Abstract: The present disclosure relates to compounds and methods which may be useful as inhibitors of KDM1A for the treatment or prevention of diseases. Methods of inhibition of KDM1A, methods of increasing gamma globin gene expression, and methods to induce differentiation in cancer cells in a human or animal subject are also provided for treatment of disease such as acute myelogenous leukemia.

Abstract: The present invention encompasses genetically-modified immune cells (and populations thereof) expressing a microRNA-adapted shRNA (shRNAmiR) that reduces the expression of a target endogenous protein. Methods for reducing the expression of an endogenous protein in an immune cell are also provided wherein the method comprises introducing a shRNAmiR that targets the endogenous protein. Using shRNAmiRs for knocking down the expression of a target protein allows for stable knockdown of expression of endogenous proteins in immune cells.

Abstract: Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human mitochondrial DNA (mtDNA). The disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been having modified or edited.

Abstract: The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.

Abstract: Synthetic human cell mimic hydrogel particles and their use in cytometric or coulter device applications are described. The synthetic human cell mimic hydrogel particles described herein are selectively tunable to have at least one optical, volumetric, or capacitance property that is substantially similar to a corresponding optical, volumetric, or capacitance property of the human cell mimic hydrogel particle's natural biological cell counterpart.

Abstract: According to at least one aspect, a system configured to count cells in a vessel is provided. The system comprises an imaging system configured to image cells in the vessel and a controller coupled to the imaging system. The controller is configured to control the imaging system to capture a focused image of the cells and estimate a number of cells in the focused image. The controller is configured to control the imaging system to capture a focused image of the cells at least in part by controlling the imaging system to capture a plurality of images of the cells in a plurality of focal planes, determining an area of at least one cell in each of the plurality of images, and selecting one image from the plurality of images as the focused image using the area of the at least one cell in the plurality of images.

Abstract: Collectively, rare diseases affect approximately 350 million people worldwide, of which half are diagnosed in childhood. Even though more than 80% of rare diseases are genetic in origin and begin in utero, drug target discovery has historically been stymied due to difficulties in obtaining fetal, neonatal, and pediatric tissues for genetic study and drug discovery. Disease modeling with patient-specific hiPSCs is an ideal platform for both rapid identification and experimental validation of early life disease mechanisms. This invention combines high content genomic assays, phenotypic measurements, and machine learning (Artificial Intelligence/Machine Learning) with hiPSC disease models to identify DNA mutations causing early life diseases.

Abstract: A cell culture incubator with an incubator cabinet has an internal chamber with a door opening from an external environment. An imager and a manipulator with a scraper are in the internal chamber. A controller is configured for controlling the manipulator to modulate the contact pressure between a scraping edge of the cell scraper and a surface of a cell culture vessel and a sensor is connected to the cell scraper that provides signal to the controller informative of a sensed pressure between a scraping edge of the cell scraper and the surface of a cell culture vessel. The controller controls the manipulator to increase or decrease the pressure between a scraping edge of the cell scraper and the surface of a cell culture vessel.

Abstract: The disclosure relates generally to the field of immune binding proteins and method for obtaining immune binding proteins from genomic or other sources. The disclosure also relates to anti-SARS-CoV-2 antibodies that have been obtained from subjects who became immune to this coronavirus, and to methods of using these anti-SARS-CoV-2 antibodies. Methods for neutralizing SARS-CoV-2 are disclosed, as well treatments for SARS-COV-2 using the anti-SARS-CoV-2 antibodies.

Abstract: Provided herein is the identification of markers associated with THCV, THCVA, CBDV, CBDVA, CBGV, or CBGVA production in Cannabis plants and their use in selecting Cannabis plants having modified THCV, THCVA, CBDV, CBDVA, CBGV, or CBGVA activity. The markers are useful for breeding plants having modified varin activity, including elevated THCV levels, by obtaining nucleic acids, detecting one or more markers that indicate modified varin activity, and establishing plant lines having such characteristics.

Abstract: Detection of pathological abnormalities in tissue samples and/or pluralities of cells is a highly specialized and time-consuming effort, usually performed by a select group of clinicians and technical personnel. Described herein are methods for more automatable, consistent and comprehensive cell sample analysis to deliver a rapid, reliable and detailed classification, e.g., diagnosis, of the status of cells present in a sample, particularly, but not limited to cancer diagnosis.

