Abstract: The present invention relates to dual-site BACE1 inhibitors, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.

Abstract: Multiplexed microarrays, multiplexed microarray cassettes, and methods for fabricating multiplexed microarrays are disclosed. In some embodiments, the multiplexed microarrays include a substrate, a chamber layer, and at least one channel layer. The topmost channel layer forms a port layer and may be compressible. The multiplexed microarrays may also include a compressible or non-compressible cover or sealing film. The multiplexed microarray cassette includes a base and may also include a cover. The base of the multiplexed microarray cassette includes a plurality of tracks to receive corresponding multiplexed microarrays.

Abstract: The present invention relates to a microarray comprising at least 50,000 oligopeptide features per cm2 where the oligopeptide features represent at least 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% of the proteome of a virus or an organism. The present invention further relates to methods for the synthesis of such microarrays and methods of using microarrays comprising at least 50,000 oligopeptide features per cm2. In an embodiment of the invention, the oligopeptide features represent proteins expressed in the same species, wherein the oligopeptide features are presented in a tiling pattern representing at least about 5,000 to-at least about 25,000 proteins expressed in a species. In some embodiments, the oligopeptide microarray features represent proteins expressed in the same species, wherein the microarray features are present in a tiling pattern that represents at least about 5,000 to at least about 50,000 expressed proteins.

Abstract: An apparatus and method for catalyzing a reaction on a substrate (24) comprising, a light source (12), a micromirror (16) positioned to redirect light (14) from the light source (12) toward a substrate (24) wherein the redirected light (14) catalyzes a chemical reaction proximate a substrate (24), is disclosed. A computer (18) is connected to, and controls, the positioning of mirrors within the micromirror (16) to specifically redirect light to specific portions of a substrate. The substrate (24) can be placed in a reaction chamber (50), wherein the light (14) that is redirected by the micromirror (16) catalyzes a chemical reaction proximate a substrate (24).

Abstract: The present invention provides methods and compositions for the enrichment of target nucleic acids in a microarray system. In particular, the present invention provides methods and compositions for uniform enrichment of target nucleic acid molecules in a microarray format. The present invention also provides for intentionally non-uniform enrichment among target nucleic acid molecules.

Abstract: A slide-loader system for preparing a microarray slide having a hybridized reaction area for washing, and which includes an immersion tray which contains a volume of wash buffer fluid, and a stripping jig that holds the microarray slide during removal of a reaction chamber housing that is mounted about the hybridized reaction area.

Abstract: The present inventions provides an apparatus and method for the parallel loading of multiple samples in a microarray containing a plurality of sub-arrays. The method makes use of a microarray containing multiple sub-arrays, a loading channel array, and a fluid handling robot or an assembly robot or machine.

Abstract: An apparatus and method for catalyzing a reaction on a substrate (24) comprising, a light source (12), a micromirror (16) positioned to redirect light (14) from the light source (12) toward a substrate (24) wherein the redirected light (14) catalyzes a chemical reaction proximate a substrate (24), is disclosed. A computer (18) is connected to; and controls, the positioning of mirrors within the micromirror (16) to specifically redirect light to specific portions of a substrate. The substrate (24) can be placed in a reaction chamber (50), wherein the light (14) that is redirected by the micromirror (16) catalyzes a chemical reaction proximate a substrate (24).

Abstract: During the light illumination period of a monomer addition cycle in synthesizing an DNA microarray, undesirable reflections of illumination light from various interfaces that the illumination light passes through near the synthesis surface of the substrate may reduce the light-dark contrast, and negatively affect the precision and resolution of the microarray synthesis. The present invention provides an flow cell that reduces the undesired reflections by constructing certain flow cell structures with materials that have similar refractive indexes as that of the solution that is in the oligomer synthesis chamber during the illumination period and/or constructing certain flow cell structures or covering the structures with a layer of a material that has a high extinction coefficient.

Abstract: The present invention provides methods for optimizing oligonucleotide hybridization probes for use in basic and clinical research. Specifically, the invention involves hybridizing serially diluted genomic sample to the oligonucleotide probes on the array, such that a signal intensity is produced for each of the probes; computationally identifying optimized probes which exhibit signal intensities that correspond to the serial dilutions of genomic sample and are reproducibly strong relative to non-optimized probes.

