Master-Copy Capture Arrays for Single-Cell Spatial Profiling
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Solution Overview
Problem
Existing spatial analysis techniques fail to provide comprehensive data on the position of single cells within a biological sample, limiting the understanding of spatial heterogeneity in analyte levels and affecting the analysis of cell morphology, differentiation, fate, viability, proliferation, and signaling in tissues.
Innovation Solution
The development of arrays of capture probes on a substrate, where each well contains a unique barcode and capture probes, allowing for the spatial tagging and identification of biological analytes within a biological sample, enabling high-resolution spatial analysis of analyte levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If existing spatial analysis techniques are used, then some analyte data can be obtained, but comprehensive spatial information at single-cell resolution is lost
Solution Approach 1:
The substrate is divided into multiple wells, each well is assigned a unique barcode, and capture probes within each well are further segmented with unique identifiers. This hierarchical segmentation enables precise tracking of analytes to their specific spatial locations (well and position within well), achieving single-cell resolution while preserving spatial context.
Solution Approach 2:
The invention creates a spatial map by copying the physical spatial arrangement of cells onto a digital framework using barcodes. Each well's unique barcode and the position-specific capture probe barcodes create a digital replica of the spatial layout, allowing spatial information to be preserved and analyzed computationally without losing the native spatial context.
2Manufacturing precision
If high-density capture probe arrays are created, then spatial detection capability is improved, but manufacturing complexity increases
Solution Approach 1:
The complex task of creating a high-density capture probe array is segmented into manageable units (wells). Each well contains a subset of capture probes with unique identifiers, reducing the complexity of any single manufacturing step while enabling high overall density through parallel processing of multiple wells.
Solution Approach 2:
Unique barcodes are assigned to each well and capture probe set during the design and preparation phase, before the actual capture probe array is manufactured. This preliminary coding simplifies the manufacturing process by pre-organizing the complex array structure and enabling automated assembly without requiring complex real-time positioning systems.
Data Source
AI summary
This disclosure provides methods for spatial profiling of biological analytes present in a biological sample. Methods include generating feature arrays using a master/copy format using recessed arrays, and methods for using such arrays. For example spatially-tagged analyte capture analytes can be used in spatial detection in methods to determine the location of analytes (e.g., proteins) in biological samples.