Systems and methods for particle focusing in microchannels

• US 8,186,913 B2
• Filed: 04/16/2008
• Issued: 05/29/2012
• Est. Priority Date: 04/16/2007
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Toner, Mehmet, DiCarlo, Dino, Edd, Jon, Irimia, Daniel
• Primary Examiner(s): Dillon, Jr., Joseph A
• Application Number:
  US12/103,885
• Publication Number:
  US 20090014360A1
• Time in Patent Office: 1,504 Days
• Field of Search: 406/92, 406/195, 406/198, 435/174, 435/325, 356/246, 356/441, 436/52, 436/180
• US Class Current: 406/92
• CPC Class Codes: B01D 21/0087 Settling tanks provided with means for ensuring a special flow pattern, e.g. even inflow or outflow B01D21/2411 takes precedence
• CPC Class Codes: B01D 21/265 by using a vortex inducer or vortex guide, e.g. coil B01D21/0054 takes precedence
• CPC Class Codes: B01D 45/04 by utilising inertia B01D45/12 takes precedence
• CPC Class Codes: B01D 45/12 by centrifugal forces centrifuges B04B; cyclones B04C
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0433 vibrational forces
• CPC Class Codes: B01L 2400/0454 radiation pressure, optical tweezers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0622 distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
• CPC Class Codes: B01L 2400/084 Passive control of flow resistance
• CPC Class Codes: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/502776 specially adapted for focusing or laminating flows
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: C12M 41/36 of biomass, e.g. colony counters or by turbidity measurements electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404
• CPC Class Codes: C12M 47/04 Cell isolation or sorting purging biological preparations of unwanted cells C12N5/0081, determining the presence or kind of microorganism C12Q1/04
• CPC Class Codes: F16L 41/02 : Branch units, e.g. made in one piece, welded, riveted
• CPC Class Codes: F17D 1/00 : Pipe-line systems conveying articles or materials through a pipe- line by means of a fluid carrier B65G51/00, B65G53/00; liquids B67D; special devices for transferring liquids from bulk storage containers into vehicles or boats or vice versa, e.g. loading or unloading vehicles or portable containers B67D7/00; conveying material which has been excavated by a dredger or soil shifter through a pipe-line E02F7/10; sewer pipe-line systems E03F3/00; thermal insulation of pipe-lines F16L59/00; central heating systems F24D
• CPC Class Codes: G01N 15/0255 : with mechanical, e.g. inertial, classification, and investigation of sorted collections with centrifuges G01N15/042
• CPC Class Codes: G01N 15/10 : Investigating individual particles
• CPC Class Codes: G01N 2015/0288 : Sorting the particles
• CPC Class Codes: G01N 2015/1006 : for cytology
• CPC Class Codes: G01N 2015/1028 : Sorting particles
• CPC Class Codes: Y10T 137/85938 : Non-valved flow dividers
• CPC Class Codes: Y10T 137/85978 : With pump
• CPC Class Codes: Y10T 436/117497 : with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

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

1. A system for focusing particles suspended within a moving fluid, the system comprising:

a substrate;

at least one channel provided on the substrate, the at least one channel having an inlet, an outlet, a plurality of sides, wherein the relative geometry of the sides defines an aspect ratio, and a channel hydraulic diameter (D_h), wherein the at least one channel is configured to allow a fluid having a substantially constant kinematic viscosity (v) that includes suspended particles, each having a particle diameter (a), to flow therethrough; and

a pumping element designed to drive the fluid that includes the suspended particles through the at least one channel;

wherein when the fluid that includes the suspended particles is flowed through the at least one channel, and the pumping element drives the fluid that includes the suspended particles at a maximum channel velocity (U_m) resulting in a 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

2. The system of claim 1, wherein the at least one channel has a width and a height that define the aspect ratio of the at least one channel, and wherein when the aspect ratio of the at least one channel is substantially 1 to 1, the particles suspended in the fluid are focused into four localized stream lines.

3. The system of claim 1, wherein the at least one channel has a width and a height that define the aspect ratio of the at least one channel, and wherein when the aspect ratio of the at least one channel is substantially 2 to 1, the particles suspended in the fluid are focused into two localized stream lines.

4. The system of claim 1, wherein the at least one channel is a straight channel, and the particles suspended in the fluid are focused into each of at least two localized stream lines.

5. The system of claim 1, wherein a ratio of the particle diameter to the at least one channel hydraulic diameter is greater than or equal to about 0.07.

6. The system of claim 5, wherein the ratio of the particle diameter to the at least one channel hydraulic diameter is less than or equal to about 0.5.

7. The system of claim 1, wherein the width defined by each localized stream line is about 1.05 times the particle diameter.

8. The system of claim 1, wherein the width defined by each localized stream line is about five times the particle diameter.

9. The system of claim 1, wherein at least first and second outlet branches are formed at an outlet portion of the at least one channel, at least one of the first and second outlet branches being located so as to receive the particles that are focused into a localized stream line.

10. The system of claim 9, wherein each of the at least first and second outlet branches are formed such that a concentration of the particles suspended in the fluid flowing through the at least one of the first and second outlet branches is greater than a concentration of the particles suspended in the fluid entering the inlet of the at least one channel.

11. The system of claim 1, wherein the at least one channel is formed to focus particles having a particle diameter in a range of 0.01 μ

m to 40 μ

m.

12. The system of claim 1, wherein when the fluid that includes the suspended particles is flowed through the at least one channel, and the pumping element drives the fluid that includes the suspended particles at a particle Reynolds Number (R_p) of greater than or equal to 0.2, the focused particles are spaced within a localized stream line approximately evenly longitudinally.

13. The system 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.

14. The system of claim 4, further comprising a curved channel connected to the outlet of the at least one channel, wherein when the pumping element drives the particles focused into each of the at least two localized stream lines in the at least one channel through the curved channel, the particles are focused into a single localized stream line formed in the curved channel.

15. The system of claim 14, wherein the curved channel is symmetric and sigmoidal.

16. The system of claim 14, wherein the curved channel is asymmetric and sigmoidal.

17. The system of claim 1, further comprising a detector for detecting and enumerating particles focused in a localized stream line.

18. The system of claim 17, further comprising a tagging system for tagging selected particles with a tag that can be detected by the detector, the detector thereby detecting and enumerating the selected particles.

19. The system of claim 18, wherein the tag comprises magnetic beads coupled to one or more antibodies.

20. The system of claim 14, further comprising a detector configured to detect the particles focused into the single localized stream line.