US 11,725,180 B2
Microfluidic sorting using high gradient magnetic fields
Philipp S. Spuhler, Boston, MA (US); Kyle C. Smith, Cambridge, MA (US); Fabio Fachin, Cambridge, MA (US); Thomas Alan Barber, Sudbury, MA (US); Ravi Kapur, Sharon, MA (US); Mehmet Toner, Charlestown, MA (US); Vincent Pai, Somerville, MA (US); and Nezihi Murat Karabacak, Cambridge, MA (US)
Assigned to The General Hospital Corporation, Boston, MA (US)
Filed by The General Hospital Corporation, Boston, MA (US)
Filed on Oct. 15, 2021, as Appl. No. 17/502,869.
Application 17/502,869 is a continuation of application No. 16/256,839, filed on Jan. 24, 2019, granted, now 11,155,779.
Application 16/256,839 is a continuation of application No. 15/029,789, granted, now 10,202,577, issued on Feb. 12, 2019, previously published as PCT/US2014/061405, filed on Oct. 20, 2014.
Claims priority of provisional application 61/892,947, filed on Oct. 18, 2013.
Prior Publication US 2022/0106553 A1, Apr. 7, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. G01N 35/00 (2006.01); C12M 1/00 (2006.01); B03C 1/01 (2006.01); G01N 15/14 (2006.01); B01L 3/00 (2006.01); B03C 1/033 (2006.01); B03C 1/28 (2006.01); G01N 1/00 (2006.01); C12M 3/06 (2006.01); G01N 15/10 (2006.01); G01N 35/10 (2006.01); C12M 1/42 (2006.01)
CPC C12M 47/04 (2013.01) [B01L 3/00 (2013.01); B01L 3/502753 (2013.01); B01L 3/502761 (2013.01); B03C 1/01 (2013.01); B03C 1/0332 (2013.01); B03C 1/288 (2013.01); C12M 23/16 (2013.01); G01N 1/00 (2013.01); G01N 15/1463 (2013.01); G01N 35/0098 (2013.01); B01L 2200/0652 (2013.01); B01L 2300/0816 (2013.01); B01L 2300/0864 (2013.01); B01L 2400/043 (2013.01); B01L 2400/0487 (2013.01); B01L 2400/086 (2013.01); B03C 2201/18 (2013.01); B03C 2201/22 (2013.01); B03C 2201/26 (2013.01); C12M 35/06 (2013.01); G01N 2015/1006 (2013.01); G01N 2015/149 (2013.01); G01N 2035/00237 (2013.01); G01N 2035/1034 (2013.01)] 24 Claims
OG exemplary drawing
 
1. A method of sorting particles in a microfluidic device, wherein the microfluidic device comprises a particle sorting region, an inertial focusing region, and a magnetophoresis region, the method comprising:
flowing a fluid sample comprising blood through the particle sorting region, wherein the fluid sample comprises:
a plurality of first particles,
a plurality of second particles, and
a plurality of third particles bound to magnetic particles, and
wherein upon flowing through the particle sorting region, the plurality of first particles are removed from the fluid sample based on a size of the first particles;
flowing the fluid sample from the particle sorting region into a first microfluidic channel located within the inertial focusing region, wherein, upon entering the first microfluidic channel, the plurality of second particles and the plurality of third particles are inertially focused along a common streamline within the fluid sample; and
flowing the fluid sample comprising the plurality of second particles and the plurality of third particles 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 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, and
wherein the magnetic flux gradient profile within the magnetophoresis region deflects the plurality of third particles from the one or more common streamlines in the fluid sample without deflecting the plurality of second particles from the one or more common streamlines.
 
13. A system for sorting particles, the system comprising:
a microfluidic device comprising:
a particle sorting region,
an inertial focusing region comprising a first microfluidic channel, and
a magnetophoresis region comprising:
a second microfluidic channel,
a first array of magnets arranged above the second microfluidic channel, and
a second array of magnets arranged beneath the second microfluidic channel,
wherein 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, and
wherein the magnetic flux gradient profile comprises a local minimum positioned within the second microfluidic channel due to the alignment of the first array and the second array with respect to one another,
wherein the microfluidic device is configured to:
receive a fluid sample comprising blood, the fluid sample comprising a plurality of first particles, a plurality of second particles, and a plurality of third particles bound to magnetic particles,
flow the fluid sample through the particle sorting region, wherein upon flowing through the particle sorting region, the plurality of first particles are removed from the fluid sample based on a size of the first particles,
flow the fluid sample from the particle sorting region into the first microfluidic channel of the inertial focusing region, wherein, upon entering the first microfluidic channel, the plurality of second particles and the plurality of third particles are inertially focused along a common streamline within the fluid sample, and
flow the fluid sample comprising the plurality of second particles and the plurality of third particles focused along the common streamline from the first microfluidic channel into the second microfluidic channel of the magnetophoresis region,
wherein during operation of the microfluidic device:
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, and
the magnetic flux gradient profile within the magnetophoresis region deflects the plurality of third particles from the one or more common streamlines in the fluid sample without deflecting the plurality of second particles from the one or more common streamlines.