Microfluidic methods for passive separation of cells and particles

Patent metadata

Field	Value
Publication number	US-9987632-B2
Application number	US-201314376450-A
Country	US
Kind code	B2
Filing date	Feb 1, 2013
Priority date	Feb 3, 2012
Publication date	Jun 5, 2018
Grant date	Jun 5, 2018

Abstract

A method of separating a plurality of particles ( 14 ) from a portion of fluid, comprising directing the plurality of particles ( 14 ) into a microchannel ( 12 ). A first portion ( 16 ) of particles ( 14 ) is focused into an equilibrium position in the microchannel ( 12 ). The focused first portion ( 16 ) is directed into a first outlet ( 18 ) aligned with the equilibrium position. A portion of the fluid is directed into one or more outlets ( 20, 22 ). A microfluidic device ( 10 ) for separating a plurality of particles ( 14 ) from a portion of fluid, comprising a microchannel ( 12 ) having a first aspect ratio and a length L, thereby focusing the particles ( 14 ) directed therein into an equilibrium position in the microchannel, wherein at least a first portion ( 16 ) of the particles ( 14 ) focuses at distance X from a beginning of the microchannel ( 12 ). A first outlet ( 18 ) disposed after distance X and aligned with the equilibrium position to receive at least the first portion ( 16 ) of the particles ( 14 ) after the first portion ( 16 ) focuses into an equilibrium position in the microchannel ( 12 ). At least a second outlet ( 20 ) for receiving a second portion of the particles ( 14 ) before the second portion focuses into an equilibrium position.

First claim

What is claimed is:

1. A microfluidic device for separating particles, comprising:
a first, upstream linear microchannel having a first aspect ratio defined as a height of said microchannel divided by a width of said microchannel and a length L 1 in order to allow the particles directed therein to focus into a first equilibrium position in the first microchannel,
a second, downstream linear microchannel in fluid communication with the first microchannel, the second microchannel having a second aspect ratio and a length L 2 , effective so that at least a portion of the particles directed into the second microchannel exit the first equilibrium position and experience a first migration away from a center axis of second microchannel and towards walls of the second microchannel, and a second migration towards a second equilibrium position, and the second migration to the second equilibrium position ends at distance X from a beginning of the second microchannel;
a plurality of outlets disposed before distance X and configured to receive the portion of the particles during the second migration thereof before the portion of the particles focus to the second equilibrium position in the second microchannel; and
wherein the first aspect ratio is greater than one and the second aspect ratio is less than one.

2. The microfluidic device of claim 1 , wherein:
the particles further comprise first and second particles of a first diameter a 1 and second diameter a 2 , respectively, a 1 being greater than a 2 ;
the first particles and second particles reach the second equilibrium position in the second microchannel at distances X 1 and X 2 from the beginning of the second microchannel, respectively, wherein X 1 is less than X 2 ;
the plurality of outlets is disposed between X 1 and X 2 ; and
each outlet is positioned to receive at least a portion of either the first or second particles therein.

3. The microfluidic device of claim 2 , further comprising:
a first outlet disposed after distance X, and aligned with the second equilibrium position and receiving the first particles after the first particles focus into the second equilibrium position; and
at least a second outlet accepting the second particles.

4. The microfluidic device of claim 3 , further comprising a third outlet, wherein the first outlet is between the second and third outlets.

5. The microfluidic device of claim 3 , further comprising:
a first receptacle in fluid communication with the first outlet, thereby receiving the first therein; and
a second receptacle in fluid communication with at least the second outlet, thereby receiving the second particles therein.

6. The microfluidic device of claim 2 , wherein a 1 is at least about 1 μm greater than a 2 .

7. The microfluidic device of claim 2 , wherein:
the particles further comprise third particles of a third diameter a 3 , a 3 being less than a 1 and a 2 ;
the third particle reaches the second equilibrium position in the second microchannel at distance X 3 from the beginning of the second microchannel, wherein X 3 is greater than X 1 and X 2 ; and
each outlet is positioned to accept either the first, second or third particles therein.

