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.
Multiple step printing methods for microbarcodes
Granted: June 10, 2014
Patent Number:
8748079
A system and method for forming encoded microparticles is described. One embodiment includes a method for forming a microparticle, the method comprising providing a pattern, wherein the pattern defines a code element, printing the pattern on a substrate to form a first code element within a microparticle region, printing the pattern on the substrate to form at least one successive code element, such that the first code element and the at least one successive code element are within the…
Parallel preparation of high fidelity probes in an array format
Granted: May 20, 2014
Patent Number:
8729251
The present invention provides massively parallel oligonucleotide synthesis and purification for applications that utilize large collections of defined high-fidelity oligonucleotides (e.g., from about 101 to about 105 different sequences, generally between 25-160 bases in length).
Method of oligonucleotide synthesis
Granted: May 20, 2014
Patent Number:
8728767
Methods and kits for synthesizing a plurality of oligonucleotides are provided. Methods for providing a plurality of oligonucleotides enriched for full length oligonucleotides are provided. Truncated oligonucleotides are preferentially removed from the sample by digestion. Methods are also provided for amplification of a plurality of oligonucleotides.
Amplification and analysis of selected targets on solid supports
Granted: May 6, 2014
Patent Number:
8716190
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. Targets are circularized by hybridization to probes followed by ligation of the ends of the target to form a closed circle. The targets are then used as template for extension of an array bound probe resulting in…
Analysis of methylation using nucleic acid arrays
Granted: April 29, 2014
Patent Number:
8709716
Arrays for genome-wide analysis of methylation are disclosed. IN a preferred aspect arrays comprising a plurality of probes complementary to a plurality of identified CpG islands in the human, mouse and rat genome are disclosed. The arrays may be used to detect methylation within cpG islands in samples from human, mouse and rat genomes.
Miniaturized microparticles
Granted: April 15, 2014
Patent Number:
8697334
An encoded microparticle having a spatial code is provided; and a set of encoded microparticles possessing subsets each provided with a distinguishable spatial code, wherein the codes comply with a pre-determined coding scheme. Presented are also methods of using the encoded microparticles in various biological assays, such as various multiplex assays and visualizing them by creating a digital image of the encoded microparticles and determining whether false positives are present.…
Highly multiplexed particle-based assays
Granted: April 1, 2014
Patent Number:
8685753
Methods are provided for detecting and optionally quantitating multiple analytes, including nucleic acid and/or polypeptide analytes, in particle-based assays that can be highly multiplexed. Compositions, systems, and kits related to the methods are also featured.
Complexity management of genomic DNA
Granted: March 25, 2014
Patent Number:
8679758
The presently claimed invention provides for novel methods and kits for analyzing a collection of target sequences in a nucleic acid sample. A sample is amplified under conditions that enrich for a subset of fragments that includes a collection of target sequences. The invention further provides for analysis of the above sample by hybridization to an array, which may be specifically designed to interrogate the collection of target sequences for particular characteristics, such as, for…
Automated method of manufacturing polyer arrays
Granted: February 18, 2014
Patent Number:
8652774
The present invention provides methods to process multiple sensors by providing a sensor plate and HT plates. In a preferred embodiment of the invention, methods for assembling microarray pegs and microarray plates are described for high throughput microarray processing.
System for photolithographic synthesis of polymer arrays
Granted: January 28, 2014
Patent Number:
8637434
The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.
Multiplex capture of nucleic acids
Granted: January 21, 2014
Patent Number:
8632970
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…
Multiplex capture of nucleic acids
Granted: January 14, 2014
Patent Number:
8628918
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. Compositions, kits, and systems related to the methods are also described.
Methods for producing codes for microparticles
Granted: November 26, 2013
Patent Number:
8592136
Methods and apparatus are provided for forming a plurality of encoded microparticles with a printing process to define a code for identifying the microparticles. In some embodiments the printing process includes printing steps performed with photolithography.
Methods of using an array of pooled probes in genetic analysis
Granted: November 19, 2013
Patent Number:
8586312
The invention provides arrays of polynucleotide probes having at least one pooled position. A typical array comprises a support having at least three discrete regions. A first region bears a pool of polynucleotide probes comprising first and second probes. A second region bears the first probe without the second probe and a third region bears the second probe without the first probe. A target nucleic acid having segments complementary to both the first and second probes shows stronger…
System, method, and product for imaging probe arrays with small feature size
Granted: August 27, 2013
Patent Number:
8520976
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.
Fabrication of fluidic features within a plastic substrate
Granted: August 27, 2013
Patent Number:
8518479
In one aspect of the invention, methods, and devices are provided for creating microfluidic and nanofluidic features. In some embodiments, such methods and devices are used to create at least one channel of a desired volume within a channel in a plastic substrate.
Manufacturing and processing polymer arrays
Granted: August 6, 2013
Patent Number:
8501122
The invention provides sensor plates, particularly plates having a plurality of sensors, and related methods for assembling such plates. The sensors can be arrays of probes, such as microarrays, including high density oligonucleotide microarrays. The methods include the steps of selecting a substrate having a plurality of sensors, aligning the substrate to a support plate, and attaching the substrate to the support plate. Moduled sensor plates, and methods of assembling such plates, are…
Nucleic acid labelling compounds
Granted: July 30, 2013
Patent Number:
8497064
Nucleic acid labeling compounds are disclosed. The compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.
Methods for high throughput genotyping
Granted: July 30, 2013
Patent Number:
8498825
Methods for genotyping polymorphisms using allele specific probes are disclosed. A training set is used to generate a model for each polymorphism to be interrogated. The training set is used to obtain an estimate of the asymmetry between an intensity measurement for a first allele and an intensity measurement for a second allele of the same polymorphism. The intensity measurement obtained for a test sample is adjusted using the estimate of asymmetry prior to using the intensity…
