Detection of nucleic acids
Granted: March 1, 2016
Patent Number:
9273349
This invention provides compositions, methods, and systems for characterizing, resolving, and quantitating single stranded and double stranded DNA and RNA in-situ. Paired sense and anti-sense probes can signal the presence of double stranded nucleic acids. DNA and RNA can be distinguished in cell and tissue samples by hybridizing with probe sets adapted to highlight differences in these targets in-situ.
Feature intensity reconstruction of biological probe array
Granted: September 29, 2015
Patent Number:
9147103
The invention provides methods and systems for reconstructing feature intensities from pixel level data. In certain embodiments, the invention uses an empirically determined transfer function to construct a theoretical estimate of pixel level data and then iteratively updates feature intensities based on a minimum multiplicative error between the pixel level data and the theoretical estimate of the pixel level data.
Methods and compositions for amplification of nucleic acids
Granted: July 21, 2015
Patent Number:
9085761
The present invention provides methods, compositions, and kits for storing and enhancing the activity of polymerases and particularly thermostable polymerases. The methods comprise mixing a thermostable polymerase with at least one zwitterionic or ylide surfactant that has at least one PEO group. In another aspect the polymerase is mixed with a blocker such as PLURONIC® or TETRONIC® or an amine N-oxide derivative thereof. The thermostable polymerase may be reversibly inactivated by…
Array-based translocation and rearrangement assays
Granted: July 7, 2015
Patent Number:
9074244
Methods for detecting genomic rearrangements are provided. In one embodiment, methods are provided for the use of paired end tags from restriction fragments to detect genomic rearrangements. Sequences from the ends of the fragments are brought together to form ditags and the ditags are detected. Combinations of ditags are detected by an on-chip sequencing strategy that is described herein, using inosine for de novo sequencing of short segments of DNA. In another aspect, translocations…
Multiplex branched-chain DNA assays
Granted: March 24, 2015
Patent Number:
8986931
Methods of detecting two or more nucleic acids in a multiplex branched-chain DNA assay are provided. Different nucleic acids are captured through cooperative hybridization events on different, identifiable subsets of particles or at different selected positions on a spatially addressable solid support. Compositions, kits, and systems related to the methods are also described.
Multiplex targeted amplification using flap nuclease
Granted: March 17, 2015
Patent Number:
8980563
Methods for multiplex amplification of a plurality of targets of distinct sequence from a complex mixture are disclosed. In one aspect targets are circularized using a single circularization probe that is complementary to two regions in the target that flank a region to be amplified. The targets may hybridize to the circularization probe so that 5? or 3? flaps are generated and methods for removing flaps and circularizing the resulting product are disclosed. In another aspect targets are…
Miniaturized microparticles
Granted: February 3, 2015
Patent Number:
8945811
A system and method for forming encoded microparticles is described. One embodiment includes an encoded microparticle, the microparticle comprising a plurality of segments aligned along an axis, wherein the plurality of segments define a code for the microparticle; and an outer cuboid encapsulating the plurality of segments, wherein the plurality of segments are detectable through the outer cuboid.
Feature intensity reconstruction of biological probe array
Granted: January 13, 2015
Patent Number:
8934689
The invention provides methods and systems for reconstructing feature intensities from pixel level data. In certain embodiments, the invention uses an empirically determined transfer function to construct a theoretical estimate of pixel level data and then iteratively updates feature intensities based on a minimum multiplicative error between the pixel level data and the theoretical estimate of the pixel level data.
Assays for affinity profiling of nucleic acid binding proteins
Granted: January 13, 2015
Patent Number:
8932819
Methods, compositions and kits are disclosed for assays to determine the binding affinity of DNA-binding proteins or RNA-binding proteins for their corresponding recognition site(s). In particular, assays are disclosed for measuring binding affinities when either the binding protein, or the recognition sequence of the recognition site, or cofactor proteins, contain one or more mutations. The disclosed assays can thus be utilized to measure the effect on transcription factor binding…
Encoded microparticles
Granted: November 11, 2014
Patent Number:
8883691
Microparticles including spatially coded microparticles, systems for imaging and methods of detecting such microparticles as well as using the same in bioassays are provided.
