IP Library Granted Patent US 11,498,071
Granted Patent B2
US 11,498,071 · App. 16/722,996 · Granted Nov 15, 2022

Systems and methods for particle focusing in microchannels

Inventors: Mehmet Toner (Charlestown, MA); Dino DiCarlo (Los Angeles, CA); Jon F. Edd (Wakefield, MA); Daniel Irimia (Charlestown, MA)
Assignee: The General Hospital Corporation
B01L3/502776B01D21/0087B01D21/265B01D45/04B01D45/12B01L3/502746B01L3/502761C12M23/16C12M41/36C12M47/04F16L41/02F17D1/00G01N15/10B01L2200/0652B01L2300/0883B01L2400/043B01L2400/0409B01L2400/0433B01L2400/0454B01L2400/0487B01L2400/0622B01L2400/084B33Y80/00G01N15/0255G01N2015/0288G01N2015/1006G01N2015/1081Y10T137/85938Y10T137/85978Y10T436/117497Y10T436/2575
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Quick Facts
Patent No.
US 11,498,071
App. No.
16/722,996
Granted
Nov 15, 2022
Kind
B2
Abstract

Various systems, methods, and devices are provided for focusing particles suspended within a moving fluid into one or more localized stream lines. The system can include a substrate and at least one channel provided on the substrate having an inlet and an outlet. The system can further include a fluid moving along the channel in a laminar flow having suspended particles and a pumping element driving the laminar flow of the fluid. The fluid, the channel, and the pumping element can be configured to cause inertial forces to act on the particles and to focus the particles into one or more stream lines.

Claims (53)

1. A method of focusing particles suspended in a fluid, the method comprising:

adding tags to particles suspended in a fluid to change a size of the particles; and

flowing the fluid and the tagged particles through a system comprising:

a substrate; and

at least one channel provided on the substrate, wherein the at least one channel has an inlet, an outlet, and a plurality of sides defining an aspect ratio and a channel hydraulic diameter (D h ), wherein the at least one channel is dimensioned and configured to allow the fluid having a kinematic viscosity (v) and including suspended tagged particles, each having a particle diameter (a), to flow therethrough such that, when the fluid is flowed therethrough at a maximum channel velocity (U m ) resulting in laminar fluid flow and a particle Reynolds Number (R p ) of greater than or equal to 0.2, wherein the particle Reynolds number is defined as

R

p

=

U

m

a

2

vD

h

,

the tagged particles suspended in the fluid are focused to flow along one or more localized stream lines that form in the fluid of the at least one channel.

2. The method of claim 1 , wherein the tags comprise beads.

3. The method of claim 1 , wherein the tags comprise antibodies.

4. The method of claim 1 , wherein the tags comprise magnetic beads.

5. The method of claim 1 , wherein the tags comprise quantum dots.

6. The method of claim 1 , further comprising focusing the tagged particles into a particular stream line based on the changed size.

7. The method of claim 1 , wherein the system further comprises a channel branch and wherein the method further comprises focusing the tagged particles into the channel branch based on the changed size.

8. The method of claim 1 , wherein the one or more localized stream lines each define a width that is substantially equal to or greater than the diameter of the tagged particles, and the tagged particles suspended in the fluid are focused into the one or more localized stream lines, and wherein the number and relative cross-sectional position of the one or more localized stream lines are uniquely defined by the aspect ratio and the particle Reynolds number.

9. The method of claim 1 , wherein the tagged particles suspended in the fluid are focused into each of at least two localized stream lines.

10. The method of claim 1 , further comprising a curved channel connected to the outlet of the at least one channel, wherein when the fluid is flowed through the at least one channel and the curved channel, the tagged particles are focused into a single localized stream line formed in the curved channel.

11. The method of claim 10 , wherein the curved channel is sigmoidal.

12. The method of claim 1 , wherein a ratio of the tagged particle diameter to the at least one channel hydraulic diameter is greater than or equal to about 0.07 and less than or equal to about 0.5.

13. The method of claim 1 , wherein the at least one channel is dimensioned and configured to focus tagged particles having a diameter in a range of 0.01 micrometers to 40 micrometers.

14. The method of claim 1 , wherein the at least one channel has a width and a height that defines the aspect ratio of the at least one channel, and wherein the aspect ratio is 1 at or substantially near the inlet and varies over the length of the at least one channel to 2 at or substantially near the outlet.

15. The method of claim 1 , further comprising a filter positioned upstream of, and in fluid communication with, the at least one channel, wherein the filter has a cut-off size selected to prevent passage of tagged particles larger than the hydraulic diameter of the at least one channel.

16. A method of focusing particles suspended in a fluid, the method comprising:

adding tags to the particles suspended in a fluid to change a size of the particles; and

flowing the fluid and the tagged particles through a system comprising:

a substrate; and

at least one channel provided on the substrate, wherein the at least one channel spans a length from an inlet to an outlet and has a channel hydraulic diameter (D h ), and comprises a plurality of curves,

wherein the at least one channel is dimensioned and configured to allow a fluid having a kinematic viscosity (v) that includes suspended tagged particles, each having a particle hydraulic diameter (a), to flow therethrough such that when the fluid is flowed therethrough at a maximum channel velocity (U m ) resulting in laminar fluid flow and a particle Reynolds Number (R p ) of greater than or equal to 0.2, wherein the particle Reynolds number is defined as

R

p

=

U

m

a

2

vD

h

,

the tagged particles suspended in the fluid are focused to flow along one or more localized stream lines that form in the fluid at the outlet of the at least one channel.

17. The method of claim 16 , wherein the tags comprise beads.

18. The method of claim 16 , wherein the tags comprise antibodies.

19. The method of claim 16 , further comprising focusing the particles into a particular stream line based on the changed size.

20. The method of claim 16 , wherein the system further comprises a channel branch and wherein the method further comprising focusing the particles into the channel branch based on the changed size.

Assignments (2)
CONFIRMATORY LICENSE Recorded Sep 11, 2023
From: MASSACHUSETTS GENERAL HOSPITAL
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 064858/0785 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 2, 2020
From: TONER, MEHMET; DICARLO, DINO; EDD, JON F.; IRIMIA, DANIEL
To: THE GENERAL HOSPITAL CORPORATION
Reel/Frame 051401/0228 →
Continuity (11)
Division 16049222 · Jul 30, 2018
Continuation 15803427 · Nov 3, 2017
Division 15162196 · May 23, 2016
Continuation 14336889 · Jul 21, 2014
Continuation 13619309 · Sep 14, 2012
Division 13480862 · May 25, 2012
Division 12103885 · Apr 16, 2008
Provisional Application 60999131 · Oct 16, 2007
Provisional Application 60923837 · Apr 17, 2007
Provisional Application 60923609 · Apr 16, 2007
Related Publication 20200139372A1 · May 7, 2020