# US 10,119,900 B2 · In-line particle characterization

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- Number: US 10,119,900 B2
- Document ID: US10119900B2
- Status: Granted
- Kind: B2
- Application number: 15/320,646
- Filed: 2015-06-24
- Published: 2017-06-29
- Granted: 2018-11-06
- Earliest claimed: 2014-06-25
- Assignees: New York University
- Applicants: New York University
- Inventors: Chen Wang; Hagay Shpaisman; Andrew Hollingsworth; David G. Grier
- Web page: https://patentgrep.com/patent/US10119900B2

## CPC

- G01N 15/1433: using image recognition
- G01N 15/0211: {Investigating a scatter or diffraction pattern}
- G02B 21/0004: {specially adapted for specific applications}
- G03H 1/0005: {Adaptation of holography to specific applications (holographic optical element G02B5/32; holographic scanner G02B26/106; recognition using holographic mask G06V10/88; holographic memories G11B7/0065, G11C13/042)}
- G03H 1/0443: {Digital holography, i.e. recording holograms with digital recording means (holobject computation G03H1/0866)}
- G03H 1/08: Synthesising holograms, {i.e. holograms synthesized from objects or objects from holograms}(using electric digital computers G06F; G06T)
- G06V 20/695: {Preprocessing, e.g. image segmentation}
- G06V 20/698: {Matching; Classification}
- G03H 2001/0033: {in hologrammetry for measuring or analysing}
- G03H 2001/005: {in microscopy, e.g. digital holographic microscope [DHM]}
- G06V 2201/12: Acquisition of 3D measurements of objects
- 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)
- G02B: OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G03H: HOLOGRAPHIC PROCESSES OR APPARATUS (holograms, e.g. point holograms, used as ordinary optical elements G02B5/32; producing stereoscopic or other three-dimensional effects G02B30/00; diffraction-grating systems G02B27/44; systems using moiré fringes G02B27/60; optical logic elements G02F3/00; stereo-photography G03B35/00; photosensitive materials or processes for photographic purposes G03C; {stereo-photographic or similar processes G03C9/00}; apparatus for processing exposed photographic materials G03D; analogue computers performing mathematical operations with the aid of optical elements G06E3/00; authentication by radiation, of concealed information carried by holograms or diffraction gratings G06K19/16; holographic storage G11B7/0065, G11C13/04; {stereoscopic or other three dimensional effects in television systems H04N13/00})
- G06V: IMAGE OR VIDEO RECOGNITION OR UNDERSTANDING

## Abstract

Holographic video microscopy yields fast and accurate measurements of the size and refractive index of individual colloidal particles. Particle-resolved characterization offers useful insights into the progress of colloidal synthesis without relying on models for the distributions of particle sizes and properties, and can be performed rapidly enough to provide feedback for process control. The measured increase in the most probable radius over the course of the reaction is consistent with the LaMer model for colloidal growth. Uniformity in the measured refractive index suggests that the spheres grow with uniform density. The joint distribution of size and refractive index provides evidence for a low rate of nucleation proceeding after the initial nucleation event. The same analysis reveals that these PDMS particles shrink by compactification in the first few days after their synthesis.

## Claims

### Claim 1

A method of characterizing a plurality of particles, comprising:
flowing the plurality of particles through a field of view of a holographic video microscopy system;
generating a hologram based upon holographic video microscopy of a first particle of the plurality of particles, which is within the field of view at a first time;
determining the refractive index, density, and the radius of the first particle at the first time;
generating a hologram based upon holographic video microscopy of a second particle of the plurality of particles, which is within the field of view at a second time; and
determining the refractive index, density, and the radius of the second particle at the second time.

### Claim 2 (depends on 1)

The method of claim 1, further comprising monitoring synthesis of the plurality of particles based upon comparison of the first particle refractive index and radius and the second particle refractive index and radius.

### Claim 3 (depends on 1)

The method of claim 1, further comprising, wherein the first time and second time are after synthesis of the plurality of particles, monitoring post-synthesis stability of the plurality of particles.

### Claim 4 (depends on 1)

The method of claim 1 wherein determining the refractive index and the radius comprises application of Lorenz-Mie theory.

### Claim 5 (depends on 1)

The method of claim 1, further comprising determining whether synthesis of the plurality of particles has concluded.

### Claim 6 (depends on 1)

The method of claim 1 further comprising a flow rate of about 50 μm/s.

### Claim 7 (depends on 1)

The method of claim 1, wherein determining the refractive index and the radius of the first particle and determining the refractive index and the radius of the second particle comprise determining a probability density for refractive index and radius for the first particle and determining a probability density for refractive index and radius for the second particle, respectively.

### Claim 8

A method of characterizing a plurality of particles, comprising generating holograms of particles of the plurality of particles, each hologram based upon holographic video microscopy of a particle PN of the plurality of particles at a different time T; and
determining a time TN refractive index and a time TN radius of the particle PN at a time TN;
determining a time TN+1 refractive index and a time TN+1 radius of the particle PN at a time TN+1;
characterizing a change in the plurality of particles over time based upon a comparison of the time TN refractive index and the time TN+1 refractive index and the time TN radius and the time TN+1 radius;
determining if the change in the plurality of particles is a chemical change or a structural change.

### Claim 9 (depends on 8)

The method of claim 8, further comprising monitoring synthesis of the plurality of particles based upon comparison of the determined refractive indices and radii.

### Claim 10 (depends on 8)

The method of claim 8, further comprising, wherein the holograms are generated after synthesis of the plurality of particles, monitoring postsynthesis stability of the plurality of particles.

### Claim 11 (depends on 8)

The method of claim 8 wherein determining the refractive index and the radius comprises application of Lorenz-Mie theory.

### Claim 12 (depends on 8)

The method of claim 8, further comprising flowing the plurality of particles through a holographic video microscopy system.

### Claim 13 (depends on 12)

The method of claim 12 further comprising a flow rate of about 50 μm/s.

### Claim 14 (depends on 8)

The method of claim 8, wherein determining the refractive index and the radius of the first particle and determining the refractive index and the radius of the second particle comprise determining a probability density for refractive index and radius for the first particle and determining a probability density for refractive index and radius for the second particle, respectively.

### Claim 15

A computer-implemented machine for characterizing a plurality of particles, comprising:
a processor; and
a tangible computer-readable medium operatively connected to the processor and including computer code configured to:
generate a hologram based upon holographic video microscopy of a first particle of the plurality of particles, the first particle flowing through a field of view of a holographic video microscopy system, at a first time; and
determine the refractive index and the radius of the first particle at the first time;
generate a hologram based upon holographic video microscopy of a second particle of the plurality of particles at a second time; and
determine the refractive index and the radius of the second particle at the second time.

### Claim 16 (depends on 15)

The computer-implemented machine of claim 15, further comprising computer code configured to monitor synthesis of the plurality of particles based upon comparison of the first particle refractive index and radius and the second particle refractive index and radius.

### Claim 17 (depends on 15)

The method of claim 15, further comprising computer code configured to monitor, wherein the first time and second time are after synthesis of the plurality of particles, post-synthesis stability of the plurality of particles.

### Claim 18 (depends on 1)

The method of claim 1, wherein, prior to generating a hologram, a colloidal suspension of the plurality of particles is diluted to a volume faction of at least 10−4.

### Claim 19 (depends on 8)

The method of claim 8, wherein determining if the change is a chemical change or a structural change, further comprises determining density of the plurality of particles.