Abstract: An apparatus and method for imaging metallic nanoparticles is provided. Preferably, the invention provides for an apparatus and method for detection of gold colloid particles and for accurate reporting to the operator. The apparatus includes a substrate holder for holding the substrate, a processor and memory device, an imaging module, an illumination module, a power module, an input module, and an output module. The apparatus may have a stationary substrate holder and imaging module which are proximate to one another. The apparatus provided for a compact sized system without the need for complex motorized devices to move the camera across the substrate. Further, the apparatus and method provide for automatic detection of the spots/wells on the substrate, automatic quantification of the spots on the substrate, and automatic interpretation of the spots based on decision statistics.

Abstract: An apparatus and method acquires and stores multiple resolution images from a specimen on a support and provides to the user a low magnification, reconstructed macro image of the entire specimen, or a large portion thereof, to aid the person in selecting points of interest to be viewed or analyzed at higher magnifications and resolution. The reconstructed image is formed of a large number of tiled, stored images which are coordinated and assembled to form the macro image of the specimen which is displayed on a monitor. Preferably, the stored, reconstructed image is reduced further in size by a software system before it is displayed to the user. The display may be on a local monitor over a local area network or sent over the Internet to the user who is typically a pathologist. The user selects by a marker such as a cursor the defined area of interest or region and then views higher magnification images or has them analyzed.

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: Provided is a method for sequencing DNA, which comprises: (a) obtaining a target DNA population comprising one or more single-stranded DNAs to be sequenced, each of which is present in a unique amount and bears a primer to provide a double-stranded portion of the DNA for ligation thereto; (b) contacting the DNA population with an array of hybridisation probes, each probe comprising a label cleavably attached to a known base sequence of predetermined length, the array containing all possible base sequences of that predetermined length; (c) removing all unligated probes; followed by the steps of: (d) cleaving the ligated probes to release each label; (e) recording the quantity of each label; and (f) activating the extended double-stranded portion to enable ligation thereto; wherein (g) steps (b) to (f) are repeated in a cycle for a sufficient number of times to determine the sequence of the or each single-stranded DNA by determining the sequence of release of each label.

Abstract: Disclosed is a biochip image analysis system which comprises an image storage unit for storing images including an original image of a biochip comprising a set of specific genes expressed in different environments by fluorescent bases of different colors; an image converter for converting the original image into a test image, forming an overlapped image and a color image, and storing the images in the image storage unit; an edge detector for separating the spot-formed genes from the test image, generating spot and background templates, and detecting an edge to measure expression degrees of the genes; a data processor for generating statistical data using the spot and background templates, and performing luminance correction; and a data storage unit for storing the statistical data.

Abstract: Computer programs and computer-implemented methods implement techniques for evaluating experimental data from a library of materials. The techniques receive a plurality of images of a library of materials that includes an array of members associated with locations in the library. User input identifying a plurality of regions of interest is received. A series of reduced data values is determined for one or more of the regions of interest as a statistical function of a plurality of pixel values for pixels in the corresponding regions. A figure of merit is calculated from one or more of the series of reduced data values for a library member at the corresponding library location. The regions of interest include a plurality of pixels in the images and correspond to locations in the library.

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: A method for analysis of DNA data. A DNA source image is generated based on the DNA data. A digital bit-map is created from the DNA source image plotting image intensity data against a two-dimensional coordinate system from an initial viewpoint. An image model is generated based on the digital bit-map. The image model comprises model data representing the image intensity data as virtual points on a three-dimensional coordinate system further incorporating the the two-dimensional coordinate system of the digital bit map. A DNA analysis image is generated based on the image model. The DNA analysis image represents the model data from an analysis viewpoint with respect to the two-dimensional coordinate system. The analysis viewpoint differs from the initial viewpoint. The DNA analysis image is then displayed.

