Abstract: The invention pertains, at least in part, to a method for determining the structure of an amphiphilic molecule using Self-Similar Microstructure Arrays.

Abstract: There is provided a cell culture evaluation system, a cell culture evaluation method, and a cell culture evaluation program which are capable of estimating and evaluating the lag time or the minimum doubling time and objectively and adequately determining whether or not a cell population is stimulated for proliferation by using an average projected area of a cultured cell population or the rate of increasing the ratio of the non-single-cells as an evaluation parameter when culturing the cells. Images of the cell population to be cultured statically are acquired in a culture vessel, the average projected areas of the cells are calculated from the images for the respective culture times, and the lag times at lag phase are calculated from the calculated average projected areas of the cells.

Abstract: The cell observation device and method aims to easily study the correlation between initial states of cells and their reactions without using a synchronous culture method. For this purpose, the cell observation device includes an image acquisition unit acquiring an image of a specimen including a plurality of cells; a stimulating unit applying a predetermined stimulation to the plural cells; a determining unit determining initial states of the plural cells from the image which is acquired by the image acquisition unit before the stimulating unit applies the stimulation; a finding unit finding reactions of the plural cells to the stimulation, from the image acquired by the image acquisition unit after the stimulating unit applies the stimulation; and a generating unit generating information on correlation between the initial states and the reactions of the plural cells.

Abstract: A method for treating a patient with cancer includes the steps of obtaining cells from a cancerous tumor in the patient. Then there is the step of performing multiple correlated measurements on each cell to obtain cell data for each cell regarding each cell's place in a genetic evolutionary pathway that had occurred in the tumor. Next there is the step of determining from the cell data a likelihood of recurrence of the cancer by minimizing false negatives. A method for treating a patient with cancer. The method includes the steps of obtaining cells from a cancerous tumor in the patient. Then there is the step of obtaining cell data for each cell regarding each cell's place in a genetic evolutionary pathway that had occurred in the tumor. Next there is the step of recognizing distinctive false negative patterns from the cell data. Then there is the step of correlating the false negative patterns to aberrations in mitogenic signaling to determine a likelihood of recurrence of the cancer in the patient.

Abstract: Process of statistic validation of corneal endothelial cells analysed samples”, refers to a process complementary to the conventional process known as cornea specular microscopy, by incorporating information obtained by currently available apparatuses, inferring their statistical, and eventually medical, validity, in order to obtain more accurate diagnosis, and better clinical and/or surgical conducts, in so increasing the quality of this procedure to a new level of medical reliability, with the advantages of avoiding that inadequate exams could be considered as valid ones, contribute to diagnosis accuracy, check validity or infirmity of exams already accomplished, guide the eyes bank in the selection and classification of reliability of donated cornea, make use of equipment currently available in the world to improve their own results, identify exams made with not significant sampling, and demonstrate, in a graphic and in numeric form (statistical-analytical rulers).

Abstract: An automatic classification method for flow cytometry includes characterizing cells or particles as a vector based on at least two-path optical signals generated when the cells or particles pass through an irradiated area one by one, calculating a distance between the effective cells or particles, in which a shorter distance indicates a higher similarity between the two cells or particles, clustering the cells or particles with high similarity into the same class, continuing to cluster similar cells or particles into the same class until the effective cells or particles are clustered into a number L of classes which should be contained in a sample and is determined based on a measuring principle. This method automatically classifies particles accurately and efficiently.

Abstract: A methodology for converting venous blood values to arterial blood values provides the advantage of obviating the need for taking arterial blood samples. The method entails (i) measuring arterial oxygenation, (ii) measuring and estimating values of venous blood acid/base status and oxygenation status of a venous blood sample, and (iii) converting the venous blood values by applying a mathematical model for deriving blood acid/base status and oxygenation status into estimated arterial blood values.

