Master-Copy Arrays for Single-Cell Spatial Analyte Detection
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Solution Overview
Problem
Current spatial analysis methodologies fail to provide comprehensive data on analyte levels within cells in a tissue while retaining the native spatial context, relying on limited pre-defined markers and separating cells from their spatial context.
Innovation Solution
The use of capture probes with spatial barcodes and capture domains to bind analytes, followed by spatially-tagging analyte capture agents, allowing for the identification of biological analytes at single-cell resolution within a biological sample.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional spatial analysis methodologies are used, then spatial context is retained, but measurement precision of analyte levels is insufficient
Solution Approach 1:
The substrate is divided into a plurality of distinct locations, each capable of capturing analyte capture agents at different spatial positions. This segmentation allows simultaneous retention of spatial context and high-resolution analyte detection across multiple discrete locations within the tissue sample
Solution Approach 2:
The invention adds a spatial dimension to traditional analyte detection by capturing analyte capture agents at multiple discrete locations on the substrate. This transforms conventional single-point measurement into multi-dimensional spatial mapping, enabling reconstruction of three-dimensional analyte distribution while maintaining native spatial context
2Measurement precision
If single-cell analysis is performed, then analyte data resolution is high, but spatial position information is lost
Solution Approach 1:
The invention merges single-cell analyte detection capability with spatial position information by capturing dissociated cells at specific discrete locations on the substrate. Each location serves as a spatial coordinate that records where the cell originated in the parent tissue, thereby combining high-resolution cellular analyte data with positional context
Solution Approach 2:
The substrate locations are pre-defined and prepared before cell dissociation and capture. This preliminary arrangement of capture sites ensures that when cells are dissociated and captured, their spatial origin information is automatically recorded at the appropriate pre-designated location, preserving spatial context without requiring post-processing
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables high-resolution spatial analysis of analyte levels within cells, providing a three-dimensional map of analyte distribution and retaining the native spatial context of the tissue sample.
Implementation Method 1
the capture probe binds to the analyte capture agent via the capture domain of the capture probes
Implementation Method 2
the spatially-tagged analyte capture agent interacts with the biological analyte within the biological sample
Data Source
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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.