Abstract: Systems and method for organizing information relating to the design of polymer probe array chips including oligonucleotide array chips. A database model is provided which organizes information interrelating probes on a chip, genomic items investigated by the chip, and sequence information relating to the design of the chip. The model is readily translatable into database languages such as SQL. The database model scales to permit storage of information about large numbers of chips having complex designs.

Abstract: Methods for high speed, high throughput analysis of polynucleotide sequences, and apparatuses with which to carry out the methods are provided in the invention.

Abstract: Feature locations are determined in an array image obtained from reading a chemical array comprising multiple features arranged in a polygon and which array optionally includes sub-arrays within the array. A complete image of the array or a sub-array is presented on a display. Magnified images of corner regions of the displayed complete image are simultaneously presented on the display with the complete image. A user selection of corners for the array or sub-array are received and an array or sub-array actual outline is genereated by linearly connecting the user selected corners. The generated actual outline is presented on the magnified image and may also be simultaneously presented on the complete image. Feature locations in the array or sub-array image may be determined based on the actual outline.

Abstract: A digital image processing-based system and method for quantitatively processing a plurality of nucleic acid species expressed in a microarray are disclosed. The microarray is a grid of a plurality of sub-grids of the nucleic acid species. The system includes a scanner that has a digital scanning sensor that scans the microarray and transmits from an output a digital image of the microarray, and a processor that receives the digital image of the microarray from the scanner and then processes the digital image, identifying each of the microarray's sub-grids. The processor then detects in each of the sub-grids a center-representing pixel of a signal of a chemical material and an approximate radius of the signal. Then, the processor segments the signal and calculates a characterizing measure for the segmented signal.

Abstract: Methods and compounds are provided for detecting target molecules in a sample using specific binding assays. In particular, methods are provided for detecting a nucleic acid target in a sample. In one embodiment, the method comprises hybridizing a nucleic acid target, comprising a target nucleic acid sequence, to a nucleic acid probe, comprising a probe nucleic acid sequence, wherein the target comprises a binding ligand. The hydridized target is contacted with a receptor comprising multiple sites capable of binding the binding ligand to complex the receptor to the binding ligand, and the receptor is contacted with an amplification reagent, comprising a plurality of the binding ligands, to complex the amplification reagent to the receptor. The presence of the complexed amplification reagent then is detected, for example, by detecting the presence of a detectable label, such as a fluorescent label, for example, on the receptor or the amplification reagent.

Abstract: An image display apparatus contains a display unit which displays information. A table displaying unit controls the display unit so as to display a measurement result table including a plurality of lists each of which is obtained from at least two corresponding measurement spots in at least two images, where the at least two corresponding measurement spots belong to the at least two images, respectively, so that the at least two images each include a plurality of measurement spots which respectively correspond to a plurality of measurement spots in every other one of the at least two images. An instruction receiving unit receives an instruction to select one of the plurality of lists in the measurement result table. An image display control unit controls the display unit so as to selectively display a portion of each of the at least two images so that the portion contains one of the plurality of measurement spots which corresponds to the one of the plurality of lists.

Abstract: The present invention provides polynucleotides having base sequences of sequence Nos. 1 to 4, as polynucleotides having polymorphism sites capable of being useful indicators for prediction of validity of interferon therapy.

Abstract: Methods and equipment are provided for the mass spectrometric measurement of a large number of genotyping profiles, each formed by several tens to several hundreds of SNPs (single nucleotide polymorphisms). A multitude of chips each carrying an array of surface-bound oligonucleotide probes for mutations are synchronously processed. The chips are attached to plates such that they can be immersed in a multitude of wells with DNA samples requiring analysis while also serving directly as sample carriers in mass spectrometers. The multitude of wells can, for instance, take the form of microtitre plates. Primers may be used which possess a photolytically or chemically cleavable linker that bridges one base pair and does not hinder either the possibility of hybridization or enzymatic extension. Light or chemicals can then be used to cleave short chains particularly suitable for ionization by matrix assisted laser desorption and mass spectrometric analysis using time-of-flight mass spectrometers.

