Abstract: An embodiment of a method of analyzing data from processed images of biological probe arrays is described that comprises receiving a plurality of files comprising a plurality of intensity values associated with a probe on a biological probe array; normalizing the intensity values in each of the data files; determining an initial assignment for a plurality of genotypes using one or more of the intensity values from each file for each assignment; estimating a distribution of cluster centers using the plurality of initial assignments; combining the normalized intensity values with the cluster centers to determine a posterior estimate for each cluster center; and assigning a plurality of genotype calls using a distance of the one or more intensity values from the posterior estimate.

Abstract: Methods of identifying allele-specific changes in genomic DNA copy number are disclosed. Methods for identifying homozygous deletions and genetic amplifications are disclosed. An array of probes designed to detect presence or absence of a plurality of different sequences is also disclosed. The probes are designed to hybridize to sequences that are predicted to be present in a reduced complexity sample. The methods may be used to detect copy number changes in cancerous tissue compared to normal tissue. The methods may be used to diagnose cancer and other diseases associated with chromosomal anomalies.

Abstract: The present invention concerns cell-penetrating peptides which comprise an amino acid sequence consisting of GLX9RALX9RX1LX2RSLX9X3X4X5X6X7X8 (SEQ ID No: 1), wherein X1 is A, L or G, X2 is W or none, X3 is R or K, X4 is K, L or S, X5 is L or K, X6 is R or W, X7 is K or S, and X8 is A, V or Q, and X9 is W, F or Y. These CPPs can be used as vectors for delivering nucleic acids and/or proteins and/or peptides to cells, in vitro or in vivo.

Abstract: Methods are provided for detecting and optionally quantitating multiple analytes, including nucleic acid and/or polypeptide analytes, in particle-based assays that can be highly multiplexed. Compositions, systems, and kits related to the methods are also featured.

Abstract: Methods for discriminating between fully complementary hybrids and those that differ by one or more base pairs and libraries of unimolecular, double-stranded oligonucleotides on a solid support. In one embodiment, the present invention provides methods of using nuclease treatment to improve the quality of hybridization signals on high density oligonucleotide arrays. In another embodiment, the present invention provides methods of using ligation reactions to improve the quality of hybridization signals on high density oligonucleotide arrays. In yet another embodiment, the present invention provides libraries of unimolecular or intermolecular, double-stranded oligonucleotides on a solid support. These libraries are useful in pharmaceutical discovery for the screening of numerous biological samples for specific interactions between the double-stranded oligonucleotides, and peptides, proteins, drugs and RNA.

Abstract: An encoded microparticle having a spatial code is provided; and a set of encoded microparticles possessing subsets each provided with a distinguishable spatial code, wherein the codes comply with a pre-determined coding scheme. Presented are also methods of using the encoded microparticles in various biological assays, such as various multiplex assays and visualizing them by creating a digital image of the encoded microparticles and determining whether false positives are present. Further are provided methods of manufacture of the encoded microparticles which employ ferromagnetic nanoparticles applied using spin-on-glass techniques.

Abstract: Fluorescently marked targets bind to a substrate 230 synthesized with polymer sequences at known locations. The targets are detected by exposing selected regions of the substrate 230 to light from a light source 100 and detecting the photons from the light fluoresced therefrom, and repeating the steps of exposure and detection until the substrate 230 is completely examined. The resulting data can be used to determine binding affinity of the targets to specific polymer sequences.

Abstract: Methods of performing confocal laser microscopy on a polymer array disposed on a silicon wafer substrate, the method comprising the steps of providing a silicon wafer substrate having a top side and a bottom side, coating the top side of the silicon wafer with an oxide coating to provide an oxide coated wafer, covalently coupling a plurality of probes to the top side of the coated wafer to provide a fixed polymer array, hybridizing the fixed polymer array with a plurality of labeled ligands, and assaying for one or more hybridized ligands using confocal laser fluorescence microscopy to detect hybridization are provided.

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: Methods and software products for analysis of alternative splicing are disclosed. In general the methods involve normalizing probe set or exon intensity to an expression level measurement of the gene. The methods may be used to identify tissue-specific alternative splicing events.

Abstract: In one embodiment, a method for analyzing data generated by probe arrays is described that comprises receiving user selections of two or more data files and an identification of one or more subsets of intensity values acquired from a biological probe array. The method includes iteratively opening each data file, identifying the selected subset of intensity values associated with each open data file, determining parameters for processing, storing the parameters and the identified intensity values, and closing the open data file prior to the subsequent iteration. The method then includes processing the stored intensity values using the parameters to identify one or more biological events.