Abstract: A biochip image analysis system comprises an image storage unit storing image information including an original image of the biochip including genes extracted from experimental and control groups' samples tagged by fluorescent dyes of different colors; an image converter converting the original image into a test image, generating an overlapped image and a color image; an edge detector separating spots of the test image into segments and detecting edges from spot and background areas to measure expression degrees of genes; a blob detector detecting blobs from the spot and background areas to generate a blob template; a blob remover generating a spot template and a background template; a data processor calculating statistical data and correcting intensity; and a data storage unit storing the data.

Abstract: The present invention relates to methods and compositions for analyzing nucleic acids, and in particular, methods and compositions for detection and characterization of nucleic acid sequences and sequence changes. The present invention also provides methods and compositions for identifying oligonucleotides with desired hybridization properties to nucleic acid targets containing secondary structure.

Abstract: The method for repetitively determining a profile of quantitative features for different cells in a sample by collecting and analyzing information on the mass distribution in cells or portions of cells and comparing the collected information to values from a relational database is disclosed.

Abstract: A method for determining relative incidence of a binding substance within two biological samples is provided. The two samples are labeled with luminescent materials having different chromatic properties. An image of the luminescent materials upon a binding site of a microarray is analyzed as two clusters of data points scattered about respective representative pairs of chromatic intensity values. The relative incidence of the binding substance is determined as a ratio of differences between corresponding indices of the representative pairs.

Abstract: Methods for correcting systematic errors in the measured position of deposited features of a nucleic acid array on a substrate. Systematic errors are modeled by an algorithmic model based on measuring the positions (and possibly other properties) of a subset of the features, and a model is constructed for predicting deviations in feature position from an ideal grid. Deviations arising in the deposition process, the scanning process, or both may be corrected.

Abstract: The system can be used for the automatic analysis of images, including a matrix of spots, such as images of DNA microarrays after hybridization. The system can be associated—and preferably integrated in a single monolithic component implementing VLSI CMOS technology—to a sensor for acquiring the images. The system includes a circuit for processing the signals corresponding to the images, configured according to a cellular neural network (CNN) architecture for the parallel analogue processing of signals.

Abstract: Disclosed are methods for determining the presence or absence of a target nucleic acid (e.g. DNA) sequence in a sample nucleic acid, the method comprising: (a) exposing the sample to a detection agent comprising a colloid metal surface associated with a SER(R)S active species (SAS) such as an azo dye and with a target binding species (TBS) which may be PNA which is complementary to the target, and (b) observing the sample agent mixture using SER(R)S to detect any surface enhancement of the label wherein the binding of the TBS to the target sequence causes surface enhancement SAS.

Abstract: The present invention relates to a method for typing a sample of a prion or spongiform encephalopathy disease, a kit suitable for use in such a typing method, a method for identifying infection in an animal and/or tissue of bovine spongiform encephalopathy (BSE), a method for assessing and/or predicting the susceptibility of an animal to BSE, a kit for use in such an assessment and/or prediction method, a method for the treatment of a prion disease, and compounds suitable for such a method.

Abstract: A method of detecting a mutation or a difference of one or more nucleotides between a nucleic acid molecule to be tested and a reference nucleic acid molecule, said method comprising subjecting the test nucleic acid molecule to base specific cleavage to generate oligonucleotide fragments, separating the resulting oligonucleotide fragments based on mass by MALDI-ATOF MS and/or other equivalent procedure to produce a fingerprint of then oligonucleotide fragments comprising one or more peaks wherein a peak represents the mass of each fragment and identifying an altered peak relative to a reference nucleic acid molecule subjected to the same procedure wherein the presence of an altered peak is indicative of a difference of one or more nucleotides in said tested nucleic acid molecule.

Abstract: Methods, systems, and computer program products for estimating the location of a probe cell in an image of a high-density microarray DNA chip interrogate a plurality of different closely spaced estimated locations to identify the most likely estimated location of the probe cell in the image.

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: 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: This invention provides in vitro processes for producing copies of specific nucleic acids using protein-nucleic acid constructs which are part of conjugates which are introduced into cells. Illustrative of the elements useful in these constructs for producing copies of specific nucleic acids are promoters, sequences coding for proteins or providing templates for transcription, and RNA polymerases.

