Sequential Analyte Capture on Permeable Substrates
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Solution Overview
Problem
Existing methods for capturing multiple analytes from biological samples often require incompatible agents, leading to inefficiencies and interference when used simultaneously, which can disrupt the native spatial arrangement of analytes in tissue samples.
Innovation Solution
A method involving sequential exposure of biological samples to different fluids containing specific reagents, allowing each analyte to be captured by capture probes on a substrate, preserving the relative spatial arrangement and enhancing the yield of analytes captured.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If single-step release and capture of multiple analytes is performed, then the process is expedient and spatial arrangement is preserved, but incompatible agents interfere with each other reducing capture efficiency
Solution Approach 1:
The single-step capture process is divided into multiple sequential steps, with each step targeting a specific analyte using a compatible release agent. This segmentation eliminates interference between incompatible agents while maintaining overall process efficiency.
Solution Approach 2:
Release agents are applied in a predetermined sequence before capture probes are introduced, ensuring that each analyte is released in advance of its corresponding capture step. This preliminary action prevents cross-interference between agents.
2Reliability
If sequential release and capture of analytes is performed, then agent incompatibility is avoided, but the process time increases
Solution Approach 1:
The sequential process maintains continuous useful action by immediately transitioning from one release-capture cycle to the next without idle intervals. Each step builds upon the previous step, ensuring that time is productively utilized throughout the entire process.
Solution Approach 2:
The method employs periodic cycles of release agent application followed by capture probe introduction, with each cycle optimized for a specific analyte. This rhythmic periodic action structures the sequential process to minimize total duration while ensuring complete capture of all target analytes.
3Productivity
If multiple analytes are captured simultaneously, then the process is efficient, but the native spatial arrangement of analytes is disrupted
Solution Approach 1:
Each release agent and capture probe combination is locally optimized for a specific analyte type or location within the tissue section. This local quality approach ensures that spatial relationships are maintained while enabling efficient capture of multiple different analytes through specialized local interactions.
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 enables the efficient and precise capture of multiple analytes while maintaining their native spatial context, improving the accuracy of spatial analysis in biological samples by avoiding interference between incompatible agents.
Implementation Method 1
Following exposure of the sample to a permeabilizing agent, released analytes diffuse out of the sample and in the direction of the array
Implementation Method 2
positioning a first substrate featuring a plurality of capture probes with respect to a second substrate on which a biological sample comprising multiple analytes is disposed, where the first substrate is permeable
Data Source
AI summary
Methods of capturing multiple analytes from a biological sample onto a substrate include: (a) positioning a first substrate that includes a plurality of capture probes with respect to a second substrate on which a biological sample that includes multiple analytes is disposed, where the first substrate is permeable; (b) delivering a first fluid to a first surface of the first substrate, where the first surface is opposite to a second surface of the first substrate that faces the second substrate; (c) allowing the first fluid to pass through the first substrate and contact the biological sample; (d) capturing a first one of the multiple analytes with one or more of the capture probes; (e) delivering a second fluid to the first surface of the first substrate; (f) allowing the second fluid to pass through the first substrate and contact the biological sample; and (g) capturing a second one of the multiple analytes with one or more of the capture probes. Other methods of capturing analytes from a biological sample are also described herein.