# US 11,027,280 B2 · Sorting particles in a microfluidic device

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- Number: US 11,027,280 B2
- Document ID: US11027280B2
- Status: Granted
- Kind: B2
- Application number: 16/112,259
- Filed: 2018-08-24
- Published: 2018-12-20
- Granted: 2021-06-08
- Earliest claimed: 2014-11-03
- Assignees: The General Hospital Corporation
- Applicants: The General Hospital Corporation
- Inventors: Ravi Kapur; Kyle C. Smith; Mehmet Toner
- Web page: https://patentgrep.com/patent/US11027280B2

## CPC

- 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}
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces}
- B01L 3/502746: {characterised by the means for controlling flow resistance, e.g. flow controllers, baffles or throttle valves}
- B01L 3/502753: {characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation}
- G01N 1/4077: {by other techniques involving separation of suspended solids}
- G01N 15/0255: {with mechanical, e.g. inertial, classification, and investigation of sorted collections (with centrifuges G01N15/042)}
- G01N 15/0618: {of the filter type (G01N15/0643 takes precedence)}
- G01N 15/1484: {microstructural devices}
- B01L 3/502776: {specially adapted for focusing or laminating flows}
- B01L 2200/0631: Purification arrangements, e.g. solid phase extraction [SPE]
- B01L 2200/0647: Handling flowable solids, e.g. microscopic beads, cells, particles
- B01L 2200/0652: Sorting or classification of particles or molecules
- B01L 2200/0668: Trapping microscopic beads
- B01L 2200/0684: Venting, avoiding backpressure, avoid gas bubbles
- B01L 2200/0694: Creating chemical gradients in a fluid
- B01L 2200/12: Specific details about manufacturing devices
- B01L 2300/0681: Filter
- B01L 2300/0858: Side walls
- B01L 2300/0877: Flow chambers
- B01L 2300/0883: Serpentine channels
- B01L 2300/0887: Laminated structure
- B01L 2300/185: using a liquid as fluid
- B01L 2400/0409: centrifugal forces
- B01L 2400/0415: electrical forces, e.g. electrokinetic
- B01L 2400/043: magnetic forces
- B01L 2400/0436: acoustic forces, e.g. surface acoustic waves [SAW]
- B01L 2400/0457: passive flow or gravitation
- B01L 2400/0487: fluid pressure, pneumatics
- B01L 2400/082: Active control of flow resistance, e.g. flow controllers
- B01L 2400/086: using baffles or other fixed flow obstructions
- G01N 15/01: specially adapted for biological cells, e.g. blood cells (investigating sedimentation of particle suspensions in blood G01N15/05)
- G01N 15/149: specially adapted for sorting particles, e.g. by their size or optical properties
- G01N 2001/4088: {filtration}
- G01N 2015/0053: {in liquids, e.g. trouble}
- G01N 2015/0288: {Sorting the particles}
- G01N 2015/1486: {Counting the particles}
- G01N 2015/1493: {Particle size}
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- 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)

## Abstract

A microfluidic device includes a particle sorting region having a first, second and third microfluidic channels, a first array of islands separating the first microfluidic channel from the second microfluidic channel, and a second array of islands separating the first microfluidic channel from the third microfluidic channel, in which the island arrays and the microfluidic channels are arranged so that a first fluid is extracted from the first microfluidic channel into the second microfluidic channel and a second fluid is extracted from the third microfluidic channel into the first microfluidic channel, and so that particles are transferred from the first fluid sample into the second fluid sample within the first microfluidic channel.