Abstract: The present invention is a method to assist in the identification of single nucleotide polymorphisms (SNP) from microarray hybridization data. Data from hybridization protocols run on microarrays often have variations in the data resulting from variations in hybridization conditions and efficiencies and variations in optical intensities. An algorithm is described to screen the results to identify those data points most likely to be real SNPs as opposed to variations in the hybridization or sensing data.

Abstract: The present invention provides a method of amplifying target DNA by PCR or multiplex PCR on a microarray using array-immobilized DNA probes synthesized in a common area on the microarray by a maskless array synthesizer (MAS). The MAS constructed array-immobilized DNA probes include a universal primer linked to a sequence-specific probe, and optionally a calibrated probe for use in quantifying amplified target DNA.

Abstract: The present invention provides a microarray for multiple sample analysis that does not require an alignment of well walls with corresponding probe sets. Methods for building and using such a microarray are also within the scope of the present invention.

Abstract: The present invention provides methods for optimizing oligonucleotide hybridization probes for use in basic and clinical research. Specifically, the invention involves hybridizing serially diluted genomic sample to the oligonucleotide probes on the array, such that a signal intensity is produced for each of the probes; computationally identifying optimized probes which exhibit signal intensities that correspond to the serial dilutions of genomic sample and are reproducibly strong relative to non-optimized probes.

Abstract: The present invention is a method for synthesizing microarrays having different oligonucleotides present within one feature area of the array. The method utilizes the techniques common to microarray synthesis, but limits the duration in which selected feature areas on the array are initially dosed with light so as to only deprotect a calculated ratio of the compounds forming the array's binding layer. The compounds initially deprotected are capped with a non-photosensitive protecting group, such as di-methoxy-trityl, to inhibit their involvement in the synthesis of a first group of DNA strands built onto the array. Once the first group of DNA strands have been synthesized, the original deprotected group may then be further processed to build one or more groups of DNA strands in the same feature area as the first group of DNA strands. The present invention also includes microarrays manufactured using the method.

Abstract: An apparatus and method for catalyzing a reaction on a substrate (24) comprising, a light source (12), a micromirror (16) positioned to redirect light (14) from the light source (12) toward a substrate (24) wherein the redirected light (14) catalyzes a chemical reaction proximate a substrate (24), is disclosed. A computer (18) is connected to, and controls, the positioning of mirrors within the micromirror (16) to specifically redirect light to specific portions of a substrate. The substrate (24) can be placed in a reaction chamber (50), wherein the light (14) that is redirected by the micromirror (16) catalyzes a chemical reaction proximate a substrate (24).

Abstract: The present invention is an improved method of resequencing DNA using microarrays to rapidly map and identify SNPs, deletions and amplification events present in the genome of an organism. The method is performed by hybridizing a reference and a test genome to two separate arrays with each array exhibiting a specific intensity pattern. The intensity differences between the reference and the test genome arrays are used to produce a mutation map. The mapped differences are resequenced on a set of resequencing arrays to identify specific genetic mutations.

Abstract: The present invention provides novel method for increasing the efficiency and accuracy of high-throughput mutation mapping and genome resequencing by using a variable length probe selection algorithm to rationally select probes used in designing oligonucleotide arrays synthesized by Maskless Array Synthesis (MAS) technology. Also disclosed is a variable length probe selection algorithm used in designing such oligonucleotide arrays.

Abstract: The present disclosure provides methods and systems for sequence specific nucleic acid target capture comprising enzymatic reactions. The present disclosure relates to a plurality of oligonucleotide probes for capture and subsequent detection of target nucleic acid sequences, using flap endonucleases, ligases, and/or additional enzymes, proteins or compounds, on substrates, for example microarray slides, and in solution formats.

Abstract: The present invention provides methods and compositions for the enrichment of target nucleic acids in a microarray system. In particular, the present invention provides methods and compositions for uniform enrichment of target nucleic acid molecules in a microarray format. The present invention also provides for intentionally non-uniform enrichment among target nucleic acid molecules.