Abstract: Methods of detecting nucleic acids, proteins and cells including methods of detecting two or more nucleic acids, proteins and cells in multiplex bDNA assays, are provided. Assays may be conducted at least in vitro, in vivo, in cellulo, and in situ. Nucleic acids are detected, through cooperative hybridization that results in specific association of a label probe system with target nucleic acids. Embodiments are directed to concurrent detection of one or more nucleic acids and/or one or more proteins. The detected proteins may be intracellular or external markers on the surface of the cell. Detection of protein components is accomplished by use of specific antibodies and a label probe system and/or coated microparticles which bind to the outside surface of specific cells and contain specific probes that can be detected using the same label probe system. Compositions, kits, and systems related to the methods are also described.

Abstract: Methods of detecting various types of nucleic acids, including methods of detecting two or more nucleic acids in multiplex branched-chain DNA assays, are provided. Detection assays may be conducted at least in vitro, in cellulo, and in situ. Nucleic acids which are optionally captured on a solid support are detected, for example, through cooperative hybridization events that result in specific association of a label probe system with the nucleic acids. Various label probe system embodiments are provided. Compositions, kits, and systems related to the methods are also described.

Abstract: Methods for discriminating between fully complementary hybrids and those that differ by one or more base pairs and libraries of unimolecular, double-stranded oligonucleotides on a solid support. In one embodiment, the present invention provides methods of using nuclease treatment to improve the quality of hybridization signals on high density oligonucleotide arrays. In another embodiment, the present invention provides methods of using ligation reactions to improve the quality of hybridization signals on high density oligonucleotide arrays. In yet another embodiment, the present invention provides libraries of unimolecular or intermolecular, double-stranded oligonucleotides on a solid support. These libraries are useful in pharmaceutical discovery for the screening of numerous biological samples for specific interactions between the double-stranded oligonucleotides, and peptides, proteins, drugs and RNA.

Abstract: An embodiment of a scanning system is described including optical elements that direct an excitation beam at a probe array, detectors that receive reflected intensity data responsive to the excitation beam, where the reflected intensity data is responsive to a focusing distance between an optical element and the probe array, a transport frame that adjusts the focusing distance in a direction with respect to the probe array, an auto-focuser that determines a best plane of focus based upon characteristics of the reflected intensity data of at least two focusing distances where the detectors further receive pixel intensity values based upon detected emissions from a plurality of probe features disposed on the probe array at the best plane of focus, and an image generator that associates each of the pixel intensity values with at least one image pixel position of a probe array based upon one or more position correction values.

Abstract: Methods of detecting one or more nucleic acids from whole blood or plasma are provided. The nucleic acids are captured on a solid support and detected. Compositions, kits, and systems related to the methods are also described.

Abstract: In one aspect of the invention, methods for analyzing nucleic acid sample are provided. In a preferred embodiment, nucleic acids are selected using affinity matrices prior hybridization with a microarray.

Abstract: Disclosed are apparatuses, systems and methods for attachment of substrates to supports. Disclosed are integrated pick-and-place curing apparatuses and systems and methods for using them. Integration of pick-and-place and curing functionalities provides higher efficiency and effectiveness compared to approaches which separate the two functions. Also disclosed are systems and methods for simultaneous attachment of a plurality of substrates to a support. Substrates include, within certain embodiments, arrays of biological polymers which are unaffected by the disclosed pick-and-place curing approaches.

Abstract: Presented are encoded microparticles, methods of use in biological assays, and flexible, modular instrument systems for conducting a variety of biological assays using the encoded microparticles. The systems include various instrumentation components which are exchangeable and offer a single flexible platform on which a large number of different types of experiments and assays may be conducted including, for example, microarray analysis, encoded microparticle single and multiplex detection, tissue dissection and isolation, and other genetic analysis techniques.

Abstract: Systems and methods for identifying, confirming, mapping, and categorizing sample polymers, such as nucleic acid sequences, are provided. An estimation of the fraction of first and second polymers in a sample of polymers can be calculated by inputting a first hybridization value indicative of hybridization affinity of the sample of polymers to polymers probes that are complementary to the first polymer and inputting a second hybridization value indicative of hybridization affinity of the sample of polymers to polymers probes that are complementary to the second polymer. The estimation of the fraction of the first and second polymers in the sample of polymers can then be calculated by dividing the first hybridization value by a sum of the first and second hybridization values. Estimations of the fractions of alleles in a sample can be clustered to form a fraction pattern usable for identifying, confirming, mapping, and genotyping sample nucleic acids.