Abstract: The present invention provides a simplified method for identifying differences in nucleic acid abundances (e.g., expression levels) between two or more samples. The methods involve providing an array containing a large number (e.g. greater than 1,000) of arbitrarily selected different oligonucleotide probes where the sequence and location of each different probe is known. Nucleic acid samples (e.g. mRNA) from two or more samples are hybridized to the probe arrays and the pattern of hybridization is detected. Differences in the hybridization patterns between the samples indicates differences in expression of various genes between those samples. This invention also provides a method of end-labeling a nucleic acid. In one embodiment, the method involves providing a nucleic acid, providing a labeled oligonucleotide and then enzymatically ligating the oligonucleotide to the nucleic acid. Thus, for example, where the nucleic acid is an RNA, a labeled oligoribonucleotide can be ligated using an RNA ligase.

Abstract: Methods and kits for amplifying nucleic acids are provided. Double stranded cDNA with uridine residues incorporated into one strand is synthesized and the uridine containing strand is nicked at uridine residues. The DNA is extended from the nicks in the presence of dUTP using a strand displacing enzyme. Repeated cycles of nicking and extension result in amplification of the nucleic acid. Methods are also provided for analysis of the above sample by hybridization to an array, which may be specifically designed to interrogate the collection of target sequences for particular characteristics, such as, for example, the presence or absence of one or more polymorphisms or the presence or absence of a transcript.

Abstract: In one aspect of the invention, methods and compositions are provided for fragmenting nucleic acid samples. Fragmented nucleic acid samples may be used for hybridization with microarrays.

Abstract: Provided are functionalized silicon compounds and methods for their synthesis and use. The functionalized silicon compounds include at least one activated silicon group and at least one derivatizable functional group. Exemplary derivatizable functional groups include hydroxyl, amino, carboxyl and thiol, as well as modified forms thereof, such as activated or protected forms. The functionalized silicon compounds may be covalently attached to surfaces to form functionalized surfaces which may be used in a wide range of different applications. In one embodiment, the silicon compounds are attached to the surface of a substrate comprising silica, such as a glass substrate, to provide a functionalized surface on the substrate, to which molecules, including polypeptides and nucleic acids, may be attached.

Abstract: Methods are provided for preparing nucleic acid arrays on a support, particularly substantially planar supports. In one group of these methods a plurality of nucleic acids are synthesized on the support and the synthesis steps include oxidizing a phosphite triester nucleic acid linkage to a phosphate triester nucleic acid linkage using a solution about 0.005 M to about 0.05 M iodine in a mixture comprising water and organic solvent. In another group of these methods a plurality of nucleic acids are synthesized on the support and the synthesis steps include oxidizing a phosphite triester nucleic acid linkage to a phosphate triester nucleic acid linkage using a solution comprising iodine and at least 4% by volume of water.

Abstract: Novel compounds are provided, which are useful as linking groups in chemical synthesis, preferably in the solid phase synthesis of oligonucleotides and polypeptides. These compounds are generally photolabile and comprise protecting groups which can be removed by photolysis to unmask a reactive group. The protecting group has the general formula Y, wherein Y is a chemical structure as shown in FIG. 1. Also provided is a method of forming, from component molecules, a plurality of compounds on a support, each compound occupying a separate predefined region of the support, using the protected compounds described above.

Abstract: Radiation-activated catalysts (RACs), autocatalytic reactions, and protective groups are employed to achieve a highly sensitive, high resolution, radiation directed combinatorial synthesis of pattern arrays of diverse polymers. When irradiated, RACs produce catalysts that can react with enhancers, such as those involved in autocatalytic reactions. The autocatalytic reactions produce at least one product that removes protecting groups from synthesis intermediates. This invention has a wide variety of applications and is particularly useful for the solid phase combinatorial synthesis of polymers.

Abstract: The present invention provides cyclic silane based compounds. In accordance with one aspect of the present invention, it has been discovered that certain linear silane compounds can cyclize under some conditions.

Abstract: Methods are provided for post incorporation labeling of a nucleic acid, including for example cRNA, labeled with nucleotide analogs having a formula selected from the group consisting of wherein A is H or a functional group that permits the attachment of the nucleic acid labeling compound to a nucleic acid; Y and Z are independently H or OH; L is linker group; and P is a connecting group. After incorporation of the nucleic acid (including cRNA) with the above nucleotide analogs, the nucleic acid is labeled with a detectable group reagent wherein said detetable group reagent comprises a chemical moiety which is capable of specifically reacting with said P group to allow coupling of the detectable group to said primed cRNA. Compounds comprising nucleotide analogs are also presented in accordance with the present invention. Methods are also presented for incorporating these compounds into nucleic acids and subsequently labeling the incorporated nucleotide analog with detectable moiety reagent.

