Microfluidic sorting with high gradient magnetic fields using opposing arrays of adjacent magnets

Patent metadata

Field	Value
Publication number	US-11155779-B2
Application number	US-201916256839-A
Country	US
Kind code	B2
Filing date	Jan 24, 2019
Priority date	Oct 18, 2013
Publication date	Oct 26, 2021
Grant date	Oct 26, 2021

Abstract

Microfluidic devices are described that include a microfluidic channel, a first array of one or more magnets above the microfluidic channel, each magnet in the first array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the first array, and a second array of one or more magnets beneath the microfluidic channel, each magnet in the second array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the second array. The first array is aligned with respect to the second array such that magnetic fields emitted by the first array and second array generate a magnetic flux gradient profile extending through the channel. An absolute value of the profile includes a first maximum and a second maximum that bound a local minimum. The local minimum is located within the microfluidic channel or less than 5 mm away from a wall of the microfluidic channel. Methods of using the new devices are also described.

First claim

What is claimed is:

1. A microfluidic device comprising:
a magnetophoresis region;
an inertial focusing region upstream of the magnetophoresis region; and
a microfluidic channel in the magnetophoresis region,
wherein the magnetophoresis region comprises a first array of magnets arranged on top of the microfluidic channel, a second array of magnets arranged below the microfluidic channel,
wherein each magnet in the first array has a magnetic pole orientation that is opposite to a magnetic pole orientation of an adjacent magnet in the first array, wherein each magnet in the second array has a magnetic pole orientation that is opposite to a magnetic pole orientation of an adjacent magnet in the second array, wherein an interface between two magnets in the first array is aligned with an interface between two magnets in the second array,
wherein the first array and the second array produce a magnetic flux gradient profile that extends transverse to a central longitudinal axis of the microfluidic channel, wherein the magnetic flux gradient profile comprises a local minimum positioned within the microfluidic channel and at least 50 microns away from walls of the microfluidic channel due to the alignment of the first array and the second array with respect to one another,
wherein the inertial focusing region is configured to localize fluid particles of a fluid sample along a common streamline, wherein the common streamline is positioned to be laterally offset from the local minimum of the magnetic flux gradient profile upon entering the magnetophoresis region.

2. The microfluidic device of claim 1 , wherein an absolute value of the magnetic flux gradient profile comprises a first maximum and a second maximum that bound the local minimum in the magnetic flux gradient profile.

3. The microfluidic device of claim 2 , wherein a distance between the first maximum and the second maximum is less than 5 mm.

4. The microfluidic device of claim 2 , wherein each of the first maximum and the second maximum is at least 400 T/m.

5. The microfluidic device of claim 2 , wherein both the first maximum and the second maximum occur within the microfluidic channel.

6. The microfluidic device of claim 1 , further comprising a hydrodynamic particle sorting region upstream of the inertial focusing region, wherein the hydrodynamic particle sorting region is configured to sort particles based on particle size.

7. The microfluidic device of claim 1 , comprising an additional inertial focusing region, wherein each inertial focusing region is configured to focus particles within a fluid sample to a corresponding streamline, and wherein the two inertial focusing regions are coupled to a common sample input port.

8. The microfluidic device of claim 1 , wherein the local minimum is greater than or equal to a distance of 100 μm away from the walls of the microfluidic channel.

9. The microfluidic device of claim 1 , wherein the local minimum is located substantially at a center of the microfluidic channel.

10. A method of sorting analytes in a microfluidic device, wherein the microfluidic device comprises an inertial focusing region and a magnetophoresis region, the method comprising:
flowing a fluid sample containing a mixture of a plurality of first analytes and a plurality of second analytes into a first microfluidic channel located within the inertial focusing region, wherein, upon entering the first microfluidic channel, the plurality of first analytes and the plurality of second analytes are inertially focused along a common streamline within the fluid sample, wherein the plurality of second analytes are bound to magnetic particles; and
flowing the fluid sample comprising the plurality of first analytes and the plurality of second analytes focused along the common streamline from the first microfluidic channel into a second microfluidic channel located within the magnetophoresis region,
wherein the magnetophoresis region comprises a first array of magnets arranged above the second microfluidic channel and a second array of magnets arranged beneath the second microfluidic channel of the magnetophoresis region such that each magnet in the first array faces a corresponding magnet in the second array,
wherein each magnet in the first array has a magnetic pole orientation that is opposite to a magnetic pole orientation of an adjacent magnet in the first array, wherein each magnet in the second array has a magnetic pole orientation that is opposite to a magnetic pole orientation of an adjacent magnet in the second array, wherein an interface between two magnets in the first array is aligned with an interface between two magnets in the second array,
wherein the first array and the second array produce a magnetic flux gradient profile that extends transverse to a central longitudinal axis of the second microfluidic channel, wherein the magnetic flux gradient profile comprises a local minimum positioned within the second microfluidic channel and at least 50 microns away from each wall of the second microfluidic channel due to the alignment of the first array and the second array with respect to one another,
wherein the common streamline within the fluid sample, as the fluid sample enters the second microfluidic channel, is aligned so as to be laterally offset from the local minimum of the magnetic flux gradient profile,
wherein the magnetic flux gradient profile within the magnetophoresis region deflects the plurality of second analytes from the one or more common streamlines in the fluid sample without deflecting the plurality of first analytes from the one or more common streamlines.

11. The method of claim 10 , wherein an absolute value of the magnetic flux gradient profile comprises a first maximum and a second maximum that bound the local minimum in the magnetic flux gradient profile.

12. The method of claim 11 , wherein a distance between the first maximum and the second maximum is less than 5 mm.

13. The method of claim 11 , wherein each of the first maximum and the second maximum is at least 400 T/m.

14. The method of claim 11 , wherein both the first maximum and the second maximum occur within the second microfluidic channel.

15. The method of claim 10 , further comprising, prior to flowing the fluid sample into the first microfluidic channel of the inertial focusing region, sorting particles within the fluid sample based on particle size in a hydrodynamic particle sorting region upstream of the inertial focusing region.

16. The method of claim 10 , wherein the microfluidic device comprises an additional inertial focusing region, and wherein the method further comprises:
flowing an additional fluid sample containing a mixture of a plurality of third analytes and a plurality of fourth analytes into the additional inertial focusing region, wherein, upon entering the additional inertial focusing region, the plurality of third analytes and the plurality of fourth analytes are inertially focused along a common streamline within the additional fluid sample, wherein the plurality of fourth analytes are bound to magnetic particles, and
wherein the common streamline of the fluid sample and the common streamline of the additional fluid sample are provided to the magnetophoresis region through a common sample input port.

17. The method of claim 16 , wherein the magnetic flux gradient profile within the magnetophoresis region deflects the plurality of second analytes and the plurality of fourth analytes to a separate third fluid streamline.

18. The method of claim 10 , wherein the common streamlin

Assignees

• Massachusetts Gen Hospital

Inventors

• Spuhler Philipp S
• Smith Kyle C
• Fachin Fabio
• Barber Thomas Alan
• Kapur Ravi
• Toner Mehmet
• Pai Vincent
• Karabacak Nezihi Murat

Classifications

• G01N35/0098 Primary

  involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation (magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C) · CPC title

• C12M35/06

  Magnetic means (C12M35/02 takes precedence) · CPC title

• G01N2015/1006

  for cytology · CPC title

• G01N2035/1034

  Transferring microquantities of liquid · CPC title

• B01L3/502761

  specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules · CPC title