Disclosed herein are detectable moieties and detectable conjugates comprising one or more detectable moieties. In some embodiments, the disclosed detectable moieties have a narrow wavelength and are suitable for multiplexing. Also disclosed are methods of labeling one or more targets within a biological specimen using any of the detectable conjugates and/or detectable moieties described herein.
C07D 209/10 - Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
C07D 279/18 - [b, e]-condensed with two six-membered rings
C07D 311/16 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 491/22 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or in which the condensed system contains four or more hetero rings
Methods and compositions for accurate identification of Parkinson's disease are disclosed. More particularly, the disclosure is directed to the determination of Parkinson's disease in ante-mortem tissue samples.
The present disclosure relates to acid fast staining compositions which are free from phenol. The present disclosure also related to a method of detecting an acid fast organism in a biological sample comprising: (a) applying an acid fast staining composition to the biological sample, the acid fast staining solution comprising a fuchsin, a base, a surfactant, and an alcohol, and wherein the acid fast staining composition is free from phenol; and (b) incubating the biological sample with the acid fast staining composition for a predetermined amount of time at a predetermined temperature.
C12Q 1/04 - Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
The present disclosure provides stabilized hematoxylin formulations having a pH of less than 2.4. The present disclosure also provides methods of using such stabilized hematoxylin formulations to stain biological samples.
The present disclosure is directed to epitope-tagged antibodies, as well as methods of employing the epitope-tagged antibodies for detecting one or more targets in a biological sample, e.g. a tissue sample.
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
6.
IMPROVED IMAGE ANALYSIS ALGORITHMS USING CONTROL SLIDES
Systems and methods for automatically excluding artifacts from an analysis of a biological specimen image are disclosed. An exemplary method includes obtaining an immunohistochemistry (IHC) image and a control image, determining whether the control image includes one or more artifacts, upon a determination that the control image includes one or more artifacts, identifying one or more artifact regions within the IHC image by mapping the one or more artifacts from the control image to the IHC image, and performing image analysis of the IHC image where any identified artifact regions are excluded from the image analysis.
A system and method for dispense characterization is disclosed. According to particular embodiments of the dispense characterization system and method, volumes of dispensed liquids can be determined. In more particular embodiments, additional characteristics and combinations of characteristics of a liquid dispensing event can be determined. Examples of additional characteristics that can be determined include the shape of the dispensing event, the velocity of the dispensing event, and the trajectory of the dispensing event. The dispense characterization system and method can be employed in automated biological sample analysis systems, and are particularly suited for monitoring liquid reagent dispensing events that deliver liquid reagents to a surface of a microscope slide holding a biological sample.
Systems and methods for selecting therapeutic agents for cancers using next generation sequencing, automated dissection, and/or automated slide stainers are disclosed. Non-responsive regions of a tumor sample having a heterogenous staining pattern for a predictive biomarker are excised using an automated dissection tool. Mutations linked to additional predictive biomarkers are identified in the excised portion of the sample by next generation sequencing. The relevance of the additional predictive biomarker(s) is confirmed by histochemical staining. Therapeutic courses may then be selected on the basis of the staining patterns of the predictive biomarkers.
In one aspect of the present disclosure is a targeted sequencing workflow where an input sample comprising a sufficient quantity of genomic material is provided such minimal or no amplification cycles are utilized prior to sequencing.
A real time assay monitoring system and method can be used to monitor reagent volume in assays for fluid replenishment control, monitor assays in real-time to obtain quality control information, monitor assays in real-time during development to detect saturation levels that can be used to shorten assay time, and provide assay results before the assay is complete enabling reflex testing to begin automatically. The monitoring system can include a real time imaging system with a camera and lights to capture images of the assay. The captured images can then be used to monitor and control the quality of the staining process in an assay, provide early assay results, and/or to measure the on-site reagent volume within the assay.
A real time assay monitoring system and method can be used to monitor reagent volume in assays for fluid replenishment control, monitor assays in real-time to obtain quality control information, monitor assays in real-time during development to detect saturation levels that can be used to shorten assay time, and provide assay results before the assay is complete enabling reflex testing to begin automatically. The monitoring system can include a real time imaging system with a camera and lights to capture images of the assay. The captured images can then be used to monitor and control the quality of the staining process in an assay, provide early assay results, and/or to measure the on-site reagent volume within the assay.
G01N 21/78 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
Systems and methods for unmixing of multichannel image data in the presence of locally varying image characteristics. Feature images created from a multi-channel input image form a feature vector for each pixel in the input image. Feature vectors are classified based on the local image characteristics, and areas are formed in the input image that share local image characteristics. Each area is unmixed separately using reference vectors that were obtained from regions in example images that have the same image characteristics. The unmixing results are combined to form a final unmixing result image created from the individually unmixed image areas.
G06V 10/56 - Extraction of image or video features relating to colour
G16H 30/40 - ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
G06V 10/764 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using classification, e.g. of video objects
G06V 10/77 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using data integration or data reduction, e.g. principal component analysis [PCA] or independent component analysis [ICA] or self-organising maps [SOM]; Blind source separation
13.
AN IMAGE SCANNING APPARATUS AND METHODS OF OPERATING AN IMAGE SCANNING APPARATUS
Image scanning apparatus and method of operating an image scanning apparatus, the image scanning apparatus including a line scan detector and being configured to image a surface of an object mounted in the image scanning apparatus in a plurality of swathes, wherein each swathe is formed by a group of scan lines, each scan line being acquired using the scan line detector from a respective elongate region of the surface of the object extending in a scan width direction, wherein each group of scan lines is acquired whilst the object is moved relative to the scan line detector in a scan length direction.
A system for applying a fluid to a substrate (1) bearing a sample for analysis (3) has an array of sensor plates (19a, 19b) positioned to sense the presence of fluid in contact with respective areas of the substrate. In a particular embodiment, fluid presence in different areas of the substrate is sensed by the effect of the fluid and its identity on the impedances of capacitors formed between sensor plates within the array. In a more particular embodiment, by polling the sensor array continually while fluid is applied to the substrate determine a coverage map, a fluid dispensing mechanism can be controlled to efficiently cover the entire substrate with fluid a minimal amount of fluid, thereby reducing waste.
The present disclosure is directed to multiplex assays, kits and methods, including automated methods, for identifying PD-L1 positive immune cells, PD-L1 positive tumor cells, and PD-L1 negative immune cells within a tissue sample.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
G01N 33/569 - Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
16.