Abstract: Nucleic acid labeling compounds including the following structure are disclosed: wherein A is a triphosphate group with apporpriate counterions, said counterions selected from the group consisting of H+, Na+, Li+, K+, and NH4+; X is O; Y is OH; Z is OH; L is selected from the group consisting of —CH?CH—C(O)—NH—CH2—CH2—NH—C(O)— and —CH2—CH2—C(O)—NH—CH2—CH2—NH—C(O); M is —(CH2)45—NH—, n is 1 and Q is biotin having the structure: The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.

Abstract: Nucleic acid labeling compounds containing heterocyclic derivatives are disclosed. The heterocyclic derivative containing compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.

Abstract: Nucleic acid labeling compounds containing heterocyclic derivatives are disclosed. Methods for making such heterocyclic compounds are also disclosed. The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.

Abstract: Methods are provided for preparing nucleic acid arrays on a support. In these methods a plurality of nucleic acids are synthesized on the support and the synthesis steps include oxidizing a phosphite triester nucleic acid linkage to a phosphate triester nucleic acid linkage using a solution about 0.005 to about 0.05 M iodine in a mixture comprising water and organic solvent.

Abstract: Provided are functionalized silicon compounds and methods for their synthesis and use. The functionalized silicon compounds include at least one activated silicon group and at least one derivatizable functional group. Exemplary derivatizable functional groups include hydroxyl, amino, carboxyl and thiol, as well as modified forms thereof, such as activated or protected forms. The functionalized silicon compounds may be covalently attached to surfaces to form functionalized surfaces which may be used in a wide range of different applications. In one embodiment, the silicon compounds are attached to the surface of a substrate comprising silica, such as a glass substrate, to provide a functionalized surface on the substrate, to which molecules, including polypeptides and nucleic acids, may be attached.

Abstract: Methods are provided for making and using thin films of porous silica substrates to synthesize arrays of polymers. Methods are also provided for assaying such polymers on porous silica substrates. The porous silica substrates offer an increase in array density and signal enhancement over conventional flat glass substrates. Examples of polymers that can be synthesized and assayed include biological polymers such as nucleic acids, polynucleotides, polypeptides, and polysaccharides. Arrays of nucleic acids or polynucleotides can be used for a variety of hybridization-based experiments such as nucleic acid sequence analysis, nucleic acid expression monitoring, nucleic acid mutation detection, speciation, effects of drug therapy on nucleic acid expression, among others.

Abstract: Methods are provided for reducing background signal associated with hybridization of nucleic acid arrays to nucleic acid samples, the method comprising hybridizing the array to the sample in the presence of a poly-anionic polymer (PAP). Background associated with hybridization of arrays to samples interferes with signal generated by specific binding to the probe array un-desirably lowers the signal to noise ratio (SNR) and generates an overall loss of sensitivity for nucleic acid arrays.

Abstract: In one aspect of the invention, photoactivatable silane compounds and methods for their synthesis and use are provided. In one embodiment, the photoactivatable silane compounds synthesized are represented by a formula: PG-LS-SN, wherein PG is a photoactivatable group, LS is a linkage and spacer group, and SN is a silane group. The silanes allow the photoactivatable silane compounds to be covalently bound to the surface of a substrate such as silica. The photoactivatable group forms a hydrophobic layer that can be photochemically cross-linked with a layer of hydrophilic functional polymers. In another embodiment, a method is disclosed to synthesize a substrate of hydrophobic layers and hydrophilic functional polymer layers thereafter onto glass surfaces. An array of biopolymers such as nucleic acids and peptides may then be covalently attached to the substrate using photolithography and biopolymer synthesis.

Abstract: Provided are functionalized silicon compounds and methods for their synthesis and use. The functionalized silicon compounds include at least one activated silicon group and at least one derivatizable functional group. Exemplary derivatizable functional groups include hydroxyl, amino, carboxyl and thiol, as well as modified forms thereof, such as activated or protected forms. The functionalized silicon compounds may be covalently attached to surfaces to form functionalized surfaces which may be used in a wide range of different applications. In one embodiment, the silicon compounds are attached to the surface of a substrate comprising silica, such as a glass substrate, to provide a functionalized surface on the substrate, to which molecules, including polypeptides and nucleic acids, may be attached.

Abstract: Provided are functionalized silicon compounds and methods for their synthesis and use. The functionalized silicon compounds include at least one activated silicon group and at least one derivatizable functional group. Exemplary derivatizable functional groups include hydroxyl, amino, carboxyl and thiol, as well as modified forms thereof, such as activated or protected forms. The functionalized silicon compounds may be covalently attached to surfaces to form functionalized surfaces which may be used in a wide range of different applications. In one embodiment, the silicon compounds are attached to the surface of a substrate comprising silica, such as a glass substrate, to provide a functionalized surface on the substrate, to which molecules, including polypeptides and nucleic acids, may be attached.

Abstract: Nucleic acid labeling compounds containing heterocyclic derivatives are disclosed. The heterocyclic derivative containing compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.