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Sequencing Patents of Note


US Patent 7,499,806. Image processing in microsphere arrays
Inventors: Bahram Ghaffarzadeh Kermani, Juergen Haas
Assignee: Illumina

Describes methods for registering analytical images, comprising obtaining an image of an array where the image depicts fiducials that can be used to register the sequential images of the array by determining their average intensity and then positioning the sequential images such that the average intensity of the fiducials attains either a maximum or minimum value.

US Patent 7,494,791. Nano-PCR: methods and devices for nucleic acid amplification and detection
Inventor: Anita Goel
Assignee: Nanobiosym

Describes methods, devices, and compositions for amplification of nucleic acid sequences without reliance on temperature cycling, thus freeing the methods from conventional benchtop thermal cycling devices. Denaturation of double stranded nucleic acids, primer annealing, and precision control over primer extension by polymerase can be accomplished by applying stress to a nucleic acid. According to the patent abstract, these methods can provide one or more benefits over conventional PCR methods, including precision control over the PCR process, generally improved fidelity, improved accuracy over problematic sequences such as GC-rich or tandem repeat regions, greater sequence length, increased reaction yield, reduced experimental time, greater efficiency, lower cost, greater portability, and robustness to various environmental parameters, such as temperature, pH, and ionic strengths.

US Patent 7,494,771. Universal method and composition for the rapid lysis of cells for the release of nucleic acids and their detection
Inventors: Francois Picard, Christian Menard
Assignee: Geneohm Sciences Canada

This invention describes a rapid, simple, flexible, and efficient method of nucleic acid extraction for nucleic acid testing assays, according to the patent abstract. The method has the following basic steps: mechanical cell lysis using solid particles in the presence of a chelating agent, followed by controlling the presence and/or activity of NAT assays inhibitors. This method is applicable to various biological samples and universal for microorganisms, as one can use it to extract nucleic acids from test samples containing target viruses, bacteria, bacterial spores, fungi, parasites, or other eukaryotic cells, including animal and human cells.

US Patent 7,491,498. Short cycle methods for sequencing polynucleotides
Inventors: Stanley Lapidus, Phillip Buzby, Timothy Harris
Assignee: Helicos BioSciences

The invention provides methods for sequencing a polynucleotide, comprising stopping an extension cycle in a sequence-by-synthesis reaction before the reaction has run to near or full completion.

US Patent 7,491,830. Phenyl xanthene dyes
Inventors: Joe Lam, Steven Menchen, Ruiming Zou, Scott Benson
Assignee: Applied Biosystems

Describes fluorescent phenyl xanthene dyes that comprise any fluorescein, rhodamine, or rhodol comprising a particular C9 phenyl ring. One or both of the ortho groups on the lower C9 phenyl ring is ortho-substituted with a group selected from alkyl, heteroalkyl, alkoxy, halo, haloalkyl, amino, mercapto, alkylthio, cyano, isocyano, cyanato, mercaptocyanato, nitroso, nitro, azido, sulfeno, sulfinyl, and sulfino. The phenyl xanthene dyes may be activated. Furthermore, the phenyl xanthene dyes may be conjugated to one or more substances including other dyes. The dyes are useful for a number of purposes, including labels for use in automated DNA sequencing as well the formation of fluorescent "bar codes" for polymeric particles used in the multiplexed analysis of analytes.

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US Patent 7,491,305. High density electrophoresis device and method
Inventors: Timothy Woudenberg, Reid Kowallis
Assignee: Applied Biosystems

The invention provides an apparatus or electrophoretic separation of analytes. In one aspect, the apparatus comprises a disc-shaped substrate defining (1) a central reservoir region, (2) several electrophoretic channels in fluid communication with, and emanating substantially radically from, the central reservoir region, the channels being coplanar with each other, and each channel having (i) a proximal end that is linked to the reservoir region, and (ii) a distal end, and preferably (3) for each channel, at least one chamber, and preferably three chambers, linked by a passageway in fluid communication with the distal end of that channel. Preferably, each passageway leads from each chamber in a direction that is initially away from the central reservoir region, whereby centrifugation of the substrate about a central axis that is perpendicular to the channels is effective to disperse liquid from the central reservoir region into the channels and chambers, such that any air bubbles in the chambers, channels, and passageways are forced towards the axis of rotation, when such liquid is present in the central reservoir region.