Abstract: A method for evaluating an orientation of a molecular array having features arranged in a pattern. An image of the molecular array is obtained by scanning the molecular array to determine data signals emanating from discrete positions on a surface of the molecular array. An actual result of a function on pixels of the image which pixels lie in a second pattern, is calculated. This actual result is compared with an expected result which would be obtained if the second pattern had a predetermined orientation on the array. Array orientation can then be evaluated based on the result.

Abstract: A method for determining a response of each probe zone on a test strip is provided. The present invention selects an average pixel value of each section of reference white respectively adjacent to the image of a target line to serve as a reference for determining a color response of the target line. When the color response is not less than a predetermined value, representing the target line has a positive response in response to a specific component of a tested solution tested by the test strip, and the specific component is present in the tested solution. The content of the specific component is proportional to the color response. When the color response is less than a predetermined value, representing the target line has a negative response in response to the specific component of the tested solution, and the specific component is absent in the tested solution.

Abstract: Method and system are disclosed for interactively developing at least one grid pattern, such as a microarray pattern, as well as an array set of such patterns, and a computer-readable storage medium having a program for executing the method given only a few user inputs through the use of a pointing device such as a mouse or trackball on a personal computer or workstation. Each array in the set typically has an identical number of rows and columns of points.

Abstract: A buffer composition, method and kit for hybridizing microarrays of nucleic acids bound to an adsorbed polymer surface of a siliceous substrate provide an envelope of conditions to hybridize nucleic acid targets, while preserving theintactness of the adsorbed polymer surface of the array. The buffer composition comprises a non-chelating buffering agent, a pH within a range of pH 6.4 and 7.5, a monovalent cation having a monovalent cation concentration that ranges from about 0.01 M to about 2.0 M, and optionally relatively lower concentrations of a chelating agent and an ionic surfactant. The total cation concentration of the buffer composition ranges from about 0.02 M to about 2.0 M. The method comprises incubating the targets with the microarray in the buffer composition at a temperature between about 55° C. and 70° C.

Abstract: The invention concerns mass spectrometric analysis of known mutation sites in the genome, such as single nucleotide polymorphisms (SNPs). The invention uses minor amounts of primers with photocleavable linkers, intermixed with a major amounts of primers without linkers, to produce short mutation-containing DNA sequences by enzymatic amplification procedures such as polymerase chain reactions (PCR). After this single amplification procedure, the linker-containing PCR by-products are extracted, washed and photolytically cleaved. Short oligonucleotides are produced which facilitate mass spectrometric analysis. Additionally to the use of linkers, some types of primers may contain blockers which stop the polymerase copying process to achieve even shorter oligonucleotides for analysis.

Abstract: The invention provides a method for reducing background in hybridization reactions of nucleic acids involving at least two homologous probes, wherein at least one of the probes is non-linear, or two homologous target sequences and a non-linear probe. Background is reduced by introducing an intended mismatch with a target sequence in at least one of the probes. The presence of the mismatch reduces the specificity of probes not entirely complementary to a target sequence to such an extent that the background signal is reduced. A set of mixed homologous probes, wherein at least one of the probes is non-linear, comprising such specific mismatch is also provided. The set can be used for the detection of variants of a family of nucleic acids, for instance a number of HIV variants. The invention also provides kits for carrying out the methods according to the invention.

Abstract: A digital image processing-based system and method for quantitatively processing a plurality of nucleic acid species expressed in a microarray are disclosed. The microarray is a grid of a plurality of sub-grids of the nucleic acid species. The system includes a scanner that has a digital scanning sensor that scans the microarray and transmits from an output a digital image of the microarray, and a processor that receives the digital image of the microarray from the scanner and then processes the digital image, identifying each of the microarray's sub-grids. The processor then detects in each of the sub-grids a center-representing pixel of a signal of a chemical material and an approximate radius of the signal. Then, the processor segments the signal and calculates a characterizing measure for the segmented signal.

Abstract: The present invention describes a partial independent component analysis (PICA) technique for blindly separating partially independent and/or gaussian-like sources from mixed observations over an informative index subspace, which allows various applications in independent component imaging. The present invention estimates a demixing matrix using only the independent and/or nongaussian portion of the observations. Specifically, rather than using all the data points which give rise to a large separation error, a subset of the data points is identified such that the partial source profiles defined over such a subset are statistically independent and/or nongaussian. The present invention describes a complete implementation of such a technique, whose steps and parameters may be achieved and estimated using an information theoretic-based neural computational algorithm.

