Spatial Barcoded Probes for Tissue Context Analysis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for spatial analysis of analytes in biological samples fail to provide accurate information on the spatial location of individual cells within a tissue, as they either focus on intact tissues or individual cells without considering the cell's position relative to the tissue microenvironment.
Innovation Solution
The method involves hybridizing probe oligonucleotides to analytes, aligning a substrate with an array containing capture probes, and releasing these probes to hybridize with a capture domain, allowing for the determination of analyte location and abundance through sequencing of connected probes and spatial barcodes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If spatial analysis methods focus on intact tissues, then tissue context is preserved, but individual cell position information is lost
Solution Approach 1:
The method segments the tissue into individual cell-level units by using spatial barcodes that are assigned to specific locations within the tissue. Each spatial barcode corresponds to a specific spatial coordinate, allowing individual cell positions to be precisely identified while maintaining the overall tissue context through the collective arrangement of all barcoded cells.
Solution Approach 2:
The patent introduces spatial barcodes as intermediary elements that bridge the gap between intact tissue analysis and individual cell positioning. These barcodes serve as mediators that carry spatial location information from the tissue microenvironment to the analyzed analytes, enabling both tissue-level and cell-level information to be captured simultaneously.
2Measurement precision
If spatial analysis methods focus on individual cells, then cell position information is obtained, but tissue microenvironment context is lost
Solution Approach 1:
The method merges individual cell analysis with tissue microenvironment context by combining spatial barcodes (which provide cell position information) with analyte detection in the context of the original tissue architecture. The spatial barcodes are designed to maintain their positional relationships, allowing individual cell data to be interpreted within the broader tissue microenvironment context.
Solution Approach 2:
The patent adds a spatial dimension to traditional single-cell analysis by incorporating spatial barcodes that encode positional information. This transforms the analysis from a one-dimensional (cell-only) view to a multi-dimensional view that includes spatial coordinates, enabling simultaneous observation of individual cell characteristics and their tissue microenvironment context.
3Measurement precision
If probe oligonucleotides are hybridized to analytes, then analyte detection sensitivity is improved, but spatial location information may be lost
Solution Approach 1:
The method maintains continuous spatial information throughout the detection process by designing probe oligonucleotides that retain spatial barcode sequences. The spatial barcodes are incorporated into the probe structure itself, ensuring that spatial location information is continuously preserved from hybridization through to final detection, eliminating information loss at any stage of the analytical process.
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
This approach enables high-resolution spatial analysis of analytes, retaining native spatial context, and providing detailed information on analyte distribution within biological samples, which is crucial for understanding spatial heterogeneity and disease models.
Implementation Method 1
hybridizing a first probe oligonucleotide and a second probe oligonucleotide to the analyte
Implementation Method 2
hybridizing the connected probe to the capture domain of the capture probe in the biological sample
Data Source
AI summary
Provided herein are methods, kits, systems, and compositions for spatial analysis using one or more substrates (e.g., slides), wherein one of the substrates can have a spatial array. The methods disclosed herein include arrays having releasable capture probes that can interact with analytes or analyte derivatives and provide abundance and/or location of an analyte in a biological sample.