Abstract: The present teachings relate to improved methods, kits, and compositions for making nucleic acid libraries and sequencing nucleic acids. In some embodiments, directionally defined concatamers are generated, facilitating sequencing efforts.

Abstract: Systems and methods are provided for processing a melting or dissociation curve of a DNA or other sample, for example, during PCR processing. In some embodiments, detection of the melting point and melting curve behavior can be enhanced by taking a derivative of the curve, and detecting peaks in the differential dissociation curve. In some embodiments, the derivative operation can comprise the use of edge-processing, or other detection algorithms. In some embodiments, the dissociation analysis can comprise removing low-frequency (or pedestal) components of the differential dissociation curve. In some embodiments, the differential dissociation curve can exhibit a smoothed or more regular appearance than the raw detected data.

Abstract: Methods and compositions for diagnosing, detecting and treating a colon disease associated with differential expression of MABA1 in comparison to healthy cells. Also provided are antagonists or agonists of MABA1, and methods for screening agents that modulate the MABA1 level or activity in vivo or in vitro.

Abstract: Apparatus and methods for detecting analytes in a sample are provided. The apparatus can include: one or more channels having a detection zone; one or more irradiation sources disposed for irradiating the detection zone with radiation; a detector capable of collecting at least one charge corresponding to an emission beam emitted from the detection zone, the detector having an output; and a time delay integration system coupled to the detector for effecting time delay integration of the at least one charge by accumulating the at least one charge before reading the at least one charge at the output of the detector. Various embodiments provide an apparatus with a multi-notch filter. Various embodiments provide a solid state laser, a micro-wire laser, or an organic light-emitting diode as a irradiation source.

Abstract: We hypothesized that gene expression patterns in peripheral blood cells may correlate with TAA disease status, and carried out a comprehensive gene expression survey on peripheral blood cells obtained from TAA patients and normal individuals. A distinct gene expression profile in peripheral blood cells can classify TAA patients from normal individuals. The genes provided by the present teachings define a set of diagnostic markers, thus providing a blood-based gene expression test to facilitate early detection of TAA disease. Methods of distinguishing ascending from descending TAA are also provided, as are methods of distinguishing familial from sporadic TAA.

Abstract: A thermal cycling device for thermally cycling samples of biological material contained in a microcard having a top and bottom surface. The thermal cycling device can include a sample block having an upper surface configured for engaging the bottom surface of a microcard, a vacuum device, and a temperature control system operatively connected with the sample block. The upper surface of the sample block may include a plurality of channels, the channels defining spaces between the sample block and the bottom surface of a microcard that may be positioned thereon. The vacuum device may be in fluid communication with the sample block for drawing gas out of the spaces defined by the channels in the sample block. The vacuum device may be configured for substantially maintaining a vacuum between the sample block and microcard so that a retention force is imparted on the microcard to urge the microcard toward the sample block.

Abstract: Methods and systems for forming water-in-oil emulsions are described. For example, an apparatus is described which includes: a first compartment containing a plurality of particles dispersed in an aqueous phase; a second compartment containing an oil phase; a porous layer separating the first and second compartments; and a device for applying pressure to the first compartment. A method is described which includes: moving an oil phase relative to a surface of a porous layer while simultaneously forcing an aqueous composition comprising particles through the porous layer and into the flowing dispersion medium thereby forming droplets of the aqueous composition containing particles dispersed in the oil phase. The aqueous composition can include one or more nucleic acid templates and reagents for amplifying the nucleic acids such as PCR reagents.

Abstract: An apparatus for detecting labeled beads is provided. The apparatus can include: one or more irradiation sources disposed for irradiating the one or more detection zones with radiation; at least one detector disposed for collecting charges corresponding to light signals emitted from labeled beads in the one or more detection zones, which have been excited by the radiation; and a system coupled to the at least one detector for effecting time delay integration of the charges by accumulating the charges before reading the charges at the output of the at least one detector.

Abstract: Apparatuses and methods in which detection is integrated with various liquid processing and environmental control functions to create integrated bioanalysis systems are disclosed. Though the various integrated bioanalysis systems are useful for any number of analysis formats, they are adaptable to high-throughput processing of samples.

