Abstract: Detection of variable nucleotide(s) is based on primer extension and incorporation of detectable nucleoside triphosphates. By selecting the detection step primers from the region immediately adjacent to the variable nucleotide, this variation can be detected after incorporation of as few as one nucleoside triphosphate. Labelled nucleoside triphosphates matching the variable nucleotide are added and the incorporation of a label into the detection step primer is measured. The selection of the detection step primer is important to the method according to this invention and is dependent on the nucleotide sequence of interest. The detection step primers are preferably selected so as to span the region immediately toward the 3? end from the variable nucleotide to be detected. The detection step primers can also be complementary to a sequence beginning several nucleotides removed from the variable nucleotide.

Abstract: Provided are compositions of compounds effective for treating a pathology, the composition comprising at least two compounds that modulate the activity of one or more target molecules associated with one or more Single Nucleotide Polymorphisms (SNPs). Methods are also provided for increasing overall treatment efficacy for a population of patients having a pathology.

Abstract: The invention provides compositions and methods for performing primer extension reactions, including employment of amplification primers having 5′ tags to incorporate into amplicons variant nucleotides of interest from target nucleic acids at known ratios, with or without sequences surrounding the variant nucleotides of interest. The invention provides identifying the variant nucleotides generated from the target nucleic acid and generated from the 5′ tags, comparing the results, evaluating the efficiency of the primer extension reactions, and monitoring the efficacy of such reactions. The invention accounts for DNA sequence and experimental variables that may affect efficiency of incorporation of nucleotides, and provides a reference point for the interpretation of polymorphisms. The invention also provides methods of breeding scrapie-resistant sheep populations.

Abstract: The invention comprises compositions and methods for performing primer extension reactions, including employment of amplification primers having 5′ tags to incorporate into amplicons variant nucleotides of interest from target nucleic acids at known ratios, along with the sequences surrounding the variant nucleotides of interest. The invention comprises identifying the variant nucleotides generated from the target nucleic acid and generated from the 5′ tags, comparing the results, evaluating the efficiency of the primer extension reactions, and monitoring the efficacy of such reactions. The invention accounts for DNA sequence and experimental variables which may affect efficiency of incorporation of nucleotides, and provides a reference point for the interpretation of polymorphisms.

Abstract: A genetic analysis device particularly for determining the presence or absence of Single Nucleotide Polymorphisms (SNPs) within specific sequences of DNA. The device includes a housing, at least one glass slide member, and an elastomeric member with channels thereon. Oligo arrays are spotted on the glass slide member(s) and subjected to DNA samples, reagents or the like. A plurality of openings or ports allow entry of samples, reagents or wash materials, while a plurality of exit ports or openings allow removal of such materials. The assay devices can be used for multiple samples or a single sample. A plurality of synthesis devices can be positioned in a support base in order to allow sampling in an automated manner. The synthesis devices can be provided in a 96 well microtiter format.

Abstract: The methods of invention include the use of control primers to monitor the efficacy of amplification and/or primer extension reactions, and possible subsequent use of these control products as sizing markers. The methods of the invention are applicable to single reactions as well as to high-throughput and multiplex systems, including array-based technologies. One embodiment of the invention comprises monitoring the efficacy of a reaction for the detection of polymorphisms in the scrapie gene.

Abstract: The present invention relates to microstructures which a fabricated from a cast or molded polymer material, such as polydimethylsiloxane (PDMS). The invention describes and claims methods and compositions from which a variety of microstructures may be prepared. The microstructures are particularly useful for use in assays and reactions in the relating to biological assays, including applications in medical diagnostics. Such assays and reactions included, but are by no means limited to, polynucleotide sequencing and polynucleotides analysis, including analysis of single nucleotide polymorphisms, and for polynucleotide amplification such as PCR. The microstructures of the invention may contain many features that are useful for such applications. For example, the microstructures may comprise wells or channels for biological fluids and/or reagents, as well as pumps and valves for directing such fluids, e.g., in a biological assay.

Abstract: This invention concerns a reagent composition comprising at least two different terminators of a nucleic acid template-dependent, primer extension reaction. This invention also concerns a method for determining the identity of a nucleotide base at a specific position in a nucleic acid of interest. This invention further concerns a method for determining the presence or absence of a particular nucleotide sequence in a sample of nucleic acids. This invention further concerns a method for identifying different alleles in a sample containing nucleic acids. This invention further concerns a method for determining the genotype of an organism at one or more particular genetic loci.

Abstract: The present invention provides a hyperspectral imaging apparatus and methods for employing such an apparatus for multi-dye/base detection of a nucleic acid molecule coupled to a solid surface.

