Microfluidic Device With Hydrofoil Pillars For CTC Capture

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Solution Overview

Problem

Current CTC isolation technologies lack sensitivity, reliability, ease of use, and cost efficiency, making them unsuitable for routine clinical use, especially due to the rarity of CTCs in blood and the complexity of sample preparation processes.

Innovation Solution

A microfluidic device with symmetric hydrofoil-shaped pillars arranged in a meandering channel, increasing entity/surface interaction by altering the attack angle and maintaining chaotic trajectories, which enhances capture efficiency and reduces clogging risks, while simplifying design and manufacturing processes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional CTC isolation technologies are used, then CTCs can be isolated from blood, but the sensitivity and capture efficiency are insufficient due to the rarity of CTCs (one in a billion blood cells)

Engineering Contradiction:
ImprovesensitivityVSAvoidCTC concentration
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent transforms the isolation approach from relying solely on chemical/biological recognition (2D interaction) to incorporating three-dimensional hydrodynamic focusing and chaotic advection. The meandering channel with pillars creates 3D flow patterns that increase the probability of CTC-pillar collisions, effectively adding a spatial dimension to the capture mechanism and dramatically improving sensitivity for rare cell detection

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The patent changes the flow regime parameters by introducing a meandering channel geometry with specific pillar arrangements. This creates chaotic advection and enhanced mixing that increases the effective collision frequency between CTCs and antibody-coated pillars, thereby improving capture efficiency without requiring higher CTC concentrations

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If pre-enrichment and off-chip immunomagnetic labeling are used, then CTCs can be concentrated before microfluidic analysis, but the pre-processing time is excessively long

Engineering Contradiction:
ImproveCTC concentrationVSAvoidpre-processing time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The patent merges the enrichment and isolation functions into a single integrated microfluidic device. The meandering channel with antibody-coated pillars performs both concentration and separation simultaneously, eliminating the need for separate pre-enrichment steps and reducing total processing time while maintaining effective CTC concentration

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent replaces traditional mechanical pre-processing steps (centrifugation, magnetic separation) with a purely microfluidic approach using hydrodynamic forces and chaotic advection. This substitution eliminates time-consuming mechanical operations while achieving the same enrichment goal through optimized flow dynamics and pillar-induced chaotic trajectories

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

3Ease of operation

If narrow and deep sinusoidal microfluidic channels are used, then cell rolling motion is favored on surfaces, but the channel design is complex and manufacturing is difficult

Engineering Contradiction:
Improvecell rolling motionVSAvoidchannel fabrication
Core Design Contradiction:
Ease of operationVSEase of manufacture

Solution Approach 1:

The patent segments the channel into straight sections connected by meandering sections with pillars, rather than using a continuous narrow deep sinusoidal channel. This segmentation allows each section to have optimized dimensions for manufacturing while collectively achieving the desired cell rolling and chaotic motion effects, simplifying fabrication

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses meandering channel geometry with curved sections connecting straight segments, providing the necessary flow disruption for cell rolling motion while maintaining broader, more manufacturable channel dimensions. The curvature is achieved through standard photolithography patterns rather than requiring complex narrow deep sinusoidal structures

Inventive Principle:
Principle #14Spheroidality (Curvature)

4Ease of operation

If cylindrical pillars with random arrangement are used, then flow path is interrupted and cells can be captured, but the design lacks optimization for maximum capture efficiency

Engineering Contradiction:
Improvecell captureVSAvoidcapture efficiency
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent employs asymmetric pillar cross-sections (e.g., triangular or rectangular) rather than symmetric cylindrical pillars. This asymmetry creates more effective flow disruption and chaotic advection patterns, increasing the probability of CTC-pillar collisions and improving capture efficiency while maintaining a regular grid arrangement for manufacturing simplicity

Inventive Principle:
Principle #4Asymmetry

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 device achieves higher sensitivity and capture efficiency for CTCs, reduces channel clogging, and simplifies design and manufacturing, making it more versatile and cost-effective for biomedical applications.

Implementation Method 1

The pillars are coated with at least one antibody suitable for the specific capture of target biological entities flowing within the capture volume along the streamlines carrying target biological entities

Methodology Applied
Scientific EffectAntibody-antigen interaction: Adsorption

Implementation Method 2

The device enables a continuous change of the attack angle, thus keeping the chaotic trajectories of the biological entities throughout the channel

Methodology Applied
Scientific EffectChaotic advection: Turbulence

Data Source

PatentUS12036554B2Microfluidic device for selective capture of biological entities
Publication Date: 2024.07.16 MIKRO BIYOSISTEMLER ELECTRONICS SANAYI & TICARET AS
  • US12036554B2 patent drawing
  • US12036554B2 patent drawing
  • US12036554B2 patent drawing

AI summary

A microfluidic device is provided. The microfluidic device is used for an in vitro selective capture of biological entities suspended in a medium based on an immunoaffinity technique. The microfluidic device includes symmetric hydrofoil pillars arranged inside ellipse segments acting as a microfluidic channel, wherein the microfluidic channel provides a continuous change of attack angles between the symmetric hydrofoil pillars and the biological entities.