Systems and methods for detection of labeled materials
Granted: July 22, 2003
Patent Number:
6597000
Labeled targets on a support synthesized with polymer sequences at known locations according to the methods disclosed in U.S. Pat. No. 5,143,854 and PCT WO 92/10092 or others, can be detected by exposing marked regions of sample to radiation from a source and detecting the emission therefrom, and repeating the steps of exposition and detection until the sample is completely examined.
Polymorphism detection
Granted: July 1, 2003
Patent Number:
6586186
The present invention generally provides a rapid efficient method for analyzing polymorphic or biallelic markers, and arrays for carrying out these analyses. In general, the methods of the present invention employ arrays of oligonucleotide probes that are complementary to target nucleic acids which correspond to the marker sequences of an individual. The probes are typically arranged in detection blocks, each block being capable of discriminating the three genotypes for a given marker,…
Proportional amplification of nucleic acids
Granted: June 24, 2003
Patent Number:
6582906
The proportional amplification of nucleic acids can increase the amount of nucleic acids while preserving the relative abundance of the individual nucleic acid species, or portions thereof, in the original sample. A proportionally amplified nucleic acid preparation may be analyzed in a gene expression monitoring system, preferably involving a nucleic acid probe array.
Oligonucleotides
Granted: June 24, 2003
Patent Number:
6582908
The present invention provides a number of oligonucleotide sequences which can be used for a wide variety of analyses applicable to the diverse fields impacted by the nature of molecular interaction, including chemistry, biology, medicine, and medical diagnostics. In certain embodiments these oligonucleotides may be used as probes to be used in, for example, gene expression analysis.
Amplification of nucleic acids
Granted: June 24, 2003
Patent Number:
6582938
The present invention relates to the amplification of nucleic acids, preferably from mRNA. A primer and promoter are added to a target sequence to be amplified and then the target is amplified in an in vitro transcription reaction.
Polymorphism detection utilizing clustering analysis
Granted: June 24, 2003
Patent Number:
6584410
Systems and methods for detecting differences in sample polymers, such as nucleic acid sequences, are provided. Hybridization affinity information for the sample polymers is clustered so that the differences, if any, between or among the sample polymers can be readily identified. By clustering the hybridization affinity information of the sample polymers, differences in the sample polymers can be accurately achieved even in the presence of random and systematic errors.
Arrays and methods for detecting nucleic acids
Granted: June 10, 2003
Patent Number:
6576424
The present invention provides methods and apparatus for sequencing, fingerprinting and mapping biological macromolecules, typically biological polymers. The methods make use of a plurality of sequence specific recognition reagents which can also be used for classification of biological samples, and to characterize their sources.
Methods for testing oligonucleotide arrays
Granted: June 10, 2003
Patent Number:
6576425
Methods for testing oligonucleotide arrays are disclosed including methods for testing the efficiency of nucleotide coupling; methods for testing amounts of deprotected oligonucleotides; methods for determining amounts of depurinated oligonucleotides; and methods of detecting the presence of cleavable structural features, such as double-stranded nucleic acids.
Methods of using chemical libraries to search for new kinase inhibitors
Granted: June 3, 2003
Patent Number:
6573044
The generation of selective inhibitors for specific protein kinases would provide new tools for analyzing signal transduction pathways and possibly new therapeutic agents. We have invented an approach to the development of selective protein kinase inhibitors based on the unexpected binding mode of 2,6,9-trisubstituted purines to the ATP binding site of human CDK2. The most potent inhibitor, purvalanol B (IC50=6 nM), binds with a 30-fold greater affinity than the known CDK2…
Photocleavable protecting groups and methods for their use
Granted: May 20, 2003
Patent Number:
6566515
Novel compounds are provided which are useful as linking groups in chemical synthesis, preferably in the solid phase synthesis of oligonucleotides and polypeptides. These compounds are generally photolabile and comprise protecting groups which can be removed by photolysis to unmask a reactive group. The protecting group has the general formula Ar—C(R1)(R2)—O—C(O)— wherein:
Ar is an optionally substituted fused polycyclic aryl or heteroaromatic group or a…
Method and apparatus for providing a bioinformatics database
Granted: May 20, 2003
Patent Number:
6567540
System and method for organizing information relating to polymer probe array chips including oligonucleotide array chips. A database model is provided which organizes information relating to sample preparation, chip layout, application of samples to chips, scanning of chips, expression analysis of chip results, etc. The model is readily translatable into database languages such as SQL. The database model scales to permit mass processing of probe array chips.
