Method and apparatus for sorting particles

• US 10,029,263 B2
• Filed: 03/22/2013
• Issued: 07/24/2018
• 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: Bohm, Sebastian, Gilbert, John R., Deshpande, Manish
• Primary Examiner(s): Rodriguez, Joseph C
• Application Number:
  US13/849,365
• Publication Number:
  US 20130313170A1
• Time in Patent Office: 1,950 Days
• Field of Search: 209155, 209552, 209576, 209906, 422502-504, 422507, 422509, 422513
• 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: B03B 5/00 Washing granular, powdered or lumpy materials; Wet separating separating by pneumatic tables or by pneumatic jigs B03B4/00
• CPC Class Codes: B07C 5/34 Sorting according to other particular properties material testing per se G01N; quality control G07C3/14
• CPC Class Codes: F15C 5/00 Manufacture of fluid circuit elements; Manufacture of assemblages of such elements integrated circuits
• CPC Class Codes: F16K 2099/0084 Chemistry or biology, e.g. "lab-on-a-chip" technology
• 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 99/0028 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: F16K 99/0061 actuated by an expanding gas or liquid volume
• 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: 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 microfluidic system for sorting particles, the microfluidic system comprising:

a first microfluidic flow channel formed in a particle processing component substrate having an upstream inlet configured to introduce a fluidic stream having a plurality of particles into the first microfluidic flow channel and downstream outlets configured to output portions of the fluidic stream of particles;

a detection region located downstream of the inlet, the detection region configured to allow a particle having a predetermined characteristic to be sensed, the sensed particle being one of the plurality of particles in the fluidic stream; and

a switching device located downstream of the detection region, the switching device operatively coupled to the first microfluidic flow channel to deliver a transient pressure pulse in a direction substantially perpendicular to a flow direction of the fluidic stream of particles,

wherein the transient pressure pulse displaces and separates a selected single sensed particle from the fluidic stream of particles,

wherein the selected particle is displaced and separated from the fluidic stream of particles in a switching region,

wherein the fluidic stream of unselected particles flows into a first downstream outlet configured to output a first portion of the fluidic stream of particles,

wherein the selected particle flows into a second downstream outlet configured to output a second portion of the fluidic stream of particles,

wherein the transient pressure pulse is not generated downstream of the switching region,

wherein the switching device, when activated, does not block or partially block flow of the fluidic stream of particles, and

wherein the particle processing component substrate includes a reservoir adapted for dampening or absorbing the transient pressure pulse propagated across the microfluidic channel.

2. The microfluidic system of claim 1,

wherein the switching device is integrally provided on the particle processing component substrate, and

wherein the switching device is configured to be activated by a first external actuator.

3. The system of claim 2, further comprising a second actuator, external to and operatively associated with the first microfluidic flow channel, for processing the sample on a particle-by-particle basis.

4. The system of claim 3, wherein the first external actuator is adapted for directing particles into a first of the one or more downstream outlets and the second external actuator is adapted for directing particles into a second of the one or more downstream outlets.

5. The system of claim 1, wherein the particle processing component substrate includes a reservoir operatively associated with the switching device and adapted for originating the transient pressure pulse.

6. The microfluidic system of claim 1, wherein

the switching device introduces liquid into the microfluidic flow channel such that the transient pressure pulse is a transient hydraulic pressure pulse.

7. The system of claim 1, wherein the switching device further includes first and second side channels in fluid communication with the first microfluidic flow channel, the second side channel positioned opposite to the first side channel.

8. The system of claim 1, further including an actuator for activating the switching device and wherein the actuator is a piezoelectric actuator.

9. The system of claim 1, further including an actuator for activating the switching device and wherein the actuator is an electromagnetic actuator.

10. The system of claim 1, further including an actuator for activating the switching device and wherein the actuator is a thermopneumatic actuator.

11. The system of claim 1, further including an actuator for activating the switching device and wherein the actuator is a heat pulse generator.

12. The system of claim 1, wherein the switching device is integrally provided on the particle processing component substrate and is configured for an external actuator to operatively engage and activate the switching device.

13. The system of claim 1, wherein the switching device is configured to direct the selected particle out of the fluidic stream of particles without generating a pressure wave that travels upstream of the switching device.

14. The system of claim 1, wherein the fluidic stream of particles maintains a laminar flow when the selected particle is displaced and separated from the fluidic stream of particles.

15. A microfluidic method for producing a particle product from a sample having particles, the method comprising:

flowing the sample as a fluidic stream of particles from an upstream inlet along a first flow path through a first microfluidic flow channel formed in a substrate of a microfluidic particle processing component;

processing the sample on a particle-by-particle basis to produce a particle product;

outputting a first portion of the processed sample via a first downstream outlet of the first microfluidic flow channel; and

outputting a second portion of the processed sample via a second downstream outlet of the first microfluidic flow channel,

wherein the step of processing includes;

activating a switch component;

redirecting a single selected particle out of the first flow path of the fluidic stream of particles at a switching region and into a second flow path flowing downstream into the second downstream outlet, and

deactivating the switch component,

wherein activating the switch component does not generate a pressure wave that travels upstream to the switching region,

wherein activating the switch component does not shift the remainder of the fluidic stream of unselected particles from the first flow path flowing downstream into the first downstream outlet, and

wherein activating the switch component includes using an actuator external to and operatively associated with the microfluidic particle processing component, to activate the switch component; and

further comprising using a reservoir operatively associated with the first microfluidic flow channel to dampen or absorb a transient pressure pulse propagated across the microfluidic channel.

16. The method of claim 15, wherein the step of processing further includes using a reservoir operatively associated with the first microfluidic flow channel to originate the transient pressure pulse propagated across the first microfluidic flow channel for sorting particles on a particle-by-particle basis into the second downstream outlet.

17. The method of claim 15, wherein activating the switch component includes flexing the switch component.

18. The method of claim 15, wherein the switch component is located in a side channel and wherein the side channel is not a flow through channel.

19. A microfluidic system for sorting particles, the microfluidic system comprising:

a first microfluidic flow channel formed in a particle processing component substrate having an upstream inlet configured to introduce a fluidic stream having a plurality of particles into the first microfluidic flow channel and downstream outlets configured to output portions of the fluidic stream of particles;

a detection region located downstream of the inlet, the detection region configured to allow a particle having a predetermined characteristic to be sensed, the sensed particle being one of the plurality of particles in the fluidic stream;

a switching device located downstream of the detection region, the switching device operatively coupled to the first microfluidic flow channel to deliver a transient pressure pulse in a direction substantially perpendicular to a flow direction of the fluidic stream of particles,

wherein the transient pressure pulse displaces and separates a selected single sensed particle from the fluidic stream of particles,

wherein the selected particle is displaced and separated from the fluidic stream of particles in a switching region,

wherein the fluidic stream of unselected particles flows into a first downstream outlet configured to output a first portion of the fluidic stream of particles,

wherein the selected particle flows into a second downstream outlet configured to output a second portion of the fluidic stream of particles,

wherein the transient pressure pulse is not generated downstream of the switching region, and

further including an actuator for activating the switching device and wherein the actuator is a piezoelectric actuator,

wherein the particle processing component substrate includes a reservoir adapted for dampening or absorbing the transient pressure pulse propagated across the microfluidic channel.

20. The system of claim 19, wherein the particle processing component substrate includes a reservoir operatively associated with the switching device and adapted for originating the transient pressure pulse.

21. The system of claim 19, wherein the switching device further includes first and second side channels in fluid communication with the first microfluidic flow channel, the second side channel positioned opposite to the first side channel.