Devices and methods for separating particles
Inventors
Mao, Leidong • Schroeder, Carsten • Zhao, Wujun
Assignees
University of Georgia Research Foundation Inc • Augusta University • Augusta University Research Institute Inc
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Publication Number
US-10676719-B2
Publication Date
2020-06-09
Expiration Date
Abstract
Devices for non-invasive, label-free separation of particles in liquid, including circulating tumors cells in blood, are provided. Embodiments of the disclosure provide for devices employing magnetic fluids and magnets for separation of circulating tumor cells from blood. Methods for separation of particles including circulating tumor cells are also provided.
Core Innovation
The invention provides a kit for separating unlabeled rare cells from a sample of whole blood. The kit includes a biocompatible magnetic fluid and a device with a serpentine microfluidic channel configured to receive whole blood and to receive the biocompatible magnetic fluid. The device uses a filtration region to remove one or both of fibrin and large debris from the sample of whole blood before further processing in the serpentine microfluidic channel.
The device further combines the magnetic fluid with the whole blood and hydrodynamically focuses the unlabeled rare cells into a stream by sheath flow. After the filtration region, the channel includes a curve along a length of the serpentine microfluidic channel having an angle of curvature about 120° to about 180°. Permanent magnets positioned adjacent and along a length of the serpentine microfluidic channel after the second inlet form a non-uniform magnetic field that produces a magnetization direction perpendicular to the flow of the stream.
With the magnetization direction perpendicular to the flow, the unlabeled rare cells and other components experience a magnetic buoyancy force that causes the unlabeled rare cells and other components to spatially separate based on particle volume. The separated unlabeled rare cells are collected into one of two or more outlet channels at the second end of the microfluidic channel, with an average separation efficiency greater than 65% when operated at a flow rate of about 20 μL/min to about 100 μL/min. The unlabeled rare cells are still alive when they are separated from the sample of whole blood.
Claims Coverage
The independent claim explicitly covers a kit and an associated microfluidic device for label-free separation of unlabeled rare cells from whole blood with magnetic buoyancy-based spatial separation and preserved cell viability. It includes five inventive features covering the magnetic fluid, serpentine microfluidic routing with filtration and sheath-flow focusing, the non-uniform magnetic field geometry, multiple outlets, and performance and viability outcomes.
Biocompatible magnetic fluid for unlabeled rare cells
A biocompatible magnetic fluid comprising a plurality of un-conjugated, nano-sized magnetic particles having an average diameter of about 5–10 nm, covered by a surfactant and suspended in a compatible carrier medium, with a volume fraction of nano-sized magnetic particles about 0.2% to about 1%.
Serpentine microfluidic channel with filtration and curve
A serpentine microfluidic channel with a filtration region disposed between the first end and the second end and after the first inlet, wherein the filtration region includes at least one filter that removes one or both of fibrin and large debris, and a curve along a length of the serpentine microfluidic channel located after the first inlet and the filtration region, wherein the angle of curvature is about 120° to about 180°.
Sheath-flow hydrodynamic focusing using a second inlet
A second inlet located after the first inlet, the filtration region, and the curve, wherein the second inlet flows the biocompatible magnetic fluid into the serpentine microfluidic channel to combine the magnetic fluid with the sample of whole blood and hydrodynamically focus the unlabeled rare cells into a stream by sheath flow.
Non-uniform magnetic field with magnetization direction perpendicular to flow
One or more permanent magnets positioned adjacent and along a length of the serpentine microfluidic channel after the second inlet, forming a non-uniform magnetic field that produces a magnetization direction perpendicular to the flow of the stream containing the unlabeled rare cells, such that the unlabeled rare cells and other components experience a magnetic buoyancy force that causes spatial separation based on particle volume.
Multiple outlets with separation efficiency and viability
Two or more outlet channels positioned after the one or more permanent magnets at the second end of the microfluidic channel, wherein the unlabeled rare cells are separated from the sample of whole blood with an average separation efficiency greater than 65% when operated at a flow rate of about 20 μL/min to about 100 μL/min, and wherein the unlabeled rare cells are still alive when they are separated from the sample of whole blood.
Overall, the independent claim combines an un-conjugated nano-sized biocompatible magnetic fluid with a serpentine microfluidic channel that includes filtration and sheath-flow focusing, followed by a non-uniform magnetic field from permanent magnets that produces magnetization perpendicular to flow to generate magnetic buoyancy-based spatial separation into multiple outlets while maintaining viability.
Stated Advantages
The unlabeled rare cells are still alive when they are separated from the sample of whole blood.
Provides an average separation efficiency greater than 65% for unlabeled rare cells at a flow rate of about 20 μL/min to about 100 μL/min.
Documented Applications
Separating unlabeled rare cells from a sample of whole blood using the claimed kit and device, including separation of circulating tumor cells.
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