair are ligated. The other element in the pair contains a detectable reporter label. After the probe pairs have been allowed to hybridize with the target polynucleotide, the hybridized polynucleotides are treated under conditions effective to ligate the end subunits of target-bound probe elements when their end subunits are base-paired with adjacent target bases.

Abstract: The present invention provides a novel class of fluorescent cyanine dye compounds that are modified at one of the hetercyclic ring nitrogen atoms with a mobility-modifying moiety that permits the electrophoretic mobilities of polynucleotides labeled with the mobility-modifying cyanine dyes to be adjusted or tuned in a predictable fashion while retaining enzymatic activity. The ability to predictably tune the relative electrophoretic mobilities of the dyes permits the creation of sets of mobility-matched fluorescent dyes of a variety of structures for a variety of applications, including fluorescence-based 4-color nucleic acid sequencing reactions.

Abstract: Long wavelength, narrow emission bandwidth fluorescein dyes are provided for detecting specially overlapping target substances. The dyes comprise 4,7-dichlorofluorescein, and particularly 2?, 4?,5?,7?-tetrachloro-4,7-dichloro-5-(and 5-) carboxyfluoresceins. Methods and kits for using the dyes in DNA analysis are provided.

Abstract: Extended rhodamine compounds exhibiting favorable fluorescence characteristics having the structure are disclosed. In addition, novel intermediates for synthesis of these dyes are disclosed, such intermediates having the structure In addition, methods of making and using the dyes as fluorescent labels are disclosed.