# US 8,784,012 B2 · Systems and methods for particle focusing in microchannels

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- Number: US 8,784,012 B2
- Document ID: US8784012B2
- Status: Granted
- Kind: B2
- Application number: 13/480,862
- Filed: 2012-05-25
- Published: 2012-11-22
- Granted: 2014-07-22
- Earliest claimed: 2007-04-16
- Assignees: The General Hospital Corporation
- Applicants: Mehmet Toner; Dino DiCarlo; Jon F. Edd; Daniel Irimia
- Inventors: Mehmet Toner; Dino DiCarlo; Jon F. Edd; Daniel Irimia
- Web page: https://patentgrep.com/patent/US8784012B2

## CPC

- B01L 3/502776: {specially adapted for focusing or laminating flows}
- B01D 21/0087: {Settling tanks provided with means for ensuring a special flow pattern, e.g. even inflow or outflow (B01D21/2411 takes precedence)}
- B01D 21/265: {by using a vortex inducer or vortex guide, e.g. coil (B01D21/0054 takes precedence)}
- B01D 45/04: by utilising inertia (B01D45/12 takes precedence)
- B01D 45/12: by centrifugal forces (centrifuges B04B; cyclones B04C)
- B01L 3/502746: {characterised by the means for controlling flow resistance, e.g. flow controllers, baffles or throttle valves}
- B01L 3/502761: {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}
- C12M 23/16: {Microfluidic devices; Capillary tubes (integrated microfluidic structures B01L3/5027; microreactors B01J19/0093)}
- C12M 41/36: {of biomass, e.g. colony counters or by turbidity measurements (electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404)}
- C12M 47/04: {Cell isolation or sorting (purging biological preparations of unwanted cells C12N5/0081, determining the presence or kind of microorganism C12Q1/04)}
- F16L 41/02: Branch units, e.g. made in one piece, welded, riveted
- 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)
- G01N 15/10: Investigating individual particles
- B01L 2200/0652: Sorting or classification of particles or molecules
- B01L 2300/0883: Serpentine channels
- B01L 2400/0409: centrifugal forces
- B01L 2400/043: magnetic forces
- B01L 2400/0433: vibrational forces
- B01L 2400/0454: radiation pressure, optical tweezers
- B01L 2400/0487: fluid pressure, pneumatics
- B01L 2400/0622: distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
- B01L 2400/084: Passive control of flow resistance
- B33Y 80/00: Products made by additive manufacturing
- G01N 15/0255: {with mechanical, e.g. inertial, classification, and investigation of sorted collections (with centrifuges G01N15/042)}
- G01N 2015/0288: {Sorting the particles}
- G01N 2015/1006: {for cytology}
- G01N 2015/1028: {Sorting particles}
- Y10T 137/85938: Non-valved flow dividers
- Y10T 137/85978: With pump
- Y10T 436/117497: with a continuously flowing sample or carrier stream
- Y10T 436/2575: Volumetric liquid transfer
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS}
- F16L: PIPES; JOINTS OR FITTINGS FOR PIPES; SUPPORTS FOR PIPES, CABLES OR PROTECTIVE TUBING; MEANS FOR THERMAL INSULATION IN GENERAL
- F17D: PIPE-LINE SYSTEMS; PIPE-LINES (pumps or compressors F04; fluid dynamics F15D; valves or the like F16K; pipes, laying pipes, supports, joints, branches, repairing, work on the entire line, accessories F16L; steam traps or the like F16T; fluid-pressure electric cables H01B9/06)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- B33Y: ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## 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

### Claim 1

A device for focusing particles suspended within a fluid and analyzing the focused particles, the device comprising:
(a) a substrate;
(b) one or more focusing channels formed in the substrate, wherein each of the focusing channels spans a length from an inlet to an outlet and has a respective channel hydraulic diameter (Dh), wherein each of the focusing channels includes a plurality of curves, and wherein each of the focusing channels is arranged to allow a fluid having a kinematic viscosity (ν) and comprising suspended particles, each having a particle hydraulic diameter (a), to flow therethrough; and
(c) one or more analysis channels formed in the substrate, wherein an inlet of each of the one or more analysis channels is in fluid communication with an outlet of a respective one of the one or more focusing channels;
wherein the one or more focusing channels are dimensioned and configured such that when the fluid that includes the suspended particles is driven through the one or more focusing channels at a maximum channel velocity (Um) resulting in a laminar fluid flow and a particle Reynolds Number (Rp) 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 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 each of the one or more focusing channels.

### Claim 2 (depends on 1)

The device of claim 1, wherein each of the one or more focusing channels has a width and a height that define an aspect ratio, each localized stream line defines a width that is substantially equal to or greater than a size of the focused particles, and wherein the number and relative cross-sectional position of the one or more localized stream lines within each focusing channel are uniquely defined by the aspect ratio and the particle Reynolds number.

### Claim 3 (depends on 1)

The device of claim 1, further comprising a filter positioned upstream of, and in fluid communication with, the one or more focusing channels, wherein the filter has a cut-off size selected to prevent passage of particles larger than the hydraulic diameter of a largest of the focusing channels.

### Claim 4 (depends on 1)

The device of claim 1, wherein the plurality of curves comprises a plurality of sigmoidal curves.

### Claim 5 (depends on 1)

The device of claim 1, wherein a plurality of curves included in at least one of the focusing channels includes a plurality of asymmetrical curves and wherein the at least one of the focusing channels has a rectangular cross-section with an aspect ratio that varies along the channel length from 1 to 1 and 2 to 1.

### Claim 6 (depends on 1)

The device of claim 1, wherein at least one of the focusing channels forms a spiral.

### Claim 7 (depends on 1)

A system comprising the device of claim 1 and a pump controlled to drive the fluid that includes the particles through the one or more focusing channels at a maximum channel velocity (Um).

### Claim 8 (depends on 7)

The system of claim 7, further comprising a detector to detect particles that flow through the one or more analysis channels.

### Claim 9 (depends on 7)

The system of claim 7, further comprising a tagging system for applying a tag to selected particles.

### Claim 10 (depends on 9)

The system of claim 9, wherein the tag comprises an optically sensitive tag.

### Claim 11 (depends on 9)

The system of claim 9, wherein the tag comprises a magnetic property.

### Claim 12 (depends on 7)

The system of claim 7, further comprising a sorting system in fluid communication with the one or more analysis channels for diverting selected particles towards an output channel.

### Claim 13 (depends on 12)

The system of claim 12, wherein the system further comprises a tagging system that applies to the selected particles a magnetic tag and the sorting system includes a magnetic biasing element that applies a force to the tagged particles that diverts the tagged particles towards the output channel.