DEP Microfluidic Device for Rare Cell Enrichment

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Solution Overview

Problem

Current methods for detecting tumor-derived biomarkers, particularly circulating tumor cells (CTCs) and circulating hybrid cells (CHCs), are limited by the rarity of these cells and the reliance on invasive biopsies. Existing technologies are low-throughput, time-consuming, and often require biased antibody panels, making them inefficient for clinical use.

Innovation Solution

A microfluidic device utilizing dielectrophoretic (DEP) forces to label-free enrich rare cells, such as CHCs, by applying electric fields that create differential polarization between cells and the surrounding media, allowing for phenotypic and genotypic downstream analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current methods (antibody panels, density-based devices, size exclusion filtration) are used to detect CTCs, then tumor-derived biomarkers can be detected, but the detection process is low-throughput and time-consuming due to the rarity of CTCs (1 per 10^6-10^8 leukocytes)

Engineering Contradiction:

Improvedetection sensitivityVSAvoidthroughput

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The patent applies dielectrophoresis to separate cells based on their dielectric properties rather than physical properties like size or density. By applying non-uniform electric fields, the system exploits differences in cellular membrane capacitance and cytoplasmic conductivity to achieve high-throughput separation of rare CTCs from abundant leukocytes, resolving the contradiction between detection sensitivity and throughput

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent replaces mechanical separation methods (density-based devices, size exclusion filtration, antibody-based capture) with an electrical field-based dielectrophoretic system. This substitution enables label-free, high-throughput separation that overcomes the limitations of mechanical and biochemical methods for rare cell detection

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If invasive biopsy methods are used for cancer detection, then accurate diagnosis can be obtained, but the procedure is risky and invasive for patients

Engineering Contradiction:

Improvediagnosis accuracyVSAvoidpatient risk

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent uses circulating tumor cells (CTCs) and circulating hybrid cells (CHCs) as intermediary biomarkers that can be non-invasively obtained from blood samples. These circulating cells serve as proxies for primary tumor tissue, enabling accurate molecular profiling and diagnosis without requiring invasive tissue biopsy procedures

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent extracts and analyzes tumor-derived biomarkers (CTCs and CHCs) from peripheral blood, removing the need to physically access and sample the primary tumor site. This extraction approach maintains diagnostic accuracy while eliminating the risks associated with invasive tissue biopsy procedures

Inventive Principle:

Principle #2Taking out (Extraction)

3Quantity of substance

If existing CTC enrichment technologies are used, then circulating biomarkers can be isolated, but the methods rely on biased antibody panels and single physical properties, limiting their effectiveness

Engineering Contradiction:

Improvecell enrichmentVSAvoidmethod flexibility

Core Design Contradiction:

Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

The dielectrophoretic system provides a universal platform for cell separation that is not limited to specific cell types or markers. By adjusting electric field parameters (frequency, amplitude, waveform), the same device can enrich various rare cell populations (CTCs, CHCs, exosomes) from different biological samples, achieving both high enrichment efficiency and broad method versatility

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 DEP-based microfluidic device enables efficient enrichment of rare cell populations like CHCs from small blood samples, improving the effectiveness and efficiency of liquid biopsy for tumor-derived biomarker detection, and facilitating clinically relevant analyses such as KRAS mutation status in PDAC tumors.

Implementation Method 1

The at least one array of electrodes is configured to apply dielectrophoretic (DEP) forces to the fluid flowing through the microfluidic chamber

Methodology Applied

Scientific EffectDielectrophoresis: Dielectric

Data Source

PatentUS20250153190A1Methods and systems for sorting particles in fluids

Publication Date: 2025.05.15 OREGON HEALTH & SCI UNIV

AI summary

Described herein are systems and methods for sorting particles in fluids. Systems may comprise a microfluidic chamber, at least one array of electrodes arranged on the substrate, and a controller. The microfluidic chamber is configured to allow fluid to flow therethrough. The microfluidic chamber includes a substrate. The at least one array of electrodes is arranged on the substrate. The at least one array of electrodes is configured to apply dielectrophoretic (DEP) forces to the fluid flowing through the microfluidic chamber. A respective electrode of the at least one array of electrodes is configured to have a V-shape. The controller is configured to control the at least one array of electrodes.