Abstract: Methods are provided for the preparation of polymer arrays on wafers wherein the wafers are rotated between synthesis steps to provide more uniform results across the entire wafer.

Abstract: VLSIPS™ manufacturing processes are of increasing commercial importance. The present invention provides methods and compositions for monitoring the efficiency and quality of polymer synthesis in VLSIPS™ arrays. Methods for monitoring polymer synthesis in an array on a substrate are provided. Mono-isomeric labels for the labeling of synthetic polymer arrays are provided. Methods and compositions for post-synthetically labeling polymers in polymer arrays are also provided.

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: Polymeric brush substrates and methods for their preparation are provided. Methods are also provided for preparing macromolecular arrays on such polymeric brush substrates. Using polymeric brush substrates allows control over functional site density as well as wettability and porosity of the substrate. These polymeric brushes are useful in solid-phase synthesis of arrays of peptides, polynucleotides or small organic molecules.

Abstract: The present invention provides methods for preparing nucleic acid samples. The methods of the present invention are particularly amenable for preparing samples that substantially represent the whole transcripts. The method is particularly suitable to use with microarray based expression analysis.

Abstract: Methods for testing oligonucleotide arrays are disclosed including methods for testing the efficiency of nucleotide coupling; methods for testing amounts of deprotected oligonucleotides; methods for determining amounts of depurinated oligonucleotides; and methods of detecting the presence of cleavable structural features, such as double-stranded nucleic acids.

Abstract: Oligonucleotide analogue arrays attached to solid substrates and methods related to the use thereof are provided. The oligonucleotide analogues hybridize to nucleic acids with either higher or lower specificity than corresponding unmodified oligonucleotides. Target nucleic acids which comprise nucleotide analogues are bound to oligonucleotide and oligonucleotide analogue arrays.

Abstract: Methods are provided for the preparation of polymer arrays on wafers wherein the wafers are rotated between synthesis steps to provide more uniform results across the entire wafer.

Abstract: Polymeric brush substrates and methods for their preparation are provided. Methods are also provided for preparing macromolecular arrays on such polymeric brush substrates. Using polymeric brush substrates allows control over functional site density as well as wettability and porosity of the substrate. These polymeric brushes are useful in solid-phase synthesis of arrays of peptides, polynucleotides or small organic molecules.

Abstract: The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.

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: 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 Ar—C(R1)(R2)—O—C(O)— wherein: Ar is an optionally substituted fused polycyclic aryl or heteroaromatic group or a vinylogous derivative thereof; R1 and R2 are independently H, optionally substituted alkyl, alkenyl or alkynyl, optionally substituted aryl or optionally substituted heteroaromatic, or a vinylogous derivative of the foregoing; and X is a leaving group, a chemical fragment linked to Ar—C(R1)(R2)—O—C(O)— via a heteroatom, or a solid support; provided that when Ar is 1-pyrenyl and R1 and R2 are H, X is not linked to Ar—C(R1)(R2)—O—C(O)— via a nitrogen atom.

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: Methods for fragmenting and labeling nucleic acids for hybridization analysis are disclosed. In one aspect of the invention, methods and compositions are provided for fragmenting nucleic acid samples by exposure to acidic conditions to generate abasic positions and then cleavage of the abasic sites by, for example, an apurinic/apyrimidinic endonuclease. The resulting fragments may be end labeled and analyzed by hybridization to an array of nucleic acid probes.

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: 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 novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.

Abstract: The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.

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: Protective groups which may be cleaved with an activatable deprotecting reagents are employed to achieve a highly sensitive, high resolution, combinatorial synthesis of pattern arrays of diverse polymers. In preferred embodiments of the instant invention, the activatable deprotecting reagent is a photoacid generator and the protective groups are DMT for nucleic acids and tBOC for amino acids. This invention has a wide variety of applications and is particularly useful for the solid phase combinatorial synthesis of polymers.