Abstract: Aspects relate to an automated cell culture incubator and to methods for using such an incubator. In one aspect, the cell culture incubator includes an incubator cabinet having a transfer chamber and an internal chamber that are arranged to form an airlock configuration. In some embodiments, objects placed into the incubator cabinet are sterilized using ozone produced by an ozone generator. The incubator may include one or more transfer devices that move objects between the transfer chamber and the internal chamber.

Abstract: Provided herein are compositions and methods for detecting the binding of a peptide to an MHC molecule, and the binding of a peptide:MHC complex to a TCR. In preferred embodiments, the compositions and methods are in a highly-multiplexed way. The compositions and methods disclosed herein can be used to provide direct information on which peptides are bound to an MHC molecule. Also provided is a method for simultaneously detecting a large number of peptides for binding to an MHC molecule and/or a T cell. A method for detecting competitive binding of a large number of peptides to an MHC molecule and/or a T cell is also disclosed. Also provided herein is a method for simultaneously detecting a large number of specific TCRs. The compositions and methods of the present invention are useful for vaccine design, research and monitoring of autoimmune and infectious disease, immunogenicity testing of therapeutics, and tissue typing.

Abstract: Methods and systems for performing assays in compartmentalized nano-volumes to screen for functional bispecific or multispecific biologics, including: providing a plurality of at least two distinct types of cells, wherein two or more first-type cells are engineered to express substantially a single genetic-variant per cell for a bispecific or multispecific biologic in a secreted form, wherein two or more second-type cells are selected or engineered to produce a positive reporter molecule signal that is triggered by a functional variant of the said biologic expressed by a first-type cell; providing a plurality of compartmentalized nano-volumes, wherein two or more nano-volumes are each provided with substantially one first-type cell, and one or more second-type cell(s); incubating the said nano-volumes over a period of time to allow the expression and secretion of the said biologics inside the said nano-volumes; collecting data representing the positive reporter molecule signal triggered by secreted biologics

Abstract: Methods and systems for image analysis are provided, and in particular for identifying a set of base-calling locations in a flow cell for DNA sequencing. These include capturing flow cell images after each sequencing step performed on the flow cell, and identifying candidate cluster centers in at least one of the flow cell images. Intensities are determined for each candidate cluster center in a set of flow cell images. Purities are determined for each candidate cluster center based on the intensities. Each candidate cluster center with a purity greater than the purity of the surrounding candidate cluster centers within a distance threshold is added to a template set of base-calling locations.

Abstract: In one embodiment, a flow cytometer is disclosed having a compact light detection module. The compact light detection module includes an image array with a transparent block, a plurality of micro-mirrors in a row coupled to a first side of the transparent block, and a plurality of filters in a row coupled to a second side of the transparent block opposite the first side. Each of the plurality of filters reflects light to one of the plurality of micro-mirrors and passes light of a differing wavelength range and each of the plurality of micro-mirrors reflects light to one of the plurality of filters, such that incident light into the image array zigzags back and forth between consecutive filters of the plurality of filters and consecutive micro-mirrors of the plurality of micro-mirrors. A radius of curvature of each of the plurality of micro-mirrors images the fiber aperture onto the odd filters and collimates the light beam on the even filters.

Abstract: The present disclosure provides methods and assay systems for use in spatially encoded biological assays, including assays to determine a spatial pattern of abundance, expression, and/or activity of one or more biological targets across multiple sites in a sample. In particular, the biological targets comprise proteins, and the methods and assay systems do not depend on imaging techniques for the spatial information of the targets. The present disclosure provides methods and assay systems capable of high levels of multiplexing where reagents are provided to a biological sample in order to address tag the sites to which reagents are delivered; instrumentation capable of controlled delivery of reagents; and a decoding scheme providing a readout that is digital in nature.

Abstract: The present disclosure relates to methods, systems, and apparatus for efficient continuous production of hydrophobic products with the simultaneous retention of substrates.

Abstract: The present disclosure provides feeder hydrogel particles that can function to support the growth, proliferation, and/or activation of a target cell in culture. The present disclosure also provides methods of culturing target cells with feeder hydrogel particles.

Abstract: Described herein are apparatuses (e.g., systems and devices) and methods of delivering nanosecond pulsed electrical fields (nsPEF). In particular, these apparatuses and methods may provide enhanced safety and robust operation over even very short (e.g., nanosecond and sub-nanosecond pulses) and high voltage pulsing; these benefits may be accomplished by multi-functional isolation of various subsystems and components of the apparatus, even including the low-voltage, control and command portions of the apparatus with extremely low capacitance, high voltage isolation.