Source: https://patents.google.com/patent/US9550215B2/en
Timestamp: 2018-06-22 18:06:37
Document Index: 364745177

Matched Legal Cases: ['Application No. 60', 'Application No. 03825178', 'Application No. 2004', 'Application No. 03814212', 'Application No. 03814212', 'Application No. 200910168699', 'Application No. 2003', 'Application No. 2003', 'Application No. 2007', 'Application No. 2007', 'Application No. 03825178']

US9550215B2 - Method and apparatus for sorting particles - Google Patents
US9550215B2
US9550215B2 US14281303 US201414281303A US9550215B2 US 9550215 B2 US9550215 B2 US 9550215B2 US 14281303 US14281303 US 14281303 US 201414281303 A US201414281303 A US 201414281303A US 9550215 B2 US9550215 B2 US 9550215B2
US14281303
US20140251879A1 (en )
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.
This application is a continuation of U.S. patent application Ser. No. 13/245,132, filed Sep. 26, 2011, which, in turn, is a continuation of U.S. patent application Ser. No. 12/499,254 filed Jul. 8, 2009 which, in turn, is a continuation of U.S. patent application Ser. No. 11/101,038, filed Apr. 6, 2005, which, in turn, is a divisional of Ser. No. 10/329,008, filed Dec. 23, 2002, which claims priority to U.S. Provisional Patent Application Ser. No. 60/411,058, filed Sep. 16, 2002, and is a continuation-in-part of U.S. patent application Ser. No. 10/179,488, filed Jun. 24, 2002, which claims priority to U.S. Provisional Patent Application No. 60/373,256, filed Apr. 17, 2002, the contents of each application is incorporated herein by reference in their entirety.
An example of a sorting device is described in U.S. Pat. No. 4,175,662, the contents of which are herein incorporated by reference (hereinafter referred to as the '662 patent). In the '662 patent, a flow of particles, cells in this case, flows through the center of a straight channel, which branches into two perpendicular channels at a branching point downstream (T-branch). The entering particles are surrounded by a sheath of compatible liquid, keeping the particles confined to the center of the channel. In normal conditions, the flow ratio through the two branches is adjusted so that the particles automatically flow through one of the branches. In a section of the channel a characteristic of the particles is determined using a detector, which can be an optical system (detection phase). The detector generates a signal when the detector detects a particle possessing a predetermined characteristic in the decision phase. Once a particle is detected, a deflector is activated for deflecting the particle in a deflection phase. In this case, the deflector comprises an electrode pair, positioned in the branch of the channel where the particles normally flow through in the inactivated state of the deflector. By the application of current pulses, the aqueous liquid is electrolyzed, yielding a gas bubble evolving between the electrode pair. As the gas bubble increases in size, the flow rate through this branch is reduced during the evolving phase. After the current pulse is applied, the bubble growth stops and the gas bubble is carried along with the flow. As a result, the flow through the specific branch is momentarily reduced and the particle of interest changes paths and flows down the other branch.
The terms “duct” “channel” and “flow channel” as used herein refers to a pathway formed in or through a medium that allows for movement of fluids, such as liquids and gases. The channel in the microfluidic system preferably have cross-sectional dimensions in the range between about 1.0 μm and about 500 μm, preferably between about 25 μm and about 250 μm and most preferably between about 50 μm and about 150 μm. One of ordinary skill in the art will be able to determine an appropriate volume and length of the flow channel. The ranges are intended to include the above-recited values as upper or lower limits The flow channel can have any selected shape or arrangement, examples of which include a linear or non-linear configuration and a U-shaped configuration.
FIG. 10 shows a particle sorting system 550 according to another embodiment, comprising a first sorting module 50 a in series with a second sorting module 50 b. The second sorting module 50 b may be equipped for sorting particles having a predetermined characteristic the same or different than the predetermined characteristic of the particles sorted by the first sorting module 50 a. The particle stream enters the first sorting module 50 a through the supply duct 52 and may contain at least two types of particles. A first type of particle is sorted in the first sorting module 50 a and exits through the first outlet duct 54 a. The remaining particles exit the first sorting module 50 a through second outlet duct 56 a and are introduced into the second sorting module 50 b via the second supply duct 52 b. From this stream of particles, particles having the other predetermined characteristic are sorted and exit through the second outlet duct 54 b . Particles that possess neither of the two predetermined characteristics exit the second sorting module 50 b via the second outlet duct 56 b. Those of ordinary skill will readily recognize that any suitable type of sorting module 50 can be used, and can be coupled together in a variety of ways, depending upon the desired results.
According to one embodiment of the invention, shown in FIGS. 14a and 14b , the particle sorting system may include sensors for measuring velocity, location and/or size of particles. The measurement of velocity, location and/or size may be made simultaneously with classification of the particles for sorting or at a different time. In parallel channel based systems, as shown in FIG. 11, the different channels may have different flow resistances, causing the velocity of the particles or cells in each channel to be different. In systems where the detection region 84 is separated from the switching region 82 by a distance L, the velocity of the particles in the channel 81 must be known in order to set the switching time delay T (i.e., the time to delay switch actuation relative to the moment of detection of a target particle).
A suitable system for forming the enrichment region is described in U.S. Ser. No. 10/329,018, filed on Dec. 23, 2002, the contents of which are herein incorporated by reference.
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 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:
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.
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.
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.
US14281303 2002-04-17 2014-05-19 Method and apparatus for sorting particles Active US9550215B2 (en)
US13245132 Continuation US8727131B2 (en) 2002-04-17 2011-09-26 Method and apparatus for sorting particles
US14828238 Continuation US9339850B2 (en) 2002-04-17 2015-08-17 Method and apparatus for sorting particles
US14828252 Continuation US20150352597A1 (en) 2002-04-17 2015-08-17 Method and apparatus for sorting particles
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