Exosome Isolation via Sequential Immunoaffinity Segmentation
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Solution Overview
Problem
Current methods for isolating exosomes from body fluids are limited in selectively detecting trace amounts of disease-associated exosomes, such as those from cancer cells, due to the heterogeneity of exosome compositions and the presence of non-specific exosomes, which hinders accurate diagnosis.
Innovation Solution
A technique involving sequential immunoaffinity isolation using solid-state immobilization members and reversible linkers to capture and separate specific disease-associated exosomes, allowing for the enrichment of subpopulations and sub-subpopulations for analysis as liquid biopsy samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional exosome isolation methods are used, then all exosomes in body fluids are obtained, but disease-associated exosomes cannot be selectively detected due to heterogeneity and non-specific exosomes
Solution Approach 1:
The patent divides the exosome population into distinct segments based on disease association. By using multiple immunoaffinity isolation steps with different capture materials targeting specific markers (e.g., EpCAM for cancer-associated exosomes, CD63 for normal exosomes), the method segments the heterogeneous exosome population to isolate disease-relevant subsets, thereby improving detection precision without requiring overly complex device architecture
Solution Approach 2:
The patent introduces solid-state immobilization members as intermediaries to facilitate selective capture. These immobilized capture materials act as mediators that bind specifically to target exosomes while allowing non-specific exosomes to pass through. The reversible linkers serve as another intermediary layer, enabling controlled attachment and release of capture materials, thus simplifying the overall isolation process while maintaining high specificity
2Measurement precision
If sequential immunoaffinity isolation is performed multiple times, then enrichment of specific exosomes is improved, but processing time increases
Solution Approach 1:
The patent performs preliminary enrichment in early isolation steps before final analysis. By conducting 1-2 rounds of immunoaffinity isolation with high-capacity solid-state immobilization members, the method pre-concentrates target exosomes to levels sufficient for detection, eliminating the need for excessive sequential processing and reducing total processing time while maintaining high enrichment levels
Solution Approach 2:
The patent uses reversible linkers to enable copying and reuse of solid-state immobilization members. After one isolation cycle, capture materials can be detached and reattached to new immobilization members, allowing the same capture materials to be used multiple times. This reduces the need for大量一次性 materials and streamlines the overall process
3Reliability
If solid-state immobilization members with reversible linkers are used, then specific exosomes are captured with high selectivity, but device structure becomes complex
Solution Approach 1:
The patent extracts the complex reversible linker chemistry from the overall device structure and concentrates it into the immobilization member fabrication process. The solid-state immobilization members are pre-functionalized with reversible linker-capture material conjugates during manufacturing, so that the final device structure remains simple while retaining high selectivity. This separates the complexity of the chemical mechanism from the physical device architecture
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 method enables the accurate separation and enrichment of specific exosomes, minimizing noise from non-specific exosomes and improving diagnostic accuracy for diseases like cancer, enabling early clinical diagnosis and companion diagnostics for personalized treatment.
Implementation Method 1
sequential immunoaffinity isolation using solid-state immobilization members and reversible linkers to capture and separate specific disease-associated exosomes
Data Source
AI summary
The present invention relates to a technique in which a target exosome subpopulation, a sub-subpopulation, or a lower population in human fluid, which is associated with a specific disease, is isolated and recovered in its intact form at high yield to prepare a liquid biopsy sample and analyzed.