Abstract: Provided are novel methods for the production of nucleic acid libraries having reduced redundancy. Also provided are methods for determination of changes in RNA expression associated with pathological conditions, and physiological or developmental state. Additional aspects provided non-redundant tags or probes produced by the disclosed methods and microarrays incorporating such tags.

Abstract: The present invention relates to a composition comprising a plurality of cDNAs which are differentially expressed in treated human C3A liver cell cultures and which may be used entirely or in part to diagnose, to stage, to treat, or to monitor the progression or treatment of liver disorders such as hyperlipidemia.

Abstract: The present invention provides a method for separation of a particulate matrix from a solution while reducing loss of particles during separation steps. Methods are also disclosed for isolation of molecules of interest using affinity particles or beads, wherein at least one step of the isolation is conducted in the presence of a detergent. The presence of detergent reduces the loss of matrix particles and enhances reproducibility and yield of the molecule of interest. The invention makes possible the manual and automated processing of affinity beads, especially magnetic beads, in multi-well as well as single-well vessels with significantly reduced bead loss, as compared with similar processes conducted in the absence of detergent.

Abstract: Methods of end-labeling ribonucleic acids with non-radioactively labeled ribonucleotides, and particularly fluorescently labeled ribonucleotides, are provided. In the subject methods, a ribonucleic acid is contacted with a non-radioactively labeled ribonucleotide in the presence of a prokaryotic, usually bacterial, poly(A) polymerase under conditions sufficient for covalent bonding of the labeled ribonucleotide to the 3′ end of the ribonucleic acid to occur. Also provided are kits for practicing the subject method. The subject methods and kits find use in a variety of applications where labeling of the 3′ end of a ribonucleic acid with a non-radioactive label, particularly a fluorescent label, is desired.

Abstract: Image analysis methods analyze images of cells and place the cells in particular cell cycle phases based upon certain features extracted from the images. The methods can also quantify the total amount of DNA in a cell based on specific features such as fluorescence intensity from fluorescent molecules that bind to DNA. Further, the methods can characterize a cell as mitotic or interphase based on chosen parameters such as the variance in intensity observed in a cell image and/or the size of a region containing DNA. In one example, image analysis methods can classify the cell into one of the following five phases: G1, S, G2, telophase, and an early stage mitotic phase comprised of prophase, metaphase, and anaphase.

Abstract: A segmentation method of a frame of image information including a plurality of spaced DNA spot images corresponding to a plurality of DNA spots. The image information includes image intensity level information corresponding to said DNA spots. The frame is stored in a memory device and a set of image information within said frame including a selected set of the DNA spot images is selected. A grid including a plurality of spaced grid points corresponding to said selected DNA spot images is generated, such that each grid point includes position information indicating the position of the grid point within said frame.

Abstract: Computer programs, systems and the like related to processing, segmenting and feature normalizing digital images. The images are of cells and the methods are useful for the detection of malignancy-associated changes (MAC) in cells, which can be used for the detection of cancer. The programs and methods detect cancer in one tissue by detecting MAC in another tissue, such as associated tissues or non-associated tissues. Examples of associated tissues include nipple aspirates or ductal washings to detect breast cancer, and sputum or bronchial lavage to detect lung cancer. Examples of non-associated tissues include buccal mucosa to detect lung or breast cancer.

Abstract: A segmentation method of a frame of image information including a plurality of spaced DNA spot images corresponding to a plurality of DNA spots. The image information includes image intensity level information corresponding to said DNA spots. A grid including a plurality of spaced grid points corresponding to selected DNA spot images is generated, such that each grid point includes position information indicating the position of the grid point within said frame. For each DNA spot image: (1) background and signal intensity levels are extracted from image characteristic values for the spot image, and (2) difference values between the background intensity levels and signal intensity levels are determined. For each DNA spot: (1) the corresponding difference values are related a range of graphic values, (2) a graphic value for each difference value is selected; and (3) the selected graphic values are displayed.

