Spatially Resolved Cellular Profiling

A method of spatially resolved cellular profiling for integrating profiling data of a cell or cell-derived material with spatial positioning of the cell or cell-derived material, the method comprising:

• (a) placing a cell or tissue sample onto a sample-receiving surface of a substrate;
• (b) contacting the surface of the sample with a population of particles, wherein the particles comprise at least 3 distinguishable subpopulations, wherein each of the at least 3 distinguishable subpopulations has a distinguishable trait that can be determined by imaging, and wherein the particles comprise binding molecules that bind to target biomolecules from the sample;
• (c) imaging the sample to provide a sample image;
• (d) imaging the population of particles to provide a particle image, wherein the distinguishable trait and spatial positioning of the particles of the at least 3 distinguishable subpopulations can be determined relative the surface of the sample;
• (e) capturing target biomolecules from the sample to the binding molecules, such that target biomolecules that are in close proximity to a particle bind to that particle;
• (f) removing the population of particles from the surface of the sample;
• (g) profiling the particles to generate profiling data corresponding to each particle, wherein the profiling step comprises profiling the target biomolecules bound to the particles;
• (h) calculating similarity scores for pairs or pluralities of particles based on the profiling data;
• (i) assigning the profiling data corresponding to a particle to a spatial position of a particle in the particle image, based on the similarity scores and/or the particle image;
• and
• (j) providing a virtual map of the spatially resolved profiling data with respect to the sample image.