Derivatization of solid supports and methods for oligomer synthesis
Granted: July 6, 1999
Patent Number:
5919523
Methods and derivatized supports which are useful in solid-phase synthesis of peptides, oligonucleotides or other small organic molecules as well as arrays of ligands. The methods provide means to control the functional site density on a solid support. Some of the derivatized supports are polymer-coated or glycan-coated. Other methods for regenerating the surface of a used ligand array are also provided.
Photolabile nucleoside protecting groups
Granted: March 30, 1999
Patent Number:
5889165
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.
Very large scale immobilized polymer synthesis using mechanically directed flow paths
Granted: March 23, 1999
Patent Number:
5885837
A method and device for forming large arrays of polymers on a substrate (401). According to a preferred aspect of the invention, the substrate is contacted by a channel block (407) having channels (409) therein. Selected reagents are flowed through the channels, the substrate is rotated by a rotating stage (403), and the process is repeated to form arrays of polymers on the substrate. The method may be combined with light-directed methodolgies.
Methods for concurrently processing multiple biological chip assays
Granted: February 23, 1999
Patent Number:
5874219
Methods for concurrently processing multiple biological chip assays by providing a biological chip plate comprising a plurality of test wells, each test well having a biological chip having a molecular probe array; introducing samples into the test wells; subjecting the biological chip plate to manipulation by a fluid handling device that automatically performs steps to carry out reactions between target molecules in the samples and probes; and subjecting the biological chip plate to a…
Array of nucleic acid probes on biological chips for diagnosis of HIV and methods of using the same
Granted: January 19, 1999
Patent Number:
5861242
The invention provides an array of oligonucleotide probes immobilized on a solid support for analysis of a target sequence from a human immunodeficiency virus. The array comprises at least four sets of oligonucleotide probes 9 to 21 nucleotides in length. A first probe set has a probe corresponding to each nucleotide in a reference sequence from a human immunodeficiency virus. A probe is related to its corresponding nucleotide by being exactly complementary to a subsequence of the…
Polymorphism detection
Granted: January 12, 1999
Patent Number:
5858659
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,…
Computer-aided engineering system for design of sequence arrays and lithographic masks
Granted: January 5, 1999
Patent Number:
5856101
An improved set of computer tools for forming arrays. According to one aspect of the invention, a computer system (100) is used to select probes and design the layout of an array of DNA or other polymers with certain beneficial characteristics. According to another aspect of the invention, a computer system uses chip design files (104) to design and/or generate lithographic masks (110).
Polymorphisms in the glucose-6 phosphate dehydrogenase locus
Granted: January 5, 1999
Patent Number:
5856104
The invention provides nucleic acid segments of the glucose-6 phosphate dehydrogenase locus of the human genome including polymorphic sites. Allele-specific primers and probes hybridizing to regions flanking these sites are also provided. The nucleic acids, primers and probes are used in applications such as forensics, paternity testing, medicine and genetic analysis.
Integrated nucleic acid diagnostic device
Granted: January 5, 1999
Patent Number:
5856174
The present invention provides a miniaturized integrated nucleic acid diagnostic device and system. The device of the invention is generally capable of performing one or more sample acquisition and preparation operations, in combination with one or more sample analysis operations. For example, the device can integrate several or all of the operations involved in sample acquisition and storage, sample preparation and sample analysis, within a single integrated unit. The device is useful…
Methods for testing oligonucleotide arrays
Granted: December 1, 1998
Patent Number:
5843655
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.
Arrays of nucleic acid probes on biological chips
Granted: November 17, 1998
Patent Number:
5837832
DNA chips containing arrays of oligonucleotide probes can be used to determine whether a target nucleic acid has a nucleotide sequence identical to or different from a specific reference sequence. The array of probes comprises probes exactly complementary to the reference sequence, as well as probes that differ by one or more bases from the exactly complementary probes.
Method and apparatus for imaging a sample on a device
Granted: November 10, 1998
Patent Number:
5834758
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 selected regions of sample 1500 to radiation from a source 1100 and detecting the emission therefrom, and repeating the steps of exposition and detection until the sample is completely examined.
Printing oligonucleotide arrays using deprotection agents solely in the vapor phase
Granted: November 3, 1998
Patent Number:
5831070
A method and apparatus for selectively applying a print material onto a substrate for the synthesis of an array of oligonucleotides at selected regions of a substrate. The print material includes a barrier material, a monomer sequence, a nucleoside, a deprotection agent, a carrier material, among other materials. The method and apparatus also relies upon standard DMT based chemistry, and a vapor phase deprotection agent such as solid TCA and the like.
Cyclic nucleic acid and polypeptide arrays
Granted: June 23, 1998
Patent Number:
5770456
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. In one particular embodiment, an array of rotated cyclic polymers is formed. In another embodiment, an array of polymers is formed based on a target polymer. The array includes systematically substituted versions of the target molecule. In another…
Surface-bound, unimolecular, double-stranded DNA
Granted: June 23, 1998
Patent Number:
5770722
Libraries of unimolecular, double-stranded oligonucleotides on a solid support. These libraries are useful in pharmaceutical discovery for the screening of numerous biological samples for specific interactions between the double-stranded oligonucleotides, and peptides, proteins, drugs and RNA. In a related aspect, the present invention provides libraries of conformationally restricted probes on a solid support. The probes are restricted in their movement and flexibility using…
Photolabile nucleoside protecting groups
Granted: May 19, 1998
Patent Number:
5753788
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.
Arrays of materials attached to a substrate
Granted: April 28, 1998
Patent Number:
5744305
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.
Computer-aided probability base calling for arrays of nucleic acid probes on chips
Granted: March 31, 1998
Patent Number:
5733729
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.
Capturing sequences adjacent to Type-IIs restriction sites for genomic library mapping
Granted: January 20, 1998
Patent Number:
5710000
The present invention relates to novel methods for sequencing and mapping genetic markers in polynucleotide sequences using Type-IIs restriction endonucleases. The methods herein described result in the "capturing" and determination of specific oligonucleotide sequences located adjacent to Type-IIs restriction sites. The resulting sequences are useful as effective markers for use in genetic mapping, screening and manipulation.
Method and apparatus for detection of fluorescently labeled materials
Granted: May 20, 1997
Patent Number:
5631734
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.
