Methods for monitoring the expression of alternatively spliced genes
Granted: September 29, 2005
Application Number:
20050214824
Methods, probe arrays and computer software products are provided for determining the arrangement of sequence elements. In one embodiment, methods for making and using exon chips are provided. The exon chips may be used to identify and quantify splice variants.
Very large scale immobilized polymer synthesis
Granted: September 29, 2005
Application Number:
20050214828
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…
Techniques for synthesis integrity evaluation utilizing cycle fidelity probes
Granted: September 29, 2005
Application Number:
20050216201
Techniques for designing polymer probes to verify the integrity of the probe synthesis are provided. Multiple probes with identical sequences are designed so that the probes will be formed utilizing at least one different monomer addition cycle. Based on the probes affinity to a control target, variations (e.g., errors) in probe synthesis may be identified.
Methods of analysis of alternative splicing in mouse
Granted: September 29, 2005
Application Number:
20050214823
The invention provides nucleic acid sequences which are complementary, in one embodiment, to a wide variety of mouse genes. The invention provides the sequences in such a way as to make them available for a variety of analyses. In one embodiment the nucleic acid sequences provided are present as an array of probes that may be used to measure gene expression of different mature RNA isoforms from at least 5,000 alternatively spliced mouse genes. As such, the invention relates to diverse…
Quantified fluorescence microscopy
Granted: September 22, 2005
Application Number:
20050206893
The present invention relates to calibration apparatuses, methods or tools used in microscopy A calibration tool for fluorescent microscopy includes a support, a solid surface layer including a fluorescent material, and a thin opaque mask of non-fluorescent material defining reference feature openings having selected dimensions exposing portions of the surface layer A first type of the calibration tool may include an adhesion promoter facilitating contact between the surface of the…
Very large scale immobilized polymer synthesis
Granted: September 22, 2005
Application Number:
20050208537
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 protecting groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.
Methods of genotyping
Granted: September 22, 2005
Application Number:
20050208555
Methods and kits are provided for genotyping a plurality of pre-selected SNPs. For each SNP a pair of oligos is synthesized. Each oligo is a perfect match to one allele of a polymorphic locus. The oligos are hybridized to genomic DNA and only those that are a perfect match to an allele that is present will hybridize. The hybridization reaction is size separated so that unbound oligos go with the small size fraction and bound oligos go with the large size fraction. The oligos in the large…
Brassica polymorphisms
Granted: September 22, 2005
Application Number:
20050208570
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.
Bioarray chip reaction apparatus and its manufacture
Granted: September 22, 2005
Application Number:
20050208646
A body 300 having a cavity 310 for mounting a substrate 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.
Expression monitoring to high density oligonucleotide arrays
Granted: September 15, 2005
Application Number:
20050202500
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…
Miniaturized genetic analysis systems and methods
Granted: September 15, 2005
Application Number:
20050202504
The present invention provides a miniaturized integrated nucleic acid diagnostic device and system.
Method and apparatus for imaging a sample on a device
Granted: September 15, 2005
Application Number:
20050200948
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.
Guided deposition in spatial arrays
Granted: September 8, 2005
Application Number:
20050196745
An apparatus and method is provided for preparing and using a very large and diverse array of compounds on a substrate having rapidly accessible locations. The substrate contains cells in which the compounds of the array are located. Surrounding the cells is a non-wetable surface that prevents the solution in one cell from moving to adjacent cells. The compounds are delivered to the individual cells of the array by a micropipette attached to an X-Y translation stage.
Analysis of methylation status using nucleic acid arrays
Granted: September 8, 2005
Application Number:
20050196792
Methods for amplifying a nucleic acid sample while preserving the methylation status of cytosines are disclosed. In some aspects the amplified methylated sample is modified by methylation sensitive modification and analyzed by hybridization to an array to identify cytosines that were methylated in the starting material and cytosines that were not methylated in the starting material. Methods for detecting methylation status are also disclosed. In one embodiment a DNA methyltransferase…
Bioarray chip reaction apparatus and its manufacture
Granted: September 1, 2005
Application Number:
20050191630
A body 300 having a cavity 310 for mounting a substrate 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.
Nucleic acid analysis techniques
Granted: September 1, 2005
Application Number:
20050191646
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…
Methods of using an array of pooled probes in genetic analysis
Granted: September 1, 2005
Application Number:
20050191675
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…
Methods for fragmenting DNA
Granted: September 1, 2005
Application Number:
20050191682
Methods for fragmenting and labeling nucleic acids for hybridization analysis are disclosed. In one aspect of the invention, methods and compositions are provided for fragmenting nucleic acid samples by exposure to acidic conditions to generate abasic positions and then cleavage of the abasic sites by, for example, an apurinic/apyrimidinic endonuclease. The resulting fragments may be end labeled and analyzed by hybridization to an array of nucleic acid probes.
Computer-aided visualization and analysis system for sequence evaluation
Granted: August 25, 2005
Application Number:
20050186581
A computer system 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 are improved by processing nucleic acid sequences together. Comparative analysis of multiple experiments is also provided by displaying reference sequences in one area and sample sequences in another area on a display…
Combinatorial strategies for polymer synthesis
Granted: August 25, 2005
Application Number:
20050186592
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 delivered 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.