Abstract: The invention relates to an image analysis process for measuring the signal on biochips organized into one or several blocks each comprising a large number of spots each composed of at least one probe, the said process being characterized in that it comprises the following steps:

Abstract: A method and system for estimating the background signal over an arbitrarily-sized region of a scanned image of a molecular array, including a background region surrounding the ROI corresponding to the feature. A bit mask is generated, based on a molecular-array, feature-based data set that includes pixel-based intensities and a list of features, including feature coordinates and feature ROI radii, to indicate those pixels in the scanned image of the molecular array corresponding to background, and those pixels in the scanned image of the molecular array corresponding to features and ROIs. An integrated intensity for a background region of arbitrary size and shape can be efficiently determined by selecting pixels within the background region that are indicated to be background pixels in the bit mask.

Abstract: An apparatus and system are provided for simultaneously analyzing a plurality of analytes anchored to microparticles. Microparticles each having a uniform population of a single kind of analyte attached are disposed as a substantially immobilized planar array inside a flow chamber where steps of an analytical process are carried out by delivering a sequence of processing reagents to the microparticles by a fluidic system under microprocessor control. In response to such process steps, an optical signal is generated at the surface of each microparticle which is characteristic of the interaction between the analyte carried by the microparticle and the delivered processing reagent. The plurality of analytes are simultaneously analyzed by collecting and recording images of the optical signals generated by all the microparticles in the planar array. A key feature of the invention is the correlation of the sequence of optical signals generated by each microparticle in the planar array during the analytical process.

Abstract: A method of embodying personal items with DNA fingerprints includes the steps of producing a DNA fingerprint from a raw biological sample provided by a consumer by a service producer, purchasing a personal item by a user, and embodying the DNA fingerprint with the personal item, so that the expensive treasured ornaments can be provided with an unmistakable signature, i.e. the DNA fingerprints, to mark these ornaments for security purpose.

Abstract: The present invention provides an integrated, fully automated, high-throughput system for two-dimensional electrophoresis comprised of gel-making machines, gel processing machines, gel compositions and geometries, gel handling systems, sample preparation systems, software and methods. The system is capable of continuous operation at high-throughput to allow construction of large quantitative data sets.

Abstract: A digital image processing-based system and method are disclosed for quantitatively assessing nucleic acid species expressed in a microarray. The microarray is a grid of a plurality of sub-grids of the nucleic acid species. The system includes a scanner that has a digital scanning sensor that-scans the microarray and transmits from an output a digital image of the microarray, and a computer that receives the digital image of the microarray from the scanner and then processes the digital image, detecting an expression signal of the nucleic acid species, segmenting the expression signal, calculating a measure of the segmented expression signal, and providing the measure at the output of the computer. Prior to segmenting the expression signal for a nucleic acid species, the expression signal is characterized by a center pixel in the digital image and an approximate radius around the center pixel.

Abstract: An area dividing unit 103 divides an ultrasound image into sub-areas in accordance with an initial contour. An evaluation value calculating unit 104 calculates evaluation values on the basis of information which includes, for example, brightness value-related information (e.g. contrast distribution) and position-related information (e.g. a distance from a reference point) of each of the sub-areas, and shape-related information (e.g. presence/absence of an edge). An area selecting unit 106 selects one or more sub-areas according to the calculated evaluation values. An each area processing unit 105 performs image processing appropriate to the selected sub-areas. An image reconstructing unit 107 reconstructs the ultrasound image using the sub-areas for which image processing has been performed.

Abstract: Systems and methods for aligning scanned images are provided. A pattern is included in the scanned image so that when the image is convolved with a filter, a recognizable pattern is generated in the convolved image. The scanned image may then be aligned according to the position of the recognizable pattern in the convolved image. The filter may also act to remove the portions of the scanned image that do not correspond to the pattern in the scanned image.

Abstract: Technology is disclosed for highly accurate automated execution of processing for alignment of a detection area to a DNA microarray image file and processing for quantitative determination of success/failure of the alignment during DNA microarray analysis. A probe reactive chip used for the technology comprises a substrate; a spot area wherein spots for fixing a probe capable of specifically reacting to a sample marked so as to be optically detectable are formed in a matrix on a surface of the substrate; and a reference pattern area, which is arranged within the spot area or approximate to the spot area, and comprises a plurality of different alignment marks in order to correct misalignment of the spot during analysis of the sample on the surface of the substrate.

