Method and apparatus for sorting particles

• US 9,550,215 B2
• Filed: 05/19/2014
• Issued: 01/24/2017
• Est. Priority Date: 04/17/2002
• Status: Expired due to Term

• Current Assignee: Cytonome/St, Llc (Cytonome Inc.)
• Original Assignee: Cytonome/St, Llc (Cytonome Inc.)
• Inventors: Deshpande, Manish, Gilbert, John R.
• Primary Examiner(s): Rodriguez, Joseph C
• Application Number:
  US14/281,303
• Publication Number:
  US 20140251879A1
• Time in Patent Office: 981 Days
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B07C 5/02 Measures preceding sorting, e.g. arranging articles in a stream orientating sorting and transport of caps B67B3/06
• CPC Class Codes: B07C 5/34 Sorting according to other particular properties material testing per se G01N; quality control G07C3/14
• CPC Class Codes: B07C 5/36 Sorting apparatus characterised by the means used for distribution sorting according to destination B07C3/003, B07C3/02
• CPC Class Codes: F15C 5/00 Manufacture of fluid circuit elements; Manufacture of assemblages of such elements integrated circuits
• CPC Class Codes: F16K 99/0001 Microvalves microdevices B81B1/00; manufacture or treatment of devices or systems in or on a substrate B81C1/00; microfluidic structures B01L3/5027; micropumps F04B19/006
• CPC Class Codes: F16K 99/0019 Valves using a microdroplet or microbubble as the valve member
• CPC Class Codes: F16K 99/0028 Valves having multiple inlets or outlets
• CPC Class Codes: F16K 99/0046 using magnets
• CPC Class Codes: F16K 99/0048 using piezoelectric means
• CPC Class Codes: G01N 15/10 Investigating individual particles
• CPC Class Codes: G01N 15/14 Optical investigation techniques, e.g. flow cytometry
• CPC Class Codes: G01N 15/149 : specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 2015/1027 : Determining speed or velocity of a particle
• CPC Class Codes: G01N 2015/1028 : Sorting particles
• CPC Class Codes: G01N 2015/1477 : Multiparameters
• CPC Class Codes: G01N 2015/1497 : Particle shape
• CPC Class Codes: Y10S 209/906 : Pneumatic or liquid stream feeding item
• CPC Class Codes: Y10S 209/932 : Fluid applied to items

Abstract

A method and a system are provided for detecting particles moving through a detection region or regions for facilitating or processing a sample having one or more particles flowing through the detection region. The particle detection system may include an optically detectable pattern associated with a detection region. The optically detectable pattern may be configured to receive a particle optical signal and produce a patterned optical signal. The detection system may further include a detector configured to analyze the patterned optical signal to determine both a particle characteristic based on a property of the particle optical signal and a particle parameter based on a property of the optically detectable pattern.

Claims

1. A particle detecting system comprising:

a first flow path having a detection region adapted to facilitate analysis or processing of a sample having one or more particles flowing through the first flow path of the detection region;

a first optically detectable pattern associated with the detection region, the first optically detectable pattern positioned to receive a particle optical signal associated with a particle flowing through the first flow path of the detection region and to produce a patterned optical signal; and

a first detector positioned to receive the patterned optical signal,

wherein the first detector is configured to analyze the patterned optical signal to independently determine both;

(i) a particle characteristic based on a property of the particle optical signal associated with the particle flowing through the detection region; and

(ii) a particle parameter based on a property of the first optically detectable pattern.

2. The particle detecting system of claim 1, wherein the first optically detectable pattern is a gradient masking pattern.

3. The particle detecting system of claim 1, wherein the first optically detectable pattern includes one or more bars having a width ranging from 10 microns to 30 microns.

4. The particle detecting system of claim 1, wherein the first optically detectable pattern includes a plurality of bars of varying width.

5. The particle detecting system of claim 1, wherein the first optically detectable pattern includes a plurality of bars of constant width.

6. The particle detecting system of claim 1, wherein the first optically detectable pattern includes at least one opening permitting exit of light from or entry of light into the detection region.

7. The particle detecting system of claim 1, wherein the first flow path is formed at least partially in a substrate and the first optically detectable pattern is deposited on a first side of the substrate.

