Systems and methods for heating and mixing fluids
Granted: May 14, 2002
Patent Number:
6386749
A mixing system comprises an elongate rotatable shaft having a rotational axis. A plurality of holding members extend radially outward from the shaft and are configured to rotate with the shaft. The system further includes a plurality of carriers that are insertable between two of the holding members. Each of the carriers includes a plurality of grooves, pairs of which are adapted to receive a cartridge having a chamber for holding a liquid.
Photolithographic and other means for manufacturing arrays
Granted: April 30, 2002
Patent Number:
6379895
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.
Method to detect gene polymorphisms and monitor allelic expression employing a probe array
Granted: April 9, 2002
Patent Number:
6368799
The invention provides methods of monitoring expression levels of different polymorphic forms of a gene. Such methods entail analyzing genomic DNA from an individual to determine the presence of heterozygous polymorphic forms at a polymorphic site within a transcribed sequence of a gene of interest. RNA from a tissue of the individual in which the gene is expressed is then analyzed to determine relative proportions of polymorphic forms in transcript of the gene. Having identified alleles…
Electrochemical denaturation of double-stranded nucleic acid
Granted: April 2, 2002
Patent Number:
6365400
A process is described for denaturing native double-stranded nucleic acid material into its individual strands in an electrochemical cell. The process disclosed is an electrical treatment of the nucleic acid with a voltage applied to the nucleic acid material by an electrode. The process may also employ a promoter compound such as methyl viologen to speed denaturation. The process may be used in the detection of nucleic acid by hybridizing with a labelled probe or in the amplification of…
Computer-aided nucleic acid sequencing
Granted: March 26, 2002
Patent Number:
6361937
A computer system for sequencing nucleic acids is provided. The computer system may be used for de novo sequencing of a nucleic acid sequence by analyzing the fluorescence intensities of hybridized nucleic acid probes on biological chips. The probes with the highest intensities are utilized to sequence the nucleic acid and related probes are analyzed to increase the accuracy of nucleic acid sequencing. The sequence of the nucleic acid sequence may be determined from hybridization…
Complexity management and analysis of genomic DNA
Granted: March 26, 2002
Patent Number:
6361947
The present invention provides for novel methods of sample preparation and analysis involving reproducibly reducing the complexity of a nucleic sample. The invention further provides for analysis of the above sample by hybridization to an array which may be specifically designed to interrogate the desired fragments for particular characteristics, such as, for example, the presence or absence of a polymorphism. The invention further provides for novel methods of using a computer system to…
Brassica polymorphisms
Granted: March 19, 2002
Patent Number:
6358686
The invention provides oligonucleotides and their complements that can be used as allele-specific probes or primers for sequencing, oligonucleotide probe hybridization, and allele-specific amplification. Such oligonucleotides can be used, for example, to facilitate genetic distinction between individual plants in plant populations.
Products for detecting nucleic acids
Granted: March 12, 2002
Patent Number:
6355432
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.
Polymer arrays
Granted: February 12, 2002
Patent Number:
6346413
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.
Nucleic acid analysis techniques
Granted: February 5, 2002
Patent Number:
6344316
The present invention provides a simplified method for identifying differences in nucleic acid abundances (e.g., expression levels) between two or more samples. The methods involve providing an array containing a large number (e.g. greater than 1,000) of arbitrarily selected different oligonucleotide probes where the sequence and location of each different probe is known. Nucleic acid samples (e.g. mRNA) from two or more samples are hybridized to the probe arrays and the pattern of…
Probe-based analysis of heterozygous mutations using two-color labelling
Granted: January 29, 2002
Patent Number:
6342355
The invention provides methods of analyzing a nucleic acid in a target sample for variant alleles. In such methods, a first-labelled control sample and a second-labelled target sample are hybridized to at least one set of probes. The control sample comprises a homozygous reference allele. The target sample comprises the homozygous reference allele, or variant alleles differing from the reference allele at a locus, or one variant allele differing from the reference allele at the locus and…
Determining signal transduction pathways
Granted: January 22, 2002
Patent Number:
6340565
Experimental and analytical methods enable reconstruction of signal transduction networks from gene expression profiles. Signal transduction pathways can be reverse-engineered by 1) experimentally manipulating individual genes, 2) generating cellular expression profiles, and 3) analyzing for common patterns among these profiles. Analysis of patterns among profiles permits reconstruction of pathways and networks of interrelationships among genes and their products.
Method and system for providing a contract management system using an action-item table
Granted: January 8, 2002
Patent Number:
6338071
Described is a novel relational database architecture that is adapted to storing information regarding the terms of one or more contracts, and the actions required to be performed under it. The database resides on a computer-readable storage medium as part of a multi-user computer network. By using simple subroutines readily apparent to one skilled in the computer arts, one can automatically generate alerts whenever an action needs to be performed. These alerts are then transmitted to…
Exploiting genomics in the search for new drugs
Granted: December 25, 2001
Patent Number:
6333155
The cellular effects of potentially therapeutic compounds are characterized in mammalian cells and yeast. In the latter case the effects can be characterized on a genome-wide scale by monitoring changes in messenger RNA levels in treated cells with high-density oligonucleotide probe arrays.
Disassociation of interacting molecules
Granted: December 25, 2001
Patent Number:
6333157
dsDNA or other interacting molecules, e.g. antibody and antigen, are disassociated by applying an electrical voltage to a solution containing said molecules in a buffer favoring said disassociation e.g. CHES, CAPS OR CAPSO.
Methods and compositions for multiplex amplification of nucleic acids
Granted: December 25, 2001
Patent Number:
6333179
A method is described for predetermining ratios of primer pairs present in a single reaction vessel so as to achieve approximately equimolar yield of products. The ratios are determined as a function of the length of the amplicon and the length of other amplicons being simultaneously tested. The primers may desirably be for p53 gene sequences.
Identification of molecular sequence signatures and methods involving the same
Granted: December 11, 2001
Patent Number:
6329140
Novel means and methods for analyzing hybridization data derived from hybridization assays between a target nucleic acid and differently sequenced polynucleotide probes involve selecting probe sets that define reference sequences for sequence signatures and deriving useful data about the nature of the target nucleic acid molecule based its hybridization to the probes. The methods are useful for determining whether the target contains a nucleic acid or polypeptide or sequence signature,…
Very large scale immobilized polymer synthesis
Granted: December 11, 2001
Patent Number:
6329143
A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection…
Method of manipulating a gas bubble in a microfluidic device
Granted: December 4, 2001
Patent Number:
6326211
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…
Method for comparing copy number of nucleic acid sequences
Granted: October 30, 2001
Patent Number:
6309822
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.
