# US 12,007,321 B2 · System and method for deforming and analyzing particles

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- Number: US 12,007,321 B2
- Document ID: US12007321B2
- Status: Granted
- Kind: B2
- Application number: 17/200,728
- Filed: 2021-03-12
- Published: 2021-11-04
- Granted: 2024-06-11
- Earliest claimed: 2012-10-24
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: Dino Di Carlo; Daniel R. Gossett; Henry T. K. Tse; Aram Chung
- Web page: https://patentgrep.com/patent/US12007321B2

## CPC

- G01N 15/147: {the analysis being performed on a sample stream}
- G01N 15/1404: Handling flow, e.g. hydrodynamic focusing
- G01N 15/1434: Optical arrangements
- G01N 15/1436: {the optical arrangement forming an integrated apparatus with the sample container, e.g. a flow cell}
- G01N 15/1459: {the analysis being performed on a sample stream}
- G01N 15/1484: {microstructural devices}
- G01N 21/6428: {Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53)}
- G01N 21/645: {Specially adapted constructive features of fluorimeters}
- G01N 33/50: Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing (measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q)
- G01N 33/5091: {for testing the pathological state of an organism}
- G06T 7/0004: {Industrial image inspection}
- G01N 15/01: specially adapted for biological cells, e.g. blood cells (investigating sedimentation of particle suspensions in blood G01N15/05)
- G01N 21/64: Fluorescence; Phosphorescence
- G01N 2015/1006: {for cytology}
- G01N 2015/1415: {Control of particle position}
- G01N 2015/1495: {Deformation of particles}
- G01N 2021/6439: {with indicators, stains, dyes, tags, labels, marks}
- G06T 7/0016: {involving temporal comparison}
- 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)
- G06T: IMAGE DATA PROCESSING OR GENERATION, IN GENERAL

## Abstract

A system for deforming and analyzing a plurality of particles carried in a sample volume includes a substrate defining an inlet, configured to receive the sample volume, and an outlet; and a fluidic pathway fluidly coupled to the inlet and the outlet. The fluidic pathway includes a delivery region configured to receive the plurality of particles from the inlet and focus the plurality of particles from a random distribution to a focused state, a deformation region defining an intersection located downstream of the delivery region and coupled to the outlet, and wherein the deformation region is configured to receive the plurality of particles from the delivery region and to transmit each particle in the plurality of particles into the intersection from a single direction, a first branch fluidly coupled to the deformation region and configured to transmit a first flow into the intersection, and a second branch fluidly coupled to the deformation region and configured to transmit a second flow, substantially opposing the first flow, into the intersection, wherein the first flow and the second flow are configured to induce extension of one or more particles in the plurality of particles.

## Claims

### Claim 1

A system for deforming and analyzing a plurality of particles carried in a fluidic sample volume, the system comprising:
a substrate defining an inlet, configured to receive the fluidic sample volume, and one or more outlets; and
a fluidic pathway fluidically coupled to the inlet and the one or more outlets and comprising:
a first focusing region comprising one or more curved channels or a hydrodynamic flow focusing region that receives a sheath fluid;
a furcation cowled to the first focusing region and located downstream from the first focusing region that includes a first channel and one or more additional channels, the first channel consisting of a second focusing region comprising one or more curved channels or a hydrodynamic flow focusing region that receives a sheath fluid: and
a deformation region formed by an intersection of the first channel and the one or more additional channels, the deformation region located downstream of the second focusing region.

### Claim 2 (depends on 1)

The system of claim 1, wherein the first channel and the one or more additional channels intersect at the deformation re ion with one another in an off-axis orientation.

### Claim 3 (depends on 1)

The system of claim 1, further comprising a pump fluidically coupled to the one or more additional channels.

### Claim 4 (depends on 3)

The system of claim 3, wherein the pump has an adjustable flow rate.

### Claim 5 (depends on 1)

The system of claim 1, wherein the inlet is coupled to a fluid containing the particles and wherein the particles comprise cells.

### Claim 6 (depends on 5)

The system of claim 5, wherein the cells comprise label-free, cells.

### Claim 7 (depends on 1)

The system of claim 1, wherein the intersection of the first channel and the one or more additional channels is fluidically connected to the fluidic pathway upstream of the deformation region.

### Claim 8 (depends on 1)

The system of claim 1, further comprising a light source configured to illuminate each of the particles passing through the deformation region and a detection module configured to capture a morphology dataset for each of the particles passing through the deformation region.

### Claim 9 (depends on 8)

The system of claim 8, wherein the detection module comprises a camera configured to capture multiple morphology datasets for each of the plurality of particles in the deformation region.

### Claim 10 (depends on 8)

The system of claim 8, wherein the detection module comprises a one-dimensional detection module configured to capture a morphology dataset for each of the plurality of particles based on multiple records of scattered light.

### Claim 11 (depends on 1)

The system of claim 1, further comprising a particle, sorter configured to sort the plurality of particles to specific outlets located downstream of the deformation region based on particle deformability.

### Claim 12 (depends on 11)

The system of claim 11, wherein the particle sorter sorts particles by focusing or flow diversion.