Spatial Analysis of Analytes Using Salt-Induced Barcode Release
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for spatial analysis of analytes in biological samples fail to provide detailed information on the spatial location of analytes within tissues, lacking specificity and sensitivity, especially when analyzing intact tissues or dissociated cells.
Innovation Solution
The method involves using analyte capture agents with binding moieties and barcode domains, aligning biological samples with spatially barcoded capture probes, and releasing barcode domains with monovalent or divalent salts to hybridize and determine the location and abundance of analytes, enhancing protein detection with sodium chloride and retaining RNA detection capabilities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If spatial analysis methods are used to determine analyte location in biological samples, then spatial heterogeneity information is obtained, but the methods lack specificity and sensitivity for intact tissue analysis
Solution Approach 1:
The patent introduces spatial barcodes as intermediary molecules that mediate between the analyte (protein, DNA, or RNA) and the detection system. These barcodes are incorporated into capture probes that specifically bind to target analytes while carrying spatial location information, thereby enabling precise and reliable spatial analysis of intact tissues without direct imaging of the analytes themselves
Solution Approach 2:
The patent replaces traditional mechanical or optical imaging methods with a molecular-based detection system using nucleic acid capture probes and spatial barcodes. This substitution allows for higher specificity and sensitivity by utilizing the high-affinity binding properties of nucleic acid hybridization and antibody-antigen interactions, rather than relying on physical sectioning or direct optical detection
2Quantity of substance
If dissociated tissue analysis is performed to obtain detailed analyte data, then single-cell analyte information is achieved, but spatial position information is lost
Solution Approach 1:
The patent applies preliminary action by incorporating spatial barcodes into capture probes before they contact the biological sample. This pre-programming of spatial information allows the system to capture both the analyte quantity and its original spatial position simultaneously, eliminating the need for subsequent spatial reconstruction that would be required after tissue dissociation
Solution Approach 2:
The patent creates a molecular copy of the spatial information through spatial barcodes that are transferred to the captured analytes. Each capture probe carries a unique spatial barcode that copies the location information from its position in the tissue array, allowing spatial position to be preserved and recorded alongside the analyte data without physically maintaining the tissue structure
3Adaptability or versatility
If conventional spatial analysis methods are used, then limited analyte information is obtained, but the methods cannot provide comprehensive data for both targeted and global analysis
Solution Approach 1:
The patent implements universality by designing a single integrated platform that can perform both targeted analysis (for specific genes or proteins of interest) and global analysis (for comprehensive transcriptome or proteome profiling) using the same capture probe technology and spatial barcode system. The system can be configured to detect any analyte type through appropriate probe design, making it adaptable to various research questions while maintaining high analytical capacity
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 allows for precise spatial analysis of analytes, improving the understanding of spatial heterogeneity in disease models by accurately determining the location and abundance of proteins, DNA, or RNA within biological samples while maintaining sensitivity and specificity.
Implementation Method 1
contacting the biological sample and/or the array with a reagent medium comprising a monovalent salt or divalent salt, and releasing the capture agent barcode domain from the analyte capture agent
Implementation Method 2
hybridizing the capture handle sequence of the capture agent barcode domain to the capture domain
Data Source
AI summary
Provided herein are methods for spatial analysis of proteins and/or nucleic acids by capturing a capture handle sequence and/or a connected probe to a capture domain of a capture probe on a spatial array. In some instances, a reagent medium including a monovalent or divalent salt, ethylene carbonate, and/or glycerol is used in the disclosed methods.