Abstract: An apparatus for assaying specific binding of a probe to a target, includes: a sample support; a light source; an optical train; a light detector; an electricity source; an electrical property detector; and a data analysis device adapted to: (a) compare an optical determination of binding with an electrical determination of binding, or (b) compare a pre-electrification determination of binding with a post-electrification determination of binding.

Abstract: The present invention relates to an oligonucleotide having a novel structure and a method of synthesizing nucleic acid by using the same as a primer. This oligonucleotide is provided at the 5?-side of the primer with a nucleotide sequence substantially the same as a region synthesized with this primer as the origin of synthesis. The present invention realizes synthesis of nucleic acid based on an isothermal reaction with a simple constitution of reagents. Further, the present invention provides a method of synthesizing highly specific nucleic acid on the basis of this method of synthesizing nucleic acid.

Abstract: The present invention describes a method for separating or partially separating heteroduplex and homoduplex DNA molecules in a mixture. In the method, the mixture is applied to an anion-exchange chromatography medium. The heteroduplex and homoduplex molecules are eluted with a mobile phase containing an eluting salt, including an anion and a cation, a buffer, and preferably including an organic solvent. The eluting is carried out under conditions effective to at least partially denature the heteroduplexes (e.g., thermal or chemical denaturing) resulting in the separation of the heteroduplexes from the homoduplexes. The method has many applications including, but not limited to, detecting mutations and comparative DNA sequencing.

Abstract: The invention features a method for multiplexed analysis of a plurality of target nucleic acid sequences in a sample. The method provides a derivative nucleic acid for each target sequence analyzed and present in the sample.

Abstract: Systems, methods, and computer program products are described for aligning multiple images of arrays of biological materials. One method includes aligning a grid with a first image, generating grid alignment data based on the alignment of the grid with the first image, storing the grid alignment data in memory, retrieving the grid alignment data responsive to an indication to align a second image, and analyzing the second image based on the retrieved grid alignment data. In some implementations, the first image and second images are generated by scanning the same array of biological materials. The array may be a spotted array, a synthesized array, or other type of parallel biological assay.

Abstract: A method of inhibiting the self-splicing of a Group I intron is disclosed. The method uses an oligonucleotide having a sequence essentially identical to a guide sequence found in the 5? flanking exon and terminates with a 3? ribonucleoside. Usually the oligonucleotide has N3??P5? phosphoramidate or N3??P5? thiophiosphoramidate linkages rather than phosphodiester linkages. A method of inhibiting the growth of organisms having Group I intron, particularly certain pathogenic fungi including P. carinii, C. albicans, and A. nidulans using the oglionucleotide is also provided.

Abstract: Interpreting data obtained by analysis of nucleic acids (DNA) by obtaining nucleic acid data in a spatial domain, transforming the nucleic acid data from the spatial domain into a frequency domain, and obtaining sequence data of the nucleic acid data by executing a data mining process on the transformed nucleic acid data. The transformation may be performed by a Hadamard transform, a Fourier transform or a Wavelet transform to obtain frequency coefficients, with less than all of the frequency coefficients being utilized in the data mining process. In addition, the frequency domain data may be normalized prior to the data mining process. The data mining process may be subjecting the frequency coefficients to a connectionist (neural network) algorithm or to a classification tree/rule induction (CART) algorithm.

Abstract: In various embodiments, the methods for analyzing a sample are provided utilizing a result dependent acquisition strategy. In various embodiments, methods for analyzing a sample are provided wherein the sample is first analyzed by MALDI and MS to produce a first result that is then used to determine a second analysis that is used to analyze the sample again by MALDI and MS/MS or MSn to produce a second result.

