Affymetrix Patent Grants

Methods and devices for reading microarrays

Granted: September 19, 2017
Patent Number: 9767342
In one embodiment of the invention, a method to image a probe array is described that includes focusing on a plurality of fiducials on a surface of an array. The method utilizes obtaining the best z position of the fiducials and using a surface fitting algorithm to produce a surface fit profile. One or more surface non-flatness parameters can be adjusted to improve the flatness image of the array surface to be imaged.

System, method, and computer software product for genotype determination using probe array data

Granted: September 12, 2017
Patent Number: 9760675
An embodiment of a method of analyzing data from processed images of biological probe arrays is described that comprises receiving a plurality of files comprising a plurality of intensity values associated with a probe on a biological probe array; normalizing the intensity values in each of the data files; determining an initial assignment for a plurality of genotypes using one or more of the intensity values from each file for each assignment; estimating a distribution of cluster…

Circulating miRNA biomaker signatures

Granted: July 18, 2017
Patent Number: 9708643
Methods for diagnosis and surveillance of complex multi-factorial disorders such as cancer by screening of easily accessible biomarkers are disclosed. Highly stable cell free Circulating Nucleic Acids (CNA) present as both RNA and DNA species have been discovered in the blood and plasma of humans. Correlations between tumor-associated genomic/epigenetic/transcriptional changes and alterations in CNA levels are strong predictors of the utility of this biomarker class as clinical…

Assays for affinity profiling of nucleic acid binding proteins

Granted: June 27, 2017
Patent Number: 9689867
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…

Multiplex capture of nucleic acids

Granted: May 30, 2017
Patent Number: 9663822
Methods of capturing two or more nucleic acids simultaneously from a single sample are provided. Different nucleic acids are captured through cooperative hybridization events on different subsets of particles or at different selected positions on a spatially addressable solid support. Methods of capturing one or more long nucleic acids and methods of capturing one or more nucleic acid for sequencing are also provided. Compositions, kits, and systems related to the methods are also…

Methods, systems and apparatuses for testing and calibrating fluorescent scanners

Granted: March 21, 2017
Patent Number: 9599561
Disclosed are calibration apparatuses for fluorescent microscopy instruments and methods of making and using them. Specifically, disclosed are calibration apparatuses with a fluorescent layer, such as photoresist, deposited on a substrate, with an optional layer of a reflective material, such as chrome. Illumination of the fluorescent and/or reflective layers, and detection and analysis of the resulting emissions allows evaluation of the instrument with respect to both reflective and…

Silane mixtures

Granted: January 31, 2017
Patent Number: 9556360
Silanation compositions containing a mixture of two or more silanation reagents, where at least one silanation reagent includes a functional group capable of supporting polymer synthesis and at least one silanation reagent includes no functional group capable of supporting polymer synthesis are useful in modulating the active site density and hydrolytic stability of a surface. These compositions are particularly useful in silanating a surface prior to preparation of a polymer array and…

Multiplex targeted amplification using flap nuclease

Granted: December 27, 2016
Patent Number: 9528148
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…

Multiplex targeted amplification using flap nuclease

Granted: December 20, 2016
Patent Number: 9523122
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…

System, method, and product for imaging probe arrays with small feature sizes

Granted: September 13, 2016
Patent Number: 9445025
An embodiment of a method for resolving features on a probe array is described that, comprises acquiring a plurality of micro-shifted images of a region of a probe array; reconstructing an image of the probe array using the micro-shifted images; and deriving intensity values for one or more probe features disposed on the probe array from the reconstructed image.

Locus specific amplification using array probes

Granted: July 12, 2016
Patent Number: 9388457
Methods are provided for multiplexed amplification of selected targets and analysis of the amplified targets. In preferred aspects the amplification and analysis take place on the same solid support and preferably in a localized area such as a bead or a feature of an array. In preferred aspects the analysis is a determination of sequence at one or more locations in the amplified target. The methods may be used for genotyping, sequencing and analysis of copy number.

Methods for genotyping

Granted: July 12, 2016
Patent Number: 9388459
The present invention provides for methods for discriminating between alleles at polymorphic positions in a genome. In general the methods employ allele specific extension of oligonucleotides that are complementary to one of the alleles at the 3? end of the oligonucleotide. The allele specific oligonucleotides are resistant to proof reading activity from a polymerase and may be extended in an allele specific manner by a DNA polymerase with a functional 3? to 5? exonuclease activity. The…

Complexity management of genomic DNA

Granted: July 12, 2016
Patent Number: 9388460
The presently claimed invention provides for novel methods and kits for reducing the complexity of a nucleic acid sample by providing non-gel based methods for amplification of a subset of the sequences in a sample. In a preferred embodiment, amplification of a subset can be accomplished by digesting a sample with two or more restriction enzymes and ligating adaptors to the fragments so that only a subset of the fragments can be amplified. The invention further provides for analysis of…

Methods for genotyping selected polymorphism

Granted: July 12, 2016
Patent Number: 9388461
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…

Methods for synthesizing pools of probes

Granted: June 7, 2016
Patent Number: 9359640
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.

Method for detecting transcription factor-protein interactions

Granted: May 10, 2016
Patent Number: 9334537
A method is provided for identifying complexes between a transcription factor and another protein, the method comprising: isolating from a biological sample transcription factor complexes based on whether the transcription factor complexes comprise a particular type of transcription factor; and identifying which of a plurality of different proteins are present in the isolated transcription factor complexes.

Manufacturing and processing polymer arrays

Granted: March 22, 2016
Patent Number: 9290798
The invention provides methods to process multiple microarrays by providing a microarray plate and processing plates. In an embodiment of the invention, methods for assembling microarray plates by using wafers are described for high throughput microarray processing.

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…