Lab-on-a-chip EV Biomarker Detection via Dielectrophoresis
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Solution Overview
Problem
Current methods for disease detection, such as cancer, are invasive, costly, and lack sensitivity and specificity, particularly in detecting low quantities of biomarkers, whereas extracellular vesicles (EVs) offer a stable and continuous source of biomarkers for early disease detection.
Innovation Solution
A digital, multiplexed lab-on-a-chip system using a filter cartridge with dielectrophoresis (DEP) for label-free, nonmechanical isolation of EV-associated biomarkers from biological samples, combined with a software-controlled device for processing and assay performance, enabling minimally invasive and accurate detection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fluorescence-based detection methods are used for EV biomarker detection, then the detection can be performed with current technology, but the sensitivity and specificity are limited
Solution Approach 1:
The patent replaces fluorescence-based optical detection with electronic field-based detection methods. Specifically, it uses dielectrophoresis (DEP) to manipulate EVs based on their electrical properties, and employs electronic sensors to detect EV-associated biomarkers. This substitution of optical methods with electrical/electronic methods enables higher sensitivity and specificity in detecting low quantities of biomarkers, directly resolving the limitation of fluorescence-based methods.
Solution Approach 2:
The patent changes the detection parameters by measuring electrical properties (dielectric characteristics, conductivity) of EVs and their biomarkers instead of optical properties (fluorescence emission). This parameter change allows for more precise detection of EV biomarkers, improving both sensitivity and specificity beyond what fluorescence methods can achieve.
2Measurement precision
If invasive diagnostic methods such as biopsy, CT, MRI, or endoscopy are used, then disease detection can be performed, but the procedures are costly, invasive, and time-intensive
Solution Approach 1:
The patent extracts and detects disease biomarkers from extracellular vesicles present in easily obtainable biological fluids (blood, urine, cerebrospinal fluid) rather than requiring invasive tissue sampling or imaging procedures. By isolating and analyzing EVs from these non-invasive samples, the system achieves accurate disease detection while eliminating the harmful effects associated with biopsy, CT, MRI, and endoscopy procedures.
Solution Approach 2:
The patent uses extracellular vesicles as intermediary carriers that transport biomarkers from diseased cells to the detection system. These EVs serve as a non-invasive proxy for direct tissue examination, allowing disease detection through fluid analysis rather than invasive procedures. The EVs protect and deliver biomarker information from the disease site to the diagnostic platform without requiring direct access to the affected tissue.
3Quantity of substance
If free circulating biomarkers are used for liquid biopsy, then the detection can be performed, but the biomarkers are released only during tumor cell death rather than continuously
Solution Approach 1:
The patent performs preliminary isolation and concentration of EVs from biological fluids before biomarker detection. By pre-concentrating EVs using dielectrophoresis and other separation techniques, the system ensures sufficient biomarker quantity is available for detection even when EV release rates vary. This preliminary preparation step decouples biomarker availability from the timing of cell death events.
Solution Approach 2:
The patent exploits the continuous secretion of EVs by living cells as a sustained source of biomarkers. Unlike intermittent release of free biomarkers during cell death, EVs are continuously produced and released by viable tumor cells, providing a constant stream of biomarker information. The system maintains continuous detection capability by processing EVs as they are present in the biological fluid, ensuring uninterrupted monitoring of disease status.
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 system provides sensitive and specific detection of EV biomarkers, enhancing early disease diagnosis with improved sensitivity and specificity, reducing costs and invasiveness compared to existing methods.
Implementation Method 1
The cartridge unit provided in the present invention consists of a plurality of parts capable of receiving a sample of biological fluid and a series of fluidic channels and valves which distribute the sample to a chip capable of performing an assay. DEP is the translation of a polarized or dielectric particle in a non-uniform electric field. DEP provides a novel isolation technology that brings new capability which exploits the electrical and material properties of EVs to achieve label-free specific capture and high yield recovery.
Implementation Method 2
By using alternating current (“AC”) signal, any electrophoretic forces are effectively averaged out to zero while the DEP force remains, thus separating the desired biomarkers from other biological molecules in a complex mixture such as human plasma or conditioned media.
Data Source
AI summary
The present invention is directed to a system and method for digital, multiplexed, extracellular vesicle-derived biomarker diagnostic lab-on-a-chip and method of use thereof. The present invention provides a minimally invasive system and method for early disease detection using extracellular vesicles as biomarkers for disease. Extracellular vesicles are collected from a fluid biological sample and subjected to a sorting process which provide a purified liquid containing the biomarkers of interest.