Hydrophobic Sealing for High-Resolution Spatial Analyte Capture
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Solution Overview
Problem
Existing spatial analysis techniques fail to provide information on the position of single cells within a biological sample, and methods to isolate regions of interest often damage analytes or generate excessive data.
Innovation Solution
A method involving a substrate with capture probes and a sealant to capture analytes from a region of interest by creating a hydrophobic seal around non-interest regions, preventing interaction with capture domains, thereby increasing sequencing depth and unique molecular identifier counts.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If mechanical or enzymatic removal is used to isolate regions of interest, then spatial resolution is improved, but analytes are damaged
Solution Approach 1:
A hydrophobic sealant is applied to create a flexible barrier around regions of interest on the tissue section. This thin film seal prevents analytes from non-interest regions from interacting with capture probes while preserving analytes in the sealed regions, achieving spatial isolation without mechanical or enzymatic damage
Solution Approach 2:
The hydrophobic sealant acts as an intermediary barrier between analytes in different tissue regions and the capture probes. By selectively sealing non-interest regions, the sealant mediates which analytes can interact with capture probes, enabling spatial resolution without direct manipulation or damage to the tissue or analytes
2Loss of information
If whole tissue analysis is performed, then comprehensive data is obtained, but resource consumption increases
Solution Approach 1:
The method extracts and isolates only the regions of interest from the whole tissue for analysis. By applying hydrophobic seals to non-interest regions, only analytes from unsealed regions interact with capture probes, extracting relevant information while excluding unnecessary data and reducing sequencing and computational resources required
3Measurement precision
If regions of interest are isolated using traditional methods, then spatial focus is improved, but tissue structure is damaged
Solution Approach 1:
The hydrophobic sealant forms a flexible barrier that isolates non-interest regions without mechanical disruption. This thin film approach maintains tissue morphology and structure in both sealed and unsealed regions, preserving tissue integrity while achieving spatial focus for analysis
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
Enhances spatial analysis resolution by increasing sequencing depth, reads per spot, and unique molecular identifier counts for the region of interest, allowing for more focused transcriptomic studies.
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.