Analysis and screening of cell secretion profiles
AssigneeIsoPlexis Corporation
InventorsPatrick Paczkowski, Sean Mackay, Sean Mccusker
Life of this patent
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Abstract
Embodiments disclose apparatus, methods and software for performing biological screening and analysis implemented using an instrument platform capable of detecting a wide variety of cell-based secretions, expressed proteins, and other cellular components. The platform may be configured for simultaneous multiplexed detection of a plurality biological components such that a large number of discrete samples may be individually sequestered and evaluated to detect or identify constituents from the samples in a highly parallelized and scalable manner.
Claims10
A method for spatial analysis of analytes, the method comprising:
- (a) placing a sample comprising a plurality of cells on a first substrate;
- (b) contacting the sample with a second substrate, the second substrate comprising (i) a plurality of analyte detection regions patterned with a plurality of discretely positioned analyte detection moieties, and (ii) a plurality of alignment markers disposed about the plurality of analyte detection regions, wherein the analyte detection moieties selectively associate with analytes released from the plurality of cells;
- (c) obtaining one or more images, the one or more images comprising at least one image of the plurality of cells and at least one image of the plurality of alignment markers;
- (d) detecting the analytes that selectively associated with corresponding analyte detection moieties of the plurality of analyte detection regions;
- (e) using the location of at least one of the plurality of alignment markers in the one or more images to interpolate positioning of the plurality of analyte detection regions in the one or more images;
- and
- (f) overlaying signals associated with the detected analytes with the interpolated positions of the plurality of analyte detection regions and the plurality of cells in the one or more images to produce a composite representation of regions of overlap between the plurality of cells and the detected analytes.
A system for spatial analysis of analytes associated with a cellular population comprising:
- a plurality of sample retention regions that receive at least one cell from a population of cells and retain an associated plurality of analytes released by the at least one cell;
- a boundary mask delineating the plurality of sample retention regions;
- a plurality of analyte detection regions patterned with a plurality of discretely positioned analyte detection regions and a plurality of alignment markers disposed about the plurality of analyte detection regions, the analyte detection regions disposed in an ordered pattern alignable with the sample retention regions whereby, upon coupling, released analytes selectively associate with analyte detection moieties in the analyte detection regions;
- an imaging apparatus that generates images of the sample retention regions delineated by the boundary mask and the analyte detection regions;
- and
- an image processor that aligns images for selected sample retention regions with corresponding analyte detection regions using the boundary mask and the plurality of alignment markers, the image processor further identifying the at least one cell in respective sample retention regions and corresponding analyte patterns to discretely resolve released analytes associated with the at least one cell based on the analyte detection moieties in the analyte detection regions.
Dependencies are inferred from the claim text.