Hybridization assays on oligonucleotide arrays
Granted: April 4, 2000
Patent Number:
6045996
This invention provides methods of performing nucleic acid hybridization assays on high-density substrate-bound oligonucleotide arrays involving including in the hybridization mixture an isostabilizing agent, a denaturing agent or a renaturation accelerant.
Integrated nucleic acid diagnostic device
Granted: March 28, 2000
Patent Number:
6043080
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…
Expression monitoring by hybridization to high density oligonucleotide arrays
Granted: March 21, 2000
Patent Number:
6040138
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…
Combinatorial strategies for polymer synthesis
Granted: March 21, 2000
Patent Number:
6040193
An array is created by moving a dispenser toward a solid support until a tip of the dispenser touches the support, withdrawing the tip from the surface and releasing a drop of 5 nanoliters or less in an area smaller than 1 mm.sup.2 to create an array of at least 100 spots.
Electrochemical denaturation of double-stranded nucleic acid
Granted: March 7, 2000
Patent Number:
6033850
Double stranded nucleic acid is denatured by subjecting a solution thereof to a voltage applied between electrodes spaced by no more than 1.5 mm in a time not previously achievable in electrochemical denaturation. PCR is practiced isothermally by periodic application of voltage to produce denaturation. Electrochemical cells and kits for use in the process are provided.
Expression profiles in adult and fetal organs
Granted: March 7, 2000
Patent Number:
6033860
Expression profiles have been constructed for liver and brain, in adult and fetal and adolescent tissue. These provide the art with probes which are highly differentially expressed among stages and organs. The profiles and probes can be used to prioritize potential drug targets, to monitor disease progression and remission, and to assess drug metabolism. Solid supports are also provided which facilitate these uses.
Arrays of nucleic acid probes and methods of using the same for detecting cystic fibrosis
Granted: February 22, 2000
Patent Number:
6027880
The invention provides arrays of immobilized probes, and methods employing the arrays, for detecting mutations in the CFTR gene.
Nucleic acid adapters containing a type IIs restriction site and methods of using the same
Granted: February 22, 2000
Patent Number:
6027894
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 imaging a sample on a device
Granted: February 15, 2000
Patent Number:
6025601
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.
Synthesis of oligonucleotide arrays using photocleavable protecting groups
Granted: February 8, 2000
Patent Number:
6022963
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(R.sub.1)(R.sub.2)--O--C(O)-- wherein:Ar is an optionally substituted fused polycyclic aryl or heteroaromatic group or a vinylogous…
P53-regulated genes
Granted: February 1, 2000
Patent Number:
6020135
Many genes are identified as being p53-regulated which were not heretofore known to be p53-regulated. This includes both genes whose expression is induced and genes whose expression is repressed by the expression of wild-type p53. Monitoring expression of these genes is used to provide indications of p53 status in a cell. Such monitoring can also be used to screen for useful anti-cancer therapeutics, as well as for substances which are carcinogenic. Defects in p53 can be bypassed by…
Nucleic acid affinity columns
Granted: January 11, 2000
Patent Number:
6013440
This invention provides nucleic acid affinity matrices that bear a large number of different nucleic acid affinity ligands allowing the simultaneous selection and removal of a large number of preselected nucleic acids from the sample. Methods of producing such affinity matrices are also provided. In general the methods involve the steps of a) providing a nucleic acid amplification template array comprising a surface to which are attached at least 50 oligonucleotides having different…
Systems and methods for detection of labeled materials
Granted: November 9, 1999
Patent Number:
5981956
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.
Computer-aided visualization and analysis system for sequence evaluation
Granted: October 26, 1999
Patent Number:
5974164
A computer system (1) for analyzing nucleic acid sequences is provided. The computer system is used to perform multiple methods for determining unknown bases by analyzing the fluorescence intensities of hybridized nucleic acid probes. The results of individual experiments may be improved by processing nucleic acid sequences together. Comparative analysis of multiple experiments is also provided by displaying reference sequences in one area (814) and sample sequences in another area (816)…
Method of Identifying a Base in a Nucleic Acid
Granted: October 19, 1999
Patent Number:
5968740
Devices and techniques for hybridization of nucleic acids and for determining the sequence of nucleic acids. Arrays of nucleic acids are formed by techniques, preferably high resolution, light-directed techniques. Positions of hybridization of a target nucleic acid are determined by, e.g., epifluorescence microscopy. Devices and techniques are proposed to determine the sequence of a target nucleic acid more efficiently and more quickly through such synthesis and detection techniques.
Substrate preparation process
Granted: September 28, 1999
Patent Number:
5959098
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.
Apparatus for packaging a chip
Granted: August 31, 1999
Patent Number:
5945334
A body 300 having a cavity 310 for mounting a chip 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.
End-complementary polymerase reaction
Granted: July 27, 1999
Patent Number:
5928905
The present invention is directed to a process for amplifying and detecting any target nucleic acid sequence contained in a nucleic acid or mixture thereof and for assembling large polynucleotides from component polynucleotides, each involving generating concatemers formed by PCR amplification of overlapping fragments.
Method of identifying nucleotide differences
Granted: July 20, 1999
Patent Number:
5925525
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.
Integrated nucleic acid diagnostic device
Granted: July 13, 1999
Patent Number:
5922591
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…