COMPUTER-IMPLEMENTED COMPOSITE TISSUE IMAGE WITH REAL-TIME ADJUSTABLE INTERFACE
The disclosure relates to devices, systems and methods for generating a digital image of a tissue section that is a composite of two or more source digital images of adjacent tissue sections and which may have a real-time adjustable boundary between different source images. The devices include computer software products for a fused-view visualization tool which permits one or more of generating and displaying the composite image and modifying the location of one or more boundaries between source images comprising the composite image. The systems include computer-implemented systems such as work stations and networked computers for analyzing tissue samples using the fused-view visualization tool. The methods include processes for visualization of a tissue sample as a composite image derived from two or more slides of adjacent tissue sections, for example as an interactive composite image wherein the proportion of each source image in the composite image may be altered.
The disclosure generally relates to the preparation of representative samples from clinical samples, e.g., tumors (whole or in part), lymph nodes, metastases, cysts, polyps, or a combination or portion thereof, using mechanical and/or biochemical dissociation methods to homogenize intact samples or large portions thereof. The resulting homogenate provides the ability to obtain a correct representative sample despite spatial heterogeneity within the sample, increasing detection likelihood of low prevalence subclones, and is suitable for use in various diagnostic assays as well as the production of therapeutics, especially "personalized" anti-tumor vaccines or immune cell based therapies.
A method of evaluating the quality state (such as a fixation status) of a cellular sample is provided. A MIR spectrum (220) of the sample is obtained, and a classification (211) or quantification (231) algorithm is applied to the MIR spectrum to identify features (221) indicative of the quality state and/or to classify the sample. The quality state may then be used to determine whether the sample is appropriate for an analytical method and/or whether remedial processing (such as further fixation) is appropriate.
G01N 21/35 - Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
The invention provides (OX40) antibodies and methods of using the same. The antibodies are reactive with a portion of the C-terminus of the human OX40 protein that includes amino acids 266277. The antibodies are useful for detecting OX40 protein expression in human tissue samples, including by immunohistochemistry, immunofluorescence, or immunoblot.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
20.
IMAGE PROCESSING SYSTEMS AND METHODS FOR DISPLAYING MULTIPLE IMAGES OF A BIOLOGICAL SPECIMEN
A system and method of displaying of multiple simultaneous views of a same region of a biological tissue sample. Logical instructions are executed by a processor to perform operations such as receiving a plurality of images of the biological tissue sample, converting the plurality of images to a common reference frame based on the individual metadata of each image, and arranging the plurality of images into a display pattern for simultaneous viewing of different aspects of the imaged biological tissue sample on a display screen. The plurality of images is produced by preprocessing images of the biological tissue sample. Each image shows a view mode of a same region of the biological tissue sample, and each image contains metadata that describe spatial orientation, such as the translation, rotation, and magnification, of the image to bring the plurality of images to a common view.
Systems and methods discussed herein include, among other things, a method comprising quantifying analyte staining of a biological compartment in a region in which said staining is intermixed with analyte staining of an analytically-distinct distinct biological compartment. Disclosed systems and methods include, for example, a system and method for identifying membrane staining of an analyte of interest in regions where diffuse membrane staining is intermixed with cytoplasmic staining and/or punctate staining is disclosed. Disclosed systems and methods include, for example, a system and method for quantifying membrane staining of an analyte of interest in tissue or cytological samples having regions in which membrane staining is intermixed with cytoplasmic staining and/or punctate staining.
G06V 10/70 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning
G06V 10/40 - Extraction of image or video features
G06V 10/762 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using clustering, e.g. of similar faces in social networks
G06V 10/764 - Arrangements for image or video recognition or understanding using pattern recognition or machine learning using classification, e.g. of video objects
22.
PROTEIN PROXIMITY ASSAY IN FORMALIN FIXED PAFFAFIN EMBEDDED TISSUE USING CAGED HAPTENS
Disclosed herein are caged haptens and caged hapten-antibody conjugates useful for enabling the detection of targets located proximally to each other in a sample.
Disclosed are specimen processing systems capable of processing specimens carried on slides. The specimen processing systems comprise opposables having at least one fluid control element (1500, 1501, 1502). The fluid control elements (1500, 1501, 1502) may be positioned between spacers or gapping elements (1450, 1452) and the opposable edges (1454, 1456). The fluid control elements may comprise an edge, such as a beveled edge or a stepped edge, as described herein, and the edge may be continuous or segmented.
The invention provides anti-human pro-epiregulin and anti-human amphiregulin antibodies and methods of using the same. Anti-EREG antibodies raised against amino acids 148- 169 and 156- 169 of the human EREG protein, and anti-AREG antibodies raised against amino acids 238-252 of the human AREG protein are disclosed. Methods of using these antibodies to detect EREG and AREG and kits and other products for perfoming such methods are also disclosed.
The invention provides anti-human pro-epiregulin and anti-human amphiregulin antibodies and methods of using the same. Anti-EREG antibodies raised against amino acids 148-169 and 156-169 of the human EREG protein, and anti-AREG antibodies raised against amino acids 238-252 of the human AREG protein are disclosed. Methods of using these antibodies to detect EREG and AREG and kits and other products for performing such methods are also disclosed.
The invention provides anti-human pro-epiregulin and anti-human amphiregulin antibodies and methods of using the same. Anti-EREG antibodies raised against amino acids 148- 169 and 156- 169 of the human EREG protein, and anti-AREG antibodies raised against amino acids 238-252 of the human AREG protein are disclosed. Methods of using these antibodies to detect EREG and AREG and kits and other products for perfoming such methods are also disclosed.
Immunohistochemistry (IHC) and in situ hybridization (ISH) have the aim of detecting, localizing and quantifying certain analytes for various diagnostic purposes. The quality of the stains which are analyzed may deviate for various reasons. Therefore, the present invention provides a method and system for assessing the stain quality and for establishing objective criteria for assessing the stain quality for application in the fields of in-situ hybridization and immunohistochemistry. In one possible embodiment, the invention comprises the steps of unmixing multi-spectral image data of a tissue specimen to obtain analyte intensity images, each analyte intensity image comprising signals from a single stain, computing metrics based on the analyte intensity images, wherein the metrics are uniformity, distribution and/or dispersion of pixel intensity values in the analyte intensity images and assessing a stain quality of a slide by comparing the computed metrics to pre-determined cutoff values regarding uniformity, distribution and/or dispersion of pixel intensity, wherein the stain quality of the slide is assessed as acceptable if the computed metrics meet or exceed the pre-determined cutoff values, and wherein the stain quality of the slide is assessed as unacceptable if the computed metrics do not meet the pre-determined cutoff values. In order to establish objective criteria for assessing stain quality, in one possible embodiment, the method and system includes the step of deriving cut-off values for uniformity, distribution and/or dispersion of pixel intensity by combining the computed metrics based on the analyte intensity images with pre-established data quantifying the stain quality.
