Abstract: Provided herein is a spatial sampling system that encodes samples with spatial barcodes that identify original spatial position of a microsample within a biological specimen or from different voxels from a biological sample. The method provides cell/nuclei-level resolution of cells and nuclei within microsamples. The method can comprise tagging cells and or nuclei in each microsample or voxel with a first barcode that encodes the original spatial position of the microsample in the biological specimen or the different voxel in the biological sample; pooling tagged microsamples; dividing the pooled sample into a plurality of subsamples, such that a plurality of subsamples comprise cells and/or nuclei from different original microsamples or voxels.

Abstract: A cartridge for dissociating tissue, comprising: a processing chamber comprising a stator, a side wall, a top orifice, and a first processing chamber port positioned in the side wall; and a grinder assembly comprising a plunger comprising a rotor, a grinder assembly slidably positioned in the processing chamber through the top orifice; wherein: the stator comprises a plurality of teeth arranged in a spaced-apart array of rings; and the rotor comprises one or more central teeth and a plurality of teeth arranged in a spaced-apart array of rings, wherein one ring of teeth is positioned at or substantially at a circumference of the rotor; wherein the rings in the stator and the rings in the rotor are positioned such that when the rotor contacts the stator, rings of teeth in the stator mesh with the one or more central teeth and rings of teeth in the rotor

Abstract: A system, methods, and apparatus are described to collect and prepare single cells and groups of cells from microsamples of specimens and encode spatial information of the physical position of the cells in the specimen. In some embodiment, beads or surfaces with oligonucleotides containing spatial barcodes are used to analyze DNA or RNA. The spatial barcodes allow the position of the cell to be defined and the nucleic acid sequencing information, such as target sequencing, whole genome, gene expression, used to analyze the cells in a microsample for cell type, expression pattern, DNA sequence, and other information, in the context of the cell's physical position in the specimen. In other embodiment, markers such as isotopes are added to a microsample to encode spatial position with mass spectoscopy or other analysis. The spatial encoded information is then readout by analysis such as DNA sequencing, mass spectrometry, fluorescence, or other methods.

Abstract: A system, methods, and apparatus are described to collect and prepare single cells, nuclei, subcellular components, and biomolecules from specimens including tissues and in some embodiments use the single cells to form organoids or microtissues. The system can perform enzymatic and/or physical disruption of the tissue to dissociate it into single-cells and then use a hanging droplet method to form organoids or microtissues.

Abstract: Provided herein is a system comprising: a) spatial sampler system configured to collect and transmit one or a plurality of cells or nuclei from a tissue specimen, the system comprising: i) a lower carrier having an array of conduits passing therethrough, each conduit comprising an opening on a first side and communicating with an opening on a second side, wherein the opening on the second side either (1) terminates in a capillary or (2) opens onto a well of a multiwell plate; ii) positioned, above the lower carrier, a perforated specimen holder configured to support a frozen tissue specimen, wherein the specimen holder comprises a plurality of perforations having a size sufficient to permit the passage of single cells or nuclei; and iii) positioned, above the specimen holder, a multifunctional head comprising an upper array of upper conduits, optionally, each aligned with a conduit opening of the lower carrier.

Abstract: A system, methods, and apparatus are described to collect and prepare single cells, nuclei, subcellular components, and biomolecules from specimens including tissues and in some embodiments use the single cells to form organoids or microtissues. The system can perform enzymatic and/or physical disruption of the tissue to dissociate it into single-cells and then use a hanging droplet method to form organoids or microtissues.

Abstract: This disclosure provides methods for producing a sample of subcellular organelles, particularly nuclei, from a tissue. In some embodiments, this disclosure provides a method of processing a tissue sample involves performing enzymatic/chemical disruption of tissue in a chamber to produce disrupted tissue comprising released cells and/or nuclei and debris; separating the released cells and/or nuclei from the debris therein; and moving the released cells and/or nuclei. In some instances, the method comprises mechanical disruption of the tissue sample.

Abstract: A system, methods, and apparatus are described to collect and prepare single cells and groups of cells from microsamples of specimens and encode spatial information of the physical position of the cells in the specimen. In some embodiment, beads or surfaces with oligonucleotides containing spatial barcodes are used to analyze DNA or RNA. The spatial barcodes allow the position of the cell to be defined and the nucleic acid sequencing information, such as target sequencing, whole genome, gene expression, used to analyze the cells in a microsample for cell type, expression pattern, DNA sequence, and other information, in the context of the cell's physical position in the specimen. In other embodiment, markers such as isotopes are added to a microsample to encode spatial position with mass spectoscopy or other analysis. The spatial encoded information is then readout by analysis such as DNA sequencing, mass spectrometry, fluorescence, or other methods.

Abstract: A system, methods, and apparatus are described to collect and prepare single cells, nuclei, subcellular components, and biomolecules from specimens including tissues and in some embodiments use the single cells to form organoids or microtissues. The system can perform enzymatic and/or physical disruption of the tissue to dissociate it into single-cells and then use a hanging droplet method to form organoids or microtissues.

Abstract: This disclosure provides methods for producing a sample of subcellular organelles, particularly nuclei, from a tissue. In some embodiments, this disclosure provides a method of processing a tissue sample involves performing enzymatic/chemical disruption of tissue in a chamber to produce disrupted tissue comprising released cells and/or nuclei and debris; separating the released cells and/or nuclei from the debris therein; and moving the released cells and/or nuclei. In some instances, the method comprises mechanical disruption of the tissue sample.

