Integrated diagnostic devices comprising peptide-DNA conjugates for analyte detection, an embedded biomolecular computing system for sample analysis, and a layered device architecture are provided herein. In particular, provided herein are devices comprising a layered architecture that enables diagnostic reagents, sample components, and reaction products to flow through the system with minimal user intervention.

The present disclosure provides, inter alia, methods and compositions (e.g., conjugates) for imaging, at high spatial resolution, targets of interest.

The present invention relates to a drum stencil printing system for reliably and automatically printing materials on the inside of a concave surface. The drum stencil printing system includes a pliable drum stencil secured in place by a stencil spring. As the printhead applies radial pressure to the drum stencil, the portion of the stencil in contact with the printhead is deflected to make contact with the container sidewall. When the printhead rotates, the portion of the stencil contacting the container sidewall also rotates to match the nozzle of the printhead. After printing is complete, the printhead retracts, and the pliable stencil is returned to its undeflected position, breaking contact between the stencil and the container, and protecting the printed material from being rubbed or worn off of the container.

Provided are systems and methods of sample preparation and analyte detection.

Provided herein are compositions and methods for identifying or quantitating one or more analytes in sample. The composition can comprise an affinity molecule reversibly conjugated to a label moiety via a double-stranded nucleic acid linker or via an adaptor molecule. The affinity molecule and the label moiety can be linked to different strands of the double-stranded nucleic acid linker. Compositions can be used in any biological assays for detection, identification and/or quantification of target molecules or analytes, including multiplex staining for molecular profiling of individual cells or cellular populations. For example, the compositions can be adapted for use in immunofluorescence, fluorescence in situ hybridization, immunohistochemistry, western blot, and the like.

A method for identifying a sub-population within a mixed population of cells is disclosed. The method involves contacting the mixed population of cells with at least one unique binding agent, wherein the at least one unique binding agent is designed to bind to a target molecule present in the sub-population, and wherein the at least one unique binding agent is attached to an epitope specific barcode that represents the identity of the target molecule. The method further involves sequentially attaching two or more assayable polymer subunits to the epitope specific barcode to create unique cell origination barcodes that represent the identities of individual cells to which the at least one unique binding agent has bound; and decoding the epitope specific barcode and cell origination barcodes, thereby identifying the sub-population within the mixed population of cells.

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.

There are provided methods and systems for detecting and/or quantifying an analyte. In particular, there are provided methods and systems for simultaneous detection and/or quantitation of two or more analytes in a sample. In some embodiments, there are provided colocalization-by-linkage assays on microparticles (CLAMP) comprising two sets of binders pre-assembled on a support, such that the two sets of binders are colocalized before contacting the sample.

Disclosed herein, inter alia, are compositions and methods of use thereof for interrogating a cell.

The present invention relates to a method of spatially barcoding a given location on a substrate, and further to spatially barcoding detection probes present in a sample such as a biological tissue specimen for the purposes of analysing molecular features present in the tissue. Such analysis may include: i) the spatial expression of one or more biological molecules, specifically; ii) the spatial analysis of the transcriptome and/or iii) the spatial analysis of the proteome, including post-translational protein modifications. The invention further relates to various component products for performing such methods that include reagents kits, instrumentation and software.