US Patent 7,491,496. Method for immobilizing nucleic acid and method for manufacturing biosensor using the same method
Inventors: Hiroshi Takiguchi, Hitoshi Fukushima
Assignee: Seiko Epson

Provides a method to enable high-density absorption when immobilizing nucleic acid probes onto a solid support surface by suppressing electrostatic repulsion among the nucleic acids. A nucleic acid immobilization method to immobilize a nucleic acid onto a solid support includes: preparing a solution containing a probe molecule that includes a nucleic acid, a spacer molecule, and at least one kind of a divalent cation; and contacting the solution with the solid support for incubation.

US Patent 7,491,495. Adsorption of nucleic acids to a solid phase
Inventors: Ralf Zielenski, Klaus Geissler, Thomas Walter
Assignee: Roche Diagnostics Operations

The invention is directed to a method for adsorbing nucleic acids to a solid phase using a two-step procedure. Furthermore, the invention pertains to a method for isolating nucleic acids from a biological sample. In the first step of the procedure, lysis is effected by mixing the biological sample with an aqueous lysis buffer containing a chaotropic agent and incubating the mixture; in the second step, the concentration of the chaotropic agent in the mixture is increased and the mixture is contacted with the solid phase, whereby the nucleic acids in the liquid phase are adsorbed to the solid phase.

US Patent 7,485,428. Recombinase polymerase amplification
Inventors: Niall Armes, Derek Stemple
Assignee: TwistDx

Describes three related novel methods for recombinase-polymerase amplification of a target DNA that exploit the properties of the bacterial RecA and related proteins to invade double-stranded DNA with single-stranded homologous DNA permitting sequence-specific priming of DNA polymerase reactions. The methods have the advantage of not requiring thermocycling or thermophilic enzymes. Further, the improved processivity of the methods allow amplification of DNA up to hundreds of megabases in length, according to the patent abstract.

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US Patent 7,486,865. Substrates for performing analytical reactions
Inventors: Mathieu Foquet, Paul Peluso, Stephen Turner, Daniel Roitman, Geoffrey Otto
Assignee: Pacific Biosciences of California

Provides substrates, including zero mode waveguide substrates, that have been fabricated to provide additional functional elements and/or components, including increased volumes for positioning of active surfaces and/or components for the mitigation of negative electrochemical properties of the underlying substrates.

US Patent 7,485,425. Methods for amplification of nucleic acids using spanning primers
Inventor: Eugene Spier
Assignee: Applied Biosystems

Provides methods and kits for detecting whether target nucleic acid sequences are present and/or quantitating target nucleic acid sequences.

US Patent 7,485,424. Labeled nucleotide phosphate (NP) probes
Inventors: Jonas Korlach, Watt Webb, Michael Levene, Stephen Turner, Harold Craighead, Mathieu Foquet
Assignee: Cornell Research Foundation

The invention is directed to a method of sequencing a target nucleic acid molecule with many bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site. Several labeled types of nucleotide analogs are provided proximate to the active site, with each distinguishable type of nucleotide analog being complementary to a different nucleotide in the target nucleic acid sequence. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand at the active site, where the nucleotide analog being added is complementary to the nucleotide of the target nucleic acid at the active site. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. The steps of providing labeled nucleotide analogs, polymerizing the growing nucleic acid strand, and identifying the added nucleotide analog are repeated so that the nucleic acid strand is further extended and the sequence of the target nucleic acid is determined.