METHOD FOR AUTOMATED TISSUE ANALYSIS

The invention provides an improved method for identifying and interpreting tissue specimens and/or cells derived from tissue specimens. A panel of cell-based reagents provides a number of readouts of cellular states or biomarkers that together define a profile of a diversity of cellular states or biomarkers in a tissue specimen representing the ‘systems” nature of biology. This cellular profile is interpreted using informatics tools, to identify similarities between specimens, in vivo medical conditions, and suggest options for treating medical conditions. 121-. (canceled)23. The method of claim 22 , wherein the panel of fluorescently labeled reagents is selected from the group consisting of fluorescently labeled antibodies claim 22 , fluorescently labeled peptides claim 22 , fluorescently labeled proteins claim 22 , fluorescently labeled aptamers claim 22 , fluorescently labeled oligonucleotides claim 22 , fluorescently labeled chemicals claim 22 , fluorescent chemicals claim 22 , and a combination thereof.24. The method of claim 22 , wherein at least one biomarker is a nucleic acid biomarker.25. The method of claim 22 , wherein the medical state of the one or more isolated tissue samples is the presence or absence of a disease claim 22 , the presence or absence of a cancer and/or the presence or absence of toxicity.26. The method of claim 25 , wherein the tissue is liver.27. The method of claim 26 , wherein the panel of fluorescently labeled reagents comprises:a) a set of fluorescently labeled reagents specific for at least four hepatocyte biomarkers;b) a set of fluorescently labeled reagents specific for at least four stromal cell biomarkers; i) a set of fluorescently labeled reagents specific for at least three hepatocyte cell biomarkers; and', 'ii) a set of fluorescently labeled reagents specific for at least three stromal cell biomarkers;', 'or, 'c) a combination ofd) a combination thereof.28. The method of claim 27 , wherein the panel of fluorescently labeled ...

Method For Automated Tissue Analysis

The invention provides an improved method for identifying and interpreting tissue specimens and/or cells derived from tissue specimens. A panel of cell-based reagents provides a number of readouts of cellular states or biomarkers that together define a profile of a diversity of cellular states or biomarkers in a tissue specimen representing the ‘systems” nature of biology. This cellular profile is interpreted using informatics tools, to identify similarities between specimens, in vivo medical conditions, and suggest options for treating medical conditions. 1. A method for producing a cellular systems biology profile of one or more tissue samples comprising:a) obtaining at least two sections from one or more tissue samples;b) labeling at least one section with a histological stain, thereby producing a histologically stained section;c) labeling at least one section with a panel of fluorescently labeled reagents, thereby producing a fluorescently labeled section, wherein each fluorescently labeled reagent is specific for a biomarker, and wherein the panel of fluorescently labeled reagents detects at least four different biomarkers, and wherein the detection of a biomarker is a read-out of one or more features of a cellular systems biology profile;d) imaging the histologically stained section with at least a first optical mode, wherein the imaging produces a first set of data;e) imaging the fluorescently labeled section with at least a second optical mode, wherein the imaging produces a second set of data;f) analyzing the first set of data and the second set of data to identify five or more features, wherein at least one feature is identified in each of the first set of data and the second set of data, and wherein the combination of the five or more features generates a cellular systems biology profile of the one or more tissue samples,wherein at least the steps of e) and f) are automated, thereby providing a method for producing a cellular systems biology profile of ...

Spatially co-registered genomic and imaging (scorgi) data elements for fingerprinting microdomains

A method of generating a plurality of spatially co-registered data elements, each spatially co-registered data element being associated with and generated from a pair of co-registered tissue sections obtained from adjacent positions of a core taken from a tissue sample and including an image data section and a genomic data section. The method includes, for each pair of co-registered tissue sections: (i) obtaining and storing as part of a data element a plurality of multi to hyperplexed images from the imaging data section of the co-registered tissue section, (ii) generating and storing as part of the data element image data from the plurality of multi to hyperplexed images, and (iii) generating and storing as part of the data element genomic data from the genomic data section of the associated co-registered tissue section.

A system for cell-based screening

The present invention provides systems, methods, screens, and kits for optic al 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 cel ls 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 t he cells. The array of locations may be an industry standard 96 well or 384 wel l microtiter plate or a microplate which is a microplate having cells in a micropatterned array of locations. The invention includes apparatus and computerized method for processing, displaying and storing the data.

Method for automated tissue analysis

The invention provides an improved method for identifying and interpreting tissue specimens and/or cells derived from tissue specimens. A panel of cell-based reagents provides a number of readouts of cellular states or biomarkers that together define a profile of a diversity of cellular states or biomarkers in a tissue specimen representing the 'systems' nature of biology. This cellular profile is interpreted using informatics tools, to identify similarities between specimens, in vivo medical conditions, and suggest options for treating medical conditions.

A system for cell-based screening

The present invention provides systems, methods, screens, and kits for 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 cells in a micropatterned array of locations. The invention includes apparatus and computerized method for processing, displaying and storing the data.

Miniaturized cell array methods and apparatus for cell-based screening

The present invention devices and methods for maximizing the number of wells that can be imaged at one time while still obtaining adequate pixel resolution in the image. This result has been achieved through the use of fluidic architectures that maximizes well density. The present invention thus provides a miniaturized microplate system with closed fluidic volumes that are internally supplied with fluid exchange, and with wells that are closely spaced to more rapidly detect spatially-resolved features of individual cells.