Methods and compositions for removing precipitates or reducing the formation of precipitates generated in hematoxylin solutions. The methods and compositions feature cleaning solutions that feature chemical compounds that initiate processes including but not limited to acidification of the waste solution, chelation of metal ions in the waste solution, reduction reactions, oxidation reactions, and metal salt addition reactions.
Methods and compositions for removing precipitates or reducing the formation of precipitates generated in hematoxylin solutions. The methods and compositions feature cleaning solutions that feature chemical compounds that initiate processes including but not limited to acidification of the waste solution, chelation of metal ions in the waste solution, reduction reactions, oxidation reactions, and metal salt addition reactions.
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor
G01N 35/10 - Devices for transferring samples to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
30.
COMPOSITIONS AND METHODS FOR SIMULTANEOUS INACTIVATION OF ALKALINE PHOSPHATASE AND PEROXIDASE ENZYMES DURING AUTOMATED MULTIPLEX TISSUE STAINING ASSAYS
Devices and methods for the deposition of reagent droplets onto cells or tissue samples are disclosed. Optionally the samples have a protective fluid layer, the droplets have volumes between about 1 pL and about 50 pL, a pH modifier is dispensed to the samples, the droplets have a velocity of between about 5 m/s to about 15 m/s, the droplets have a kinetic energy of greater than 9.52x10-10 Joules, and the spatial density of reagents deposited on the samples ranges from about 50 dpi to about 1200 dpi. Also disclosed are reagent compositions suitable for dispensing via a droplet-on-demand system, whereby the reagent composition is selected from the group consisting of a primary stain reagent composition, an antibody reagent composition and a large molecule staining composition. Also an inkjet deposition system and means for imaging a slide containing a sample are disclosed.
Methods, systems, compositions, and thermochemical processes for inactivating proteinaceous binding entities (PBEs) such as antibodies in between staining cycles for preventing cross-reactivity in subsequent staining cycles. The thermochemical methods, compositions, or systems may feature incubating a sample in a solution comprising a buffer at a temperature sufficient to reduce or eliminate further detectability of the PBE. The methods, compositions, and systems may be beneficial for automated assays in automated staining devices that are adapted to dispense buffers and reagents and to heat samples to various temperatures.
Antibodies, compositions, systems, and methods for detecting C4.4a, for example immunohistochemistry methods for detecting C4.4a using a C4.4a antibody. The antibody may be obtained by immunizing a host with a C4.4a protein such as a peptide downstream of the signal peptide. The antibodies may be adapted to detect the uPAR-like domain 1 and uPAR-like domain 2. Also featured are methods for diagnosing C4.4a-associated tumors using C4.4a antibodies disclosed herein.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
An image segmentation method is disclosed that allows a user to select image component types, for example tissue types and or background, and have the method of the present invention segment the image according to the user's input utilizing the superpixel image feature data and spatial relationships.
Devices and methods for providing and dispensing opposables onto slides are provided in which magazines loaded with opposables include retention arms to reduce movement of the opposables during shipment and processing and to reduce or eliminate contamination.
A method and system for processing a sample in a fluid is provided. An assembly comprising a cap prefilled with a fixative solution, a valve, and a container for storing a tissue sample are provided. The valve is adapted to be situated between the cap and the container such that fluid can flow from the cap into the container when the assembly is upright, but the fluid cannot backflow from the container to the cap when the assembly is horizontal or inverted.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
A61B 10/00 - Other methods or instruments for diagnosis, e.g. for vaccination diagnosis; Sex determination; Ovulation-period determination; Throat striking implements
The subject disclosure presents systems and methods for evaluating a tissue sample that has been removed from a subject. Movement of fluid through the tissue sample is monitored by measuring time of flight of acoustic waves passed through the tissue sample. A system for performing the method can include a transmitter that outputs the energy and a receiver configured to detect the transmitted energy. Using the methods and systems, an optimized protocol for ensuring adequate distribution of the fluid throughout a variety of tissues can be developed.
The subject disclosure presents systems and methods for evaluating a tissue sample that has been removed from a subject. Movement of fluid through the tissue sample is monitored by measuring time of flight of acoustic waves passed through the tissue sample. A system for performing the method can include a transmitter that outputs the energy and a receiver configured to detect the transmitted energy. Using the methods and systems, an optimized protocol for ensuring adequate distribution of the fluid throughout a variety of tissues can be developed.
An extended tissue fixation method is provided including at least one soak in a cold aldehyde-based fixative solution followed by a soak in a warm aldehyde-based fixative solution over a period greater than 2 days. Using the processes disclosed herein, improved tissue morphology and IHC staining as well as superior preservation of post-translation modification signals, e.g. biomarkers, have been accomplished relative to standard room temperature fixation protocols. Moreover, the tissue can be left in the fixative solution up to at least 14 days using these methods, which provides improved flexibility relative to other protocols, enabling fixation to be conducted during transportation, shipping, and over weekends or vacations, while still achieving acceptable staining results.
The subject disclosure presents systems and methods for automatically selecting meaningful regions on a whole-slide image and performing quality control on the resulting collection of FOVs. Density maps may be generated quantifying the local density of detection results. The heat maps as well as combinations of maps (such as a local sum, ratio, etc.) may be provided as input into an automated FOV selection operation. The selection operation may select regions of each heat map that represent extreme and average representative regions, based on one or more rules. One or more rules may be defined in order to generate the list of candidate FOVs. The rules may generally be formulated such that FOVs chosen for quality control are the ones that require the most scrutiny and will benefit the most from an assessment by an expert observer.
