Microfluidic Chip Isolates Tumor-Derived Extracellular Vesicles

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Solution Overview

Problem

Current methods for isolating tumor-derived extracellular vesicle-miRNAs from plasma for breast cancer diagnosis are time-consuming, have low efficiency, and low selectivity, limiting the effectiveness of liquid biopsy for early detection.

Innovation Solution

A microfluidic chip-based system for continuous flow and molecular reaction engineering is used to isolate and measure miR-9, miR-16, miR-21, and miR-429, providing high throughput, efficiency, and selectivity for breast cancer diagnosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If ultracentrifugation is used to isolate EVs from plasma, then the isolation process is widely applicable, but the process is time-consuming and has low isolation efficiency

Engineering Contradiction:
Improveapplicability of isolation methodVSAvoidisolation efficiency
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

The patent replaces the mechanical ultracentrifugation system with a microfluidic chip-based system that uses affinity capture and continuous flow. The microfluidic device incorporates magnetic beads with antibodies that specifically bind to EV surface markers, allowing isolation through magnetic separation rather than mechanical centrifugation. This substitution enables faster processing while maintaining high isolation efficiency.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Ease of manufacture

If ultracentrifugation is used to isolate EVs from plasma, then the method is widely applicable, but the selectivity for cancer-related EVs is low

Engineering Contradiction:
Improveapplicability of isolation methodVSAvoidselectivity for cancer-related EVs
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent applies local quality by functionalizing specific regions of the microfluidic chip with cancer-specific antibodies. The magnetic beads are coated with antibodies that recognize tumor-specific surface markers on EVs, creating localized capture zones with high specificity for cancer-related EVs while leaving other regions unaffected. This targeted approach enhances selectivity without requiring complete redesign of the isolation system.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent introduces magnetic beads coated with cancer-specific antibodies as an intermediary between the plasma sample and the isolation process. These beads selectively bind to cancer-related EVs through antigen-antibody recognition, acting as a mediator that enriches the target population before final separation. This intermediary step significantly improves selectivity for tumor-derived EVs.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If affinity-based EV purification is used, then selectivity for cancer-related EVs is improved, but the process requires complex steps including binding, washing, and concentrating

Engineering Contradiction:
Improveselectivity for cancer-related EVsVSAvoidprocess complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges multiple isolation steps into a single integrated microfluidic device. The chip combines affinity capture, magnetic separation, and concentration functions in one continuous flow process. Sample loading, EV capture on magnetic beads, and bead separation occur sequentially within the same device without requiring separate binding, washing, and concentrating steps, thereby simplifying the overall process while maintaining high selectivity.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent implements continuous flow processing where plasma samples continuously pass through the microfluidic chip, allowing constant EV capture and separation. This continuous operation eliminates the batch processing interruptions inherent in traditional methods, maintaining uninterrupted affinity capture and magnetic separation throughout the isolation process, thus reducing complexity and improving throughput.

Inventive Principle:
Principle #20Continuity of useful action

Data Source

PatentUS20240115660A1Soluble TREM2 protein and uses thereof
Publication Date: 2024.04.11 THE CATHOLIC UNIV OF KOREA IND ACADEMIC COOP FOUND
  • US20240115660A1 patent drawing
  • US20240115660A1 patent drawing
  • US20240115660A1 patent drawing

AI summary

The present invention relates to a composition for preventing or treating heart failure including TREM2 protein or a fragment thereof as an active ingredient. The TREM2 protein or fragment thereof according to the present invention can be prepared as a soluble form and used as an injection, and when injected into the body, it promotes functional and structural improvement of the infarcted heart, and is effective for preventing or treating heart failure, and more specifically, it can be advantageously used for preventing or treating heart failure that appears as a sequela of myocardial infarction.