Multistage Dielectrophoretic Filter for Extracellular Vesicle Purification

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Solution Overview

Problem

Current methods for detecting extracellular vesicle biomarkers are limited by low sensitivity and specificity, requiring laborious concentration techniques and often resulting in inaccurate results.

Innovation Solution

A multistage dielectrophoretic (DEP) filter system and an extracellular vesicle (EV) analysis system are used to purify and quantify EV-associated biomarkers. The DEP filter system employs a chip-based electrode array to separate and concentrate EVs from biological samples, while the EV analysis system enhances biomarker detection through improved quantitation methods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescence-based detection methods are used for EV biomarker analysis, then detection can be performed, but sensitivity and specificity are limited

Engineering Contradiction:

Improvedetection sensitivity and specificityVSAvoiddetection accuracy

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The system segments the detection process into multiple independent stages: EV concentration, purification, and detection. Each stage is performed in separate microfluidic chambers, allowing optimization of each individual step and eliminating the limitations of single-step fluorescence detection

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent replaces fluorescence-based optical detection with label-free detection methods such as interferometric reflectance imaging sensor (IRIS) technology. This substitution eliminates the need for fluorescent labels and enables detection without the sensitivity and specificity limitations of fluorescence-based methods

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Ease of operation

If dilute circulating concentrations of EV are used for detection, then liquid biopsy can be performed, but sensitivity and accuracy are reduced

Engineering Contradiction:

Improveliquid biopsy capabilityVSAvoiddetection sensitivity and accuracy

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The system performs preliminary concentration and purification of EVs from dilute biological samples before detection. Microfluidic devices pre-concentrate EVs from large volumes of blood or other body fluids, transforming dilute samples into concentrated formats suitable for sensitive detection

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent introduces microfluidic concentration and purification chambers as intermediary steps between sample collection and detection. These intermediary devices serve as mediators that enhance the concentration of EVs from dilute samples, enabling sensitive detection without requiring large volumes of concentrated starting material

Inventive Principle:

Principle #24Intermediary (Mediator)

3Quantity of substance

If laborious concentration methods like centrifugation are used, then EV concentration can be achieved, but the process becomes time-intensive and complex

Engineering Contradiction:

ImproveEV concentrationVSAvoidprocessing time

Core Design Contradiction:

Quantity of substanceVSLoss of time

Solution Approach 1:

The patent replaces traditional mechanical centrifugation methods with electric field-based manipulation techniques in microfluidic devices. Dielectrophoresis and other electric field methods concentrate EVs rapidly without the mechanical complexity and time requirements of centrifugation

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The system changes the physical parameters of the detection environment by controlling temperature, electric field strength, and fluid flow rates in microfluidic channels. These parameter changes enable rapid EV concentration and purification without requiring time-intensive centrifugation protocols

Inventive Principle:

Principle #35Parameter changes

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 proposed systems achieve a high recovery and purity of EVs, with EV recovery ranging from 15% to 99% and purity up to 99%. Additionally, the EV analysis system provides improved biomarker quantification, capable of detecting biomarkers across several orders of magnitude in the input sample.

Implementation Method 1

A multistage dielectrophoretic (DEP) filter system employs a chip-based electrode array to separate and concentrate EVs from biological samples

Methodology Applied

Scientific EffectDielectrophoresis: Dielectric

Data Source

PatentUS20250114799A1Multistage Dielectrophoretic Filter System for Extracellular Vesicles

Publication Date: 2025.04.10 EXOKERYX INC

AI summary

In one embodiment, a system includes a multistage dielectrophoretic filter system for purification of extracellular vesicles from a complex sample comprising an array of fluidic cells having electrodes that receive and process the sample, fluid transfer devices, actuated valves, storage containers, an electronic control board and power supply. In another embodiment, an extracellular vesicle analysis system for analyzing biomarkers in the purified extracellular vesicles is described. In yet another embodiment are described methods for purifying extracellular vesicles, and analyzing extracellular vesicle biomarker profiles for identifying subjects for treatment or for diagnosis.