Actuation of parallel microfluidic arrays

• US 9,260,693 B2
• Filed: 10/17/2014
• Issued: 02/16/2016
• Est. Priority Date: 12/03/2004
• Status: Active Grant

• Current Assignee: Cytonome/St, Llc (Cytonome Inc.)
• Original Assignee: Cytonome/St, Llc (Cytonome Inc.)
• Inventors: Johnson, Andrew, Gilbert, John R., Deshpande, Manish, Lewis, Hugh, Bunner, Bernard
• Primary Examiner(s): MATTHEWS, TERRELL HOWARD
• Application Number:
  US14/517,396
• Publication Number:
  US 20150140545A1
• Time in Patent Office: 487 Days
• Field of Search: 209/552, 209/559, 422/73, 422/100, 422/102, 435/325
• US Class Current: 1/1
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/028 Modular arrangements
• CPC Class Codes: B01L 2200/0636 Focussing flows, e.g. to laminate flows
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2400/04 Moving fluids with specific forces or mechanical means
• CPC Class Codes: B01L 2400/0439 ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 2400/0442 thermal energy, e.g. vaporisation, bubble jet
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0622 distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
• 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: B01L 3/52 Containers specially adapted for storing or dispensing a reagent B01L3/02 takes precedence; containers for medical or pharmaceutical purposes A61J1/00; containers in general B65D; storing or dispensing test elements G01N33/4875; automated reagent dispensing G01N35/1002
• CPC Class Codes: B07C 5/34 Sorting according to other particular properties material testing per se G01N; quality control G07C3/14
• CPC Class Codes: C12N 5/0081 Purging biological preparations of unwanted cells

Abstract

An improved actuator for use in a microfluidic particle sorting system utilizes a staggered packing scheme for a plurality of actuators used to selectively deflect a particle in an associated sorting channel from a stream of channels. An actuator block may be provided for housing a two-dimensional array of actuators, each configured to align with an actuation port in an associated sorting chip containing a plurality of sorting channels. The actuator block may include a built-in stressing means to pre-stress each actuator housed by the block. An actuator comprising a piezo-electric stack may employ contact-based electrical connection rather than soldered wires to improve packing density. The actuator may be an external actuator. That is, the external actuator is external to the substrate in which the sorting channels are formed.

Claims

1. A particle processing cartridge assembly for sorting individual particles on a particle-by-particle basis from a stream of particles, the particle processing cartridge assembly comprising:

a microfluidic chip having;

at least one microsorter having fluid contact surfaces including a microfluidic channel having a sample input, a switching region, a keep output and a waste output; and

at least one switch element operatively interfaced with the switching region and configured to selectively sort individual particles on a particle-by-particle basis from the stream of particles flowing within the microfluidic channel; and

a cartridge having fluid contact surfaces including a sample chamber, a keep chamber and a waste chamber, wherein the sample chamber of the cartridge is in fluid communication with the sample input of the microfluidic channel, wherein the keep chamber of the cartridge is in fluid communication with the keep output of the microfluidic channel, wherein the waste chamber of the cartridge is in fluid communication with the waste output of the microfluidic channel; and

wherein the at least one switch element is configured to operatively and removably interface with at least one actuator located external to the particle processing cartridge assembly and configured to actuate the at least one switch element to deflect a selected particle from the stream of particles, and

wherein all the fluid contact surfaces of the particle processing cartridge assembly are enclosed and configured to be sealed against liquid transfer to an exterior environment during a sorting operation.

2. The cartridge assembly of claim 1, wherein the cartridge includes a sorted sample extraction port in fluid communication with the keep chamber and configured to be unsealed after the sorting operation has ended to provide access to fluid within the keep chamber.

3. The cartridge assembly of claim 1, further comprising a plurality of microsorters.

4. The cartridge assembly of claim 1, wherein all the fluid contact surfaces needed for the sorting operation are enclosed within the particle processing cartridge assembly.

5. The cartridge assembly of claim 1, wherein the microfluidic channel includes a detection region wherein particle characteristics of individual particles of a sample are detected on a particle-by-particle basis during the sorting operation.

6. The cartridge assembly of claim 1, wherein the microfluidic chip and the cartridge are provided as a unitary particle processing cartridge assembly.