Abstract: Technology is disclosed for highly accurate automated execution of processing for alignment of a detection area to a DNA microarray image file and processing for quantitative determination of success/failure of the alignment during DNA microarray analysis. A probe reactive chip used for the technology comprises a substrate; a spot region wherein spots for fixing a probe capable of specifically reacting to a sample marked so as to be optically detectable are formed in a matrix on a surface of the substrate; and a reference pattern area, which is arranged within the spot region or approximate to the spot region, and comprises a plurality of different alignment marks in order to correct misalignment of the spot during analysis of the sample on the surface of the substrate.

Abstract: A method for correcting quantitative DNA measurements in a tissue section in which an operator measures, using an image analysis apparatus, the DNA content, profile area, and profile perimeter data for a plurality of nuclei and truncated nuclei in a Feulgen-stained histologic tissue section. The operator then operates a computer program embodying a method of analyzing ploidy measurements in a tissue section. The program includes a routine for obtaining an eccentricity index, which reflects the shape of each of the profiles of the nuclei and truncated nuclei in the tissue section. The program uses the eccentricity index of each nucleus and truncated nucleus to improve the accuracy of the calculation of the DNA content of the whole nuclei that existed in the tissue prior to making the tissue section, and to improve the discrimination of subpopulations of nuclei of different DNA content.

Abstract: High throughput electrophoresis having a plurality of samples migrating through a highly resistive separatory media under an electric field. Multiple electrophoresis runs are conducted using a single separatory media. Automated methods of data analysis yields quantitative and qualitative data using optical densitometer or other detection systems. Controlled operating temperatures and small geometry reduces dispersion inaccuracy in banded data.

Abstract: A physics based model of the absorption of light by histological stains used to measure the amount of one or more stains at locations within tissue is disclosed. The subsequent analysis results in several improvements in the detection of tissue on a slide, improvements to autofocus algorithms so focusing during image acquisition is confined to tissue, improvements to image segmentation and identification of tissued and its features, improvements to the identification of stain where multiple stains are used, and improvements to the quantification of the extent of staining. The invention relates to the application of these improvements to stain detection and quantification to provide for objective comparison between tissues and closer correlation between the presentations of such features and concurrent patterns of gene or protein expression.

Abstract: The invention relates to an optical system for determining the distribution, environment, or activity of fluorescently labeled reporter molecules in cells for the purpose of screening large numbers of compounds for specific biological activity. The invention involves providing cells containing fluorescent reporter molecules in an array of locations and scanning numerous cells in each location with a fluorescent microscope, converting the optical information into digital data, and utilizing the digital data to determine the distribution, environment or activity of the fluorescently labeled reporter molecules in the cells. The array of locations may be an industry standard 96 well or 384 well microtiter plate or a microplate which is a microplate having a cells in a micropaterned array of locations. The invention includes apparatus and computerized method for processing, displaying and storing the data.

Abstract: A method and system for employing pixel-based, signal-intensity data contained within areas of a scanned image of a molecular array corresponding to features and feature backgrounds in order to determine whether or not the features or feature backgrounds have non-uniform signal intensities and are thus outlier features and outlier feature backgrounds. A calculated, estimated variance for the signal intensities within a feature or feature background is compared to a maximum allowable variance calculated for the feature or feature background based on a signal intensity variance model. When the experimental variance is less than or equal to the maximum allowable variance, the feature or feature background is considered to have acceptable signal-intensity uniformity. Otherwise, the feature or feature background is flagged as an outlier feature or outlier feature background.

Abstract: Data traces from four channels of an automated electrophoresis detection apparatus are aligned by identifying peaks in each of the four data traces; optionally normalizing the data traces to achieve a uniform peak height; combining the four data traces in an initial alignment; and determining coefficients of shift and stretch for selected data points within each data trace. The coefficients are determined by optimizing a cost function which reflects the extent of overlap of peaks in the combined normalized data traces to which the coefficients have been applied. The cost function is optimized when the extent of overlap is at a minimum. The coefficients are then used to generate a warp function for each data trace. These warp functions are applied to their respective data traces to produce four warped data traces which are aligned to form an aligned data set. The aligned data set may be displayed on a video screen of a sequencing apparatus, or may be used as the data set for a base-calling process.

