Methods for photolithographic synthesis of polymer arrays utilizing anti-reflective coatings
Granted: November 13, 2012
Patent Number:
8309496
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.
System, method, and product for multiple wavelength detection using single source excitation
Granted: November 6, 2012
Patent Number:
8305565
An embodiment of a method for adjusting system gain of a biological probe array scanner for a plurality of fluorophore species is described that comprises setting an excitation beam comprising an excitation wavelength at a first power level that elicits an optimal signal to noise ratio response from a first fluorophore species; scanning a biological probe array with the excitation beam; setting the excitation beam comprising the excitation wavelength at a second power level different…
Detection of nucleic acids through amplification of surrogate nucleic acids
Granted: October 16, 2012
Patent Number:
8288522
Methods for detecting and optionally quantitating one or more target nucleic acids are provided, in which a surrogate nucleic acid is captured to each target nucleic acid, amplified, and detected. Compositions, kit, and systems related to the methods are also described.
Analytical biochemistry system with robotically carried bioarray
Granted: September 25, 2012
Patent Number:
8273304
An analytical biochemistry system featuring a substrate with reactants immobilized thereon at fixed, known locations, a holder supporting the substrate and a manipulator for transporting the holder to a fixed sample and to an inspection station. The reactants are binding agents for a target biomolecule in a sample which forms a bound substance having a detectable characteristic. The holder may be a standard pipettor, optionally carried by a robot arm or hand as the manipulator to contact…
Photoacid generators for the synthesis of oligo-DNA in a polymer matrix
Granted: September 4, 2012
Patent Number:
8258199
Compounds represented by the following structural formulas can be used as photoacid generators: Such compounds are useful, for example, in fabricating arrays of polymers.
Cell penetrating peptides for intracellular delivery of molecules
Granted: August 14, 2012
Patent Number:
8242081
The present invention concerns cell-penetrating peptides which comprise an amino acid sequence consisting of GLX9RALX9RX1LX2RSLX9X3X4X5X6X7X8 (SEQ ID No: 1), wherein X1 is A, L or G, X2 is W or none, X3 is R or K, X4 is K, L or S, X5 is L or K, X6 is R or W, X7 is K or S, and X8 is A, V or Q, and X9 is W, F or Y. These CPPs can be used as vectors for delivering nucleic acids and/or proteins and/or peptides to cells, in vitro or in vivo.
Methods of enzymatic discrimination enhancement and surface-bound double-stranded DNA
Granted: August 7, 2012
Patent Number:
8236493
Methods for discriminating between fully complementary hybrids and those that differ by one or more base pairs and libraries of unimolecular, double-stranded oligonucleotides on a solid support. In one embodiment, the present invention provides methods of using nuclease treatment to improve the quality of hybridization signals on high density oligonucleotide arrays. In another embodiment, the present invention provides methods of using ligation reactions to improve the quality of…
Methods and apparatus for detection of fluorescently labeled materials
Granted: July 31, 2012
Patent Number:
8233735
Fluorescently marked targets bind to a substrate 230 synthesized with polymer sequences at known locations. The targets are detected by exposing selected regions of the substrate 230 to light from a light source 100 and detecting the photons from the light fluoresced therefrom, and repeating the steps of exposure and detection until the substrate 230 is completely examined. The resulting data can be used to determine binding affinity of the targets to specific polymer sequences.