Method for modeling a disease

The invention described herein provides for methods of profiling cellular models of disease. Cellular systems biology is the investigation of the integrated and interacting networks of genes, proteins, and metabolites that are responsible for normal and abnormal cell functions. Methods and reagents for the profiling a disease state, the treatment of a disease state and assaying of treatments of a disease state are provided.

A system for cell-based screening

The present invention provides systems, methods, and screens for an optic al system analysis of cells to rapidly determine the distribution, environment, or activity of fluorescently labeled reporter molecules in cells for the purpos e 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 numerou s 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 microplate having cells in a micropaterned array of locations. The invention includes apparatu s and computerized method for processing, displaying and storing the data.

Environmental chamber for the analysis of live cells

This invention provides environmental control devices and methods for live cell analysis. The devices of the invention combine a plate space that can hold specimen plates of a variety of sizes, gas flow control, and temperature control of the entire specimen plate.

Method For Predicting Biological Systems Responses

The inventive method employs a “systems biology” approach to predicting biological responses resulting from exposure to the test substance. In one embodiment, the invention provides an automated method for predicting the biological systems effects of a test substance. In another embodiment, the invention provides a method for constructing a knowledgebase (or database) of response profiles for reference substances with known biological systems effects. In another embodiment, the invention provides a set of protocols and software tools used to carry out the profiling. Another embodiment of the invention is a panel of reagents and protocols required for generating response profiles, either to create an knowledgebase, or to use with an existing knowledgebase and informatics software to profile substance physiological effects. Another embodiment of the invention is a database of physiological profiles.

A system for cell-based screening

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 microplate having cells in a micropaterned array of locations. The invention includes apparatus and computerized method for processing, displaying and storing the data.

Miniaturized cell array methods and apparatus for cell-based screening

The present invention devices and methods for maximizing the number of wells that can be imaged at one time while still obtaining adequate pixel resolution in the image. This result has been achieved through the use of fluidic architectures that maximizes well density. The present invention thus provides a miniaturized microplate system with closed fluidic volumes that are internally supplied with fluid exchange, and with wells that are closely spaced to more rapidly detect spatially-resolved features of individual cells.

Method for automated tissue analysis

The invention provides an improved method for identifying and interpreting tissue specimens and/or cells derived from tissue specimens. A panel of cell-based reagents provides a number of readouts of cellular states or biomarkers that together define a profile of a diversity of cellular states or biomarkers in a tissue specimen representing the 'systems" nature of biology. This cellular profile is interpreted using informatics tools, to identify similarities between specimens, in vivo medical conditions, and suggest options for treating medical conditions.

Quantitative systems pharmacology methods for identifying therapeutics for disease states

An example method for quantitative systems pharmacology (QSP) includes analyzing, using a computing device, RNA sequencing (RNA-seq) data for a plurality of patients having a disease. The analysis identifies a plurality of differentially expressed genes (DEGs) and a plurality of differentially enriched biological pathways. Additionally, the method includes deriving, using the computing device, a plurality of gene expression signatures associated with each of a plurality of disease states of the disease using the DEGs and the differentially enriched biological pathways. The method also includes identifying, using the computing device, a plurality of drugs predicted to reverse a particular gene expression signature associated with a particular disease state of the disease. The method further includes prioritizing, using the computing device, the drugs predicted to normalize the particular gene expression signature associated with the particular disease state of the disease for further experimental testing.

Ein system zur zellbasierten reihenuntersuchung

Method and system for general purpose analysis of experimental data

Spatially co-registered genomic and imaging (SCORGI) data elements for fingerprinting microdomains

A method of generating a plurality of spatially co-registered data elements, each spatially co-registered data element being associated with and generated from a pair of co-registered tissue sections obtained from adjacent positions of a core taken from a tissue sample and including an image data section and a genomic data section. The method includes, for each pair of co-registered tissue sections: (i) obtaining and storing as part of a data element a plurality of multi to hyperplexed images from the imaging data section of the co-registered tissue section, (ii) generating and storing as part of the data element image data from the plurality of multi to hyperplexed images, and (iii) generating and storing as part of the data element genomic data from the genomic data section of the associated co-registered tissue section.

An environmental chamber for the analysis of live cells

This invention provides environmental control devices and methods for live cell analysis. The devices of the invention combine a plate space that can hold specimen plates of a variety of sizes, gas flow control, and temperature control of the entire specimen plate.

Spatially co-registered genomic and imaging (scorgi) data elements for fingerprinting microdomains

A method of generating a plurality of spatially co-registered data elements, each spatially co-registered data element being associated with and generated from a pair of co-registered tissue sections obtained from adjacent positions of a core taken from a tissue sample and including an image data section and a genomic data section. The method includes, for each pair of co-registered tissue sections: (i) obtaining and storing as part of a data element a plurality of multi to hyperplexed images from the imaging data section of the co-registered tissue section, (ii) generating and storing as part of the data element image data from the plurality of multi to hyperplexed images, and (iii) generating and storing as part of the data element genomic data from the genomic data section of the associated co-registered tissue section.