Microfluidic Magnetic Cell Isolation Device

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Solution Overview

Problem

Current methods for isolating rare cells, such as circulating tumor cells, from complex biological samples are inefficient and result in significant sample loss due to wasteful transfer steps and centrifugation, especially when dealing with large particulates or debris that impede the isolation process.

Innovation Solution

A microfluidic device with an input zone, isolation zone, and passage system that utilizes a magnetic force to capture and isolate a fraction-bound solid phase substrate, minimizing sample loss by using surface tension to separate fluids and prevent intermixing, allowing for efficient and specific isolation of cells from non-target cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If macroscale methods are used to isolate CTCs, then a wide range of downstream assays can be performed, but significant sample loss occurs due to wasteful transfer steps and centrifugation

Engineering Contradiction:
Improverange of downstream assaysVSAvoidsample loss
Core Design Contradiction:
Adaptability or versatilityVSLoss of substance

Solution Approach 1:

The patent replaces macroscale mechanical separation methods (centrifugation, manual transfer) with a microfluidic system that uses magnetic forces and surface tension to isolate cells. The microfluidic device captures cells bound to magnetic beads in a controlled flow environment, eliminating the need for wasteful mechanical transfer steps while maintaining versatility for downstream assays through the microfluidic platform's capabilities.

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

Solution Approach 2:

The patent changes the scale of operation from macroscale to microscale, fundamentally altering the physical parameters of the separation process. By operating at the microfluidic level, the system achieves cell isolation through magnetic forces and surface tension effects that are negligible at macroscale, thereby eliminating sample loss associated with bulk mechanical handling while preserving analytical versatility.

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If traditional macroscale methods are used, then flexibility for downstream assays is maintained, but cell loss increases due to transfer steps

Engineering Contradiction:
Improveflexibility for downstream assaysVSAvoidcell loss
Core Design Contradiction:
Adaptability or versatilityVSLoss of substance

Solution Approach 1:

The patent substitutes macroscale mechanical transfer operations with a microfluidic magnetic capture system. Cells bound to magnetic beads are captured and transported through controlled microfluidic flows rather than manual or automated macro transfers, eliminating cell loss from transfer steps while maintaining flexibility for downstream applications through the microfluidic platform's assay capabilities.

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

3Measurement precision

If functionalized micropost arrays or patterned surfaces are used, then cell isolation sensitivity and specificity improve, but device complexity increases

Engineering Contradiction:
Improveisolation sensitivity and specificityVSAvoiddevice complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts the complex functionalization steps and patterned surface structures from the device design, replacing them with a simpler magnetic bead-based capture mechanism. The magnetic beads naturally bind to target cells through magnetic properties, eliminating the need for complex functionalized surfaces while maintaining high isolation specificity. This extraction of complexity achieves the same separations ability with a simpler device architecture.

Inventive Principle:
Principle #2Taking out (Extraction)

4Productivity

If macroscale centrifugation and resuspension steps are used, then processing capacity is maintained, but sample loss increases due to centrifugation

Engineering Contradiction:
Improveprocessing capacityVSAvoidsample loss
Core Design Contradiction:
ProductivityVSLoss of substance

Solution Approach 1:

The patent replaces macroscale centrifugation with a microfluidic magnetic separation system that operates at the microscale. The magnetic forces and surface tension effects at this scale enable cell isolation without requiring high-speed centrifugation, thereby eliminating sample loss from centrifugal damage while maintaining processing capacity through parallel microfluidic channels and high-flow-rate capabilities.

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

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 effectively reduces sample loss and improves the purity of the isolated fraction by suspending the target cells above the sample's non-desired material, enabling higher recovery rates and simpler, more efficient processing without the need for costly or laborious macroscale methods.

Implementation Method 1

A force, generally perpendicular to gravity, is movable between a first position adjacent the input zone and a second position adjacent the isolation zone. The force captures the fraction-bound solid phase substrate such that the fraction-bound solid phase substrate moves from the input zone to the isolation zone in response to the force moving from the first position to the second position.

Methodology Applied
Scientific EffectMagnetic force: Magnetic Field

Data Source

PatentUS9459189B2Device for isolating a fraction in a biological sample
Publication Date: 2016.10.04 WISCONSIN ALUMNI RES FOUND
  • US9459189B2 patent drawing
  • US9459189B2 patent drawing
  • US9459189B2 patent drawing

AI summary

A device and a method are provided for isolating a fraction in a biological sample. The fraction is bound to solid phase substrate to define a fraction-bound solid phase substrate. The device includes an input zone for receiving the biological sample therein and a second zone for receiving an isolation fluid therein. A force is provided that is generally perpendicular to gravity. The force is movable between a first position adjacent the input zone and a second position adjacent the isolation zone. The force captures the fraction-bound solid phase substrate and the fraction-bound solid phase substrate moves from the input zone to the isolation zone in response to the force moving from the first position to the second position.