Abstract: The present invention provides methods for the convenient, economical and sensitive assessment of the risk of whether a person will suffer from a thrombotic stroke. The present invention also provides methods for diagnosing or monitoring cerebrovascular thrombosis in a person as well as assessing the degree of severity of a cerebrovascular thrombosis in a person. More specifically, it has been determined that persons at risk of, or has been afflicted with, a cerebrovascular thrombosis have an elevated deposition of C4d on their platelets.

Abstract: A method of classifying cells into subpopulations using cell classifying data is described. The method comprises receiving and analyzing image data to identify object areas in the image data to determine, for at least one selected first cell, one or more measurements. A first parameter set is derived from the measurements for the first cell, the first parameter set comprising at least one of said one or more measurements. The first set of cells are classified into subpopulations, and identified to produce first identifying data. Cell classifying data for use in classifying a second set of cells into subpopulations is derived from the first parameter set and the first identifying data. A second set of cells is classified into subpopulations on the basis of one or more measurements taken for cells in the second set of cells, by use of the cell classifying data. The parameter sets of cells may be represented as vectors in an n-dimensional space.

Abstract: Heterogeneous compound databases can be searched for compounds which are likely to have the same biological activity as a known (query) molecule. Query molecules and the molecules in the database are split into fragments according to common fragmentation rules. Fragments are aligned in a uniform conformation according to a topomeric alignment process and interaction energy fields, typically steric fields, between a probe and the fragment atoms are generated to capture the fragment shapes. Comparison of the fields for the query fragments with the fields for the database compound fragments yields a measure of shape similarity. Searches for similarly shaped substructures and cores can also be readily accomplished. Pharmacophoric style features can be defined for the topomerically aligned fragments but with user specified weighting of the importance of each. Differences in features are defined with the same dimensionality as shape so that both shape and features can be used to search.

Abstract: Most automatic particle classification methods produce errors. The invention provides a method for improving the accuracy of particle classification while shortening the amount of manual review time required from the operator. The method uses class weights, which are statistically-derived correction factors that accounts for frequency of classification errors. A first class weight and a second class weight are assigned to the first class and the second class, respectively. The number of particles in each of the first and the second classes is multiplied by the first class weight and the second class weight, respectively, to generate a corrected number of particles in each of the classes. If particles are reclassified, the class weights are recalculated in response to the reclassification. The method is usable with a complete classification where all the particles in a sample are classified, or a selective classification of a subset of the particles in the sample.

Abstract: Systems and methods for identifying populations of events in a multi-dimensional data set are described. The populations may, for example, be sets or clusters of data representing different white blood cell components in sample processed by a flow cytometer. The methods use a library consisting of one or more one finite mixture models, each model representing multi-dimensional Gaussian probability distributions with a density function for each population of events expected in the data set. The methods further use an expert knowledge set including one or more data transformations and one or more logical statements. The transformations and logical statements encode a priori expectations as to the populations of events in the data set. The methods further use program code by which a computer may operate on the data, a finite mixture model selected from the library, and the expert knowledge set to thereby identify populations of events in the data set.

Abstract: A multi-analyte diagnostic system for use with a computer. The diagnostic system includes a flow analyzer including a co-planar light source-optical detector array, the flow analyzer being communicatable with the computer. The diagnostic system also includes a memory medium readable by the computer and storing computer instructions. The instructions include the following steps. A biological sample is run through the flow analyzer. The identity and quantity of at least one analyte of interest in the biological fluid is determined substantially simultaneously to the sample-running step.

Abstract: The present invention relates to a computer program product or code in memory for detecting and transmitting sensory data from a portable field device 10 to a processor 12 via a computer network 10 for analytic purposes. The product includes a code directed to capturing analyte data pertaining to an unknown analyte using a field device 10. The product further includes a code directed to encoding the captured analyte data and transmitting the encoded analyte data via a computer network 18 to a processor 12 for analysis. The product also includes a code directed to performing an analysis of the captured analyte data at a remote location by the processor 12 using data of known analytes retrieved from an electronic library 14. This code and others can be used with the present invention to perform the functionality described herein as well as others.

