Abstract: System and methods for analyzing single molecules and performing nucleic acid sequencing. An integrated device includes multiple pixels with sample wells configured to receive a sample, which when excited, emits radiation. The integrated device includes at least one waveguide configured to propagate excitation energy to the sample wells from a region of the integrated device configured to couple with an excitation energy source. A pixel may also include at least one element for directing the emission energy towards a sensor within the pixel. The system also includes an instrument that interfaces with the integrated device. The instrument may include an excitation energy source for providing excitation energy to the integrated device by coupling to an excitation energy coupling region of the integrated device.

Abstract: Apparatus and techniques for electrokinetic loading of samples of interest into sub-micron-scale reaction chambers are described. Embodiments include an integrated device and related apparatus for analyzing samples in parallel. The integrated device may include at least one reaction chamber formed through a surface of the integrated device and configured to receive a sample of interest, such as a molecule of nucleic acid. The integrated device may further include electrodes patterned adjacent to the reaction chamber that produce one or more electric fields that assist loading the sample into the reaction chamber. The apparatus may further include a sample reservoir having a fluid seal with the surface of the integrated device and configured to hold a suspension containing the samples.

Abstract: Provided herein are methods and kits for parallel detection one or more target sequences across multiple samples, comprising separating a set of samples into one or more pooled sets, wherein each sample may comprise an initial amplicon comprising one or more target sequences and at least one barcode; conducting an amplification reaction on the one or more pooled sets to further amplify the amplicons, and optionally further adding an additional barcode to the amplicon; sequencing the amplicons; identifying individual samples from the pooled sample set that are positive for the one or more target sequences based on sequencing of the amplicons, wherein identification is based, at least in part, on detection of the unique combination of barcodes.

Abstract: An engineered system for modulating a nucleic acid molecule. In some examples, the system comprises a programmable inducer of DNA damage; one or more functional domain such as a reverse transcriptase domain, topoisomerase domain and/or polymerase domain; a recombination enhancer domain; and an RNA template encoding a donor polynucleotide and capable of forming a complex with the RT domain.

Abstract: The present invention is directed to methods and kits for gene analysis. The methods of the invention comprise the steps of providing nucleic acid; synthesis of a single-stranded DNA that is complementary to said nucleic acid molecule by contacting the nucleic acid with a DNA polymerase, a primer and a mixture of dNTPs under conditions that allow the generation of the DNA, wherein the primer comprises a target-complementary region and wherein the dNTP mixture comprises dATP, dGTP, dCTP, dTTP and dUTP; cleaving the DNA 5? to dU sites by (i) contacting the DNA with an uracil deglycosylase to generate a basic sites at positions of dUTP incorporation in the DNA; and (ii) contacting the DNA with an apurinic/apyrimidinic (AP) endonuclease; contacting the DNA comprising at its 5?-end the nucleotide sequence of the primer with a ssDNA ligase to circularize the DNA; and sequencing the circularized cDNA. The kits comprise the components necessary to perform the methods of the invention.

Abstract: The present invention is directed to methods and kits for gene analysis. The methods of the invention comprise the steps of providing nucleic acid; synthesis of a single-stranded DNA that is complementary to said nucleic acid molecule by contacting the nucleic acid with a DNA polymerase, a primer and a mixture of dNTPs under conditions that allow the generation of the DNA, wherein the primer comprises a target-complementary region and wherein the dNTP mixture comprises dATP, dGTP, dCTP, dTTP and dUTP; cleaving the DNA 5? to dU sites by (i) contacting the DNA with an uracil deglycosylase to generate a basic sites at positions of dUTP incorporation in the DNA; and (ii) contacting the DNA with an apurinic/apyrimidinic (AP) endonuclease; contacting the DNA comprising at its 5?-end the nucleotide sequence of the primer with a ssDNA ligase to circularize the DNA; and sequencing the circularized cDNA. The kits comprise the components necessary to perform the methods of the invention.

Abstract: A method for designing an engine case static structure of a gas turbine engine includes creating signals representing an engine case static structure knowledge base of information. The knowledge base has a plurality of design rule signals with respect to a corresponding plurality of parameter signals of associated elements of an engine case static structure, wherein the knowledge base comprises at least one data value signal for each of the plurality of design rule signals. A desired data value signal is entered for a selected one of the plurality of parameter signals of an associated element of the engine case static structure and compared to the corresponding data value signal in the knowledge base for the corresponding one of the plurality of design rule signals. Signals representative of a geometric representation of the selected parameter signal may be created.