Spatial Analysis Hydrophobic Sealing for Analyte Isolation
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Solution Overview
Problem
Existing spatial analysis techniques fail to provide high-resolution data on the position of single cells within a biological sample, often damaging analytes through mechanical or enzymatic removal of non-interest areas, and lack efficient methods to isolate specific regions of interest within a tissue.
Innovation Solution
A method involving a sealant to create a hydrophobic seal around non-interest regions, preventing analyte interaction with capture probes, while allowing analytes from the region of interest to be captured and hybridized with spatially-barcoded capture probes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If mechanical or enzymatic removal is used to isolate regions of interest, then spatial resolution is improved, but analyte damage increases
Solution Approach 1:
The tissue section is segmented into regions of interest and regions not of interest using hydrophobic seals that create distinct compartments. This allows selective analysis of specific areas without physically removing or damaging the tissue, resolving the contradiction between spatial resolution and analyte preservation.
Solution Approach 2:
A hydrophobic seal acts as an intermediary barrier between regions of interest and regions not of interest. This seal prevents analytes from non-interest areas from interacting with capture probes while allowing analytes from interest areas to be captured, achieving high spatial resolution without damage.
2Loss of information
If whole tissue analysis is performed, then comprehensive data is obtained, but resource consumption increases
Solution Approach 1:
The method applies local quality by treating different regions of the tissue differently - regions of interest are left open for analyte capture while regions not of interest are sealed off. This selective approach reduces resource consumption by focusing analysis only on relevant areas while maintaining data comprehensiveness for those specific regions.
Solution Approach 2:
Instead of analyzing the entire tissue section, the method applies partial action by selectively opening only the regions of interest for analyte capture. This reduces the amount of data generated and resources consumed while still obtaining comprehensive information for the specific areas under investigation.
3Ease of manufacture
If regions not of interest are left open, then processing is simpler, but data quality decreases
Solution Approach 1:
The method extracts or removes the influence of regions not of interest by sealing them off with hydrophobic barriers. This prevents analytes from non-interest areas from contaminating the signal from regions of interest, thereby maintaining data quality without requiring complex processing to distinguish between regions.
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
Increases sequencing depth, read number, and unique molecular identifier counts per spot, enhancing the resolution and focus of spatial analysis by isolating and capturing analytes from specific regions of interest.
Implementation Method 1
contacting the second region with a sealant in order to create a hydrophobic seal thereby preventing an interaction between an analyte from the second region with a capture domain of a capture probe
Data Source
AI summary
Provided herein are methods for capturing an analyte from a first region of interest of a biological sample on a substrate, where the biological sample comprises the first region of interest and a second region, and where the method includes contacting the second region with a sealant in order to create a hydrophobic seal thereby preventing an interaction between an analyte from the second region with a capture domain of a capture probe.