Abstract: A tissue microarray imaging system autonomously images, analyzes, and stores data for samples in a tissue microarray. The system may include a tissue microarray, a robotic microscope, and an imaging workstation that executes software to automatically control operation of the microscope to capture images from the microarray and analyze image results. A low magnification may be used to register samples within the microarray and obtain coordinates for each tissue specimen. Progressively higher magnifications may be used to analyze images of each registered specimen. Where multiple dyes are used to stain specimens, color separation techniques may be applied to independently measure and analyze each staining intensity. Images and quantitative data from the images may then be stored in a relational database for subsequent review. The system may be local, or may be Web-based for distributed control and sharing of results.

Abstract: A sample archive method and system implement a plurality of sample carriers configured to support a plurality of sample nodes in a predetermined spatial relationship, sample storage devices for selectively placing the plurality of sample carriers in an archive, and sample node removal apparatus for locating and removing selected ones of the plurality of sample nodes. Alternative embodiments are disclosed wherein the sample node removal apparatus comprises a laser and a mechanical clipping tool, which may be manually operated or automated. An optical component may be operative to detect the location of selected sample carriers in the archive, selected ones of the plurality of sample nodes, or both. A positioning component may position the sample node removal apparatus responsive to signals transmitted by the optical component. Various apparatus and methods of archiving samples and preparing the same for analysis are also disclosed.

Abstract: The present invention provides systems, methods, and screens for an optical system analysis of cells to rapidly determine the distribution, environment, or activity of fluorescently labeled reporter molecules in cells for the purpose of screening large numbers of compounds for those that specifically affect particular biological functions. The invention involves providing cells containing fluorescent reporter molecules in an array of locations and scanning numerous cells in each location with a high magnification fluorescence optical system, 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.

Abstract: A plurality of different kinds of reagents are supported at different positions on a reagent layer. A humoral testing apparatus irradiates measuring light which has a wavelength adapted to one of the plurality of the reagent areas which forms a color, and detects the intensity of the light reflected from the reagent areas with the photodetector with respect to each of the reagents, and thus detects the optical densities of the reagent areas.

Abstract: A blood component collection system with manipulation and optimization capabilities. In one embodiment, process parameters are derived from an input/configured predetermined blood component yield and which is based upon the maximization of at least one process parameter. Thereafter, the blood component collection procedure is performed with these derived process control parameters. In another embodiment, process parameters are derived from an input total procedure time from a maximized value for at least one of the other process control parameters so as to maximize blood component yield in this fixed time. Thereafter, the blood component collection procedure is performed with these derived parameters.

Abstract: A method and apparatus for providing a zero dead time for flow analyzers, flow cytometers, and other measurement devices. A circular buffer is used to store data from a flow analyzer in a plurality of data storage areas, until it is convenient to implement more time-consuming data processing procedures. User specified parameters, including sampling rate and/or sampling period, size and number of data storage areas, size of the circular or other buffer, signal-to-noise threshold, order of processing when a plurality of Digital Signal Processors (DSPs) is used, and fixed trailing distance, are used to provide flexible and convenient operation by a user. The probability of missing a rare event occurring within the laser beam or other light beam of a flow analyzer or other measurement device is reduced to zero.

Abstract: A flow cytometry apparatus and methods to process information incident to particles or cells entrained in a sheath fluid stream allowing assessment, differentiation, assignment, and separation of such particles or cells even at high rates of speed. A first signal processor individually or in combination with at least one additional signal processor for applying compensation transformation on data from a signal. Compensation transformation can involve complex operations on data from at least one signal to compensate for one or numerous operating parameters. Compensated parameters can be returned to the first signal processor for provide information upon which to define and differentiate particles from one another.

