Flow Cell Solid Support Assembly for Tissue Adherence Stability
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Solution Overview
Problem
Flow cells used in next-generation sequencing face challenges in maintaining tissue integrity during sequencing processes, particularly for in situ transcript detection in tissues, due to tissue delamination and wrinkling of thin sections, leading to non-uniform reagent exposure and target detection inefficiencies.
Innovation Solution
A flow cell assembly is developed with a first solid support, a polymer or resist attached to it, a coupling agent, and a second solid support configured to define a reaction chamber, ensuring robust tissue adherence and fluidic communication through ports, using pressure-sensitive adhesives for leak-free seals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If thin tissue sections (5-7 μm) are used for sequencing, then detection sensitivity is improved, but tissue structural integrity deteriorates due to wrinkling and delamination
Solution Approach 1:
The patent introduces an intermediary layer comprising a polymer coating and coupling agent between the thin tissue section and the solid support. This intermediary structure mediates the interaction, providing mechanical reinforcement to the fragile tissue while maintaining its thin profile for sensitive detection, thereby preventing wrinkling and delamination during processing
Solution Approach 2:
The patent employs a composite structure consisting of multiple functional layers: a polymer coating layer (such as poly-L-lysine or poly-D-lysine) combined with a coupling agent layer (such as silane-based agents). This composite material system provides both mechanical support to prevent tissue deformation and chemical bonding capability to secure tissue adherence, resolving the contradiction between tissue thinness and structural integrity
2Productivity
If repetitive reagent exchanges are performed during sequencing, then sequencing throughput is improved, but tissue delamination increases
Solution Approach 1:
The patent applies preliminary action by pre-coating the solid support with polymer and coupling agent layers before tissue section placement. This preliminary preparation creates a robust adhesive interface that is established in advance, enabling the tissue to withstand subsequent repetitive reagent exchanges and mechanical handling without delamination, thus maintaining reliable adherence throughout the sequencing process
3Productivity
If thermal changes are applied during sequencing, then sequencing efficiency is improved, but tissue degradation accelerates
Solution Approach 1:
The patent implements beforehand cushioning by creating a protective polymer-coupling agent interface layer prior to thermal processing. This cushioning layer acts as a protective barrier that stabilizes the tissue-solid support interface during thermal changes, reducing thermal stress-induced delamination and degradation while allowing necessary thermal cycles for sequencing to proceed
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
The assembly maintains tissue stability and integrity during sequencing, enabling efficient detection of biomolecules and preserving biological information, even after multiple cycles, with improved uniformity and accuracy.
Implementation Method 1
a polymer attached to the first solid support; a resist attached to the first solid support
Implementation Method 2
a coupling agent attached to the first polymer; a coupling agent attached to the resist
Implementation Method 3
using pressure-sensitive adhesives for leak-free seals
Data Source
AI summary
Disclosed herein, inter alia, are compositions and methods of use of solid supports useful for tissue adherence and/or retention.