156results about "Library linkers" patented technology

Families of compositions are provided as labels, referred to as eTag reporters for attaching to polymeric compounds and assaying based on release of the eTag reporters from the polymeric compound and separation and detection. For oligonucleotides, the eTag reporters are synthesized at the end of the oligonucleotide by using phosphite or phosphate chemistry, whereby mass-modifying regions, charge-modifying regions and detectable regions are added sequentially to produce the eTag labeled reporters. By using small building blocks and varying their combination large numbers of different eTag reporters can be readily produced attached to a binding compound specific for the target compound of interest for identification. Protocols are used that release the eTag reporter when the target compound is present in the sample.

A method of modulation of synthesis capacity on and cleavage properties of synthetic oligomers from solid support is described. The method utilizes linker molecules attached to a solid surface and co-coupling agents that have similar reactivities to the coupling compounds with the surface functional groups. The preferred linker molecules provide an increased density of polymers and more resistance to cleavage from the support surface. The method is particularly useful for synthesis of oligonucleotides, oligonucleotides microarrays, peptides, and peptide microarrays. The stable linkers are also coupled to anchor molecules for synthesis of DNA oligonucleotides using on support purification, eliminating time-consuming chromatography and metal cation presence. Oligonucleotides thus obtained can be directly used for mass analysis, DNA amplification and ligation, hybridization, and many other applications.

The invention provides a method of tracking, identifying, and/or sorting classes or subpopulations of molecules by the use of oligonucleotide tags. Oligonucleotide tags of the invention each consist of a plurality of subunits 3 to 6 nucleotides in length selected from a minimally cross-hybridizing set. A subunit of a minimally cross-hybridizing set forms a duplex or triplex having two or more mismatches with the complement of any other subunit of the same set. The number of oligonucleotide tags available in a particular embodiment depends on the number of subunits per tag and on the length of the subunit. An important aspect of the invention is the use of the oligonucleotide tags for sorting polynucleotides by specifically hybridizing tags attached to the polynucleotides to their complements on solid phase supports. This embodiment provides a readily automated system for manipulating and sorting polynucleotides, particularly useful in large-scale parallel operations, such as large-scale DNA sequencing, mRNA fingerprinting, and the like, wherein many target polynucleotides or many segments of a single target polynucleotide are sequenced simultaneously.

The present invention includes methods and compositions relating to locus-specific arrays. More specifically, this invention includes methods for making locus-specific arrays from universal arrays in situ, the custom arrays made using those methods, and methods of using the custom arrays to detect target nucleotides.

The disclosure provides a method of sequencing a nucleic acid molecule that contains two or more target regions to be sequenced (such as, for example, barcodes). The invention is advantageous for sequencing by synthesis two or more target regions whose combined lengths plus the length of any intermediate sequence exceeds the available read length on a given sequencing platform. The methods of the invention utilize nucleic acid constructs containing at least the following elements: a complement of a first universal primer, a first target sequence, an optional polynucleotide spacer, a complement of a second universal primer, and a second target sequence. A first round of sequencing by synthesis is performed to sequence the first target sequence by elongating the first universal primer. Once the sequence of the first target region is obtained, and before the complement of the second primer is reached, the first round of sequencing is terminated. Thereafter, a second round of sequencing by synthesis is initiated—this time, by elongating the second universal primer, thereby sequencing the second target region.

The present invention provides a method of synthesizing libraries of molecules which include an encoding oligonucleotide tag.

Optical disk-based assay devices and methods are described, in which analyte-specific signal elements are disposed on an optical disk substrate. In preferred embodiments, the analyte-specific signal elements are disposed readably with the disk's tracking features. Also described are cleavable signal elements particularly suitable for use in the assay device and methods. Binding of the chosen analyte simultaneously to a first and a second analyte-specific side member of the cleavable signal element tethers the signal-responsive moiety to the signal element's substrate-attaching end, despite subsequent cleavage at the cleavage site that lies intermediate the first and second side members. The signal responsive moiety reflects, absorbs, or refracts incident laser light. Described are nucleic acid hybridization assays, nucleic acid sequencing, immunoassays, cell counting assays, and chemical detection. Adaptation of the assay device substrate to function as an optical waveguide permits assay geometries suitable for continuous monitoring applications.