Abstract: Fast microbial detection is accomplished by identifying quantities of microorganisms accurately and easily. A cell 5 is placed on a loading portion. A coherent laser beam source 2 emits laser beam to a cell 5. A CCD area image sensor 4 is an array of light sensitive detectors. An image sensor 4 receives light projection image that passes through a cell 5 illuminated by the beam from a laser beam source 2, generating projection image signals on each light sensitive detectors. The projection image data is fed into a computer and analyzed.

Abstract: We disclose quantitative geometrical analysis enabling the measurement of several features of images of tissues including perimeter, area, and other metrics. Automation of feature extraction creates a high throughput capability that enables analysis of serial sections for more accurate measurement of tissue dimensions. Measurement results are input into a relational database where they can be statistically analyzed and compared across studies. As part of the integrated process, results are also imprinted on the images themselves to facilitate auditing of the results. The analysis is fast, repeatable and accurate while allowing the pathologist to control the measurement process.

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: A particle analyzer includes a detecting section for detecting respective characteristic parameters of a plurality of particles, a distribution map preparing section for preparing at least two kinds of two-dimensional frequency distribution maps of the particles by using the detected characteristic parameters, a classifying section for classifying the particles into particle clusters on the two kinds of distribution maps, a calculating section for calculating and comparing the respective numbers of particles in the particle clusters containing particles of common kind to the two kinds of distribution maps, and a judging section for judging a classification error on the distribution maps based on a comparison result.

Abstract: The invention provides a method for a method for determining a best initial focal position estimate for a current sample location on a substrate comprising multiple sample locations, comprising determining the best initial focal position estimate by using a result from one or more techniques selected from the group consisting of linear regression analysis of focal positions determined for at least two other sample locations on the substrate and quadratic regression analysis of focal positions determined for at least three other sample locations on the substrate.

Abstract: Waveform diagrams of cholesterol and triglyceride, for example, obtained by electrophoresis are overlappedly displayed (superimposed). To compare or overlappedly display two waveform diagrams, one unit of absolute concentration is related to one unit of waveform size for normalization. With this method, phenotype classification of lipid can be easily performed. Further, phenotype can also be performed quantitatively and automatically from two waveform diagrams. Thus, a plurality of waveform diagrams of lipid in serum (plasma) obtained by a densitometer or the like can be quantitatively compared.

Abstract: A method and apparatus for examining data from a chemical analyzer for artifactual results. A set of rules are established to identify artifactual results based upon experience with the analyzer. Moreover, each rule can be associated with a sample collection or testing problem which potentially caused the artifactual result. Using these rules, output data from the analyzer can be tested to see if any of the rules are satisfied. If a rule is satisfied, then an artifactual result can be indicated, as well as the potential cause of the artifactual result. An output file can be created which indicates the artifactual data samples and the potential artifactual causes. Preferably, the rules are provided in a user-modifiable data file, so that the rules may be modified based upon additional experience.

Abstract: The present invention provides methods and software for tracking individual cells during a kinetic cell screening assay.

Abstract: An apparatus and method in which a still image, or still images, are obtained of a plurality of particles suspended in a fluid medium. Each still image is transferred to an image analyzing unit that measures a set of dimensional characteristics per particle for particles appearing in the image and determine an occurrence characteristic for particles having a matching set of dimensional characteristics. Preferably, a three dimensional representation of the characteristics is displayed in real time. More preferably, the displayed three-dimensional representation is continuously updated and further entries are accumulated on the display as image analysis is performed. The display provides information to a viewer enabling the viewer to determine a shape distribution of the particles within the suspension even when multiple particle shapes are present.

