System and methods for analyzing particles in a fluid

Patent metadata

Field	Value
Publication number	US-10794808-B2
Application number	US-201716072572-A
Country	US
Kind code	B2
Filing date	Feb 3, 2017
Priority date	Feb 5, 2016
Publication date	Oct 6, 2020
Grant date	Oct 6, 2020

Abstract

Methods and systems suitable for tracking Brownian motion of particles suspended in a fluid and determining the diffusion coefficient of the particles therefrom in order to characterize the particles, their synthesis, and/or their surface modifications. The methods include providing a sample having particles suspended in a fluid, obtaining and recording at least first and second images of the sample wherein the first image obtained at a first time and the second image subsequently obtained at a second time, determining the average displacement of the particles in an area of the first and second images during a time period between the first time and the second time based on the first and second images, and then determining a diffusion coefficient of the particles in the area of the first and second images based on the average displacement of the particles during the time period.

First claim

The invention claimed is:

1. A system comprising:
an imaging device;
means for recording a series of images of a fluid sample comprising particles suspended therein over a period of time;
means for analyzing the series of images to determine an average displacement of the particles over the time period using a cross-correlation that correlates an area from a first image of the series of images obtained at a first time (t 1 ) with the area from a second image of the series of images subsequently obtained at a second time (t 2 ); and
means for determining a diffusion coefficient of the particles based on the average displacement of the particles using the cross-correlation;
wherein the particles have biomolecules bound thereto, and the system further comprises means for determining an average thickness of the biomolecules bound to the particles based on the diffusion coefficient.

2. The system of claim 1 , further comprising means for determining the uniformity of the particles within the fluid sample based on the diffusion coefficient.

3. The system of claim 1 , further comprising means for determining a number of biomolecule layers on the particles and a variation of the number of biomolecule layers on the particles.

4. The system of claim 1 , wherein the system is configured to analyze particles having a diameter or maximum dimension of two micrometers or less.

5. The system of claim 1 , wherein the analyzing means further uses a second correlation and the determining means calculates the diffusion coefficient from peak widths of the cross-correlation and the second correlation.

6. The system of claim 5 , wherein the determining means calculates the diffusion coefficient from the peak widths of the cross-correlation and the second correlation using:

D
=

s
c
2

-

s
a
2

16
⁢

M
2

⁢
Δ
⁢

⁢
t

where D is the diffusion coefficient, s c and s a are, respectively, the peak widths of the cross-correlation and the second correlation measured at 1/e of peak heights thereof, M is magnification under which the series of images were recorded, and Δt is time between the first and second times (t 1 ,t 2 ).

7. A method comprising:
providing a sample having particles suspended in a fluid;
obtaining and recording at least first and second images of the sample, the first image obtained at a first time (t 1 ) and the second image subsequently obtained at a second time (t 2 );
determining an average displacement of the particles in an area of the first and second images during a time period (Δt) between the first time (t 1 ) and the second time (t 2 ) using a cross-correlation that correlates the area from the first and second images; and then
determining a diffusion coefficient of the particles in the area of the first and second images based on the average displacement of the particles during the time period (Δt) using the cross-correlation;
wherein the particles have biomolecules bound thereto, further comprising characterizing the conjugation of the biomolecules and the particles, wherein an increase in an absolute hydrodynamic radius of the particles relates to a decrease in the diffusion coefficient of the of the particles.

8. The method of claim 7 , further comprising determining the uniformity of the particles within the sample based on the diffusion coefficient.

9. The system of claim 7 , further comprising determining an average thickness of the biomolecules bound to the particles based on the diffusion coefficient.

10. The system of claim 7 , further comprising determining a number of biomolecule layers on the particles and a variation of the number of biomolecule layers on the particles.

11. The method of claim 7 , wherein the determining of the average displacement of the particles further uses a second correlation and the determining of the diffusion coefficient of the particles calculates the diffusion coefficient from peak widths of the cross-correlation and the second correlation.

12. The method of claim 11 , wherein the determining of the diffusion coefficient of the particles calculates the diffusion coefficient from peak widths of the cross-correlation and the second correlation using:

D
=

s
c
2

-

s
a
2

16
⁢

M
2

⁢
Δ
⁢

⁢
t

where D is the diffusion coefficient, s c and s a are, respectively, the peak widths of the cross-correlation and the second correlation measured at 1/e of peak heights thereof, M is magnification under which the series of images were recorded, and Δt is the time period between the first and second times (t 1 ,t 2 ).

13. A method comprising:
providing a sample having particles suspended in a fluid;
obtaining and recording a series of images of the sample over a period of time;
partitioning each of the series of images into interrogation areas;
determining the average displacement of the particles in each of the interrogation areas in each of the series of images over the time period;
determining a diffusion coefficient of the particles in each of the interrogation areas in each of the series of images based on the average displacement of the particles; and then
determining an average diffusion coefficient of the particles by averaging the diffusion coefficients in each of the interrogation areas in each of the series of images.

14. The method of claim 13 , wherein the particles have biomolecules bound thereto, wherein the diffusion coefficient of the particles is represented in the determining step as a ratio of particles without biomolecules bound thereto to biomolecule conjugated particles.

15. The method of claim 13 , wherein the particles have biomolecules bound thereto, further comprising characterizing the conjugation of the biomolecules and the particles, wherein an increase in an absolute hydrodynamic radius of the particles relates to a decrease in the diffusion coefficient of the of the particles.

16. The method of claim 13 , further comprising determining a number of biomolecule layers on the particles and a variation of the number of biomolecule layers on the particles.

17. The method of claim 13 , wherein the determining of the average displacement of the particles us

Assignees

• Purdue Research Foundation

Inventors

• Clayton Katherine Noel
• Kinzer-Ursem Tamara Lea
• Wereley Steven Truitt
• Salameh Janelle Weslyn

Classifications

• G01N15/0227 Primary

  using imaging; using holography · CPC title

• G01N2015/0238

  Single particle scatter · CPC title

• G01N2015/0038

  Investigating nanoparticles · CPC title

• G01N2015/0053

  in liquids, e.g. trouble · CPC title