Abstract: Multiple fluid sample processors and systems for high throughput chemical synthesis and biological assays and/or processing. A multi-layered fluidic array having microchannels, reservoirs and reaction wells is subject to robotic and automated handling. A pressure pumping system is utilized for fluid delivery and control through the synthesis process. The sizes of the micro-sized channels, apertures, and valves are adjusted to optimize fluid distribution and channel filling. The fluid sample processors can be grouped together in a microtiter format to increase the speed, quantity and efficiency of the processing.

Abstract: Provided are compositions of compounds effective for treating a pathology, the composition comprising at least two compounds that modulate the activity of one or more target molecules associated with one or more Single Nucleotide Polymorphisms (SNPs). Methods are also provided for increasing overall treatment efficacy for a population of patients having a pathology.

Abstract: A microfluidic fluid delivery system includes a microfluidic chip having a fluid input. A fluid reservoir is coupled to the fluid input. A gas delivery system has a gas pressure source and a variable amplitude function generator generating an alternating signal. A valve is coupled to the function generator and the gas pressure source. The valve controls the gas pressure pulse in response to said alternating signal. The gas pressure pulse displaces fluid from the fluid reservoir into the fluid input.

Abstract: A microfluidic device has a layer with a capillary break formed by a capillary sluice. The capillary sluice has a lower surface and an upper surface. A first electrode is disposed on the lower surface. The first electrode is coupled to the voltage source. A second electrode spaced a predetermined distance from the first electrode is coupled to the voltage source. A controller may be used to control the voltage applied to the electrodes. The controller may alter the operation of the microfluidic chip in response to fluid sensed at the electrodes.

Abstract: A microfluidic device has a layer that has a capillary break formed by a capillary sluice. The capillary sluice has a lower surface and an upper surface. An input channel is coupled to the capillary break. A first electrode is disposed proximate the lower surface. The first electrode is coupled to the voltage source. A second electrode is spaced a first predetermined distance from the first electrode coupled to the voltage source. A third electrode is spaced apart from the second electrode and positioned within the input channel from the first electrode coupled to the voltage source.

Abstract: A microfluidic device has a seal or other component between two adjacent layers. The seal or other component is formed of a sheet of material having a first thickness. The seal material has boss portions that have a second thickness greater than the first thickness. A plurality of holes are formed through the boss portion. A method for making the seal layer includes the step of thinning the seal material between a first film and a second film. Bosses are formed in the film. Holes are cut through the boss area. One film is removed from the seal material and the seal material is applied to a substrate. The seal material is cured to a substrate and the second film is removed from the seal material. Other components such as diaphragm may be formed using the above process without punching holes through the seal material.

Abstract: A method for single well addressability in a sample processor with row and column feeds. A sample processor or chip has a matrix of reservoirs or wells arranged in columns and rows. Pressure or electrical pumping is utilized to fill the wells with materials. In a preferred embodiment, single well addressability is achieved by deprotecting a single column (row) and coupling each transverse row (column) independently. After the coupling step, the next column (row) is deprotected and then coupling via rows (columns) is performed. Each well can have a unique coupling event. In other embodiments, the chemical events could include, for example, oxidation, reduction or cell lysis.

Abstract: A microfluidic fluid delivery system includes a microfluidic device having a fluid input. A fluid reservoir is fluidically coupled to the fluid input. A gas delivery system has a pulse generator that generates an electric pulse. An electrically operated valve is coupled to the pulse generator and the gas pressure source. The valve controls the gas pressure pulse in response to said electric pulse. The gas pressure pulse displaces fluid from the fluid reservoir into the plurality of capillaries.

Abstract: The invention relates to a simple, cost effective method for immobilizing synthetic nucleic acid molecules onto a solid support The invention further concerns the use of such immobilized molecules in nucleic acid hybridization assays, sequencing by hybridization assays, and genetic analyses and combinatorial analyses involving nucleic acids or proteins for screening applications.

Abstract: A method and apparatus for fluid transportation includes a fluid reservoir and a pump that supplies fluid to a microfluidic device. The microfluidic device has an opening and an electrode positioned proximate the opening. The pump pressurizes fluid within the microfluidic device to form a droplet at the opening. When a desired volume of droplet is formed, a potential difference is generated between an electrode and a target plate. The potential difference causes the drop to form a fluid delivery therebetween. The fluid delivery may take many shapes, including a Taylor cone or a stream of droplets.

Abstract: The present invention describes a novel nucleic acid sequencing reagent which consists of a capture moiety, a spacer region and a sequence specific hybridizing region of 4-8 bases. The nucleic acid sequencing reagent of the present invention can also contain an attachment moiety. The nucleic acid sequencing reagent can be arranged into a nested array. This array configuration can then be used to sequence a given template without prior knowledge (de novo) of the wild type or expected sequence in conjunction with primer extension in the presence of a labeled chain terminating nucleotide.