Oxide layers on silicon substrates for effective confocal laser microscopy
Granted: July 24, 2012
Patent Number:
8227253
Methods of performing confocal laser microscopy on a polymer array disposed on a silicon wafer substrate, the method comprising the steps of providing a silicon wafer substrate having a top side and a bottom side, coating the top side of the silicon wafer with an oxide coating to provide an oxide coated wafer, covalently coupling a plurality of probes to the top side of the coated wafer to provide a fixed polymer array, hybridizing the fixed polymer array with a plurality of labeled…
System, method, and computer product for exon array analysis
Granted: July 17, 2012
Patent Number:
8224586
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…
System, method, and product for scanning of biological materials
Granted: June 26, 2012
Patent Number:
8208710
An embodiment of a scanning system is described including optical elements that direct an excitation beam at a probe array, detectors that receive reflected intensity data responsive to the excitation beam, where the reflected intensity data is responsive to a focusing distance between an optical element and the probe array, a transport frame that adjusts the focusing distance in a direction with respect to the probe array, an auto-focuser that determines a best plane of focus based upon…
Techniques for identifying, confirming, mapping, and categorizing polymers
Granted: June 19, 2012
Patent Number:
8204695
Systems and methods for identifying, confirming, mapping, and categorizing sample polymers, such as nucleic acid sequences, are provided. An estimation of the fraction of first and second polymers in a sample of polymers can be calculated by inputting a first hybridization value indicative of hybridization affinity of the sample of polymers to polymers probes that are complementary to the first polymer and inputting a second hybridization value indicative of hybridization affinity of the…
System, method, and computer software product for genotype determination using probe array data
Granted: June 12, 2012
Patent Number:
8200440
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…
Methods for identifying DNA copy number changes
Granted: May 29, 2012
Patent Number:
8190373
Methods of identifying allele-specific changes in genomic DNA copy number are disclosed. Methods for identifying homozygous deletions and genetic amplifications are disclosed. An array of probes designed to detect presence or absence of a plurality of different sequences is also disclosed. The probes are designed to hybridize to sequences that are predicted to be present in a reduced complexity sample. The methods may be used to detect copy number changes in cancerous tissue compared to…
Miniaturized microparticles
Granted: May 15, 2012
Patent Number:
8178278
A system and method for encoded microparticles is described. One embodiment includes an encoded microparticle comprising a plurality of segments, wherein the plurality of segments form a spatial code; contrast coating on at least one segment of the plurality of segments, wherein the contrast coating further encodes the microparticle; an outer surface, wherein the outer surface encloses the spatial code and contrast coating, and wherein the spatial code and contrast coating are detectable…
Miniaturized microparticles
Granted: May 1, 2012
Patent Number:
8168368
A system and method for forming encoded microparticles is described. One embodiment includes a system for forming encoded microparticles, the system comprising a step and repeat exposure system capable of performing a method comprising: printing at a first time a first portion of a code of a microparticle; and printing at a second time after the first time a second portion of the code of the microparticle; and a computer readable medium having a sequence of computer executable…
Methods and computer software for detecting splice variants
Granted: May 1, 2012
Patent Number:
8170808
Methods and software products for analysis of alternative splicing are disclosed. In general the methods involve normalizing probe set or exon intensity to an expression level measurement of the gene. The methods may be used to identify tissue-specific alternative splicing events.
Methods for genotyping with selective adaptor ligation
Granted: March 13, 2012
Patent Number:
8133667
The present invention provides methods for reducing the complexity of a nucleic acid sample to interrogate a collection of target sequences. Complexity reduction can be accomplished by fragmenting the nucleic acid sample with a restriction enzyme that has at least one variable position in the recognition sequence. In some aspects adaptors that ligate to some but not all possible overhangs generated by digestion are ligated to the fragments. This selective adaptor ligation allows for…
Primer array synthesis and validation
Granted: March 13, 2012
Patent Number:
8133987
Methods are presented for generating large sets for polymers. The methods employ high density oligonucleotide array.
Recombinant colwellia psychrerythraea alkaline phosphatase and uses thereof
Granted: March 6, 2012
Patent Number:
8129168
A heat labile alkaline phosphatase enzyme and methods of using the same and kits including the same are disclosed. Specifically, a nucleotide sequence of, peptide sequence of, methods of using, and kits comprising, a heat labile alkaline phosphatase isolated from Colwellia psychrerythraea are provided. Methods of over-expression and purification of the recombinant alkaline phosphatase and mutants thereof are also disclosed. Methods of over-expressing and purifying commercially useful…
