US-12616972-B2 - Magnetic particle isolation device and methods of use

US12616972B2US 12616972 B2US12616972 B2US 12616972B2US-12616972-B2

Abstract

The present invention provides for devices and methods of isolating particles. A fluidics particle isolation device is disclosed having a fluidic channel extending therethrough, wherein a segment of the fluidic channel is exposed to an asymmetric magnetic field such that when a solution containing the particles in a paramagnetic medium are passed through the magnetic field, the particles are isolated within the solution.

Inventors

Geoffrey Facer
Kevin Travers
Andreja Jovic
Theodorus Evan de Groot

Assignees

LevitasBio, Inc.

Dates

Publication Date: 20260505
Application Date: 20200925

Claims (18)

1 . A method of separating cells of a first cell type from a heterogeneous population of cells comprising: (a) providing a processing solution comprising the heterogeneous population of cells and a paramagnetic medium; (b) passing the processing solution through a cell isolation device, wherein the cell isolation device comprises (i) a fluidic channel, wherein the fluidic channel comprises a substantially linear portion, and (ii) an upper magnetic component and a lower magnetic component that are positioned on opposite sides of a substantial portion of the substantially linear portion of the fluidic channel along a substantially vertical axis between the upper magnetic component and the lower magnetic component, and wherein the upper magnetic component and the lower magnetic component create an asymmetric magnetic field within the substantially linear portion of the fluidic channel and along the substantially vertical axis between the upper magnetic component and the lower magnetic component, wherein the upper magnetic component emits a magnetic field that is different from a magnetic field emitted by the lower magnetic component; (c) magnetically levitating, by the asymmetric magnetic field, the heterogeneous population of cells within the fluidic channel to cause; (i) substantially all of the cells of the first cell type to reach the same first cell-type specific equilibrium height and (ii) cells of a different cell type to reach an equilibrium height that is different from the first cell-type specific equilibrium height, based at least in part on a difference in magnetic susceptibility between the cells of the first cell type and the cells of the different cell type, wherein the first cell-type specific equilibrium height is a vertical position at which magnetic force and corrected gravitational force are sufficiently balanced to cause the cells of the first cell type to remain stationary under conditions of zero fluid flow in the vertical direction, thereby separating the cells of the first cell type from the heterogeneous population of cells.
2 . The method of claim 1 , further comprising observing, analyzing, recording, or collecting the cells of the first cell type.
3 . The method of claim 1 , wherein the substantially linear portion of the fluidic channel further comprises at least one input port and at least two output ports.
4 . The method of claim 3 , wherein the at least two output ports comprise a plurality of vertically spaced channels in the substantially linear portion of the fluidic channel.
5 . The method of claim 3 , wherein the cell isolation device further comprises one or more pumps configured to drive fluid from the at least one input port through the substantially linear portion of the fluidic channel and out at least one output port of the at least two output ports.
6 . The method of claim 1 , wherein substantially all of the heterogeneous population of cells each reaches a respective equilibrium height, wherein a difference between a highest equilibrium height of the heterogeneous population of cells and a lowest equilibrium height of the heterogeneous population of cells is less than 35% of a vertical gap between the upper magnetic component and the lower magnetic component.
7 . The method of claim 6 , wherein an equilibrium height distribution of substantially all of the heterogeneous population of cells is less than 5000 microns.
8 . The method of claim 7 , wherein the equilibrium height distribution of substantially all of the heterogeneous population of cells is from about 1 micron to about 5000 microns.
9 . The method of claim 6 , wherein the substantially all the heterogeneous population of cells comprise at least 70% of the heterogeneous population of cells.
10 . The method of claim 6 , further comprising, after substantially all of the heterogeneous population of cells each reaches a respective equilibrium height, passing the heterogeneous population of cells through a splitter that geometrically divides the processing solution into multiple effluent fractions, wherein one or more effluent fractions of the multiple effluent fractions comprise substantially all of the heterogeneous population of cells collected.
11 . The method of claim 10 , wherein the heterogeneous population of cells comprises a microorganism, bacteria, or combinations thereof.
12 . The method of claim 1 , further comprising separating the cells of the first cell type from the paramagnetic medium.
13 . The method of claim 11 , wherein the paramagnetic medium comprises a paramagnetic material and a solvent.
14 . The method of claim 11 , wherein the paramagnetic medium comprises a paramagnetic material, salts, and other additives that function to maintain cellular integrity.
15 . The method of claim 1 , wherein a density of the heterogeneous population of cells is greater than a density of the paramagnetic medium, and wherein a magnetic field emitted by the lower magnetic component is greater than a magnetic field emitted by the upper magnetic component.
16 . The method of claim 1 , wherein a density of the heterogeneous population of cells is less than a density of the paramagnetic medium, and wherein a magnetic field emitted by the lower magnetic component is less than a magnetic field emitted by the upper magnetic component.
17 . The method of claim 1 , wherein the upper magnetic component emits a greater magnetic field than the magnetic field created by the lower magnetic component.
18 . The method of claim 1 , wherein the upper magnetic component emits a smaller magnetic field than the magnetic field created by the lower magnetic component.

