Microwell Slide for High-Resolution Spatial Omic Detection
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Solution Overview
Problem
Current spatial omic detection methods, such as the 10×Visium product, face limitations including low resolution, uneven printing, cross-contamination, and high costs due to the inkjet printing technique and requirement for full-length oligonucleotide synthesis, which restricts high-resolution single-cell analysis and increases operational complexity.
Innovation Solution
A method utilizing a slide with a microwell reaction chamber array where microcarriers are dispersed, allowing for high-resolution spatial omic detection by ligating unique molecular identifiers to the microcarriers, reducing cross-contamination through a porous membrane, and simplifying the preparation process, thereby enhancing resolution and cost-effectiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If inkjet printing technique is used to prepare oligonucleotide sequence array, then device complexity is reduced, but manufacturing precision deteriorates due to uneven printing and maximum resolution limit of 55 μm
Solution Approach 1:
The patent replaces the mechanical inkjet printing system with a microfluidic-based chemical bonding system. Microchannels guide liquid reagents to precisely deposit oligonucleotide sequences at designated positions through fluid flow control and chemical bonding, eliminating the mechanical printing head and achieving higher precision without increasing device complexity
Solution Approach 2:
The patent employs a porous membrane within the microfluidic device to enable selective transport and positioning of oligonucleotide sequences. The porous structure allows precise control of liquid flow and sequence deposition at the micrometer scale, achieving manufacturing precision beyond inkjet printing capabilities
2Measurement precision
If full-length oligonucleotide synthesis is performed, then detection precision is improved, but loss of substance increases due to high material consumption and cost
Solution Approach 1:
The patent segments the oligonucleotide synthesis process into modular components within the microfluidic device. Instead of synthesizing full-length sequences in one step with high material consumption, the device performs sequential assembly of shorter oligonucleotide fragments, reducing material loss while maintaining detection precision through stepwise construction
Solution Approach 2:
The patent applies partial action by synthesizing only the necessary portions of oligonucleotide sequences required for detection, rather than producing complete full-length sequences. This partial synthesis approach reduces material consumption while maintaining sufficient detection precision for the application
3Productivity
If tissue permeabilization is performed without spatial confinement, then productivity is improved, but object-generated harmful factors increase due to cross-contamination between adjacent regions
Solution Approach 1:
The patent segments the tissue sample into spatially isolated compartments using microwell structures. Each microwell contains individual microcarriers and processes tissue regions separately, enabling high-throughput processing while preventing cross-contamination between adjacent tissue areas through physical compartmentalization
Solution Approach 2:
The patent introduces a porous membrane as an intermediary barrier between adjacent microwell compartments. This membrane allows controlled substance transfer while maintaining spatial separation, enabling productivity improvement through parallel processing while minimizing cross-contamination through the intermediary filtering structure
4Measurement precision
If single-cell resolution is achieved, then measurement precision is improved, but device complexity increases due to high requirements on detection techniques and imaging systems
Solution Approach 1:
The patent replaces complex single-molecule fluorescence imaging systems with a microfluidic-based chemical detection system. By using controlled chemical bonding and fluid transport at the microscale, the device achieves single-cell resolution through simpler mechanical and chemical mechanisms rather than sophisticated optical imaging
Solution Approach 2:
The patent changes the detection parameter from fluorescence signal intensity to spatial positioning and chemical bonding specificity. By measuring the position and bonding characteristics of oligonucleotide sequences rather than relying on sensitive fluorescence detection, the system achieves single-cell resolution with reduced device complexity
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 method achieves high-resolution spatial omic detection with reduced cross-contamination and operational complexity, enabling single-cell resolution and cost-effective analysis, while avoiding full-length synthesis and transverse diffusion issues.
Implementation Method 1
transverse diffusion of spatial omic information in a tissue sample is effectively reduced
Implementation Method 2
spatial omic information of the tissue sample is captured in situ by the oligonucleotide sequence
Data Source
AI summary
A device, system, and method for high-resolution spatial omic detection of a tissue sample are provided, which include a slide with a microwell reaction chamber array capable of accommodating microcarriers, a method for modifying a nucleic acid molecular identifier, and a method for reducing cross pollution of omic information in a process of capturing spatial omic information of a tissue sample, respectively. By using the method for spatial omic detection, the resolution of the spatial omic detection is significantly improved and the detection cost is reduced, and the cross pollution of the spatial omic information is fundamentally reduced.