<heading lvl="0">Abstract of Disclosure</heading> An array of selectively addressible microelectrodes for combinatorial synthesis of complex polymers or alloys.

Methods and apparatus for the preparation and use of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by delivering components of materials to predefined regions on a substrate, and simultaneously reacting the components to form at least two materials. Materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. More particularly, materials which can be prepared using the methods and apparatus of the present invention include, for example, inorganic materials, intermetallic materials, metal alloys, ceramic materials, organic materials, organometallic materials, non-biological organic polymers, composite materials (e.g., inorganic composites, organic composites, or combinations thereof), etc. Once prepared, these materials can be screened for useful properties including, for example, electrical, thermal, mechanical, morphological, optical, magnetic, chemical, or other properties. Thus, the present invention provides methods for the parallel synthesis and analysis of novel materials having useful properties.

Improved composite microarray slides for use in micro-analytical diagnostic applications are disclosed. Specifically, composite microarray slides useful for carrying a microarray of biological polymers on the surface thereof including composite microarray slides having a porous membrane formed by a phase inversion process effectively attached by covalent bonding through chemical agents that comprise anchor/linker moieties to a substrate that prepares the substrate to sufficiently bond to the porous membrane formed by a phase inversion process such that the combination produced thereby is useful in microarray applications and wherein the composite microarray slides are covalently bonded to a solid base member, such as, for example, a glass or Mylar microscope slide, such that the combination produced thereby is useful in microarray applications. Apparatus and methods for fabricating the composite microarray slides are also disclosed.

Rolling circle amplification is used to amplify and detect target nucleic acid molecules by affixing a first and/or second linker nucleic acid molecule or a second linker nucleic acid molecule to the target nucleic acid molecule, then circularizing the target nucleic acid molecule, and then amplifying the circularized nucleic acid molecule to generate reiterated nucleic acid sequences. The methods may be used to amplify nucleic acids, particularly RNA, for detection and cloning.

This invention provides oligonucleotide based arrays and methods for speciating and phenotyping organisms, for example, using oligonucleotide sequences based on the Mycobacterium tubercluosis rpoB gene. The groups or species to which an organism belongs may be determined by comparing hybridization patterns of target nucleic acid from the organism to hybridization patterns in a database.

Microarray devices fabricated using microfluidic reagent distribution techniques are provided. As described herein, the invention encompasses microfluidic microarray assemblies (MMA) and subassemblies and methods for their manufacture and use. In one embodiment first and second channel plates are provided which may be sealed to a test chip in consecutive steps. Each channel plate includes microfluidic channels configured in a predetermined reagent distribution pattern. For example, the first channel plate may have a radial (linear) reagent distribution pattern and the second channel plate may have a spiral (curved) reagent distribution pattern, or vice versa. In one embodiment the first channel plate is connected to the test chip and at least one first reagent is distributed on the test chip in a first predetermined reagent pattern. The first reagent is then immobilized on the test chip. Next, the first channel plate is removed, the second channel plate is connected to the test chip and at least one second reagent is distributed on the test chip in a second predetermined reagent pattern. The first and second reagent patterns intersect to define a plurality of microarray test positions on the test chip. In one embodiment, the first reagent may comprise a plurality of separate probes each distributed to selected test position(s) of the microarray and the second reagent may comprise a plurality of test samples each distributed to selected test position(s) of the microarray. Positive or negative reactions between the probes (or other first reagent) and test samples (or other second reagent) may then be detected at the microarray test positions. For example, hybridization between selected nucleic acid probes and selected nucleic acid samples may be detected at particular test positions. The invention thus provides an efficient means to fabricate high density multi-probe, multi-sample microarrays. Preferably the test chips and channel plates are circular and centrifugal force is used to achieve fluid flow through the microfluidic channels, such as by rotating the MMA in a disc spinner.