Description

CROSS-REFERENCE This application is a continuation of International Application No. PCT/US2019/024138, filed Mar. 26, 2019, which claims the benefit of U.S. Provisional Application No. 62/648,300, filed Mar. 26, 2018, and U.S. Provisional Application No. 62/728,684, filed Sep. 7, 2018, each of which is herein incorporated by reference in its entirety. TECHNICAL FIELD OF THE INVENTION The present invention relates generally to the magnetic levitation of particles, such as cells or biomolecules, in order to isolate such particles within a medium. BACKGROUND OF THE INVENTION Isolation of particles contained within a medium is an important step in many chemical and biological processes. In some processes there may be a need to simply isolate a particle to facilitate the use or manipulation of the particle, whereas in other processes there may be a need to separate the particle from other particles that are also present in the medium. Devices can rely on the magnetic properties of the particles and their surrounding medium in order to separate out particles of interest from heterogenous populations of particles. For example, a levitation system can have a microcapillary channel that is positioned between a set of two magnets. A heterogeneous population of cells in a magnetically-responsive medium can be sent through the microcapillary channel and can be exposed to a magnetic field created by the two adjacent magnets. Upon exposure to the magnetic field cells of the same type within the heterogeneous population of cells can levitate to a specific height within the microcapillary channel, thereby separating cells from one another. The levitation height of a given cell can be determined based on the balancing of magnetic force and corrected gravitational force on the individual cells. The two magnets can be positioned symmetrically relative to the capillary channel so that the magnetic field strength distribution is symmetric with respect to each axis of the capillary channel. In some cases, a symmetrical configuration of magnets can limit the capabilities of a device to separate particles. In some cases, with a vertically symmetric configuration of magnets, all of the particles in the magnetically-responsive medium which are denser than the medium itself can levitate to positions below the symmetry axis (i.e., the vertical midpoint between the two magnets). This can have two consequences: (1) the spread of levitation heights can be constrained to half of the available space between the magnets; and (2) fluidic paths can be captured within a smaller space (i.e., the lower half of the channel), which can pose difficulties in fabrication and can increase flow resistance. Moving the magnets further apart and using a larger capillary, all other factors being consistent, can result in shallower field gradients, which can result in weaker separating forces on the particles. Accordingly, there is a need for a cell isolation device that improves selectivity by increasing the spread of levitation positions for a given surface strength of magnet and improves the manufacturability and operability of fluidic devices coupled to the levitation region. SUMMARY OF THE INVENTION The inventive embodiments provided in this Summary of the Invention are meant to be illustrative only and to provide an overview of selected embodiments disclosed herein. The Summary of the Invention, being illustrative and selective, does not limit the scope of any claim, does not provide the entire scope of inventive embodiments disclosed or contemplated herein, and should not be construed as limiting or constraining the scope of this disclosure or any claimed inventive embodiment. Provided herein is a particle isolation device that includes a fluidic channel and two magnetic components that are positioned on opposite sides of the fluidic channel along a substantially vertical axis, wherein the two magnetic components are configured to create an asymmetric magnetic field within the fluidic channel. Also provided herein is a particle isolation device having a fluidic channel structure, at least two magnetic components, and one or more pumps configured to drive fluid from an input port through the fluidic channel structure, and out an output port. In accordance with this embodiment the fluidic channel structure includes at least one input port and at least one output port interconnected by a fluidic channel, wherein the fluidic channel includes a substantially linear portion that includes a leading end that is in fluidic communication with the input port and a terminal end that is in fluidic communication with the output port. This embodiment further includes two magnetic components that are substantially vertically positioned on opposite sides of the substantially linear portion of the fluidic channel, wherein the two magnetic components are configured to create an asymmetric magnetic field within the substantially linear portion of the fluidic channel. Fu