Multiplex Assay Chip for Spatially Resolved Multi-Omics Analysis
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods lack the capability to perform simultaneous, spatially resolved analysis of proteomic, transcriptomic, and genomic information from biological samples, particularly in high-throughput formats, which hinders understanding of molecular distribution within tissues and organs.
Innovation Solution
A multiplex assay chip device with capture beads and a substrate having chambers of varying dimensions, allowing for the capture and sequencing of nucleic acid sequences and proteins, enabling spatially resolved analysis by forming fluidically isolated enclosures with the sample.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional analysis methods are used, then individual molecular analysis is possible, but simultaneous spatially resolved analysis of multiple intracellular components is not achievable
Solution Approach 1:
The device segments the sample into thousands of individual chambers, each containing single cells or small cell groups. This segmentation enables parallel processing of multiple cells while preserving their spatial positions through coordinate mapping, thereby achieving high-throughput analysis without losing spatial distribution information.
Solution Approach 2:
The invention implements a nested structure where chambers are nested within the substrate, capture beads are nested within chambers, and multiple intracellular components (nucleic acids, proteins, metabolites) are analyzed within each chamber. This nested architecture enables simultaneous multi-omics analysis while maintaining spatial resolution.
2Productivity
If high-throughput analysis format is implemented, then parallel processing of multiple cells is achieved, but spatially resolved information is lost
Solution Approach 1:
The device performs preliminary actions by pre-positioning capture beads in specific chambers before sample loading, and establishing the chamber array structure in advance. This preliminary setup enables automatic spatial mapping when cells are loaded, preserving spatial information without compromising high-throughput capability.
Solution Approach 2:
The invention introduces coordinate mapping as an intermediary that links chamber positions to spatial locations in the original tissue sample. This intermediary mechanism enables the translation of high-throughput parallel data back into spatially resolved information, maintaining measurement precision while achieving high productivity.
3Adaptability or versatility
If multiple intracellular components are analyzed simultaneously, then comprehensive molecular profiling is achieved, but device complexity increases
Solution Approach 1:
The device implements universality through standardized chambers that can accommodate various capture beads targeting different analyte types (nucleic acids, proteins, metabolites). The same chamber structure and basic workflow are used for all analyte types, enabling multi-omics analysis without proportionally increasing device complexity.
Solution Approach 2:
The invention achieves multiplexing capability through parameter changes in the capture beads (different capture sequences, antibodies, or probes) rather than changing the fundamental chamber structure. This allows different analytes to be analyzed in parallel using the same device architecture, minimizing complexity increase while maximizing versatility.
4Volume of moving object
If chambers with dimensions larger than bead diameter are used, then capture beads can be properly contained, but fluidic isolation between chambers becomes challenging
Solution Approach 1:
The device applies local quality by creating regions with different dimensional characteristics: larger first regions for bead containment and smaller second regions for fluidic isolation. This local variation in chamber geometry enables both proper bead containment and reliable fluidic separation between adjacent chambers.
Solution Approach 2:
The invention resolves the contradiction by transitioning to three-dimensional chamber design with varying depths and geometries. Chambers have different dimensional characteristics in different regions, allowing sufficient volume for bead containment while maintaining thin separation regions for effective fluidic isolation through the substrate.
Data Source
AI summary
Disclosed are devices and methods capable of determining spatially resolved information from a biological sample including genomic, transcriptomic, and proteomic information.