The subject disclosure provides systems and methods for determination of Area of Interest (AOI) for different types of input slides. Slide thumbnails may be assigned into one of five different types, and separate algorithms for AOI detection executed depending on the slide type. Slide types include ThinPrep (RTM) slides, tissue micro-array (TMA) slides, control HER2 slides with 4 cores, smear slides, and a generic slide. The slide type may be assigned based on a user input. Customized AOI detection operations are provided for each slide type. If the user enters an incorrect slide type, operations include detecting the incorrect input and executing the appropriate method. The result of each AOI detection operations provides as its output a soft-weighted image having zero intensity values at pixels that are detected as not belonging to tissue, and higher intensity values assigned to pixels detected as likely belonging to tissue regions.
A tissue sample that has been removed from a subject can be evaluated. A transporter system for carrying a tissue sample includes a transport container, a fixative in the transport container, and a cooling device that reduces and/or maintains the temperature of the fixative to perform a pre-soaking process. A portable transporter system adapted to carry a tissue sample contacting a fixative, can include: a transport container including: a holding chamber; and a fixative; and a container lid including: a cassette holder operable to be coupled to the standard histology cassette and including a first seal; and a cassette receiver operable to be releasably coupled to said transport container and including a second seal, where the cassette holder and cassette receiver are operable to be attachably coupled to one another upon insertion of a standard histology cassette coupled to the cassette holder into the cassette receiver.
Described herein are methods for co-expression analysis of multiple markers in a tissue sample comprising: computing a heat map of marker expression for each of a plurality of single marker channel images, wherein each of the plurality of single marker channel images comprise a single marker; identifying one or more candidate regions of interest in each heat map of marker expression; computing overlay masks comprising the identified one or more candidate regions of interest from each heat map of marker expression; determining one or more co-localized regions of interest from the overlay masks; mapping the one or more co-localized regions of interest to a same coordinate position in each of the plurality of single marker channel images; and estimating a number of cells in at least one of the determined one or more co-localized regions of interest in each of the plurality of single marker channel images.
Systems (100) and methods for analyzing vessels in multiplexed images (101) include detecting large vessels using a spoke feature detection method (113), detecting long and narrow vessels using a line feature detection method (114), detecting smaller vessels using rolling-ball filtering and binary image operations to generate a mask (115), and evaluating any contour polygons resulting from these operations using quality measurements and other thresholds. Maturity determination (117) and nuclei detection (118) are also performed, resulting in an output of vessel characteristics and co-locations enabling enhanced analysis of multispectral images.
The subject disclosure presents systems and computer-implemented methods for calculating the diffusivity constant of a sample using acoustic time-of-flight (TOF) based information correlated with a diffusion model to reconstruct a sample's diffusivity coefficient. Operations disclosed herein such as acoustically determining the phase differential accumulated through passive fluid exchange (i.e. diffusion) based on the geometry of the tissue sample, modeling the impact of the diffusion on the TOF, and using a post-processing algorithm to correlate the results to determine the diffusivity constant, are enabled by monitoring the changes in the speed of sound caused by penetration of fixative such as formalin into several tissue samples. A tissue preparation system may be adapted to monitor said diffusion of a tissue sample and determine an optimal processing workflow.
This disclosure relates to hematoxylin staining formulations and particularly to formulations for use in autostainers. The disclosed compositions were discovered to possess atypical stability under storage while having high stain quality and sufficiently fast staining performance. The disclosed hematoxylin staining compositions include a solvent system, hematoxylin, a chemical oxidant, and a mordant. Illustrative embodiments also have a Cl-/SO4- molar ratio of between about 2.5/1 and about 1/4.
The subject disclosure presents systems and computer-implemented methods for evaluating a tissue sample that has been removed from a subject. A change in speed of the energy traveling through the sample is evaluated to monitor changes in the biological sample during processing. The rate of change in the speed of the energy is correlated with the extent of diffusion. A system for performing the method can include a transmitter that outputs the energy and a receiver configured to detect the transmitted energy. A time-of- flight of acoustic waves and rate of change thereof is monitored to determine an optimal time for soaking the tissue sample in a fixative.
The subject disclosure presents systems and computer-implemented methods for determining an acoustic time-of- flight (TOF) of sound waves through a sample material with greater accuracy and in a more repeatable fashion, by invoking one or more of an envelope generation for an error function, fitting a non-linear curve to an ultrasound frequency sweep, or performing a clustered piece-wise linear regression on individual linear parts of the ultrasonic frequency sweep. The systems and methods are useful for, among other things, monitoring diffusion of fluids through porous materials, such as tissue samples.
The subject disclosure presents systems and computer-implemented methods for evaluating a tissue sample that has been removed from a subject. A change in speed of the energy traveling through the sample is evaluated to monitor changes in the biological sample during processing. The rate of change in the speed of the energy is correlated with the extent of diffusion. A system for performing the method can include a transmitter that outputs the energy and a receiver configured to detect the transmitted energy. A time-of-flight of acoustic waves and rate of change thereof is monitored to determine an optimal time for soaking the tissue sample in a fixative.
The subject disclosure presents systems and computer-implemented methods for determining an acoustic time-of- flight (TOF) of sound waves through a sample material with greater accuracy and in a more repeatable fashion, by invoking one or more of an envelope generation for an error function, fitting a non-linear curve to an ultrasound frequency sweep, or performing a clustered piece-wise linear regression on individual linear parts of the ultrasonic frequency sweep. The systems and methods are useful for, among other things, monitoring diffusion of fluids through porous materials, such as tissue samples.
The subject disclosure presents systems and computer-implemented methods for providing reliable risk stratification for early-stage cancer patients by predicting a recurrence risk of the patient and to categorize the patient into a high or low risk group. A series of slides (1',2',3') depicting serial sections of cancerous tissue (4') are automatically analyzed by a digital pathology system, a score for the sections is calculated, and a Cox proportional hazards regression model is used to stratify the patient into a low or high risk group. The Cox proportional hazards regression model may be used to determine a whole-slide scoring algorithm based on training data comprising survival data for a plurality of patients and their respective tissue sections. The coefficients may differ based on different types of image analysis operations applied to either whole-tumor regions or specified regions within a slide.
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
Methods, systems, and apparatuses for detecting and describing heterogeneity in a cell sample are disclosed herein. A plurality of fields of view (FOV) are generated for one or more areas of interest (AOI) within an image of the cell sample are generated. Hyperspectral or multispectral data from each FOV is organized into an image stack containing one or more z-layers, with each z-layer containing intensity data for a single marker at each pixel in the FOV. A cluster analysis is applied to the image stacks, wherein the clustering algorithm groups pixels having a similar ratio of detectable marker intensity across layers of the z-axis, thereby generating a plurality of clusters having similar expression patterns.
Methods for in situ detecting proximity of two targets of interest featuring an antibody conjugated with a cleavable bridge component having a detectable moiety and an antibody conjugated with a non-cleavable bridge component. The bridge components each have a chemical ligation group adapted to form a covalent bond under particular conditions and when the targets are in close proximity. Following covalent bond formation, the cleavable bridge component can be cleaved from the antibody, effectively transferring the detectable moiety to the non-cleavable bridge component. Detection of the detectable moiety is indicative of the targets being in close proximity. The methods are compatible with both chromogenic and fluorogenic detection systems. The methods may be used to perform assays wherein one or more than one proximity event is detected on the same slide.
Disclosed is a computer device (14) and computer-implemented method of classifying cells within an image of a tissue sample comprising (1) providing the image of the tissue sample as input; (2) computing (111) nuclear feature metrics from features of nuclei within the image; (3) computing (112) contextual information metrics based on nuclei of interest with the image; (4) classifying (113) the cells within the image using a combination of the nuclear feature metrics and contextual information metrics.
G06V 20/69 - Microscopic objects, e.g. biological cells or cellular parts
G06V 10/44 - Local feature extraction by analysis of parts of the pattern, e.g. by detecting edges, contours, loops, corners, strokes or intersections; Connectivity analysis, e.g. of connected components
G06V 10/50 - Extraction of image or video features by summing image-intensity values; Projection analysis
G01N 33/52 - Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper
Polymers and conjugates comprising polymers are disclosed herein. In some embodiments, the conjugates disclosed are suitable for use as detection probes in immunohistochemical and in situ hybridization assays.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
Polymers and conjugates comprising polymers are disclosed herein. In some embodiments, the conjugates disclosed are suitable for use as detection probes in immunohistochemical and in situ hybridization assays.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C09K 11/02 - Use of particular materials as binders, particle coatings or suspension media therefor
Imaging systems, methods, and apparatuses for automatically identifying fields of view (FOVs) for regions in an image encompassing melanoma is disclosed. In embodiments and in further aspects of the present invention, a computer-implemented method is disclosed for a tumor region based immune score computation. The method, in accordance with the present invention, involves identifying regions, for example, tumor areas or regions around a tumor area, partitioning a whole slide image or portion of a whole slide image into multiple regions related to the tumor, selecting FOVs within each identified region, and computing a number of cells present in each FOV. An immune score and/or immune-related score is generated based on the cells counted in each FOV.
The present disclosure relates to an image analysis system for identifying objects belonging to a particular objet class in a digital image (102-108) of a biological sample, the system comprising a processor and memory, the memory comprising interpretable instructions which, when executed by the processor, cause the processor to perform a method comprising: - analyzing (602) the digital image for automatically or semi-automatically identifying objects in the digital image; - analyzing (604) the digital image for identifying, for each object, a first object feature value (202, 702) of a first object feature of said object; - analyzing (606) the digital image for computing one or more first context feature values (204, 704), each first context feature value being a derivative of the first object feature values or of other object feature values of a plurality of the objects in the digital image or being a derivative of a plurality of pixels of the digital image; - inputting (608) both the first object feature value of each of the objects in the digital image and the first context feature value of said digital image into a first classifier (210, 710); and - executing (610) the first classifier, the first classifier thereby using the first object feature value of each object and the one or more first context feature values as input for automatically determining, for said object, a first likelihood (216, 714) of said object of being a member of the object class.
An apparatus and method for selecting and dispensing coverglasses over specimens on slides for the purpose of viewing specimens through a microscope. The selecting device contains suctioning mechanisms for picking up a coverglass from a stack of coverglasses. It also contains the ability to shape the coverglass to assist in separating and laying down of the coverglasses with a reduction in the creation of bubbles in the fluid.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Systems and methods for generating a locally adaptive threshold image for foreground detection performing operations including creating a saliency edge strength image or layer indicating edge or border pixels of the nuclei by performing tensor voting on pixels neighboring the initial edge pixels within an image region to refine true edges are featured. Further, for each of a plurality of regions or blocks of the image, an adaptive threshold image is determined by sampling a foreground pixel and a background pixel for each initial edge pixel or refined edge pixel, generating histograms for both background and foreground saliency (or gradient magnitude) modulated histograms, determining a threshold range for each block of the image, and interpolating the threshold at each pixel based on the threshold range at each block. Comparing the input image with the resulting locally adaptive threshold image enables extraction of significantly improved foreground.
Systems and methods for processing a specimen slide using an automated specimen processing system. The automated specimen processing system has a slide ejector with a first portion for pushing the slides to break a bond between the slides and a slide carrier, and a second portion for ejecting one slide from the slides from slide carrier. The slides are horizontally aligned in the slide carrier to enable alignment and even spacing via gravitational forces.
Systems and methods that enable automated processing of specimens carried on microscope slides are described herein. In some embodiments, the system can include, for example, a slide ejector assembly having a slide staging device configured to receive a slide and an over-travel inhibitor that includes a first vacuum port positioned to draw a first vacuum between the slide and a standby platform as the slide is moved across at least a portion of the standby platform. The over-travel inhibitor includes a first sensor for detecting a presence of the slide on the standby platform. The system can also include a transfer assembly to transport slides away from the slide ejector assembly. The transfer assembly can include a floating transfer head having a vacuum port for drawing a partial vacuum for holding the slide.
The invention provides antibodies that bind specifically to human indoleamine 2,3-dioxygenase 1 (IDO1), and methods of using the same. The antibodies are capable of binding to a sequence comprising SEQ ID NO: 1 and specifically bind to human IDO1 in formalin fixed paraffin embedded tissues. The antibodies are useful in a number of different analytical techniques, including immunohistochemistry (IHC) and immunocytochemistry (ICC).
Provided herein are B7-H3 antibodies, fragments of such antibodies, and compositions comprising the same. The antibodies, antibody fragments and compositions are useful in a number of analytical methods, including immunohistochemical and immunocytochemical detection and analysis of B7-H3. Also provided herein are isolated peptides and fusion proteins containing immunogenic determinants for said B7-H3 antibodies, animals immunized with the peptides and fusion proteins, isolated B cells obtained from the animals, and hybridomas made from the isolated B cells.
