Fluid Delivery Chamber With Spacer for Spatial Analyte Capture
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Solution Overview
Problem
Existing methods fail to provide spatial context for analyte data from biological samples, particularly in preserving the position of single cells within a tissue, necessitating improved fluidics behavior to maintain analyte spatial context for capture.
Innovation Solution
A method involving substrates with spacers to form a chamber that maintains separation distance and uses hydrophobic areas to remove bubbles, along with controlled fluid delivery and permeabilization reagents to deliver fluids to biological samples and arrays, ensuring spatial context is preserved.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If analytes are released through disruption of the biological sample, then analyte data can be obtained, but spatial context of the analytes is lost
Solution Approach 1:
A reagent medium is introduced as an intermediary substance that facilitates the migration of analytes from the disrupted biological sample to the array while preserving spatial information. The medium enables controlled transport without losing the positional context of the analytes throughout the migration process.
Solution Approach 2:
The patent replaces traditional mechanical disruption methods with a permeabilization approach that allows controlled release of analytes. This substitution enables analyte release while maintaining spatial structure, as the permeabilization process allows diffusion through modified cell membranes rather than complete mechanical breakdown.
2Loss of information
If reagent medium is used to deliver analytes to the array, then spatial context is preserved, but fluidics behavior must be optimized
Solution Approach 1:
The patent optimizes fluidics behavior by carefully controlling parameters of the reagent medium, including its composition, viscosity, and flow characteristics. These parameter adjustments ensure that the medium maintains analytes in their spatial context while enabling effective migration to the array for capture.
3Loss of information
If substrates are used to hold biological sample and array, then spatial context is maintained, but bubble removal is challenging
Solution Approach 1:
The patent converts the harmful effect of bubbles into a beneficial process by utilizing hydrophobic areas on the substrates. These hydrophobic regions cause bubbles to be repelled and automatically removed from the chamber during fluid delivery, transforming a common problem into an automated solution that maintains spatial context without requiring manual bubble removal.
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
Preserves the spatial context of analytes during capture, enabling effective analysis of biological samples by maintaining the position of single cells within a tissue.
Implementation Method 1
The second substrate includes a hydrophobic area positioned away from a region of interest. The hydrophobic area may be configured to remove bubbles in the fluid from the chamber.
Implementation Method 2
The spacer is configured to maintain the fluid within the chamber and maintain a separation distance between the first substrate and the second substrate.
Implementation Method 3
Analytes from a biological sample (e.g., within the biological sample) can be released through disruption (e.g., via permeabilization).
Data Source
AI summary
Provided herein is a fluid delivery method for permeabilizing a biological sample. The method includes delivering the fluid to a first substrate and/or a second substrate. At least one of the first substrate and the second substrate includes a spacer. The method further includes assembling, subsequent to the delivering, a chamber comprising the first substrate, the second substrate, the biological sample, and the spacer. The spacer may be disposed between the first substrate and second substrate. The spacer may be configured to maintain the fluid within the chamber and maintain a separation distance between the first substrate and the second substrate. The spacer may be positioned to at least partially surround an area on the first substrate on which the biological sample is disposed and/or at least partially surround the array disposed on the second substrate.