Abstract: The present invention represents a new approach to data analysis for multivariate classification, particularly as used in medical diagnostics. The invention is in part an intuitive decision making tool for rapid classification of “objects” (e.g., cell, tissue or tumor samples) from evaluation of many simultaneous “variables” (e.g., quantitative gene expression profiles). The data analysis methods of the invention provide the end user with a simplified and robust output for diagnostic classification of objects based on identifying and evaluating multiple variables of predetermined diagnostic relevance. The raw data generated by analysis of the variables is transformed by application or appropriate algorithms to scaleless rank differentials between the variables. The rank orders of variables are used to classify tissues based on readily observable user interfaces, such as a graphical (e.g., visual) user interface or an auditory user interface.

Abstract: Optical detection techniques for the assessment of the physiological state, health and/or viability of biological materials are provided. Biological materials which may be examined using such techniques include cells, tissues, organs and subcellular components. The inventive techniques may be employed in high throughput screening of potential diagnostic and/or therapeutic agents.

Abstract: The present invention is directed to the making of library of conformationally constrained peptides and peptidomimetics including chiral azacrowns for use as conformational templates when complexed with metals for the production of conformationally constrained bioactive peptides for use in elucidation of the binding sites and functional groups on the receptor/peptide ternary complex.

Abstract: A method and an apparatus for inspecting microbes, etc. including, as an apparatus for detecting microbes, etc., a cultivating device, an image taking-in device, and an arithmetic processing unit, in which an image of a medium to be inspected obtained from a sample collected from a substance or a physical solid having proper color microbes or the medium subjected to illumination treatment, dyeing treatment, etc. prior to or after cultivation in accordance with necessity is separated into the three primary colors, or the like, then, chromatic information of histogram, color and hue for each primary color are calculated, and the information thus obtained is compared with integrated data obtained by combining second data of generic information of microbes, etc. with first data of microbes, etc.

Abstract: A signal processing operator successfully expands the dynamic range of a histogram of digital data, such as that representative of biological cell populations, including human blood cells subjected to flow cytometry processing, without introducing binning artifacts into the transformed data. The inventive data mapping scheme effectively preserves statistical probability distribution characteristics of the original data, that would otherwise be removed or lost in the course of expanding the dynamic range of a quantized histogram data set through the use of a conventional log transformation. Filtering is unnecessary, as the binning effect is countered early in the process, to preserve statistical properties of the cell populations under study.

Abstract: A reproduction method and system supports rapid convergence of a genetic optimization process. Mating, mutation, or both may be combined with biased parent selection during each mating season.

Abstract: The present invention provides a method for analyzing a process based on displaying data to a user from a plurality of different sources and a machine-readable medium for implementing such a method. The present invention also provides a mapping system and a method for displaying data to a user employing a hierarchy including data nodes and data leaves.

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: In this invention, a measurement of cell permeability is determined by obtaining a measure of the volume of fluid which crosses a sample cell membrane in response to an altered environment. A lytic agent may be used to drive fluid across the cell membranes and thereby cause a change in cell volume. An alteration in osmolality of a sample suspension is preferred, in which the sample suspension is subjected to a continuous osmotic gradient.

Abstract: A method and apparatus for providing a zero dead time for flow analyzers, flow cytometers, and other measurement devices. A circular buffer is used to store data from a flow analyzer in a plurality of data storage areas, until it is convenient to implement more time consuming data processing procedures. User specified parameters, including sampling rate and/or sampling period, size and number of data storage areas, size of the circular or other buffer, signal-to-noise threshold, order of processing when a plurality of Digital Signal Processors (DSPs) is used, and fixed trailing distance, are used to provide flexible and convenient operation by a user. The probability of missing a rare event occurring within the laser beam or other light beam of a flow analyzer or other measurement device is reduced to zero.

Abstract: The recovery of the sequence of bases in a dideoxyribonucleic acid (DNA) molecule is important for both research and medical applications. The standard processing techniques are prone to error. This invention creates from the template a new set of molecules which introduce an error correcting code as might be used in data communications. After the usual processing associated with DNA sequencing, the code can be used to reduce the errors in the estimated sequence.