Abstract: The present invention includes methods of and devices to create, maintain and take advantage of a cytogenetic database. Particular aspects of the present invention are described in the claims, specification and drawings.

Abstract: Marker compounds suitable for gel electrophoresis are disclosed. The compounds are natural, non-natural compounds or a mixture thereof, but not a protein. The compounds comprise at least one monomer unit, at least one functional group unit and optionally at least one core unit. Also contemplated is a method for positioning the marker compounds or a set of the compounds according to the invention and a method for the detection and/or quantification of s sample molecule in a two-dimensional gel.

Abstract: The invention relates to a set of combinatorially labeled oligonucleotide probes each member thereof: (i) having a predetermined label distinguishable from the label of any other member of said set, and (ii) being capable of specifically hybridizing with a predetermined chromosome or nucleic acid molecule, and to the use of such molecules, alone or in concert with nucleic acid amplification methods.

Abstract: Data acquisition and cataloging are used to classify polypeptides into a reference index or database. The database can be used to identify previously unidentified samples. New polypeptides are characterized and added to the database.

Abstract: A biological sample is scanned with Time-Delay Integration (TDI) by a CCD camera having columns and rows. When the light from a location of the sample falls onto a picture element (pixel) on the camera, the photons of the light are converted to electrons. The electrons within that pixel are shifted down one row to the pixel directly beneath it. The shifts occur in the columnar direction of the camera while the sample is moved synchronously with the electrons. The electrons shifted off the bottom row of the camera are measured and converted into a digital value for that picture element in the sample image.

Abstract: A method is provided for the identification of polymorphic markers in a population. The method includes genotypically characterizing a first sample of a population, selecting one or more individuals of the first sample based upon the genotypic characterization, fabricating a microarray with genomic DNA from each individual selected, and genotyping a second sample of the population using each fabricated microarray as a reference, thereby identifying the polymorphic markers in the population. Also provided is a method for the identification of polymorphic markers in a bacterial population. The method includes phenotypically characterizing a first sample of a population, selecting one or more individuals of the first sample based upon the phenotypic characterization, fabricating a microarray with genomic DNA from each individual selected, and genotyping a second sample of the population using each fabricated microarray as a reference, thereby identifying the polymorphic markers in the population.

Abstract: A Picture Archiving and Communications System (PACS) having multi-level image data processing is provided. The system includes imaging a patient with an imaging modality to generate raw digital image data and then sending the raw image data to an acquisition workstation. The acquisition workstation then performs a first level of image data processing to form partially processed raw image data with regard to a predetermined subset of the set of control parameters to form a partially processed image. The subset of control parameters may comprise frequency control parameters or contrast control parameters, for example. The partially processed image may then be sent to an external connection, stored in a database in the PACS, or sent to a display workstation for a second level of image data processing to complete the image processing and display the image.

Abstract: The optical imaging of two-dimensional solute zone arrays in electrophoresis gels is corrected for nonuniformities in the optical system such as those arising from the light source or from light dispersion underneath the gel. The correction is achieved by the use of a reference plate that responds to a light source uniformly along its length and width by being either uniformly light absorptive or uniformly light transmissive, or by emitting light upon excitation. Thus, any nonuniformities or deviations in the image of the reference plate arise only from nonuniformities or deviations within the optical system. Analogous corrections are made in other two-dimensional assay images, such as microarrays and microtiter plates.

Abstract: A particle image analyzer that facilitates display by designating on a distribution an image desired to be displayed from among a large number of recorded images is disclosed. The particle image analyzer is provided with a parameter computation means for computing at least one characterizing parameter for respective particle images obtained by image capture; a storing means for storing correlations between the particle images and the characterizing parameters with regard to the respective particle images; distribution-diagram generation means for generating characteristic-parameter distribution diagram; designation means for designating the area within the distribution diagram; read-out means for reading out from the memory means particle images corresponding to characterizing parameters within the areas designated by the designation means; and display means for displaying the read-out particle images.

Abstract: The present invention provides a biochip reader for reading the image information of samples using a photodetector device, by irradiating a corresponding beam of excitation light at each site of a biochip on which a plurality of the samples are arranged at equal pitches, the biochip reader comprising: