Abstract: Systems and methods described herein relate, among other things, to unmixing more than three stains, while preserving the biological constraints of the biomarkers. Unlimited numbers of markers may be unmixed from a limited-channel image, such as an RGB image, without adding any mathematical complicity to the model. Known co-localization information of different biomarkers within the same tissue section enables defining fixed upper bounds for the number of stains at one pixel. A group sparsity model may be leveraged to explicitly model the fractions of stain contributions from the co-localized biomarkers into one group to yield a least squares solution within the group. A sparse solution may be obtained among the groups to ensure that only a small number of groups with a total number of stains being less than the upper bound are activated.

Abstract: A method is provided for operating a microscope scanner 1 comprising a line scanner 3. Pre-scan data is generated for a target 6 comprising a sample, wherein generating the pre-scan data comprises: obtaining a pre-scan image of the target 6 from a pre-scan; and identifying one or more sample-containing regions 24 and one or more sample-free regions 26 of the target 6 from the pre-scan image. An imaging scan is then performed of a scanning region of the target 6 including the one or more sample-containing regions 24 and the one or more sample-free regions 26. The scanning speed of the line scanner 3 is adjusted along the image scan path based on the pre-scan data so that the target 6 is imaged at a higher scanning speed within the one or more sample-free regions 26 than in the one or more sample-containing regions 24.

Abstract: 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.

Abstract: A method for fixing a biological sample includes delivering energy through a biological sample that has been removed from a subject, while fixing the biological sample. A change in speed of the energy traveling through the biological sample is evaluated to monitor the progress of the fixation. A system for performing the method can include a transmitter that outputs the energy and a receiver configured to detect the transmitted energy. A computing device can evaluate the speed of the energy based on signals from the receiver.

Abstract: 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 can be 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.

Abstract: 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.

Abstract: Embodiments described herein pertain to systems and methods for imaging. An imaging system may include a castellated optical element, a CMOS image sensor, and color filtering elements. The CMOS image sensor may include focus areas, a line-scan area, a 2D imaging area, and look-ahead gaps. The imaging system may be configured scan and capture bi-directionally, forward-focused brightfield and fluorescence images of one or more slides comprising at least one biological material.

Abstract: Methods, computer-program products and systems are provided to perform actions including: receiving an image and displaying the image using a graphical user interface; receiving at least one first image annotation provided by a user via the graphical user interface; producing a first segmented image using a deep learning model, wherein the deep learning model uses the digital pathology image and the at least one first image annotation; and displaying the first segmented image using the graphical user interface; receiving at least one second image annotation provided by the user via the graphical user interface; producing a second segmented image using the deep learning model, wherein the deep learning model uses the digital pathology image, the at least one first image annotation, and the at least one second image annotation; and displaying the second segmented image using the graphical user interface.

Abstract: A method of preparing a stage for use in a slide imaging apparatus including positioning a stage in relation to a flat surface so that the flat surface is positioned in front of the top surfaces of slide support pin bases on the top surface of the stage. The method also includes injecting a fluid pin surfacing material configured to solidify into the hole of each slide support pin base so that at least some of the fluid pin surfacing material exits the hole at the top surface of the slide support pin bases and pushes up against the flat surface. The method also includes removing the flat surface so that a tip of solid pin surfacing material is formed on the top surface of each slide support pin base, thereby providing the stage with a plurality of slide support pins.

Abstract: 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 can be 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.

Abstract: A method is disclosed that permits calculation of reagent concentrations (in SI units) over time and space within a tissue sample as the sample is immersed in the reagent and the reagent diffuses into the tissue sample. The disclosed method has yielded the surprising result that once a formaldehyde concentration at all points within a tissue sample exceeds about 90 mM during a cold step of a cold+hot fixation protocol, the hot step of the fixation protocol can be commenced to provide reliable detection of molecular targets and preservation of tissue morphology in downstream analyses.

Abstract: The present disclosure relates to techniques for segmenting and detecting cells within image data using transfer learning and a multi-task scheduler. Particularly, aspects of the present disclosure are directed to accessing a plurality of images of one or more cells, extracting three labels from the plurality of images, where the three labels are extracted using a Voronoi transformation, a local clustering, and application of repel code, training, by a multi-task scheduler, a convolutional neural network model based on three loss functions corresponding to the three labels, generating, by the convolutional neural network model, a nuclei probability map and a background probability map for each of the plurality of images based on the training with the three loss functions, and providing the nuclei probability map and the background probability map.

Abstract: 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.

Abstract: The present disclosure is directed to conjugates of a specific binding entity and an oligomer, i.e. [Specific Binding Entity]-[Oligomer]n, wherein n is an integer ranging from 1 to 12, and where the Oligomer includes, in some embodiments, a PNA sequence having at least one substituent at a gamma carbon position. In some embodiments, the substituent at the gamma carbon position, e.g. an amino acid, a peptide, a miniPEG, or a polymer, includes at least one reporter moiety.

Abstract: A computer-based specimen analyzer (10) is configured to detect a level of expression of genes in a cell sample by detecting dots that represent differently stained genes and chromosomes in a cell. The color of the stained genes and the chromosomes is enhanced and filtered to produce a dot mask that defines areas in the image that are genes, chromosomes, or non-genetic material. Metrics are determined for the dots and/or pixels in the image of the cell in areas corresponding to the dots. The metrics are fed to a classifier that separates genes from chromosomes. The results of the classifier are counted to estimate the expression level of genes in the tissue samples.

Abstract: 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 an automated staining system including a dispensing instrument that receives a processing module to deliver reagent to a reaction chamber of the slide processing module. The processing module can carry fresh reagents, waste material, and the side.

Abstract: 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.

Abstract: Embodiments disclosed herein generally relate to identifying necrotic tissue in a multiplex immunofluorescence image of a slice of specimen. Particularly, aspects of the present disclosure are directed to accessing a multiplex immunofluorescence image of a slice of specimen comprising a first channel for a nuclei marker and a second channel for an epithelial tumor marker, wherein the slice of specimen comprises one or more necrotic tissue regions; providing the multiplex immunofluorescence image to a machine-learning model; receiving an output of the machine-learning model corresponding to a prediction that the multiplex immunofluorescence image includes one or more necrotic tissue regions at one or more particular portions of the multiplex immunofluorescence image; generating a mask for subsequent image processing of the multiplex immunofluorescence image based on the output of the machine-learning model; and outputting the mask for the subsequent image processing.

Abstract: 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.

Abstract: An aldehyde fixative solution at a first temperature is caused to contact a tissue sample for a first time period, additionally an aldehyde fixative solution is caused to contact the tissue sample at a second temperature higher than the first temperature for a second time period. The first time period typically ranges from about 15 minutes up to about 4 hours, and the first temperature typically is from greater than 0° C. to at least 15° C. The second temperature typically is from greater than about 22° C. to about 55° C., and the second time period ranges from about 1 hour to about 4 hours. Using this process, improved tissue morphology and IHC staining as well as superior preservation of post-translation modification signals have been accomplished in approximately 4 hours compared to 24 hours for room temperature protocols, and more even morphology and antigen preservation are observed.