Method and apparatus for sorting particles

• US 8,567,608 B2
• Filed: 07/08/2009
• Issued: 10/29/2013
• 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
• Primary Examiner(s): Rodriguez, Joseph C
• Application Number:
  US12/499,254
• Publication Number:
  US 20100032350A1
• Time in Patent Office: 1,574 Days
• Field of Search: 209/210, 209/552, 209/644, 209/906, 209/932, 422502-504
• US Class Current: 209/552
• 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 apparatus for sorting particles moving through a closed channel system of capillary size comprises a bubble valve for selectively generating a pressure pulse to separate a particle having a predetermined characteristic from a stream of particles. The particle sorting system may further include a buffer for absorbing the pressure pulse. The particle sorting system may include a plurality of closely coupled sorting modules which are combined to further increase the sorting rate. The particle sorting system may comprise a multi-stage sorting device for serially sorting streams of particles, in order to decrease the error rate.

Claims

1. A particle sorting system, comprising:

a plurality of primary sorting channels each of which is adapted to receive a stream of suspended particles confined in a carrier liquid, wherein each of the primary sorting channels extends through one of one or more detection regions adapted for detecting one or more predetermined characteristics in a particle, wherein at least one of the detection regions comprises one or more sensors for measuring a velocity of a particle in a primary sorting channel, and wherein each of the primary sorting channels includes a switching region adapted for separating particles into first and second receiving channels based on the one or more predetermined particle characteristics;

an aggregation chamber downstream of the switching regions adapted for aggregating the particles from at least three of the first receiving channels corresponding to at least three of the switching regions into one or more outlet channels;

an enrichment region downstream of the aggregation chamber adapted for adjusting a volume of carrier liquid; and

at least one secondary sorting channel in series with the plurality of parallel primary sorting channels and downstream of the enrichment region, the at least one secondary sorting channel adapted for receiving particles from one of the outlet channels and for separating the particles received from the one of the outlet channels based on the same one or more predetermined particle characteristics as used in the switching regions corresponding to the primary sorting channels.

2. The system of claim 1, wherein the enrichment region is adapted for removing excess carrier liquid.

3. The system of claim 1, wherein the enrichment region comprises:

an enrichment channel intersecting one of said receiving channels; and

a membrane separating the enrichment channel from said receiving channel.

4. The system of claim 1, wherein the enrichment region comprises:

an enrichment channel intersecting said aggregation chamber; and

a membrane separating the enrichment channel from the aggregation chamber.

5. The system of claim 1, wherein the enrichment region comprises:

an enrichment channel intersecting one of said outlet channels; and

a membrane separating the enrichment channel from said outlet channel.

6. The system of claim 2, further comprising a hydration device for adding secondary carrier fluid to the particles after the enrichment region.

7. The system of claim 2, further comprising a recycling channel connecting the enrichment region to the primary sorting channel for introducing the removed excess carrier liquid into the primary sorting channel.

9. The system of claim 1, wherein each of the primary switching regions is adapted to sort selected particles substantially all of which have the one or more predetermined particle characteristics into the first receiving channel and all other particles into the second receiving channel and wherein the secondary sorting channel is adapted to further sort the selected particles.

10. The system of claim 9, wherein the enrichment region is adapted for adjusting a volume of carrier liquid around the selected particles.

11. The system of claim 1, wherein the enrichment region is adapted for adjusting a volume of carrier liquid around aggregated particles from the aggregation chamber.

12. The system of claim 1, wherein the number of secondary sorting channels is fewer than the number of primary sorting channels.

8. A method of sorting particles, comprising:

conveying a plurality of streams of suspended particles confined in a carrier liquid through a plurality of parallel primary sorting channels, wherein each of the primary sorting channels extends through one of one or more detection regions adapted for detecting one or more predetermined characteristics in a particle, wherein at least one of the detection regions comprises one or more sensors for measuring a velocity of a particle in a primary sorting channel, and wherein each of the primary sorting channels includes a switching region adapted for separating particles into first and second receiving channels based on the one or more predetermined particle characteristics;

separating particles into the first and second receiving channels based on the one or more predetermined particle characteristics;

aggregating the particles from at least three of the first receiving channels corresponding to at least three of the switching regions into one or more outlet channels in an aggregation chamber downstream of the switching regions;

adjusting a volume of carrier liquid in an enrichment region downstream of the aggregation chamber;

conveying particles from one of the outlet channels through at least one secondary sorting channel in series with the plurality of parallel primary sorting channels and downstream of the enrichment region; and

separating the particles in the at least one secondary sorting channel based on the same one or more predetermined particle characteristics as used in the switching regions corresponding to the primary sorting channels.

13. A particle sorting system, comprising:

a plurality of primary sorting channels each of which is adapted to receive a stream of suspended particles confined in a carrier liquid, wherein each of the primary sorting channels extends through one of one or more detection regions adapted for detecting one or more predetermined characteristics in a particle, wherein at least one of the detection regions comprises one or more sensors for measuring a velocity of a particle in a primary sorting channel, and wherein each of the primary sorting channels includes a switching region adapted for separating particles into first and second receiving channels based on the one or more predetermined particle characteristics;

an aggregation chamber downstream of the switching regions adapted for aggregating the particles from each of the first receiving channels;

an enrichment region downstream of the aggregation chamber adapted for adjusting a volume of carrier liquid; and

a plurality of secondary sorting channels in series with the plurality of parallel primary sorting channels and downstream of the enrichment region, the plurality of secondary sorting channels adapted for receiving the aggregated particles from the aggregation chamber and for separating the received particles based on the same one or more predetermined particle characteristics as used in the switching regions corresponding to the primary sorting channels.