Antireflective coatings for high-resolution photolithographic synthesis of DNA arrays
Granted: October 14, 2014
Patent Number:
8859196
The present invention provides an array of polymers and methods of forming arrays of polymers by providing a substrate having a first layer including one or more dielectric coatings on a solid support and a second layer including a plurality of polymers disposed on the first layer. The invention also provides methods for forming an array of polymers on a substrate using light-directed synthesis by providing a substrate having a first layer including one or more dielectric coatings on a…
System, method, and computer product for exon array analysis
Granted: October 7, 2014
Patent Number:
8855939
In one embodiment, a method for analyzing data generated by probe arrays is described that comprises receiving user selections of two or more data files and an identification of one or more subsets of intensity values acquired from a biological probe array. The method includes iteratively opening each data file, identifying the selected subset of intensity values associated with each open data file, determining parameters for processing, storing the parameters and the identified…
Methods and compositions for selective labeling of different biotinylated targets within multicolor or multilabel assays
Granted: September 16, 2014
Patent Number:
8835125
Disclosed are compositions and methods for the labeling of two or more targets with different labels. Specifically, disclosed are compositions for biotin and the protection of biotin within multilabel assays which employ the biotin-biotin binding protein binding relationship for each distinct label in relation to targets such as nucleic acids, polypeptides, antibodies or cells. These multilabel assays are enabled through the use of biotin with desthiobiotin, orthogonal protecting schemes…
Methods of analysis of allelic imbalance
Granted: September 16, 2014
Patent Number:
8835116
Methods are provided for identification of genes that are imprinted. In another embodiment methods are provided for identification and analysis of genes whose expression shows allelic imbalance. The expression products transcribed from genes that are present in the genome as two or more alleles may be distinguished by hybridization to an array designed to interrogate individual alleles. Genes whose transcription products are present in amounts that vary from expected are candidates for…
Multiplex amplification methods
Granted: September 9, 2014
Patent Number:
8828688
Compositions and methods for amplifying selected polynucleotides, including DNA and RNA, particularly in multiplex amplification reactions using common primers amplification. Generally, methods of the invention employ multiple steps such as template-specific hybridization, a linear amplification, partial degradation of nucleic acid, and ligation. At the end of the process the sequences of selected polynucleotides are flanked by the common sequences which can be used for exponential…
Combinatorial affinity selection
Granted: August 26, 2014
Patent Number:
8815510
In one aspect of the invention, methods for analyzing nucleic acid sample are provided. In a preferred embodiment, nucleic acids are selected using affinity matrices prior hybridization with a microarray.
Methods for genotyping selected polymorphism
Granted: August 19, 2014
Patent Number:
8808995
Methods for genotyping polymorphisms using a locus specific primer that is complementary to a region near a selected polymorphism are described. Methods for synthesizing pools of locus specific primers that incorporate some degenerate positions are also disclosed. A plurality of different sequence capture probes are synthesized simultaneously using degenerate oligonucleotide synthesis. The sequence of the locus specific regions of the capture probes are related in that they have some…
System and method for processing large number of biological microarrays
Granted: August 5, 2014
Patent Number:
8796186
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…
DNA ligation on RNA template
Granted: July 29, 2014
Patent Number:
8790873
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…
Methods for synthesizing pools of probes
Granted: June 24, 2014
Patent Number:
8759036
Compositions, methods and kits are disclosed for synthesizing and amplifying pools of probes using precursor oligonucleotides. In some aspects the precursor is amplified and nicking enzymes are used to separate the full length probes from the amplification products. The methods enable the preparation of single stranded DNA probes of defined sequence and length that are suitable for use in target detection assays.
