Lab-on-a-Chip EV Biomarker Detection via Dielectrophoresis

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Solution Overview

Problem

Current methods for detecting extracellular vesicle biomarkers for early disease diagnosis, such as cancer and neurodegenerative diseases, are limited by low sensitivity and specificity, often relying on invasive and costly techniques, and lack efficient concentration and detection methods.

Innovation Solution

A lab-on-chip diagnostic platform utilizing dielectrophoresis for the concentration and isolation of extracellular vesicles, combined with electrochemical sensors and machine learning algorithms for sensitive and specific biomarker detection, enabling the analysis of multiple biomarkers from biological samples using fluidic multiplexing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

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

Engineering Contradiction:
Improvedetection sensitivityVSAvoiddetection method complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces fluorescence-based optical detection with electrochemical detection methods. Electrochemical sensors directly measure electrical signals from biomarkers, providing superior sensitivity and specificity without requiring complex optical systems. This substitution of detection mechanism resolves the contradiction by achieving higher measurement precision through a fundamentally different detection approach.

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

Solution Approach 2:

The patent changes the detection parameter from optical fluorescence intensity to electrical signals (current, voltage, impedance). This parameter transformation enables direct measurement of biomarker presence and concentration with higher precision, as electrical measurements can detect single-molecule events and provide quantitative data with better signal-to-noise ratios.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If invasive methods such as tissue biopsy and imaging are used for disease detection, then diagnostic accuracy can be achieved, but the procedures are costly and invasive

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidinvasiveness and cost
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses extracellular vesicles as an intermediary carrier to transport biomarkers from tissues to blood. Instead of directly sampling tissues through invasive biopsy, the system detects EVs in minimally invasive blood samples that contain biomarker information from tumor cells, neurons, or other target tissues. This intermediary approach maintains diagnostic accuracy while eliminating the need for direct tissue invasion.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent substitutes mechanical tissue sampling methods with electrochemical detection of biomarkers in fluid samples. By using electrochemical sensors to detect EV-derived biomarkers in blood or other body fluids, the system achieves diagnostic accuracy without requiring physical tissue removal, thereby reducing invasiveness and associated costs.

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

3Productivity

If conventional concentration methods such as centrifugation are used for EV isolation, then the process is simple, but the methods are dirty and brute force lacking efficiency

Engineering Contradiction:
Improveconcentration efficiencyVSAvoidconcentration method complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent replaces mechanical centrifugation and size exclusion methods with dielectrophoresis-based concentration. Dielectrophoresis uses electric fields to selectively concentrate EVs based on their dielectric properties, achieving higher concentration efficiency with cleaner isolation. This electrical field-based approach eliminates the need for harsh mechanical forces and complex multi-step protocols.

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

Solution Approach 2:

The patent changes the concentration mechanism from mechanical force-based (centrifugation) to electrical field-based (dielectrophoresis). By applying alternating electric fields that exploit the dielectric contrast between EVs and surrounding media, the system achieves efficient concentration with minimal contamination, improving productivity through a more elegant physical principle.

Inventive Principle:
Principle #35Parameter changes

4Adaptability or versatility

If single biomarker detection methods are used, then the test is simple, but the ability to detect multiple biomarkers simultaneously is limited

Engineering Contradiction:
Improvemultiplexing capabilityVSAvoidtest system complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent designs a universal electrochemical sensor platform that can detect multiple different biomarkers simultaneously through multiplexing. The sensor array can be configured with different recognition elements (antibodies, aptamers, DNA probes) specific to different biomarkers, allowing a single device to perform multiple detection functions. This multi-functionality enables comprehensive disease profiling without requiring separate tests for each biomarker.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent segments the detection system into parallel electrochemical sensing channels, each capable of detecting a specific biomarker. By organizing sensors in arrays or parallel configurations with independent signal readout, the system can simultaneously monitor multiple biomarkers. This segmentation allows independent optimization of each detection channel while maintaining overall system integration.

Inventive Principle:
Principle #1Segmentation

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 approach enhances the sensitivity and specificity of biomarker detection, facilitating early disease diagnosis with minimally invasive methods, improving the odds of survivability by providing a more efficient and cost-effective means for detecting diseases at an early stage.

Implementation Method 1

A lab-on-chip diagnostic platform utilizing dielectrophoresis for the concentration and isolation of extracellular vesicles

Methodology Applied
Scientific EffectDielectrophoresis:

Implementation Method 2

combined with electrochemical sensors and machine learning algorithms for sensitive and specific biomarker detection

Methodology Applied
Scientific EffectElectrochemical detection:

Data Source

PatentUS20240319201A1Systems and Methods for Digital, Multiplexed, Extracellular Vesicle-Derived Biomarker Diagnostic Lab-on-a-Chip
Publication Date: 2024.09.26 RICE BRYAN JOSEPH
  • US20240319201A1 patent drawing
  • US20240319201A1 patent drawing
  • US20240319201A1 patent drawing

AI summary

This disclosure relates generally to lab-on-chip diagnostic platforms, and in particular, relates to detection of extracellular vesicle biomarkers using lab-on-a-chip diagnostics. The properties of extracellular vesicles provide the opportunity for early detection of biomarkers corresponding to early disease. Combinatorial detection of the presence of multiple cancer-associated biomarkers from extracellular vesicles along with analysis with advanced machine learning algorithms, may be useful for sensitive and specific diagnosis of early cancer and other diseases from biological fluids. Disclosed herein are compositions, methods, and exosome detection apparatus for biomarker detection.