## Claims

### Claim 1

A method of producing a sample enriched in particles of a first type, the method comprising:
obtaining a fluid sample comprising particles of the first type;
altering a size of the particles of the first type in the fluid sample to provide particles of the first type having an increased effective size in the fluid sample; and
flowing the fluid sample containing the particles of the first type having the increased effective size into a region of a microfluidic device comprising a first microfluidic channel, a second microfluidic channel extending along the first microfluidic channel, and a first array of islands separating the first microfluidic channel from the second microfluidic channel,
wherein the first microfluidic channel, the second microfluidic channel, and the islands are arranged so that a ratio of a fluidic resistance of the first microfluidic channel to a fluidic resistance of the second microfluidic channel increases along a longitudinal direction of the first microfluidic channel such that a portion of the fluid sample flowing through the first microfluidic channel passes through one or more openings between adjacent islands into the second microfluidic channel, and
wherein, for a particular fluid velocity of the fluid sample within the first microfluidic channel, inertial lift forces cause the particles of the first type having the increased effective size to remain within the first microfluidic channel, thereby producing a sample enriched in particles of the first type.

### Claim 2 (depends on 1)

The method of claim 1, wherein altering the size of the particles of the first type comprises binding the particles of the first type to one or more other particles.

### Claim 3 (depends on 2)

The method of claim 2, wherein the one or more other particles comprise beads.

### Claim 4 (depends on 1)

The method of claim 1, wherein altering the size of the particles of the first type comprises binding the particles of the first type to one or more other particles of a second type that is different from the first type.

### Claim 5 (depends on 1)

The method of claim 1, wherein the particles of the first type are cells, and wherein altering the size of the particles of the first type comprises forming cell aggregations.

### Claim 6 (depends on 1)

The method of claim 1, wherein the particles of the first type are cells, and wherein altering the size of the particles of the first type comprises causing osmotic swelling of the cells.

### Claim 7 (depends on 1)

The method of claim 1, comprising focusing the particles of the first type having the increased effective size along one or more streamlines within the first microfluidic channel.

### Claim 8 (depends on 1)

The method of claim 1, wherein the fluid sample comprises particles of a second type, and a size of the particles of the second type is smaller than the effective size of the particles of the first type, and
wherein the inertial lift forces cause the particles of the second type to flow with the portion of the fluid sample passing through the one or more openings between adjacent islands into the second microfluidic channel.

### Claim 9 (depends on 8)

The method of claim 8, wherein a size of each of the particles of the first type and the particles of the second type is an average hydrodynamic particle size.

### Claim 10 (depends on 8)

The method of claim 8, wherein a size of each of the particles of the first type and the particles of the second type is an average diameter.

### Claim 11 (depends on 1)

The method of claim 1, wherein a size of the particles of the first type is an average hydrodynamic particle size.

### Claim 12 (depends on 1)

The method of claim 1, wherein a size of the particles of the first type is an average diameter.

### Claim 13 (depends on 1)

The method of claim 1, wherein the inertial lift forces shift the particles of the first type having the increased effective size across fluid streamlines within the first microfluidic channel.

### Claim 14 (depends on 1)

The method of claim 1, wherein the increase in the ratio of the fluidic resistance of the first microfluidic channel to the fluidic resistance of the second microfluidic channel is a result of an increase in a cross-sectional area of the second microfluidic channel along the longitudinal direction for a predefined section of the microfluidic device.

### Claim 15 (depends on 14)

The method of claim 14, wherein a cross-sectional area of the first microfluidic channel is substantially constant along the longitudinal direction for the predefined section of the microfluidic device.

### Claim 16 (depends on 1)

The method of claim 1, wherein the increase in the ratio of the fluidic resistance of the first microfluidic channel to the fluidic resistance of the second microfluidic channel is a result of a decrease in a cross-sectional area of the first microfluidic channel along the longitudinal direction for a predefined section of the microfluidic device.

### Claim 17 (depends on 16)

The method of claim 16, wherein a cross-sectional area of the second microfluidic channel is substantially constant along the longitudinal direction for the predefined section of the microfluidic device.

### Claim 18 (depends on 1)

The method of claim 1, wherein the first array of islands consists of a one-dimensional array of islands.

### Claim 19 (depends on 1)

The method of claim 1, wherein the first array of islands comprises a two-dimensional array of islands.