Actuation of parallel microfluidic arrays

• US 10,065,188 B2
• Filed: 02/12/2016
• Issued: 09/04/2018
• 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 H
• Application Number:
  US15/042,996
• Publication Number:
  US 20160158758A1
• Time in Patent Office: 935 Days
• Field of Search: 209559
• 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 assembly for sorting individual particles on a particle-by-particle basis from a stream of particles, the particle processing assembly comprising:

a microfluidic chip including at least one microsorter having a switching region and a microfluidic channel formed in the microfluidic chip fluidically coupled to a sample input a keep output, a waste output, and the switching region,

wherein the switching region interfaces with at least one actuator external to the microfluidic chip, and

wherein the switching region, when actuated by the actuator upon detection of a predetermined characteristic of a selected particle, directs a pressure pulse across the microfluidic channel to deflect the selected particle from the stream of particles.

2. The particle processing assembly of claim 1, further comprising:

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

3. The particle processing assembly of claim 2, 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.

4. The particle processing assembly of claim 2, wherein all the fluid contact surfaces needed for the sorting operation are enclosed within the particle processing assembly.

5. The particle processing assembly of claim 2, wherein the particle processing assembly is configured to allow pressurized air to drive the stream of particles through the microfluidic channel.

6. The particle processing assembly of claim 2, 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.

7. The particle processing assembly of claim 2, wherein the microfluidic chip and the cartridge are provided as a unitary particle processing cartridge assembly.

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

9. The particle processing assembly of claim 1, further comprising a plurality of microsorters.

10. The particle processing 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.

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

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

a particle processing assembly including a microfluidic chip, the microfluidic chip including at least one microsorter having a switching region, and a microfluidic channel formed in the microfluidic chip fluidically coupled to a sample input a keep output, a waste output, the switching region; and

at least one actuator configured to generate a pressure pulse in the microfluidic channel,

wherein the switching region directs the pressure pulse generated by the at least one actuator to deflect a selected particle from the stream of particles, and

wherein the at least one actuator is external to the particle processing assembly and is interfaced with the switching region of the microfluidic chip and wherein the at least one actuator is configured to be actuated in response to a desired particle characteristic of an individual particle being detected in a detection region of the microfluidic channel.

13. The system of claim 12,

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

14. The system of claim 12, further including 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 12, wherein the at least one actuator is configured to supply at least one of a mechanical, electrical, pneumatic or magnetic force to at least one switch element associated with the switching region.

16. The system of claim 12, wherein the operative interface between the at least one actuator and the switching region of the microfluidic chip includes a pre-stressed state between the at least one actuator and the particle processing assembly.

17. A method for sorting particles comprising:

obtaining a microfluidic particle sorting component including at least one microsorter having a switching region and a microfluidic channel formed in the microfluidic chip fluidically coupled to a sample input a keep output, a waste output, and the switching region;

operatively interfacing the microfluidic particle sorting component with an operating machine, including aligning the switching region of the microfluidic particle sorting component with a pressure pulse generator external to the microfluidic particle sorting component and provided by the operating machine;

operating the operating machine to process a sample having particles to be sorted, 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 pressure pulse generator provided on the operating machine to generate a pressure pulse in the switching region of the microsorter 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 one of the keep output and the waste output; and

removing the microfluidic particle sorting component from the operating machine.

18. The method of claim 17, further including the steps:

providing the microfluidic particle sorting component as part of a cartridge assembly, the cartridge assembly having internal fluid contact surfaces including a sample fluid input reservoir and a selected particle fluid output reservoir;

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

sealing the cartridge assembly against liquid transfer into and out of the cartridge assembly.

19. The method of claim 18, wherein the cartridge assembly 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 assembly and are isolated from exposure to an exterior environment during the microfluidic particle sorting operation.

20. The method of claim 18, further comprising:

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

21. The method of claim 18, further comprising:

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