Abstract: Compositions and methods for detecting 5-methylcytosine in a nucleic acid are disclosed. A 5-methylcytosine discriminator, which is a deoxyribonucleosidetriphosphate comprising a cytosine-pairing moiety such as a guanosine and a moiety which hinders hydrogen bonding between the cytosine-pairing moiety and a 5-methylcytosine is described. The discriminator is able to base pair with a cytosine but not a 5-methylcytosine. A 5-methylcytosine comprised by a target nucleotide can be detected in a reaction using a DNA polymerase and a primer hybridized immediately adjacent to the target nucleotide. In the reaction, pyrophosphate released upon incorporation of a dNTP complementary to a target nucleotide is detected. Lack of incorporation of the discriminator, but incorporation of a dGTP, can indicate that the target nucleotide is a 5-methylcytosine.

Abstract: An optical instrument is provided for simultaneously illuminating two or more spaced-apart reaction regions with excitation beams generated by a light source. The light source can include an area light array of light emitting diodes, one or more solid state lasers, one or more micro-wire lasers, or a combination thereof. According to various embodiments, a Fresnel lens can be disposed along a beam bath between the light source and the reaction regions. Methods of analysis using the optical instrument are also provided.

Abstract: A method and system for characterizing and quantifying various error and calibration components of signals associated with photo-detectors. By varying the detector operational parameters such as input light intensity and integration times, measured signals can be analyzed to separate out and quantify various components of the measured signals. The various components thus determined may be categorized according to their dependencies on the operational parameters. Such component characterization allows better understanding of the detector system and ways in which such system can be improved so as to yield an improved measurement result for which the detector is being utilized.

Abstract: The present invention relates to a method of separating a sample comprising biological compounds, such as nucleic acids. The nucleic acids are subjected to electrophoresis using a matrix that is essentially free of denaturants and having at least one random, linear copolymer comprising a first comonomer of acrylamide and at least one secondary comonomer. A temperature of at least a portion of the matrix is at least about 80° C.

Abstract: Methods and apparatuses that improve the flatness of the microplates. In some embodiments, a pair of opposing channels that extends along a length of a rigid member is used to retain the microplate on the rigid member and to impart a level of flatness of at least a predetermined value. In some embodiments, one or more rigid framing members each having a channel therein are disposed along the edges of a microplate and impart a level of flatness of at least a predetermined value to the microplate. In some embodiments, a method of flattening the microplate comprises securing the microplate to a rigid member so the microplate has a flatness of at least a predetermined value and maintaining the microplate secured to the rigid member during a subsequent spotting or filling operation.

Abstract: The present teachings provide methods, compositions, and kits for nucleic acid amplification. In some embodiments of the present teachings, amplification reactions are performed with at least one high stability primer. In some embodiments, the present teachings provide a method comprising a high stability primer for amplification of a nucleic acid sequence in a sample comprising a target nucleic acid sequence and a PCR inhibitor.

Abstract: Microfluidic devices having a diffusion-aided system for loading samples into the microfluidic device are provided. Methods of gas-venting a microfluidic device through a non-porous, gas permeable material sealing cover layer, for example, during liquid sample loading, are also provided. The non-porous, gas-permeable material can be, for example, a polysiloxane, for example, polydimethylsiloxane.

Abstract: A microplate assembly for performing an analytical method on an assay, comprising a microplate base structure having a plurality of apertures formed therethrough, and a plurality of well inserts coupled to the microplate base structure adjacent the apertures. Each of the plurality of well inserts has an open top portion and is adapted to receive an assay. The microplate base structure and the plurality of well inserts can comprise different materials. Methods of manufacturing the microplate assembly are also provided.

Abstract: A device is provided that comprises one or more fluid retainment regions each having at least one wall, and one or more loops in heat-transfer communication with the at least one wall. Each of the loops can comprise an electrical conductor that surrounds the same or a different fluid retainment region. A device is provided that comprises one or more fluid retainment regions each having particulates disposed therein. A system is provided that includes a platen adapted to hold a device including fluid retainment regions and one or more electrical conductors in heat-transfer communication with the fluid retainment regions. Methods of heating a sample are also provided.

Abstract: The present invention is based on the discovery of genetic polymorphisms that are associated with liver fibrosis and related pathologies. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, including groups of nucleic acid molecules that may be used as a signature marker set, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.

Abstract: A thermal cycler for automatic performance of the polymerase chain reaction is provided. The thermal cycler comprises a heater control that provides close temperature control of the reaction.