Spatial Barcode Capture Probes for Biological Analyte Localization
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Solution Overview
Problem
Current methods for studying spatial heterogeneity in biological samples, such as tissues, fail to provide comprehensive information on the position of single cells within a tissue sample, often relying on a limited set of pre-defined markers and introducing selection bias, which is costly and laborious.
Innovation Solution
The use of substrates with immobilized capture probes that include spatial barcodes and capture domains, allowing for the binding, amplification, and detection of biological analytes within a sample to determine their location through sequential hybridization and detection processes, including techniques like RNA-Seq and fluorescence in situ hybridization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If traditional methods using pre-defined markers are used to study spatial heterogeneity, then the analysis can be performed with established protocols, but the methods introduce selection bias, provide limited analyte coverage, and require costly and laborious procedures
Solution Approach 1:
The patent employs universal capture probes that can bind to multiple different analyte types (mRNA, DNA, proteins) through a common capture mechanism. The spatial barcode system provides a universal framework for localizing any analyte of interest, eliminating the need for analyte-specific localization protocols and enabling comprehensive multi-analyte analysis within a single experimental workflow
Solution Approach 2:
The method segments the complex task of spatial analysis into distinct functional components: (1) capture probes with specific binding domains for target recognition, (2) spatial barcodes for location encoding, and (3) sequencing/detection systems for data readout. This modular segmentation allows each component to be optimized independently while maintaining overall system versatility and reducing procedural complexity
2Loss of information
If comprehensive spatial analysis of multiple analytes is performed, then detailed insights into analyte distribution are obtained, but the cost and labor required increase significantly
Solution Approach 1:
The patent merges multiple analytical functions into a single integrated workflow: spatial localization, analyte capture, and molecular identification are combined into one sequential process using the same physical substrate and detection system. This consolidation eliminates the need for separate experimental procedures for each analyte, thereby retaining comprehensive spatial information while reducing overall analysis time and resource requirements
Solution Approach 2:
The method uses molecular copying through PCR amplification of captured analytes, generating sufficient signal from minimal starting material. This amplification step enables comprehensive analysis of multiple analytes without requiring large amounts of sample or repeated experiments, thus preserving spatial information while accelerating the analysis 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
Enables high-resolution, cost-effective localization of biological analytes within biological samples while retaining native spatial context, providing detailed insights into analyte distribution and function.
Implementation Method 1
contacting the biological sample with the substrate; permeabilizing the biological sample under conditions sufficient to allow a biological analyte within the biological sample to bind to a capture probe
Implementation Method 2
amplifying the biological analyte bound to the capture probe to generate an amplicon
Implementation Method 3
analyzing the amplicon by sequential hybridization and detection with a plurality of labelled probes, thereby determining the location of the biological analyte within the biological sample
Data Source
AI summary
Provided herein are methods of determining a location of a biological analyte in a biological sample.