# US 10,307,760 B2 · Inertio-elastic focusing of particles in microchannels

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- Number: US 10,307,760 B2
- Document ID: US10307760B2
- Status: Granted
- Kind: B2
- Application number: 15/114,050
- Filed: 2015-01-30
- Published: 2016-11-24
- Granted: 2019-06-04
- Earliest claimed: 2014-01-30
- Assignees: The General Hospital Corporation; Massachusetts Institute of Technology
- Applicants: The General Hospital Corporation; Massachusetts Institute of Technology
- Inventors: Mehmet Toner; Gareth McKinley; Eugene Lim; Thomas Ober
- Web page: https://patentgrep.com/patent/US10307760B2

## CPC

- B01L 3/502776: {specially adapted for focusing or laminating flows}
- B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces}
- B01L 3/50273: {characterised by the means or forces applied to move the fluids}
- B01L 2200/0636: Focussing flows, e.g. to laminate flows
- B01L 2200/12: Specific details about manufacturing devices
- B01L 2400/0487: fluid pressure, pneumatics
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

One example of systems and methods for inertio-elastic focusing of particles in microchannels includes a substrate including a channel having an inlet and an outlet. A viscoelastic fluid, i.e., a fluid having a dynamic viscosity that varies with shear rate, and that carries suspended particles is driven through the channel. The volumetric flow rate at which the fluid is driven results in the formation of a localized pathline in the fluid at or near a center of the channel. The localized pathline defines a width that is equal to or slightly greater than a hydraulic diameter of the particle. The particles in the fluid are focused into the localized pathline.

## Claims

### Claim 1

A method for focusing particles suspended within a moving Newtonian fluid, the method comprising:
adding a drag-reducing polymer to the Newtonian fluid;
providing a substrate including a channel having an inlet and an outlet; and
driving the Newtonian fluid that carries suspended particles through the channel at a volumetric flow rate of at least 0.6 ml/minute that results in the formation of a laminar flow and a localized pathline in the Newtonian fluid at or near a center of the channel, wherein the localized pathline defines a width that is substantially equal to or greater than a hydraulic diameter of the particles;
wherein the particles in the Newtonian fluid are focused into the localized pathline.

### Claim 2 (depends on 1)

The method of claim 1, wherein the drag-reducing polymer includes hyaluronic acid (HA).

### Claim 3 (depends on 2)

The method of claim 2, wherein a molecular weight of the HA is between 350 kDa and 1650 kDa.

### Claim 4 (depends on 1)

The method of claim 1, wherein the volumetric flow rate is between 0.6 ml/min and 50 ml/min.

### Claim 5 (depends on 4)

The method of claim 4, wherein the Newtonian fluid is driven through the channel at a volumetric flow rate resulting in a Reynolds number of the flow of between 100 and 10,000.

### Claim 6 (depends on 5)

The method of claim 5, wherein the Newtonian fluid is driven through the channel at a volumetric flow rate resulting in a Reynolds number of the flow of between 100 and 4500.

### Claim 7 (depends on 1)

The method of claim 1, wherein the suspended particles comprise at least one of rigid beads, mammalian cells, hydrogel particles or white blood cells (WBCs).

### Claim 8 (depends on 1)

The method of claim 1, wherein the particles suspended within the moving Newtonian fluid have a diameter a, and the channel has a hydraulic diameter D selected such that a ratio of particle diameter a to channel hydraulic diameter D is greater than 0.1.

### Claim 9

A system for focusing particles suspended within a moving Newtonian fluid, the system comprising:
a substrate including a channel having an inlet and an outlet;
a Newtonian fluid having a dynamic viscosity that varies with shear rate and that carries suspended particles, mixed with a drag-reducing polymer;
a pump to drive the Newtonian fluid through the channel at a volumetric flow rate that results in the formation of a laminar flow and a localized pathline in the Newtonian fluid at or near a center of the channel, wherein the localized pathline defines a width that is substantially equal to or greater than a hydraulic diameter of the particles; and
a controller configured to control operation of the pump based on dynamic viscosity and volumetric flow rate of the Newtonian fluid, wherein during use the controller is configured to control the pump to drive the Newtonian fluid through the channel at a volumetric flow rate of at least 0.6 ml/minute while maintaining a laminar flow such that the system focuses the particles in the Newtonian fluid into the localized pathline.

### Claim 10 (depends on 9)

The system of claim 9, wherein the drag-reducing polymer includes hyaluronic acid (HA).

### Claim 11 (depends on 9)

The system of claim 9, wherein the pump is configured to control to drive the fluid through the channel at a volumetric flow rate resulting in a Reynolds number of the flow of between 100 and 10,000.

### Claim 12 (depends on 11)

The system of claim 11, wherein the pump is configured to control to drive the fluid through the channel at a volumetric flow rate resulting in a Reynolds number of between 2,000 and 4500.

### Claim 13

A method for focusing particles suspended within a moving viscoelastic Newtonian fluid, the method comprising:
adding a drag-reducing polymer to the viscoelastic Newtonian fluid;
providing a substrate including a channel having an inlet and an outlet; and
driving the viscoelastic Newtonian fluid that carries suspended particles through the channel at a volumetric flow rate of at least 0.6 ml/minute that results in the formation of a laminar flow and a localized pathline in the viscoelastic Newtonian fluid at or near a center of the channel, wherein the localized pathline defines a width that is substantially equal to or greater than a hydraulic diameter of the particles,
wherein the particles in the viscoelastic Newtonian fluid are focused into the localized pathline.

### Claim 14 (depends on 13)

The method of claim 13, wherein the viscoelastic Newtonian fluid is driven at a Weissenberg number that is at least 10% of a Reynolds number of the viscoelastic Newtonian fluid flow, wherein the Weissenberg number is defined as λ*U/H, where λ is a relaxation time of the viscoelastic Newtonian fluid, U represents the volumetric flow rate and H is a cross-sectional dimension of the channel.

### Claim 15 (depends on 13)

The method of claim 13, wherein the drag-reducing polymer includes hyaluronic acid (HA).

### Claim 16 (depends on 13)

The method of claim 13, wherein the volumetric flow rate is between 0.6 ml/min and 50 ml/min.

### Claim 17 (depends on 16)

The method of claim 16, wherein the viscoelastic Newtonian fluid is driven through the channel at a volumetric flow rate resulting in a Reynolds number of the flow of between 100 and 4500.