Abstract: A system, methods, and apparatus are described to collect and prepare cells, nuclei, subcellular components, and biomolecules from specimens including FFPE and OCT preserved tissues. The system can perform deparaffinization, rehydration, enzymatic and/or chemical and physical disruption of the FFPE tissue, or residue removal of the OCT tissue, to dissociate it into a single cell or nuclei suspension.

Abstract: A system, methods, and apparatus are described to collect and prepare single cells and groups of cells from microsamples of specimens and encode spatial information of the physical position of the cells in the specimen. In some embodiment, beads or surfaces with oligonucleotides containing spatial barcodes are used to analyze DNA or RNA. The spatial barcodes allow the position of the cell to be defined and the nucleic acid sequencing information, such as target sequencing, whole genome, gene expression, used to analyze the cells in a microsample for cell type, expression pattern, DNA sequence, and other information, in the context of the cell's physical position in the specimen. In other embodiment, markers such as isotopes are added to a microsample to encode spatial position with mass spectoscopy or other analysis. The spatial encoded information is then readout by analysis such as DNA sequencing, mass spectrometry, fluorescence, or other methods.

Abstract: A system, methods, and apparatus are described to collect and prepare single cells, nuclei, subcellular components, and biomolecules from specimens including tissues and in some embodiments use the single cells to form organoids or microtissues. The system can perform enzymatic and/or physical disruption of the tissue to dissociate it into single-cells and then use a hanging droplet method to form organoids or microtissues.

Abstract: A system, methods, and apparatus are described to collect and prepare single cells, nuclei, subcellular components, and biomolecules from specimens including tissues and in some embodiments use the single cells to form organoids or microtissues. The system can perform enzymatic and/or physical disruption of the tissue to dissociate it into single-cells and then use a hanging droplet method to form organoids or microtissues.

Abstract: A system, methods, and apparatus are described to collect and prepare single cells, nuclei, subcellular components, and biomolecules from specimens including tissues. The system can perform enzymatic and/or physical disruption of the tissue to dissociate it into single-cells or nuclei in suspension or subcellular components including nucleic acids. In some embodiments, the titer of dissociated cells is monitored at intervals and the viability determined. In some embodiments, the processing is adjusted according to the measurements of the titer and viability. In some embodiments, the single-cells or nuclei in suspension are washed and resuspended in the buffer or media of choice. In some embodiments, the conditions are chosen to produce nuclei. In other embodiments, the single-cells or nuclei are purified by affinity paramagnetic bead processing. In some embodiments, matched bulk nucleic acid to the single-cells is produced.

Abstract: This disclosure provides methods for producing a sample of subcellular organelles, particularly nuclei, from a tissue. In some embodiments, this disclosure provides a method of processing a tissue sample involves performing enzymatic/chemical disruption of tissue in a chamber to produce disrupted tissue comprising released cells and/or nuclei and debris; separating the released cells and/or nuclei from the debris therein; and moving the released cells and/or nuclei. In some instances, the method comprises mechanical disruption of the tissue sample.

Abstract: A system, methods, and apparatus are described to collect and prepare single cells, nuclei, subcellular components, and biomolecules from specimens including tissues. The system can perform enzymatic and/or physical disruption of the tissue to dissociate it into single-cells or nuclei in suspension or subcellular components including nucleic acids. In some embodiments, the titer of dissociated cells is monitored at intervals and the viability determined. In some embodiments, the processing is adjusted according to the measurements of the titer and viability. In some embodiments, the single-cells or nuclei in suspension are washed and resuspended in the buffer or media of choice. In some embodiments, the conditions are chosen to produce nuclei. In other embodiments, the single-cells or nuclei are purified by affinity paramagnetic bead processing. In some embodiments, matched bulk nucleic acid to the single-cells is produced.

Abstract: A system, methods, and apparatus are described to collect and prepare single cells and groups of cells from microsamples of specimens and encode spatial information of the physical position of the cells in the specimen. In some embodiment, beads or surfaces with oligonucleotides containing spatial barcodes are used to analyze DNA or RNA. The spatial barcodes allow the position of the cell to be defined and the nucleic acid sequencing information, such as target sequencing, whole genome, gene expression, used to analyze the cells in a microsample for cell type, expression pattern, DNA sequence, and other information, in the context of the cell's physical position in the specimen. In other embodiment, markers such as isotopes are added to a microsample to encode spatial position with mass spectoscopy or other analysis. The spatial encoded information is then readout by analysis such as DNA sequencing, mass spectrometry, fluorescence, or other methods.

Abstract: A system, methods, and apparatus are described to collect and prepare single cells, nuclei, subcellular components, and biomolecules from specimens including tissues and in some embodiments use the single cells to form organoids or microtissues. The system can perform enzymatic and/or physical disruption of the tissue to dissociate it into single-cells and then use a hanging droplet method to form organoids or microtissues.

Abstract: Provided herein is a system comprising: a) spatial sampler system configured to collect and transmit one or a plurality of cells or nuclei from a tissue specimen, the system comprising: i) a lower carrier having an array of conduits passing therethrough, each conduit comprising an opening on a first side and communicating with an opening on a second side, wherein the opening on the second side either (1) terminates in a capillary or (2) opens onto a well of a multiwell plate; ii) positioned, above the lower carrier, a perforated specimen holder configured to support a frozen tissue specimen, wherein the specimen holder comprises a plurality of perforations having a size sufficient to permit the passage of single cells or nuclei; and iii) positioned, above the specimen holder, a multifunctional head comprising an upper array of upper conduits, optionally, each aligned with a conduit opening of the lower carrier.