Abstract: According to the present invention, computer based techniques for using information technology in therapeutics or drug discovery. In an exemplary embodiment, computer based techniques for determining information about the properties of substances based upon information about structure of living or non-living cells exposed to substances are provided. Computer software according to the present invention enables researchers and/or scientists to identify promising candidates in the search for new and better medicines or treatments using, for example, a cellular informatics database.

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: Methods and apparatus are described for enhancing operator independent image cytometry. Aspects of the invention include enhanced tissue surface tracking which can detect both tissue surfaces. The surface detection can aid cytometry, such as by reducing the amount of image data to be stored. Segmentation is described for 3D images in which 3D least squares filtering is applied to increase contrast for simplifying the delineation of objects from backgrounds. A method of creating 3D FIR image filters based on ideal objects is also described. A data structure is defined by which 3D object data may be organized for image representations if samples. Methods of performing remote segmentation processing are also described toward centralizing the necessary processor power and applications and reducing the burden on researchers and clinicians.

Abstract: In connection with a fluidic medical diagnostic device that permits measurement of the coagulation time of blood, software, methods and associated devices for quality control are disclosed. The fluidic device preferably comprises a test strip with one end having a sample port for introducing a sample and a bladder at the other end for drawing the sample to a measurement area. A channel carries sample from the sample port to an assay measurement area and first and second control measurement areas. Preferably a stop junction, between the measurement areas and bladder, halts the sample flow for measurement. If results from measurements taken for each control fall within a predetermined zone or defined limits, the assay measurement is qualified. If not, an error is registered and the test strip is counted as unfit.

Abstract: In connection with a fluidic medical diagnostic device that permits measurement of the coagulation time of blood, software, methods and associated devices for quality control are disclosed. The fluidic device preferably comprises a test strip with one end having a sample port for introducing a sample and a bladder at the other end for drawing the sample to a measurement area. A channel carries sample from the sample port to an assay measurement area and first and second control measurement areas. Preferably a stop junction, between the measurement areas and bladder, halts the sample flow for measurement. If results from measurements taken for each control fall within a predetermined zone or defined limits, the assay measurement is qualified. If not, an error is registered and the test strip is counted as unfit.

Abstract: A single-laser flow cytometric method for the enumeration of micronucleated erythrocyte populations is disclosed which affords superior fluorescent resolution of young reticulocytes from normochromatic erythrocytes, particularly in mammals that exhibit efficient splenic sequestering.

Abstract: A multi-analyte diagnostic system for use with a computer. The diagnostic system includes a flow analyzer including a co-planar light source-optical detector array, the flow analyzer being communicatable with the computer. The diagnostic system also includes a memory medium readable by the computer and storing computer instructions. The instructions include the following steps. A biological sample is run through the flow analyzer. The identity and quantity of at least one analyte of interest in the biological fluid is determined substantially simultaneously to the sample-running step.

Abstract: A method of performing an assay to detect and quantify changes in morphology or intracellular events in living or dead cells. The method comprises the step of presenting the cells on a surface for analysis in a single sample or array of samples and providing a means of fluorescently labelling cell structures, engulfed or associated particles or molecules contained on or within the cells. The cells are scanned with a detection system to obtain a linearseries of intensity values at intervals of 10 microns or less across each cell to produce line amplitude data in at least one emission band. A threshold algorithm is applied to determine the beginning and end of each feature on the line amplitude data, whereina feature is any perturbation from a determined background signal.

Abstract: Systems for recommending an optimal treatment protocol for a specific individual are disclosed. The systems comprise generally a system model, a plurality of treatment protocols, a system model modifier, wherein said system model is modified by the system model modifier based on parameters specific to the individual; and a selector to select an optimal treatment protocol from said plurality of treatment protocols based on the modified system model. Systems embodying the above techniques but for a general patient are also disclosed. Systems for a general patient and an individual for various specific diseases are disclosed. Methods and computer program products embodying the above techniques are also disclosed.