Very large scale immobilized polymer synthesis
Granted: May 20, 2003
Patent Number:
6566495
A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protective groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.
Capillary array electrophoresis scanner
Granted: April 29, 2003
Patent Number:
6554986
An improved rotary confocal fluorescence scanner capable of detecting analytes separated on over a 1,000 capillaries simultaneously. This system uses a confocal microscope objective and mirror assembly that rotates inside a vertical ring of capillaries to provide rapid and efficient excitation and detection of fluorescently labeled fragments separated within a cylindrical capillary array. Use of automated procedures to load and run all capillaries permits one to read more than 350,000…
Method of comparing nucleic acid sequences
Granted: April 22, 2003
Patent Number:
6551784
The present invention provides methods for comparing and identifying differences in nucleic acid sequences using a plurality of sequence specific recognition reagents (i.e., probes comprising a nucleic acid complementary to a nucleic acid sequence in collections to be compared) bound to a solid surface.
Method and apparatus for hybridization
Granted: April 22, 2003
Patent Number:
6551817
A body 300 having a cavity 310 for mounting a substrate 120 fabricated with probe sequences at known locations according to the methods disclosed in U.S. Pat. No. 5,143,854 and PCT WO 92/10092 or others, is provided. The cavity includes inlets 350 and 360 for introducing selected fluids into the cavity to contact the probes. Accordingly, a commercially feasible device for use in high throughput assay systems is provided.
Methods of identifying nucleic acid probes to quantify the expression of a target nucleic acid
Granted: April 15, 2003
Patent Number:
6548257
This invention provides methods of monitoring the expression levels of a multiplicity of genes. The methods involve hybridizing a nucleic acid sample to a high density array of oligonucleotide probes where the high density array contains oligonucleotide probes complementary to subsequences of target nucleic acids in the nucleic acid sample. In one embodiment, the method involves providing a pool of target nucleic acids comprising RNA transcripts of one or more target genes, or nucleic…
Method for marking samples
Granted: April 8, 2003
Patent Number:
6544739
The present invention provides methods and apparatus for sequencing, fingerprinting and mapping biological macromolecules, typically biological polymers. The methods make use of a plurality of sequence specific recognition reagents which can also be used for classification of biological samples, and to characterize their sources.
Systems and methods for high performance scanning
Granted: April 8, 2003
Patent Number:
6545264
The present invention provides a scanning confocal microscope image detection system having a simple and inexpensive objective lens and a high acceleration/high speed voice coil driven translation system. The objective lens provides high light collection efficiency at low cost. The voice coil provides improved acceleration for fast scanning of at least one axis (scanning direction; fast scan axis) of a polymer array that can be used effectively with the inexpensive objective lens having…
Computer-aided probability base calling for arrays of nucleic acid probes on chips
Granted: April 8, 2003
Patent Number:
6546340
A computer system for analyzing nucleic acid sequences is provided. The computer system is used to calculate probabilities for determining unknown bases by analyzing the fluorescence intensities of hybridized nucleic acid probes on biological chips. Additionally, information from multiple experiments is utilized to improve the accuracy of calling unknown bases.
Gene expression and evaluation system using a filter table with a gene expression database
Granted: March 11, 2003
Patent Number:
6532462
A filter table provides a framework in which queries are efficiently and easily developed to access a gene expression database. The filter table is used to filter a plurality of expression levels to return a reduced set of expression levels, which may be further queried to provide more specific results. Using the filtering and querying provided one can easily identify genes or expressed sequence tags whose expression correlates to particular tissue types. Various tissue types may…