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
Multiplex assays for improved scoring of tumor tissues stained with PD-L1 featuring PD-L1 staining in a first color plus staining of one or more differentiating markers, such as a marker specific for tumor cells and a marker specific for immune cells, are disclosed. The differentiation between the tumor cells and immune cells may improve the ease of scoring, the accuracy and speed of scoring, and the reproducibility of scoring of PD-L1 positive samples for therapy purposes.
Systems and methods for automatic FOV selection in immunoscore computation that involve reading images for individual markers from an unmixed multiplex slide or single stain slides, and computing the tissue region mask from the individual marker image. The heat map of each marker is determined by applying the low pass filter on the individual marker image channel and selecting the top K highest intensity regions from the heat map as the candidate FOVs for each marker. The candidate FOVs from the individual marker images are merged together in the same coordinate system by either adding all of the FOVs together or by only adding the FOVs from the selected marker images depending on the user's choice, and registering all the individual marker images to a common coordinate system and transferring the FOVs back to the original images.
Provided herein are PD-L1 antibodies and methods for using the same for diagnosing a medical condition associated with elevated PD-L1 levels (e.g., cancer) in subjects in need thereof. PD-L1 antibodies are also useful in evaluating the efficacy of a particular therapeutic regime in a subject diagnosed as having a PD-L1-related medical condition.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A microscope scanner is provided comprising a detector array for obtaining an image from a sample and a sample holder configured to move relative to the detector array. The sample holder is configured to move to a plurality of target positions relative to the detector array in accordance with position control signals issued by a controller and the detector array is configured to capture images during an imaging scan based on the position control signals.
A microscope scanning apparatus is provided comprising a detector array for obtaining an image from a sample and a sample holder adapted to hold the sample when in use and to move relative to the detector array along a scan path. A controller is further provided to monitor the position of the sample holder relative to the detector array and to trigger image capture by the detector array in accordance with said monitored position.
The subject disclosure presents systems and computer-implemented methods for automatic immune cell detection that is of assistance in clinical immune profile studies. The automatic immune cell detection method involves retrieving a plurality of image channels from a multi-channel image such as an RGB image or biologically meaningful unmixed image. A cell detector is trained to identify the immune cells by a convolutional neural network in one or multiple image channels. Further, the automatic immune cell detection algorithm involves utilizing a non-maximum suppression algorithm to obtain the immune cell coordinates from a probability map of immune cell presence possibility generated from the convolutional neural network classifier.
Process and reagent system for removing hematoxylin precipitate, and in particular automated processes for the removal of hematoxylin precipitate from automated staining equipment utilizing said reagent system.
Systems and methods that enable automated processing of specimens carried on microscope slides are described herein. Aspects of the technology are directed, for example, to automated specimen processing systems and methods for dispensing liquids onto slides. The system can concurrently or sequentially perform lock cycles. Each lock cycle can include lock steps for addressing respective slides to dispense liquid. The lock steps of different lock cycles can be synchronized to prevent any collision between dispensers.
The present disclosure concerns novel methods for analyzing biological samples using photo-cleavable moieties that facilitate target detection and/or biomarker isolation. In some embodiments, the method concerns using a probe comprising a photo-cleavable moiety and a selective irradiation technique for activating/cleaving the photo-cleavable moiety thereby providing facile isolation of the probe or probe components. Also disclosed herein is a system and kit for implementing the methods disclosed herein.
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
C40B 70/00 - Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or barcodes
75.
MEDICAL IMAGE ANALYSIS FOR IDENTIFYING BIOMARKER-POSITIVE TUMOR CELLS
The invention relates to a medical image analysis method for identifying biomarker- positive tumor cells, the method comprising: - reading a first digital image (223) and a second digital image (222) into memory, the first and second digital image depicting the same area of a first slide; the first slide comprising multiple tumor cells having being stained with a first stain and with a second stain; the first stain selectively staining nuclei and the second stain selectively staining a particular biomarker, the presence and/or amount of the biomarker in a tumor cell being indicative of a tumor cell belonging to a particular cancer-subtype; - identifying a plurality of nuclei and positional information of said nuclei by analyzing the light intensities in the first digital image; - identifying cell membranes which comprise the biomarker by analyzing the light intensities in the second digital image and by analyzing the positional information of the identified nuclei; - identifying biomarker-positive tumor cells in said area, wherein a biomarker- positive tumor cell is a combination of one identified nucleus and one identified cell membrane that surrounds the identified nucleus.
Single-stranded oligonucleotide probes, systems, kits and methods for chromosome enumeration, gene copy enumeration, or tissue diagnostics. The probes are particularly suited for detecting gene amplification, deletion, or rearrangement in tissue samples in a single, dual, or multiplexed assay. The probes exhibit improved performance compared to industry leading dual-stranded probes; particularly in terms of the rate of hybridization.
This disclosure describes methods, kits, and systems for scoring the immune response to cancer through examination of tissue infiltrating lymphocytes (TILs). Methods of scoring the immune response in cancer using tissue infiltrating lymphocytes include detecting CD3, CD8, CD20, and FoxP3 within the sample and scoring the detection manually or scoring the digital images of the staining with the aid of image analysis and algorithms.
Disclosed herein are methods and compositions for detecting differential expression of certain miRNAs in cancer cells or their surrounding normal tissues in the tumor microenvironment. The disclosure describes an automated, highly sensitive and specific method for detection of any cellular RNA molecule, including microRNA, messenger RNA and non-coding RNA. The technology includes probe design as well as probe use in an automated fashion for detection of RNA molecules in formalin-fixed paraffin-embedded tissue (FFPET) samples.
C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
C40B 40/02 - Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cells; Libraries contained in or displayed by vectors, e.g. plasmids; Libraries containing only microorganisms or vectors
Disclosed herein are novel quinone methide analog precursors and embodiments of a method and a kit of using the same for detecting one or more targets in a biological sample. The method of detection comprises contacting the sample with a detection probe, then contacting the sample with a labeling conjugate that comprises an enzyme. The enzyme interacts with a quinone methide analog precursor comprising a detectable label, forming a reactive quinone methide analog, which binds to the biological sample proximally to or directly on the target. The detectable label is then detected. In some embodiments, multiple targets can be detected by multiple quinone methide analog precursors interacting with different enzymes without the need for an enzyme deactivation step.