8. The microfluidic device of 1 , wherein the number of outlets required to separate the particles corresponds to an amount N of differently sized particles.

9. The microfluidic device of 8 , wherein the number of outlets required is calculated with the formula 2N−1.

10. A method of separating a plurality of particles from a portion of a fluid medium, comprising:
directing the plurality of particles into a first linear microchannel having a first aspect ratio and length L 1 ;
focusing at least a portion of the particles into a first equilibrium position in the first microchannel;
directing the particles into a second linear microchannel in fluid communication with the first microchannel, the second microchannel having a second aspect ratio and length L 2 , whereby a portion of the particles experience a first migration away from a center axis of second microchannel and towards walls of the second microchannel, and a second migration to a second equilibrium position, the second migration ending at distance X from a beginning of the second microchannel; and
directing at least the portion of the particles into a plurality of outlets in fluid communication with the second microchannel during the second migration before the portion of the particles focuses to the second equilibrium position by positioning a plurality of outlets before X; and
the particles further comprise first and second particles of a first diameter a 1 and second diameter a 2 , a 1 being greater than a 2 ;
the first and second particles focus to the second equilibrium position in the second microchannel at distances X 1 and X 2 from the beginning of the second microchannel, respectively, wherein X 1 is less than X 2 , and the method further comprises:
positioning the plurality of outlets between X 1 and X 2 , each outlet positioned to accept either the first or second particles therein.

11. The method of claim 10 , further comprising:
directing the portion of the particles focusing to the second equilibrium position into a first outlet aligned with the second equilibrium position; and
directing the portion of the particles not focusing to the second equilibrium position in at least a second outlet.

12. The method of claim 10 , further comprising:
directing the first particles into a first outlet aligned with the second equilibrium position; and
directing the second particles into at least a second outlet.

13. The method of claim 10 , wherein:
the particles further comprise third particles of a third diameter a 3 , a 3 being less than a 1 and a 2 ;
the third particles focus to the third equilibrium position in the second microchannel at distance X 3 from the beginning of the second microchannel, wherein X 3 is greater than X 1 and X 2 and the method further comprises:
positioning the outlets to said first, second or third particles.

14. The method of claim 13 , further comprising:
directing the first particles into a first outlet aligned with the second equilibrium position; and
directing the second and third particles into at least a second outlet.

15. The method of claim 10 , wherein the second aspect ratio is less than one and the first aspect ratio is greater than one.

16. The method of claim 10 , further comprising:
directing the first particles into a first outlet, the first outlet aligned with the second equilibrium position; and
directing the second particles into second and third outlets, wherein the first outlet is between the second and third outlets.

17. The method of claim 10 , further comprising:
depositing the first particles into a first receptacle in fluid communication with the first outlet; and
depositing the second particles into a second receptacle in fluid communication with at least the second outlet.

18. The method of claim 17 , further comprising:
increasing at least one of L 1 or L 2 according to an alteration of X.

19. A method of separating a plurality of particles from a portion of a fluid medium, comprising:
directing the plurality of particles into a microchannel having a first aspect ratio and length L;
focusing at least a portion of the particles into a first equilibrium position in the microchannel;
directing the particles into a chamber in fluid communication with the microchannel, the chamber having a second aspect ratio and

Assignees

• Univ Cincinnati

Inventors

• Papautsky Ian
• Zhou Jian

Classifications

• B01J19/0093

  Microreactors, e.g. miniaturised or microfabricated reactors (laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027) · CPC title

• B03B5/62

  by hydraulic classifiers, e.g. of launder, tank, spiral or helical chute concentrator type · CPC title

• B01L2200/0636

  Focussing flows, e.g. to laminate flows · CPC title

• Y10T137/0318

  Processes · CPC title

• B07B7/00

  Selective separation of solid materials carried by, or dispersed in, gas currents (sieves or filters for separating dispersed particles from gases or vapours B01D) · CPC title