Abstract: Disclosed are methods and compositions for detection and amplification of nucleic acids, wherein two DNA strands hybridized to an RNA strand are ligated. In one aspect, the disclosed methods include removal of an energy source, such as ATP, upon charging a ligase to form an enzyme-AMP intermediate, and then adding substrate, which results in one complete round of RNA-templated DNA ligation. In another aspect, the ligation reaction is accomplished by use of a mixture of at least two different ligase enzymes. The disclosed methods and compositions for RNA-templated DNA ligation may be particularly useful for detection of RNA sequence variants, for example RNA splice variants, and for quantitative expression analysis.

Abstract: Methods for appending oligonucleotides directly to nucleic acid templates, particularly to defined sites internal to single-stranded templates, are described. Appending first and second common priming sites to each of a plurality of templates of distinct sequence allows the subsequent stoichiometric amplification of a plurality of templates of distinct sequence.

Abstract: A method of forming a plurality of encoded microparticles with a lithography process to define codes for identifying the particles is disclosed herein.

Abstract: An encoded microparticle carrying a code is provided; and a set of encoded microparticles are provided with distinguishable codes, wherein the codes comply with a pre-determined coding scheme.

Abstract: The presently claimed invention provides for novel methods and kits for reducing the complexity of a nucleic acid sample by providing non-gel based methods for amplification of a subset of the sequences in a sample. In a preferred embodiment, amplification of a subset can be accomplished by digesting a sample with two or more restriction enzymes and ligating adaptors to the fragments so that only a subset of the fragments can be amplified. The invention further provides for analysis of the above amplified sample by hybridization to an array, which may be specifically designed to interrogate the desired fragments for particular characteristics, such as, for example, the presence or absence of a polymorphism.

Abstract: The present invention relates to systems and methods for examining a number of components that have been assembled onto a substrate. In general, the invention relates to the calibration of inspection tools for inspecting components on the substrate. In particular, the invention relates to the calibration of inspection tools for detecting the accuracy of the array pegs positions on an assembled HTA plate.

Abstract: A method and device for forming large arrays of polymers on a substrate (401). According to a preferred aspect of the invention, the substrate is contacted by a channel block (407) having channels (409) therein. Selected reagents are delivered through the channels, the substrate is rotated by a rotating stage (403), and the process is repeated to form arrays of polymers on the substrate. The method may be combined with light-directed methodologies.

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 for genotyping polymorphisms using allele specific probes are disclosed. A training set is used to generate a model for each polymorphism to be interrogated. The training set is used to obtain an estimate of the asymmetry between an intensity measurement for a first allele and an intensity measurement for a second allele of the same polymorphism. The intensity measurement obtained for a test sample is adjusted using the estimate of asymmetry prior to using the intensity measurements to make a genotyping call. In preferred embodiments the adjustment is applied to polymorphisms that have a likelihood of being heterozygous that is above a specified threshold.

Abstract: An embodiment of a method for adjusting system gain of a biological probe array scanner for a plurality of fluorophore species is described that comprises setting an excitation beam comprising an excitation wavelength at a first power level that elicits an optimal signal to noise ratio response from a first fluorophore species; scanning a biological probe array with the excitation beam; setting the excitation beam comprising the excitation wavelength at a second power level different than the first power level that elicits the optimal signal to noise ratio response from a second fluorophore species; and scanning the biological probe array with the excitation beam.

Abstract: A method and device for forming large arrays of polymers on a substrate (401). According to a preferred aspect of the invention, the substrate is contacted by a channel block (407) having channels (409) therein. Selected reagents are delivered through the channels, the substrate is rotated by a rotating stage (403), and the process is repeated to form arrays of polymers on the substrate. The method may be combined with light-directed methodolgies.

Abstract: A fluidic system and method for processing biological sensors. The fluidic system includes a fluidic component including at least a first container and a second container. The first container is capable of holding a first volume of a first fluid, and the second container is capable of holding a second volume of a second fluid. Additionally, the fluidic system includes a support component configured to support at least the first container and the second container. The first container and the second container are substantially stationary with respect to the support component. Moreover, the fluidic system includes a transport component configured to move a first sensor, with respect to the support component, into the first container and in contact with the first volume of the first fluid, and move a second sensor, with respect to the support component, into the second container and in contact with the second volume of the second fluid.

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: An embodiment of a method for adjusting system gain of a biological probe array scanner for a plurality of fluorophore species is described that comprises setting an excitation beam comprising an excitation wavelength at a first power level that elicits an optimal signal to noise ratio response from a first fluorophore species; scanning a biological probe array with the excitation beam; setting the excitation beam comprising the excitation wavelength at a second power level different than the first power level that elicits the optimal signal to noise ratio response from a second fluorophore species; and scanning the biological probe array with the excitation beam.

Abstract: A system and method for processing biological sensors. The system includes a support component configured to support a fluidic component. The fluidic component includes at least a first container and a second container. The first container is capable of holding a first volume of a first fluid, and the second container is capable of holding a second volume of a second fluid. Additionally, the system includes a hybridization component configured to perform a hybridization process on a first sensor and a second sensor. Moreover, the system includes a transport component configured to move the first sensor, directly or indirectly, from the hybridization component into the first container and in contact with the first volume of the first fluid.

Abstract: The present invention generally provides a rapid efficient method for analyzing polymorphic or biallelic markers, and arrays for carrying out these analyses. In general, the methods of the present invention employ arrays of oligonucleotide probes that are complementary to target nucleic acids which correspond to the marker sequences of an individual. The probes are typically arranged in detection blocks, each block being capable of discriminating the three genotypes for a given marker, i.e., the heterozygote or either of the two homozygotes. The method allows for rapid, automatable analysis of genetic linkage to even complex polygenic traits.

Abstract: The invention provides arrays of polynucleotide probes having at least one pooled position. A typical array comprises a support having at least three discrete regions. A first region bears a pool of polynucleotide probes comprising first and second probes. A second region bears the first probe without the second probe and a third region bears the second probe without the first probe. A target nucleic acid having segments complementary to both the first and second probes shows stronger normalized binding to the first region than to the aggregate of binding to the second and third regions due to cooperative binding of pooled probes in the first region. The invention provide methods of using such arrays for e.g., linkage analysis, sequence analysis, and expression monitoring.

Abstract: The present invention relates to novel methods for sequencing and mapping genetic markers in polynucleotide sequences using Type-IIs restriction endonucleases. The methods herein described result in the “capturing” and determination of specific oligonucleotide sequences located adjacent to Type-IIs restriction sites. The resulting sequences are useful as effective markers for use in genetic mapping, screening and manipulation.

Abstract: Four novel water soluble cholesterol derivative compounds are disclosed. These compounds have various applications in studies of membrane proteins, including drug screening and studies of receptor stability and folding. In one aspect the water soluble cholesterol derivatives disclosed may be used to replace cholesterol in micelle-solubilized membrane protein preparations.

Abstract: Methods for genotyping polymorphisms using allele specific probes are disclosed. A training set is used to generate a model for each polymorphism to be interrogated. The training set is used to obtain an estimate of the asymmetry between an intensity measurement for a first allele and an intensity measurement for a second allele of the same polymorphism. The intensity measurement obtained for a test sample is adjusted using the estimate of asymmetry prior to using the intensity measurements to make a genotyping call. In preferred embodiments the adjustment is applied to polymorphisms that have a likelihood of being heterozygous that is above a specified threshold.