Method of manufacturing biological chips
Granted: October 30, 2001
Patent Number:
6309831
A method of manufacturing items in parallel. Selected samples of items to be manufactured are subjected to additional steps in a manufacturing process. If such sample items meet the requisite quality control standard, remaining items are subjected to further manufacturing steps. If the sample items which have been further processed do not meet the requisite quality control standard, the lot from which the samples do not undergo the additional manufacturing step. Invention provides an…
Nucleotides and analogs having photoremoveable protecting groups
Granted: October 30, 2001
Patent Number:
6310189
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 nucleic acid probes for analyzing biotransformation genes and methods of using the same
Granted: October 30, 2001
Patent Number:
6309823
The invention provides arrays of immobilized probes, and methods employing the arrays, for detecting mutations in the biotransformation genes, such as cytochromes P450. For example, one such array comprises four probe sets. A first probe set comprises a plurality of probes, each probe comprising a segment of at least three nucleotides exactly complementary to a subsequence of a reference sequence from a biotransformation gene, the segment including at least one interrogation position…
Methods of using an array of pooled probes in genetic analysis
Granted: October 23, 2001
Patent Number:
6306643
The invention provides arrays of polynucleotide probes having at least one pooled position. A typical array comprises a support having at least three discrete regions. A first region bears a pool of polynucleotide probes comprising first and second probes. A second region bears the first probe without the second probe and a third region bears the second probe without the first probe. A target nucleic acid having segments complementary to both the first and second probes shows stronger…
Substrate preparation process
Granted: October 23, 2001
Patent Number:
6307042
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.
Gene expression and evaluation system
Granted: October 23, 2001
Patent Number:
6308170
An efficient and easy to use query system for a gene expression database. Using such a system, one can easily identify genes or expressed sequence tags whose expression correlates to particular tissue types. Various tissue types may correspond to different diseases, states of disease progression, different organs, different species, etc. Researchers may now use large scale gene expression databases to full advantage.
Expression monitoring for gene function identification
Granted: October 16, 2001
Patent Number:
6303301
This invention provides methods, compositions and apparatus for mapping the regulatory relationship among genes by massive parallel monitoring gene expression. In some embodiments, mutations in the up-stream regulatory genes are detected by monitoring the change in down-stream gene expression. Similarly, the function of a specific mutation in a up-stream gene is determined by monitoring the down-stream gene expression. In addition, regulatory function of a target gene can be determined…
Polymorphism detection
Granted: October 9, 2001
Patent Number:
6300063
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,…
Apparatus and method for detecting samples labeled with material having strong light scattering properties, using reflection mode light and diffuse scattering
Granted: September 25, 2001
Patent Number:
6294327
A system and method for imaging a sample labeled with a material having a strong light scattering and reflecting properties are provided. A typical material having strong light scattering and reflecting properties is a metal colloid. The imaging system employs a light scattering and reflecting illumination technique. The sample can be imaged with reflection mode imaging along or with a combination of reflection mode and scatter mode imaging.
Very large scale immobilized polymer synthesis
Granted: September 18, 2001
Patent Number:
6291183
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…
Electrochemical denaturation of double-stranded nucleic acid
Granted: September 18, 2001
Patent Number:
6291185
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 practised isothermally by periodic application of voltage to produce denaturation. Electrochemical cells and kits for use in the process are provided.
Nucleic acid adapters containing a type IIs restriction site and methods of using the same
Granted: September 18, 2001
Patent Number:
6291181
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.
Allele detection using primer extension with sequence-coded identity tags
Granted: September 11, 2001
Patent Number:
6287778
A method for determining the genotype of one or more individuals at a polymorphic locus employs amplification of a region of DNA, labeling of allele-specific extension primers containing tags, and hybridization of the products to an array of probes. The genotype is identified from the pattern of hybridization. The method can also be used to determine the frequency of different alleles in a population.
Bioarray chip reaction apparatus and its manufacture
Granted: September 11, 2001
Patent Number:
6287850
Agitation systems for reversibly directing fluid samples flow back and forth across a nucleic acid array, thereby promoting hybridization between targets in the fluid sample and probes on the nucleic acid array.
Hybridization and sequencing of nucleic acids using base pair mismatches
Granted: September 4, 2001
Patent Number:
6284460
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.
Miniature reaction chamber and devices incorporating same
Granted: September 4, 2001
Patent Number:
6284525
The present invention generally relates to miniaturized devices for carrying out and controlling chemical reactions and analyses. In particular, the present invention provides devices which have miniature temperature controlled reaction chambers for carrying out a variety of synthetic and diagnostic applications, such as PCR amplification, nucleic acid hybridization, chemical labeling, nucleic acid fragmentation and the like.
Nucleic acid affinity columns
Granted: August 28, 2001
Patent Number:
6280950
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…
Capillary array electrophoresis scanner
Granted: August 7, 2001
Patent Number:
6270644
A Monster Capillary Array Electrophoresis scanner measures four-color electropherograms from over a thousand capillary electrophoretic separations in parallel. The system consists of a two-dimensional confocal rotary scanner and a four-color detection unit.
Methods involving direct write optical lithography
Granted: August 7, 2001
Patent Number:
6271957
An improved optical photolithography system and method provides predetemined light patterns generated by a direct write system without the use of photomasks. The Direct Write System provides predetermined light patterns projected on the surface of a substrate (e.g., a wafer) by using a computer controlled component for dynamically generating the predetermined light pattern, e.g., a spatial light modulator. Image patterns are store in computer and through electronic control of the spatial…
Probe kit for identifying a base in a nucleic acid
Granted: July 31, 2001
Patent Number:
6268152
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.
