Tetanus Toxin Fragment for Selective Neuron-Derived Extracellular Vesicle Capture

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Solution Overview

Problem

Current methods for isolating and measuring neuron-derived extracellular vesicles (NDEVs) from biological samples are not selective enough, making it difficult to accurately evaluate neurodegeneration.

Innovation Solution

A method using a tetanus toxin C-terminal fragment (TTC) to selectively capture NDEVs by forming a complex with a detector and labeling substance on a solid phase, allowing for their measurement and isolation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If ultracentrifugation or size exclusion chromatography is used to collect EVs, then EVs can be comprehensively collected from biological samples, but the method lacks selectivity and cannot specifically isolate neuron-derived EVs

Engineering Contradiction:
ImproveEV collection efficiencyVSAvoidEV source identification accuracy
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent uses an affinity ligand as an intermediary substance that specifically recognizes and binds to neuron-derived EVs. This ligand acts as a mediator between the biological sample containing mixed EVs and the collection system, enabling selective capture of neuron-derived EVs while excluding other EV types through specific molecular recognition

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies local quality by functionalizing specific regions of the collection substrate with affinity ligands that have neuron-specific binding properties. This creates localized binding sites with selective recognition capability, allowing the system to differentiate and capture neuron-derived EVs from other EV populations based on their unique surface characteristics

Inventive Principle:
Principle #3Local quality

2Quantity of substance

If conventional EV collection methods are used, then all EVs are captured, but the complexity of the sample increases making it difficult to evaluate neurodegeneration

Engineering Contradiction:
ImproveEV recovery rateVSAvoidSample composition complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent extracts neuron-derived EVs from the complex mixture of all EVs in the biological sample by using affinity-based selective binding. This extraction process isolates the specific subpopulation of neuron-derived EVs that are relevant to neurodegeneration evaluation, removing other EV types that would complicate the analysis

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The affinity ligand serves as an intermediary that selectively bridges neuron-derived EVs to the collection system, enabling the separation of this specific EV subpopulation from the complex biological sample matrix, thereby simplifying the sample composition for downstream neurodegeneration assessment

Inventive Principle:
Principle #24Intermediary (Mediator)

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

Enables specific capture and measurement of NDEVs, providing indicators for neurodegeneration and allowing for the isolation of these vesicles for further analysis.

Implementation Method 1

it has been reported that a substance contained in EV functions as an intercellular information transfer molecule and is involved in various physiological or pathological processes. For example, in the nervous system, EVs containing a causative protein of neurodegenerative disease may be released from cells at the lesion site and spread to other cells

Methodology Applied
Scientific EffectAffinity binding:

Implementation Method 2

a detector that specifically binds to a target molecule of NDEV

Methodology Applied
Scientific EffectSpecific binding:

Implementation Method 3

measuring extracellular vesicles having the target molecule based on a signal generated by the labeling substance contained in the complex

Methodology Applied
Scientific EffectSignal generation:

Data Source

PatentUS20240329060A1Method for measuring extracellular vesicles, method for acquiring information on neurodegeneration, method for isolating extracellular vesicles, and reagent kit
Publication Date: 2024.10.03 SYSMEX CORP
  • US20240329060A1 patent drawing
  • US20240329060A1 patent drawing
  • US20240329060A1 patent drawing

AI summary

Disclosed is a method for measuring neuron-derived extracellular vesicles in a biological sample in vitro, the method comprising: forming a complex comprising a capture body comprising a tetanus toxin C-terminal fragment, the extracellular vesicle, a detector that specifically binds to a target molecule of the extracellular vesicle, and a labeling substance on a solid phase; and measuring extracellular vesicles having the target molecule based on a signal generated by the labeling substance comprised in the complex.