7. The cartridge assembly of claim 6, wherein the unitary particle processing cartridge assembly is a rigid and integral assembly.

8. The cartridge assembly of claim 1, wherein the particle processing cartridge assembly is configured to allow pressurized air to drive the stream of particles through the microfluidic channel.

9. The cartridge assembly of claim 1, wherein the particle processing cartridge assembly includes a unique identifier.

10. The cartridge assembly of claim 1, wherein the fluid contact surfaces of the cartridge include a sheath chamber configured to supply sheath fluid to the microsorter upstream of the switching region.

11. The cartridge assembly of claim 1, wherein the fluid contact surfaces of the cartridge include at least one recycling channel.

12. The cartridge assembly of claim 1, wherein the fluid contact surfaces of the cartridge include at least one filter element.

13. A system for sorting individual particles on a particle-by-particle basis from a stream of particles, the system comprising:

a particle processing cartridge assembly including a microfluidic chip and a cartridge,

the microfluidic chip having;

at least one microsorter having fluid contact surfaces including a microfluidic channel having a sample input, a switching region, a keep output and a waste output; and

at least one switch element operatively interfaced with the switching region and configured to selectively sort individual particles on a particle-by-particle basis from the stream of particles flowing within the microfluidic channel; and

the cartridge having fluid contact surfaces including a sample chamber, a keep chamber and a waste chamber, wherein the sample chamber of the cartridge is in fluid communication with the sample input of the microfluidic channel, wherein the keep chamber of the cartridge is in fluid communication with the keep output of the microfluidic channel, wherein the waste chamber of the cartridge is in fluid communication with the waste output of the microfluidic channel; and

at least one actuator configured to actuate the at least one switch element and to deflect a selected particle from the stream of particles, wherein the at least one switch element of the microfluidic chip is operatively and removably interfaced with the at least one actuator, and

wherein all the fluid contact surfaces of the particle processing cartridge assembly are enclosed and configured to be sealed against liquid transfer to an exterior environment during a sorting operation.

14. The system of claim 13, further comprising a plurality of microsorters and a plurality of actuators wherein each actuator is associated with one of the plurality of microsorters.

15. The system of claim 13, wherein the at least one switch element is configured to be actuated by the at least one actuator in response to a desired particle characteristic of an individual particle being detected in a detection region of the microfluidic channel, and wherein the at least one actuator is external to and separately formed from the particle processing cartridge assembly.

16. The system of claim 13, wherein the actuator is configured to supply at least one of a mechanical, electrical, pneumatic or magnetic force to the at least one switch element to cause the switch element to sort the selected particle from the stream.

17. A method for sorting particles comprising:

obtaining a cartridge having internal fluid contact surfaces, the internal fluid contact surfaces including a sample fluid input reservoir, a selected particle fluid output reservoir and a microfluidic particle sorting component operationally positioned therebetween, the microfluidic particle sorting component including a switch element;

loading a sample containing particles into the sample fluid input reservoir of the cartridge via a sealable sample input port;

sealing the cartridge against liquid transfer into and out of the cartridge;

operatively interfacing the sealed cartridge with an operating machine, including aligning the switch element of the microfluidic particle sorting component with a switch actuation element external to the sealed cartridge and provided by the operating machine;

operating the operating machine to process the sample, including the steps of;

flowing the sample containing particles through the microfluidic particle sorting component;

detecting whether individual particles flowing within the microfluidic particle sorting component have a predetermined characteristic;

causing the switch actuation element provided on the operating machine to actuate the switch element included in the microfluidic particle sorting component in response to the predetermined characteristic of an individual particle being detected;

deflecting the individual particle from the particles flowing within the microfluidic particle sorting component into the selected particle fluid output reservoir, and

removing the sealed cartridge from the operating machine.

18. The method of claim 17, wherein the cartridge remains sealed during the steps of operatively interfacing, operating, and removing, and wherein all fluid contact surfaces required for a microfluidic particle sorting operation are enclosed by the cartridge and are isolated from exposure to an exterior environment during the microfluidic particle sorting operation.

19. The method of claim 17, further comprising:

extracting a sample containing selected particles from the selected particle fluid output reservoir of the cartridge via a processed sample output port.

20. The method of claim 17, further comprising:

applying an external source of pressure to the sample fluid input reservoir.