8. The particle detecting system of claim 1, wherein the first optically detectable pattern is located between the detection region and a light source.

9. The particle detecting system of claim 1, wherein the first optically detectable pattern is located between the detection region and the first detector.

10. The particle detecting system of claim 1, wherein the first optically detectable pattern is located between the first flow path and at least one of a light source and the first detector.

11. The particle detecting system of claim 1, wherein the first optically detectable pattern is located within the detection region associated with a sorting chip.

12. The particle detecting system of claim 1, wherein the first optically detectable pattern is used to identify a location of a particle.

13. The particle detecting system of claim 1, wherein the first optically detectable pattern produces a pattern enabling the detector to identify a location of the first optically detectable pattern.

14. The particle detecting system of claim 1, wherein the particle characteristic includes one of an optical absorption particle characteristic, a fluorescent intensity particle characteristic or a scattered light particle characteristic.

15. The particle detecting system of claim 1, wherein the first optically detectable pattern is associated with a first microfluidic flow path.

16. The particle detecting system of claim 1, wherein the first optically detectable pattern includes a plurality of edges and the first detector is configured to detect the edges.

17. The particle detecting system of claim 1, wherein the first optically detectable pattern is used to identify both a location particle parameter and a velocity particle parameter of a particle.

18. The particle detecting system of claim 1,

wherein the detector is configured to detect at least one of an optical absorption particle characteristic, a fluorescent intensity particle characteristic, or a scattered light particle characteristic for a particle flowing through the first flow path and is configured to detect the first optically detectable pattern associated with the first flow path.

19. The particle detecting system of claim 1, further comprising:

an actuator for sorting the particle flowing through the detection region into one of a plurality of outlets based on the one or more particle characteristics detected by the first detector.

20. The particle detecting system of claim 1, wherein the particle parameter includes at least one of a particle velocity, a particle location or a particle size.

21. The particle detecting system of claim 1, further comprising:

a second flow path; and

a second optically detectable pattern associated with the second flow path.

22. The particle detecting system of claim 21,

wherein the detector is configured to independently determine:

at least one of an optical absorption particle characteristic, a fluorescent intensity particle characteristic or a scattered light particle characteristic for a particle flowing through at least one of the first and second flow paths; and

a velocity based on the property of the optically detectable pattern for the same flow path.

23. The particle detecting system of claim 21, wherein the first or second optically detectable pattern is used to determine at least one of a velocity, a size, or a location of a particle flowing through the first or second flow path, respectively.

24. A method of operating a particle detecting system, the method comprising:

providing the particle detecting system of claim 1;

flowing particles through the detection region of the particle detecting system; and

sensing the patterned optical signal exiting from the detection region with the first detector; and

analyzing the patterned optical signal to independently determine both;

(i) a particle characteristic based on a property of the particle optical signal associated with the particle flowing through the detection region; and

(ii) a particle parameter based on a property of the first optically detectable pattern.

25. The method of claim 24, wherein analyzing the patterned optical signal includes determining at least one of a velocity particle parameter and a location particle parameter associated with the particle within the detection region, and further determining at least one of an optical absorption particle characteristic, a fluorescent intensity particle characteristic and a scattered light particle characteristic associated with the same particle within the detection region.

26. The method of claim 24, wherein

flowing particles through the detection region includes flowing particles along the first flow path;

sensing the patterned optical signal includes sensing the patterned optical signal exiting from the first flow path;

determining a velocity particle parameter and a location particle parameter from the patterned optical signal; and

determining at least one of an optical absorption particle characteristic, a fluorescent intensity particle characteristic and a scattered light particle characteristic from the same patterned optical signal.

27. The method of claim 26, further including:

flowing particles through a second flow path included in the detection region;

sensing a second patterned optical signal exiting from the second flow path;

determining a velocity particle parameter from the second patterned optical signal; and

determining at least one of an optical absorption particle characteristic, a fluorescent intensity particle characteristic and a scattered light particle characteristic from the second patterned optical signal.

28. The method of claim 24, wherein the patterned optical signal associated with the detection region includes spatially modulated information.