Abstract: Combinatorially-synthesized deoxyribonucleic acid (DNA) oligonucleotides attached to encoded beads that are hybridized to amplified and labeled genomic DNA or ribonucleic acid (RNA) are analyzed using a flow imaging system. Oligonucleotides and corresponding reporters are bound to the surfaces of a plurality of small beads such that different beads bear different oligo sequences. Each bead bears a unique optical signature comprising a predefined number of unique reporters, where each reporter comprises a predefined combination of different fluorochromes. The composite spectral signature in turn identifies the unique nucleotide sequence of its attached oligo chains. This optical signature is rapidly decoded using an imaging system to discriminate the different reporters attached to each bead in a flow in regard to color and spatial position on the bead.

Abstract: The present invention aims at easy and efficient selection of bands present on a lane. A region 502 is set on a display of a lane 503 having a plurality of bands 504 to 508, based on an input cursor 501 of a pointing unit. The bands 506 to 508 within the region 502 are displayed to be in a selection candidate state. The size of the region 502 may be altered by an input of a predetermined key of a keyboard. Along with the size alteration of the region 502, bands to be displayed in the selection candidate state also change. By selecting with the mouse button, a band of interest is accurately selected from the bands in the selection candidate state.

Abstract: The present invention provides a 4D biochip containing m 3D biochips having n capillaries, wherein the n capillaries each contain a biological factor, and methods for preparing and using the 4D biochip to provide rapid, efficient assays of large quantities of samples and/or factors.

Abstract: Methods for correlating genes and gene function are provided. Such methods generally involve selecting a candidate gene that appears to be correlated with a particular cellular state or activity and then validating the role of the candidate gene in establishment of such a cellular state or activity. Certain methods utilize RNA interference techniques in the validation process.

Abstract: The present invention relates to a process for labeling a synthetic or natural ribonucleic acid (RNA). It also relates to RNA fragments, which have been labeled by fragmenting the RNA to free a terminal phosphate of each fragment for further reaction, and labeling each fragment at the freed terminal phosphate which is located at the 3? end and/or the 5? end of each fragment of the RNA, and to the use of such RNA fragments, for example, in the field of medical diagnosis.

Abstract: A procedure for the release and isolation of nucleic acids from biological compartments of a sample always uses an instrument that can hold one or more sample processsing vessels, maintain the sample processing vessels at a constant temperature, shake the sample processing vessels and separate magnetic particles by means of magnetic force. This system greatly simplifies the isolation of nucleic acids.

Abstract: The present invention is directed to methods, compositions, kits and apparatus to identify and detect the presence or absence of target analytes. The embodiments of the present invention have utility in medical diagnosis and analysis of various chemical compounds in specimens and samples, as well as the design of test kits and apparatus for implementing such methods.

Abstract: Certain transcription factors (enhancer binding proteins) significantly increase transcription rates from genes by nicking a single DNA strand in the vicinity of their DNA binding sites, thereby allowing RNA polymerase to gain access to the transcribed DNA strand by a process of “threading”. DNA template nicking is a detectable and quantifiable byproduct indicative of transcriptional activation that can be used to design practical assays. These assays are used to determine which transcription factors (enhancer binding proteins) are actively catalyzing the transcription of a gene in any cell type, or in any cell in response to any drug or treatment. This group of transcription factors have a predictable molecular biological activity in addition to transcription activation, namely site-specific DNA strand cleavage.

Abstract: An image processing system and method visually documents and displays changes between historical and later mammographic images, preferably in three dimensions. A composite image is created which visually emphasizes temporal differences between the historical and later images. Preferably three-dimensional, digitized images, displayable in various projections, are stored for archival purposes on computer readable media. An image processor preferably exploits an optical correlator to register the historical and later images accurately and provide correlation values as temporal scalars of the differences. The registered images are then compared, voxel-by-voxel, to detect temporal differences. The composite image is displayed with synthetic colors or other visual clues to emphasize apparent changes (for example, tumor growth or shrinkage).

