Spatial Analysis Using Degradable Hydrogels
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Solution Overview
Problem
Current spatial transcriptomics methods fail to efficiently select and analyze specific regions of interest within biological samples, leading to unnecessary downstream processing and resource wastage, as they lack the ability to pinpoint analyte locations and abundances at a high spatial resolution.
Innovation Solution
The use of a hydrogel with modifiable properties, such as degradation by chemical or physical means, to expose regions of interest for analyte detection, allowing for targeted analysis by aligning the biological sample with a substrate containing capture probes, degrading the hydrogel at specific areas, and hybridizing analytes to capture domains for sequence determination.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If spatial transcriptomics is performed on the entire biological sample, then comprehensive analyte data is obtained, but downstream processing time, reagent consumption and cost increase significantly
Solution Approach 1:
The biological sample is divided into distinct regions of interest (ROIs) based on spatial coordinates. Only the ROI containing the target analyte undergoes downstream processing, while other regions are excluded. This segmentation approach maintains comprehensive analyte data coverage for the relevant region while dramatically reducing processing time and resource consumption compared to analyzing the entire sample.
Solution Approach 2:
The method applies different processing qualities to different regions of the sample. The ROI receives full analytical processing with high-quality downstream steps, while non-ROI regions are excluded from processing. This local quality differentiation ensures comprehensive data for the target analyte location while minimizing unnecessary processing elsewhere, resolving the contradiction between data completeness and processing efficiency.
2Quantity of substance
If spatial transcriptomics is performed on the entire biological sample, then comprehensive analyte data is obtained, but reagent consumption and cost increase
Solution Approach 1:
By segmenting the sample into ROI and non-ROI regions, the method limits reagent consumption to only the necessary area. The ROI is identified through spatial coordinates, and downstream reagents are applied exclusively to this region, preventing wasteful consumption across the entire sample while maintaining comprehensive analyte data for the target region.
Solution Approach 2:
The method implements local quality by providing full analytical processing with all necessary reagents only to the ROI, while excluding non-ROI regions from processing. This ensures that reagent consumption is optimized for the specific location of interest, reducing overall reagent usage and cost while preserving complete analyte data coverage for the relevant region.
3Loss of information
If the entire biological sample is processed, then complete spatial information is obtained, but experimental settings and complexity increase
Solution Approach 1:
The method performs preliminary identification of the ROI using spatial coordinates before initiating downstream processing. This preliminary action establishes the exact location and boundaries of the region containing the target analyte, allowing subsequent experimental steps to be configured specifically for this region. This reduces experimental complexity by pre-defining processing parameters for the ROI while maintaining complete spatial information for the target analyte.
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 reduces downstream reagents and time, increases targeted analysis, and provides high spatial resolution data by selectively processing only the region of interest, thereby enhancing the efficiency and cost-effectiveness of spatial transcriptomics.
Implementation Method 1
degrading the portion of the hydrogel comprises exposing the region of interest to UV light, laser light
Implementation Method 2
degrading the portion of the hydrogel comprises exposing the region of interest to UV light, laser light
Data Source
AI summary
Provided are methods of capturing an analyte from a biological sample using a hydrogel that includes capture probes to capture the analyte, identifying a region of interest of the biological sample, and isolating the region of interest from the biological sample by removing a portion of the hydrogel that corresponds to the region of interest. Compositions and kits for performing the methods are also provided.