Microfluidic Separation Device for Rare Cell Isolation

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Solution Overview

Problem

Conventional magnetic-activated cell sorting methods for isolating circulating rare cells, such as circulating tumor cells, are inefficient due to manual processes that lead to particle loss and require multiple stages, making it difficult to capture and detect these cells at low concentrations in blood samples.

Innovation Solution

A microfluidic separation device with a mixing channel, incubation channel, and separation channel that forms an MNP complex using magnetic nanoparticles, enhancing binding forces through vortex formation and residence regions, allowing for continuous and automatic separation of target particles using magnetic forces within a single chip.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional magnetic-activated cell sorting methods are used, then target particles can be separated, but particle loss occurs and multiple manual stages are required

Engineering Contradiction:
Improveparticle recovery rateVSAvoidnumber of separation stages
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines mixing, incubation, and separation functions into a single integrated microfluidic chip. The mixing channel merges magnetic nanoparticle solution with sample solution, the incubation channel allows complex formation, and the separation channel with magnetic material captures target particles - all in one continuous automated process, eliminating manual transfer between multiple containers and reducing particle loss

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The microfluidic device enables continuous automated processing where samples flow continuously through the mixing channel, incubation channel, and separation channel without interruption. This continuous flow system eliminates the discontinuous manual operations of conventional methods, maintaining constant processing and reducing particle loss during transfer operations

Inventive Principle:
Principle #20Continuity of useful action

2Productivity

If manual processing is used, then separation can be performed, but particle loss increases and detection efficiency decreases

Engineering Contradiction:
Improveseparation speedVSAvoidparticle recovery rate
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The microfluidic device is designed to perform all separation operations automatically without manual intervention. The device self-regulates the mixing process, incubation time, and separation capture through its integrated channel design and magnetic material placement, eliminating human error and particle loss associated with manual pipetting and container handling while maintaining high separation speed

Inventive Principle:
Principle #25Self-service

3Measurement precision

If multiple separation stages are used, then separation can be achieved, but processing time increases and manual errors occur

Engineering Contradiction:
Improvedetection efficiencyVSAvoidprocessing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent segments the separation process into three functional zones within a single chip: mixing channel for reagent combination, incubation channel for complex formation, and separation channel for target capture. This spatial segmentation allows all steps to occur simultaneously in different regions rather than sequentially in different containers, reducing total processing time while maintaining detection precision through optimized local conditions in each zone

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

The microfluidic device minimizes particle loss and enables efficient, high-speed separation of circulating rare cells, particularly circulating tumor cells, by continuously processing samples in a single chip, improving detection efficiency and reducing manual errors.

Implementation Method 1

a microfluidic separation device for forming an MNP complex comprising target particles bound to magnetic nanoparticles (MNPs) and for capturing and separating the MNP complex using a magnetic force

Methodology Applied
Scientific EffectMagnetic force: Magnetism

Implementation Method 2

a wave-shaped curved channel which communicates with the inlets and which has two or more curved portions

Methodology Applied
Scientific EffectVortex formation: Vortex Ring

Data Source

PatentUS9908117B2Microfluidic separation device, separation method using the same and kit for separating circulating rare cells from blood using the same
Publication Date: 2018.03.06 IND ACADEMIC COOP FOUND YONSEI UNIV
  • US9908117B2 patent drawing
  • US9908117B2 patent drawing
  • US9908117B2 patent drawing

AI summary

The present invention relates to a microfluidic separation device, a separation method using the same and a kit for separating circulating rare cells from blood using the same, and more particularly, to a microfluidic-based separation technology for fixing target particles of a sample, which have a specific affinity for magnetic nanoparticles, to a device by use of a magnetic material, and for isolating the sample from which the target particles have been removed. The present invention may be effectively applied to remove leukocytes from a blood sample in order to isolate circulating rare cells (CRCs), particularly circulating tumor cells (CTCs).