Abstract: Methods for screening for agonists and antagonists of GPI-anchored independent intracellular signaling resulting in [Ca2+]i elevation, ERK1, ERK2 and CREB phosphorylation, and Src family kinase activation are described, as well as methods for treatment involving administration of agonists/antagonists of such signaling.

Abstract: A method is disclosed for rapid molecular profiling of tissue or other cellular specimens by placing a donor specimen in an assigned location in a recipient array, providing copies of the array, and performing a different biological analysis of each copy. The results of the different biological analyses are compared to determine if there are correlations between the results of the different biological analyses at each assigned location. In some embodiments, the specimens may be tissue specimens from different tumors, which are subjected to multiple parallel molecular (including genetic and immunological) analyses. The results of the parallel analyses are then used to detect common molecular characteristics of the genetic disorder type, which can subsequently be used in the diagnosis or treatment of the disease.

Abstract: A method for isolating and purifying nucleic acids with an improved recovery yield is provided. A mixed solution containing the nucleic acids, salts, and an organic solvent is contacted with an adsorption support to cause the nucleic acids to be adsorbed on the support. Then, the nucleic acids are desorbed from the support using an elution buffer. At least one compound containing 2 to 10 carbon atoms as selected from the group consisting of aliphatic ether, aliphatic ester, and aliphatic ketone is used as the organic solvent. The method improves the yield of nucleic acids collection, is easy to implement and less susceptible to contamination.

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: The present invention provides methods and systems to facilitate pattern recognition in complex biological data using component plane presentations of clustered data.

Abstract: The present invention provides methods for modulating cell death in a eukaryotic cell, and methods for reducing DNA damage in a eukaryotic cell. The methods generally comprise modulating a biological activity of DNA-PK in a cell. The invention further provides methods of treating a condition related to cell death in an individual. The invention further provides methods of identifying agents which modulate a biological activity of DNA-PK, as well as agents identified by the methods. Methods of modulating an immune response using an identified agent are also provided.

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 process for detecting a complementary DNA fragment is performed utilizing a DNA micro-array, a radiation image storage panel containing a stimulable phosphor, and a spacer sheet having plural openings.

Abstract: Expression profiling using DNA microarrays is an important new method for analyzing cellular physiology. In “spotted” microarrays, fluorescently labeled cDNA from experimental and control cells is hybridized to arrayed target DNA and the arrays imaged at two or more wavelengths. Statistical analysis is performed on microarray images and show that non-additive background, high intensity fluctuations across spots, and fabrication artifacts interfere with the accurate determination of intensity information. The probability density distributions generated by pixel-by-pixel analysis of images can be used to measure the precision with which spot intensities are determined. Simple weighting schemes based on these probability distributions are effective in improving significantly the quality of microarray data as it accumulates in a multi-experiment database. Error estimates from image-based metrics should be one component in an explicitly probabilistic scheme for the analysis of DNA microarray data.

Abstract: A medical image storage system is provided that integrates a clinical information system with a medical image management system. Such an integrated system can be used in a method that uses clinical information associated with a medical image to determine when and where the medical image should be stored. Because the probability of a medical image being accessed is generally governed by the diagnostic significance of the image, this integrated system provides more efficient storage of medical images as compared to conventional systems that operate independently of diagnostic information.

Abstract: The present invention relates to a gene examining apparatus utilizing a computer, the apparatus comprising (1) DNA microarrays in each of which a large number of fine liquid accommodating sections are two-dimensionally arranged so that openings of the fine liquid accommodating sections are located on the same plane, in which each of the liquid accommodating sections can three-dimensionally accommodate a liquid, and in which hybridization reaction occurs in the liquid accommodating section between a target nucleic acid already labeled with an optical marker substance and the nucleic acid probe, and (2) a microscope comprising a stage supporting the DNA microarrays set forth in (1), a temperature regulating section that regulates the temperature of each DNA microarray, and imaging means for picking up an image of an optical signal from the DNA microarray.

Abstract: In a microarray image analysis system, when one of a plurality of statuses is set for a spot of a microarray by the user, the status of a similar spot is automatically determined.