Spatial Barcode Capture Probes for Context-Preserving Analyte Transfer
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Solution Overview
Problem
Existing methods fail to provide spatial context for analyte analysis in biological samples, particularly for nucleic acid and protein analytes, limiting the understanding of spatial heterogeneity and disease models.
Innovation Solution
Methods involving RNA-templated ligation (RTL) and a 'sandwich process' are used to transfer analytes from a first substrate to a second substrate for downstream processing, utilizing capture probes with spatial barcodes and capture domains to retain spatial context.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If traditional analyte analysis methods are used, then analyte data can be obtained, but spatial context information is lost
Solution Approach 1:
The patent introduces spatial barcodes as intermediary molecules that bridge the analyte and its spatial location. These barcodes are incorporated into capture probes or attached to analytes, serving as mediators that carry spatial information from the tissue section to the detection platform, thereby resolving the loss of spatial context during analysis
Solution Approach 2:
The patent creates a spatial map by copying spatial location information onto detectable signals. Through RNA-templated ligation, the spatial coordinates (encoded in barcodes) are copied from the physical tissue position to molecular tags that can be read and reconstructed into a spatial map, preserving location information without requiring the original tissue structure
2Loss of information
If RNA-templated ligation and sandwich process are used, then spatial context is retained, but process complexity increases
Solution Approach 1:
The patent performs preliminary actions by pre-designing and pre-positioning capture probes with integrated spatial barcodes on the detection platform before sample analysis. The RNA-templated ligation reactions are pre-configured with all necessary components, so that when the sample is introduced, the spatial mapping occurs automatically through the pre-established molecular architecture, reducing operational complexity
Solution Approach 2:
The patent merges multiple functions into unified molecular constructs. Capture probes combine analyte binding capability, spatial encoding (barcodes), and RNA-templated ligation functionality into single integrated molecules. The sandwich process merges sample capture, spatial encoding, and signal generation into a unified workflow, simplifying the overall process despite the sophisticated chemistry involved
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 analytes, allowing for precise determination of location and abundance, enhancing understanding of spatial heterogeneity and disease models.
Implementation Method 1
hybridizing a first probe and a second probe to the nucleic acid analyte, wherein the first probe and the second probe each comprise a sequence that is substantially complementary to sequences of the nucleic acid analyte
Implementation Method 2
the methods, compositions, and systems disclosed herein utilize RNA-templated ligation (RTL) for analyzing an analyte (e.g., RNA) in a biological sample
Implementation Method 3
RTL is used in combination with a 'sandwich process,' wherein the analyte is transferred from a first substrate to a second substrate for further downstream processing
Data Source
AI summary
Provided herein are methods for capturing a connected probe and/or a capture handle sequence to a capture domain of a capture probe.