C07F 9/12 - Esters of phosphoric acids with hydroxyaryl compounds
C07C 235/34 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
C07C 237/20 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
C07C 275/28 - Derivatives of urea, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
C07C 305/24 - Esters of sulfuric acids having oxygen atoms of sulfate groups bound to carbon atoms of six-membered aromatic rings of non-condensed six-membered aromatic rings
C07D 501/24 - 7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
Automated system configured to perform and methods for performing one or more slide processing operations on slides bearing biological samples. The system and methods enable high sample throughput while also minimizing or limiting the potential for cross-contamination of slides. The automated systems can include features that facilitate consistency, controllability of processing time, and/or processing temperature.
Processing specimens in an automated histological staining system comprising robotically moving a slide carrier into a stainer of the system, the slide carrier carrying slides which respectively carry the specimens, and the specimens being at least partially embedded in paraffin. Liquids are automatically dispensed onto the slides according to a predetermined recipe for at least deparaffinizing, staining, and counterstaining the specimens. The slide carrier can be robotically moved out of the stainer after automatically dispensing the liquids. In some embodiments, a total of all liquid dispensed onto the slides after moving the slide carrier into the stainer and before moving the slide carrier out of the stainer has a greater volumetric concentration of polyol than of monohydric alcohol.
Methods and system capable of processing specimens carried by slides within an automated histological staining system. A slide carrier is moved toward and into a temperature-controlled internal environment of a stainer within the system. The slide carrier carries a first slide and a second slide, and the first and second slides can carry a first specimen and a second specimen, respectively. The first and second specimens are stained with at least one of a staining reagent and a counterstaining reagent while the first and second slides are within the internal environment and while an average temperature of the internal environment is greater than ambient temperature. The slide carrier can be moved out of the internal environment after staining one or both specimens.
Methods and apparatus that enable drying and curing a plurality of specimens carried by a plurality of microscope slides. Slide carriers are positioned at a first position while the slide carrier holds the microscope slides. Each of the specimens can be carried by one of the microscope slides. The slide carrier can be robotically moved to move the slide carrier into a circulation loop defined by a heater apparatus. The specimens and/or microscope slides can be convectively heated while the slide carrier is located in the circulation loop.
Disclosed herein are methods for detecting the presence and/or amount of HER2 protein, HER2 nucleic acid (for example, HER2 genomic DNA), ER protein, and Chromosome 17 centromere DNA in a single sample. Samples stained for HER2 protein, HER2 DNA, ER protein, and Chromosome 17 DNA allow for the identification of various types of cancer cells, for example HER2 protein positive/ER protein positive/HER2 gene positive cells, HER2 protein positive/ER protein negative/HER2 gene positive cells, HER2 protein negative/ER protein positive/HER2 gene positive cells, and HER2 protein negative/ER protein negative/HER2 gene positive cells.
The subject disclosure presents systems and methods for receiving a plurality of assay information along with a query for one or more features of interest, and projecting anatomical information from an anatomical assay onto a staining assay, for example an immunohistochemical (IHC) assay that is commonly registered with the anatomical assay, to locate or determine features appropriate for analysis. The anatomical information may be used to generate a mask that is projected on one or more commonly registered staining assays. A location of the feature of interest in the staining assay may be correlated with the anatomical context provided by the mask, with any features of interest that match the anatomical mask being selected or indicated as appropriate for analysis.
G01N 21/77 - Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
The present invention relates to isolated antibodies, or an antigen portions thereof, which bind to human HER3. The novel antibodies are of great utility since they allow for the sensitive and specific detection of human HER3. Detection of human HER3 is, e.g., possible in a tissue sample, even when such tissue sample is a formalin- fixed paraffin embedded tissue (FFPET) sample.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
87.
LINE-BASED IMAGE REGISTRATION AND CROSS-IMAGE ANNOTATION DEVICES, SYSTEMS AND METHODS
The disclosure relates to devices, systems and methods for image registration and annotation. The devices include computer software products for aligning whole slide digital images on a common grid and transferring annotations from one aligned image to another aligned image on the basis of matching tissue structure. The systems include computer-implemented systems such as work stations and networked computers for accomplishing the tissue-structure based image registration and cross-image annotation. The methods include processes for aligning digital images corresponding to adjacent tissue sections on a common grid based on tissue structure, and transferring annotations from one of the adjacent tissue images to another of the adjacent tissue images. The basis for alignment may be a line-based registration process, wherein sets of lines are computed on the boundary regions computed for the two images, where the boundary regions are obtained using information from two domains soft-weighted foreground images and gradient magnitude images. The binary mask image, based on whose 15 boundary the line features are computed, may be generated by combining two binary masks a first binary mask is obtained on thresholding a soft-weighted (continuous valued) foreground image, which is computed based on the stain content in an image, while a second binary mask is obtained after thresholding a gradient magnitude domain image, where the gradient is computed from the grayscale image obtained from the color image.
The present invention relates to systems and methods for adaptively optimizing broadband reference spectra for a multi-spectral image or adaptively optimizing reference colors for a bright-field image. The methods and systems of the present invention involve optimization techniques that are based on structures detected in an unmixed channel of the image, and involves detecting and segmenting structures from a channel, updating a reference matrix with signals estimated from the structures, subsequently unmixing the image using the updated reference matrix, and iteratively repeating the process until an optimized reference matrix is achieved.
Techniques for acquiring focused images of a microscope slide are disclosed. During a calibration phase, a "base" focal plane is determined using non-synthetic and/or synthetic auto-focus techniques. Furthermore, offset planes are determined for color channels (or filter bands) and used to generate an auto-focus model. During subsequent scans, the auto-focus model can be used to quickly estimate the focal plane of interest for each color channel (or filter band) rather than re- employing the non-synthetic and/or synthetic auto-focus techniques.
The subject disclosure presents systems and methods for separating colors in an image by automatically and adaptively adjusting reference vectors based on information specific to the assay being imaged, resulting in an optimized unmixing process that provides stain information that is physically and physiologically plausible. The reference vectors are optimized iteratively, based on minimizing non-negative color contributions, background contributions, high-frequencies in color channels specific to background or unwanted fluorescence, signals from known immunohistochemical markers, and pairs of stains known to carry physiologically independent information. Adjustments to the reference vectors may be allowed within a range that is predetermined based on measuring colors from multiple input images.
