Ferrofluid Cell Sorting via Magnetic Field Patterns

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Solution Overview

Problem

Current methods for the rapid and accurate separation of rare cells, such as metastatic cancer cells or low-level bacteremia, and genetic conditions like sickle cell anemia, face challenges in achieving high throughput, resolution, and cost-effectiveness, with existing techniques like optical tweezers causing sample heating, dielectrophoresis being medium-dependent, and magnetic bead methods requiring lengthy incubation times.

Innovation Solution

A microfluidic platform using biocompatible ferrofluids with a microfluidic channel and electrodes that generate a magnetic field pattern, allowing for the separation of cells based on size, shape, and elasticity, with a focus on efficient and rapid sorting without the need for labels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If optical tweezers are used to manipulate single cells, then high resolution and sensitivity are achieved, but sample heating occurs and manipulation area is limited

Engineering Contradiction:
ImproveresolutionVSAvoidsample heating
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent replaces optical tweezers (optical field) with a magnetic field-based system using ferrofluids and electromagnetic coils. The magnetic field interacts with the ferrofluid particles to manipulate cells without optical heating, achieving the same manipulation function through a different physical mechanism that avoids the harmful thermal effect.

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

Solution Approach 2:

The patent changes the physical state and properties of the manipulation medium by using ferrofluids (magnetic particles suspended in liquid) instead of pure optical fields. This parameter change allows magnetic field interaction to achieve cell manipulation while avoiding optical heating, and enables parallel manipulation of multiple cells simultaneously.

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If magnetic bead-based separators are used, then cellular manipulation is achieved, but lengthy incubation time and wash cycles are required

Engineering Contradiction:
Improvecellular manipulation capabilityVSAvoidincubation time
Core Design Contradiction:
Ease of operationVSLoss of time

Solution Approach 1:

The patent extracts the magnetic beads from the mixture and replaces them with a ferrofluid-based magnetic field system. This extraction eliminates the need for physical bead addition, incubation, and subsequent wash cycles, achieving direct magnetic manipulation of cells in the ferrofluid without time-consuming steps.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent enables continuous cell manipulation and separation through sustained magnetic field application in the ferrofluid system, eliminating the intermittent nature of bead-based methods (add beads -> incubate -> wash -> remove beads). The magnetic field can be applied continuously and adjusted dynamically throughout the process.

Inventive Principle:
Principle #20Continuity of useful action

3Productivity

If dielectrophoresis is used to manipulate multiple cells, then integrated device potential is achieved, but performance depends sensitively on electrical properties of liquid medium

Engineering Contradiction:
ImprovethroughputVSAvoidmedium dependency
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent substitutes the electric field-based dielectrophoresis system with a magnetic field-based ferrofluid system. This substitution replaces the sensitive dependency on electrical properties (dielectric constant, conductivity) with dependency on magnetic properties (magnetic susceptibility, viscosity), which are more stable and easier to control in biological samples.

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

4Measurement precision

If deterministic hydrodynamics is used for high resolution separation, then no electromagnetic fields are required, but high-resolution lithography on large area is needed increasing cost

Engineering Contradiction:
Improveseparation resolutionVSAvoiddevice cost
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent replaces deterministic hydrodynamics (fluid flow control) with magnetic field-based ferrofluid manipulation. This substitution achieves high separation resolution through magnetic field gradients acting on ferrofluid particles, eliminating the need for complex high-resolution lithography and precise flow control systems, thereby reducing manufacturing cost.

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 platform achieves high separation efficiency, with over 90% separation in less than a minute, and can differentiate between cell types such as healthy and sickle red blood cells, reducing incubation times and increasing diagnostic sensitivity.

Implementation Method 1

a power source for applying a current to the plurality of electrodes to create a magnetic field pattern along the length of the microfluidic channel

Methodology Applied
Scientific EffectElectromagnetic induction: Electromagnetic Induction

Implementation Method 2

A device for separating a sample of particles suspended in a biocompatible ferrofluid

Methodology Applied
Scientific EffectFerrofluid: Ferrofluid

Data Source

PatentUS10782223B2Label-free cellular manipulation and sorting via biocompatible ferrofluids
Publication Date: 2020.09.22 YALE UNIVERSITY
  • US10782223B2 patent drawing
  • US10782223B2 patent drawing
  • US10782223B2 patent drawing

AI summary

A device for separating a sample of cells suspended in a bio-compatible ferrofluid is described. The device includes a microfluidic channel having a sample inlet, at least one output, and a length between the sample inlet and the at least one output, wherein a sample can be added to the sample inlet and flow along the length to the at least one outlet. The device includes a plurality of electrodes, wherein the microfluidic channel length transverses the plurality of electrodes, and further includes a power source for applying a current to the plurality of electrodes to create a magnetic field pattern along the length of the microfluidic channel. The present invention also includes a method for separating at least one cell type. The method includes the steps of suspending cells in a bio-compatible ferrofluid to form a sample, passing the sample through a microfluidic channel that transverses a plurality of electrodes, applying a current to the plurality of electrodes to create a magnetic field pattern along the length of the microfluidic channel, and sorting the cells into at least one output channel based on a variation of at least one of cell size, shape and elasticity.