IP Library Granted Patent US 9,476,819
Granted Patent B2
US 9,476,819 · App. 13/822,986 · Granted Oct 25, 2016

Hydrodynamic particle separation and detection systems and methods

Inventors: Tza-Huei Jeff Wang (Timonium, MD); Kelvin Jeng-Fang Liu (Baltimore, MD)
Assignee: The Johns Hopkins University
G01N15/1484C12Q1/686G01N21/645G01N33/48G01N15/0255G01N2015/149G01N2015/1486G01N2015/1493
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Quick Facts
Patent No.
US 9,476,819
App. No.
13/822,986
Granted
Oct 25, 2016
Kind
B2
Abstract

A method of separating, detecting and determining a size of each of a plurality of particles in a fluid includes compelling the fluid to flow through a fluid channel such that larger particles of the plurality of particles travel through the fluid channel faster than smaller particles of the plurality of particles; illuminating a detection zone of the fluid channel substantially uniformly across an entire cross section of the fluid channel such that each of the plurality of particles passes through illumination light upon passing through the detection zone; detecting each of the plurality of particles based on corresponding responses to the illuminating to determine a time that each of the plurality of particles passes through the detection zone; and determining a size of each of the plurality of particles based on the time that each of the plurality of particles passes through the detection zone.

Claims (39)

1. A method of separating, detecting and determining a size of each of a plurality of particles in a fluid, comprising:

compelling said fluid to flow through a fluid channel such that larger particles of said plurality of particles travel through said fluid channel faster than smaller particles of said plurality of particles;

illuminating a detection zone of said fluid channel substantially uniformly across an entire cross section of said fluid channel such that each of said plurality of particles passes through illumination light upon passing through said detection zone;

detecting each of said plurality of particles based on corresponding responses to said illuminating to determine a time that each of said plurality of particles passes through said detection zone; and

determining a size of each of said plurality of particles based on said time that each of said plurality of particles passes through said detection zone,

wherein said detection comprises quantification of said plurality of particles, and

wherein said quantification is quantification by analyzing aggregate signals to correlate said aggregate signals with a quantity of particles in said plurality of particles.

2. The method of claim 1 , wherein said plurality of particles is a plurality of molecules.

3. The method of claim 1 , wherein said plurality of particles comprises at least one of polymer, pharmaceutical, fluorophore, DNA, RNA, lipid, emulsion, carbohydrate, metabolite, antibody, or protein molecules, vesicle or cells.

4. The method of claim 1 , wherein said plurality of particles is between 1 to 10 6 molecules in 1 pL to 1 μL of a sample.

5. The method of claim 1 , wherein said fluid channel is defined by a capillary.

6. The method of claim 1 , wherein said fluid channel is defined by a microfluidic chip.

7. The method of claim 6 , wherein said fluid channel defines a plurality of fluid channels.

8. The method of claim 1 , wherein said compelling is applying a pressure to said fluid.

9. The method of claim 1 , wherein said illuminating is illuminating with a cylindrical illumination system.

10. The method of claim 1 , further comprising collecting said plurality of particles after being separated in fractions based on time or size.

11. A system for separating, detecting and determining a size of each of a plurality of particles in a fluid, comprising:

a hydrodynamic fluid separation system comprising a fluid channel;

an illumination system arranged to illuminate a detection zone of said fluid channel substantially uniformly across an entire cross section of said fluid channel such that each of said plurality of particles passes through illumination light upon passing through said detection zone;

a detection system arranged to detect each of said plurality of particles based on corresponding responses to said illumination light to determine a time that each of said plurality of particles passes through said detection zone; and

a data processing system adapted to communicate with said detection system and configured to determine a size of each of said plurality of particles based on said time that each of said plurality of particles passes through said detection zone,

wherein said detection system also is configured to quantify a number of particles in said plurality of particles, and

wherein said quantification is quantification by analyzing aggregate signals to correlate said aggregate signals with a quantity of particles in said plurality of particles.

12. A system for separating, detecting and determining a size of each of a plurality of particles in a fluid according to claim 11 , further comprising a pressure application and control system operatively connected to said hydrodynamic fluid separation system.

13. A system for separating, detecting and determining a size of each of a plurality of particles in a fluid according to claim 11 , wherein said illumination system is a cylindrical illumination system.

14. A system for separating, detecting and determining a size of each of a plurality of particles in a fluid according to claim 13 , further comprising an alignment system configured to align an illumination beam provided by said cylindrical illumination system with said detection zone of said fluid channel.

15. A system for separating, detecting and determining a size of each of a plurality of particles in a fluid according to claim 11 , wherein said hydrodynamic fluid separation system comprises a micro-capillary that defines at least a portion of said fluid channel therein.

16. A system for separating, detecting and determining a size of each of a plurality of particles in a fluid according to claim 11 , wherein said hydrodynamic fluid separation system comprises a microfluidic chip that defines at least a portion of said fluid channel therein.

17. A system for separating, detecting and determining a size of each of a plurality of particles in a fluid according to claim 11 , wherein said hydrodynamic fluid separation system comprises a plurality of fluid channels.

18. A system for separating, detecting and determining a size of each of a plurality of particles in a fluid according to claim 17 , wherein said detection system is configured to detect said plurality of fluid channels in parallel simultaneously.

19. A system for separating, detecting and determining a size of each of a plurality of particles in a fluid, comprising:

a hydrodynamic fluid separation system comprising a fluid channel;

an illumination system arranged to illuminate a detection zone of said fluid channel substantially uniformly across an entire cross section of said fluid channel such that each of said plurality of particles passes through illumination light upon passing through said detection zone;

a detection system arranged to detect each of said plurality of particles based on corresponding responses to said illumination light to determine a time that each of said plurality of particles passes through said detection zone; and

a data processing system adapted to communicate with said detection system and configured to determine a size of each of said plurality of particles based on said time that each of said plurality of particles passes through said detection zone,

wherein said hydrodynamic fluid separation system comprises a plurality of fluid channels, each having a respective detection zone arranged to be illuminated substantially uniformly across an entire cross-sectional region of each said respective detection zone by said illumination system,

wherein said detection system is configured to detect each of a plurality of particles that pass through each of said respective detection zone based on corresponding responses to said illumination system to determine a time that each of said plurality of particles passes through each said respective detection zone,

wherein said data processing system is further configured to determine a size of each of said plurality of particles based on said time that each of said plurality of particles passes through each said respective detection zone to process a plurality of fluid samples in parallel, and

wherein said detection system is configured to detect said plurality of fluid channels serially by scanning across said channels.

Assignments (3)
CONFIRMATORY LICENSE Recorded May 11, 2016
From: JOHNS HOPKINS UNIVERSITY
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 038667/0866 →
CORRECTIVE ASSIGNMENT TO CORRECT THE SECOND ASSIGNOR'S NAME PREVIOUSLY RECORDED ON REEL 030235 FRAME 0122. ASSIGNOR(S) HEREBY CONFIRMS THE 2ND ASSIGNOR SHOULD APPEAR AS: LIU, KELVIN JENG-FANG. Recorded May 1, 2013
From: WANG, TZA-HUEI JEFF; LIU, KELVIN JENG-FANG
To: THE JOHNS HOPKINS UNIVERSITY
Reel/Frame 030326/0376 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 17, 2013
From: WANG, TZA-HUEI JEFF; LIU, KELVIN JENG-FENG
To: THE JOHNS HOPKINS UNIVERSITY
Reel/Frame 030235/0122 →
Continuity (2)
Provisional Application 61394585 · Oct 19, 2010
Related Publication 20130167623A1 · Jul 4, 2013