Processing of images acquired via fluorescence microscopy by identifying broadband and other undesired signals from the component signals of a scanned image, and processing selected regions of the image that are known to contain signals of interest, thereby extracting or identifying desired signals while subtracting undesired signals. One or more broadband signals are recognized by their unique signature and ubiquitous dispersion through the image. Regions of the scanned image may be tagged as consisting of predominantly broadband signals and are ignored during a spectral unmixing process. The remaining regions of the image, or selected regions of the image known to contain desired signals, may be unmixed, and the plurality of reference spectra subtracted from the components to extract or identify the target signals. The set of target signals may be refined by eliminating known or obvious sources of noise by, for instance, being compared to known or ideal sets of signals from similar materials.
G01N 21/27 - Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection
The disclosure relates to devices, systems and methods for image registration and annotation. The devices include computer software products for aligning whole slide digital images on a common grid and transferring annotations from one aligned image to another aligned image on the basis of matching tissue structure. The systems include computer-implemented systems such as work stations and networked computers for accomplishing the tissue-structure based image registration and cross-image annotation. The methods include processes for aligning digital images corresponding to adjacent tissue sections on a common grid based on tissue structure, and transferring annotations from one of the adjacent tissue images to another of the adjacent tissue images.
A facility includes systems and methods for providing a learning-based image analysis approach for the automated detection, classification, and counting of objects (e.g., cell nuclei) within digitized pathology tissue slides. The facility trains an object classifier using a plurality of reference sample slides. Subsequently, and in response to receiving a scanned image of a slide containing tissue data, the facility separates the whole slide into a background region and a tissue region using image segmentation techniques. The facility identifies dominant color regions within the tissue data and identifies seed points within those regions using, for example, a radial symmetry based approach. Based at least in part on those seed points, the facility generates a tessellation, each distinct area in the tessellation corresponding to a distinct detected object. These objects are then classified using the previously-trained classifier. The facility uses the classified objects to score slides.
A multispectral imaging system (100) for imaging a specimen located on a microscope slide (134) comprise: an imaging apparatus (112) including an illuminator (140) with a plurality of different color light sources (180a-d) for sequentially producing light for sequentially illuminating the specimen, an image capture device (120) for capturing a plurality of specimen images each corresponding to the specimen being exposed to light from a respective one of the light sources, and a processing device (122) configured to produce contrast enhanced color image data and/or spectrally deconvolved image data based on the captured specimen images; at least one lens positioned along an optical path extending from the specimen to the image capture device; and a display (114) in communication with the imaging apparatus and configured to display contrast enhanced output (144) and/or spectrally deconvolved output (144) of the specimen based on the contrast enhanced color image data and/or spectrally deconvolved image data from the processing device.
A proximity detection method is described that utilizes enzymatic biotinylation to detect targets in a sample, particularly formalin fixed paraffin embedded samples using automated staining platforms. One disclosed embodiment comprises contacting the sample with a first conjugate comprising a biotin ligase and a first specific binding moiety that binds proximally to the first target; contacting the sample with a second conjugate comprising a biotin ligase substrate and a second specific binding moiety that binds proximally to the second target; subjecting the sample to conditions that allow biotinylation of the biotin ligase substrate by the biotin ligase when the first target and the second target have a proximal arrangement; and detecting biotinylation of the biotin ligase substrate. The conditions that allow biotinylation of the substrate include addition of biotin and ATP. The method also may comprise contacting the sample with a streptavidin-enzyme conjugate. Signal amplification also can be used.
C12Q 1/25 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving enzymes not classifiable in groups
G01N 33/535 - Production of labelled immunochemicals with enzyme label
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
96.
SYSTEMS AND METHODS FOR CALIBRATING, CONFIGURING AND VALIDATING AN IMAGING DEVICE OR SYSTEM FOR MULTIPLEX TISSUE ASSAYS
A system and method for characterization and/or calibration of performance of a multispectral imaging (MSI) system equipping the MSI system for use with a multitude of different fluorescent specimens while being independent on optical characteristics of a specified specimen and providing an integrated system level test for the MSI system. A system and method are adapted to additionally evaluate and express operational parameters performance of the MSI system in terms of standardized units and/or to determine the acceptable detection range of the MSI system.
G01N 21/27 - Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection
G02B 21/36 - Microscopes arranged for photographic purposes or projection purposes
97.
SYSTEMS AND METHODS FOR CALIBRATING, CONFIGURING AND VALIDATING AN IMAGING DEVICE OR SYSTEM FOR MULTIPLEX TISSUE ASSAYS
A system and method for characterization and/or calibration of performance of a multispectral imaging (MSI) system equipping the MSI system for use with a multitude of different fluorescent specimens while being independent on optical characteristics of a specified specimen and providing an integrated system level test for the MSI system. A system and method are adapted to additionally evaluate and express operational parameters performance of the MSI system in terms of standardized units and/or to determine the acceptable detection range of the MSI system.
Heterogeneity for biomarkers in a tissue sample can be calculated. A heterogeneity score can be combined with an immunohistochemistry combination score to provide breast cancer recurrence prognosis. Heterogeneity can be based on percent positivity determinations for a plurality of biomarkers according to how many cells in the sample stain positive. An immunohistochemistry combination score can be calculated. An imaging tool can support a digital pathologist workflow that includes designating fields of view in an image of the tissue sample. Based on the fields of view, a heterogeneity metric can be calculated and combined with an immunohistochemistry combination score to generate a breast cancer recurrence prognosis score.
G01N 33/574 - Immunoassay; Biospecific binding assay; Materials therefor for cancer
G16H 30/20 - ICT specially adapted for the handling or processing of medical images for handling medical images, e.g. DICOM, HL7 or PACS
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
99.
METHODS, KITS, AND SYSTEMS FOR CLARIFYING PIGMENTED SAMPLES
Methods, kits, and systems for clarifying biological samples containing obfuscating pigment are disclosed. An automated method of treating a sample mounted on a substrate to alleviate staining obfuscations associated with pigments within the sample includes applying a clarifying reagent so that the clarifying reagent contacts the sample and the pigments within the sample are decolorized. The pigments within the sample being decolorized enable the specifically stained sample to be interpretable by a qualified reader.
The present description refers to photocleavable compounds which can be used as a photocleavable linker in order to link two biomolecules, such as oligonucleotides and peptides. The present description further refers to a method for the synthesis of said photocleavable compounds.
C07F 9/6561 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
C07H 19/00 - Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro derivatives thereof
patents
