Sample dispensing

• US 8,968,659 B2
• Filed: 01/07/2010
• Issued: 03/03/2015
• Est. Priority Date: 09/05/2003
• Status: Active Grant

• Current Assignee: Stokes Bio
• Original Assignee: Stokes Bio Ltd. (Perspecta, Inc.)
• Inventors: Davies, Mark, Dalton, Tara
• Primary Examiner(s): Mui, Christine T
• Application Number:
  US12/683,882
• Publication Number:
  US 20100120635A1
• Time in Patent Office: 1,881 Days
• Field of Search: 422/57, 422/50, 422/68.1, 422/500, 506/26, 506/40, 506/33
• US Class Current: 422/68.1
• CPC Class Codes: B01F 25/10 Mixing by creating a vortex flow, e.g. by tangential introduction of flow components
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/3021 the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
• CPC Class Codes: B01L 2200/0636 Focussing flows, e.g. to laminate flows
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/185 using a liquid as fluid
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• 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 7/525 with physical movement of samples between temperature zones
• CPC Class Codes: G01N 2035/00514 Stationary mixing elements
• CPC Class Codes: G01N 35/08 using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
• CPC Class Codes: G01N 35/1095 for supplying the samples to flow-through analysers for a specific analyser see relevant groups, e.g. under G01N15/00, G01N21/00, G01N27/00, G01N30/00, H01J49/00

Abstract

The present invention generally relates to systems and methods for mixing and dispensing a sample droplet from a microfluidic system, such as a liquid bridge system. In certain embodiments, the invention provides systems for mixing and dispensing sample droplets, including a sample acquisition stage, a device for mixing sample droplets to form sample droplets wrapped in an immiscible carrier fluid, a dispensing port, and at least one channel connecting the stage, the droplet mixing device, and the port, in which the system is configured to establish a siphoning effect for dispensing the droplets.

Claims

1. A system for mixing and dispensing sample droplets, the system comprising:

at least one sample acquisition stage;

a device for mixing sample droplets to produce a mixed sample droplet wrapped in an immiscible fluid;

a variable height dispensing port;

at least one channel fluidly communicating the stage, the droplet mixing device, and the port, and

a vessel for collecting the sample droplet dispensed from the port, the vessel configured to contain a carrier fluid for receiving and protecting the sample droplet;

wherein the dispensing port is positioned below the level of the sample acquisition stage, and wherein the system is configured to establish a siphoning effect for dispensing the droplets.

2. The system according to claim 1, wherein the droplet mixing device is a liquid bridge.

3. The system according to claim 1, further comprising a priming pump.

4. The system according to claim 1, further comprising a thermocycler.

5. The system according to claim 1, further comprising at least one valve to control flow through the system.

6. The system according to claim 1, wherein the sample droplets are dispensed into separate wells of a well plate.

7. The system according to claim 1, wherein the system dispenses the sample droplets as discrete spots on a surface to form an array of droplets.

8. The system according to claim 1, wherein the dispensing port dispenses the sample droplet to a first vessel, moves over a second vessel to dispense the carrier fluid, and then moves back over the first vessel to dispense another sample droplet.

9. The system according to claim 1, wherein the droplet comprises nucleic acids.

10. The system according to claim 1, wherein height between the sample acquisition stage and the dispensing port varies during sample acquisition and sample dispensing.

11. The system according to claim 1, wherein the system dispenses wrapped droplets.

12. A system for generating sample droplets comprising:

at least one sample acquisition stage;

a droplet generator, in fluid communication with the stage, for producing a sample droplet wrapped in an immiscible fluid;

a dispensing port in fluid communication with the droplet generator for dispensing the wrapped droplet into a carrier fluid filled vessel,

a thermocycler for amplifying the sample droplet; and

at least one channel fluidly communicating the stage, the generator, the thermocycler and the port,

wherein the droplet generator and the dispensing port are located lower than the at least one sample acquisition stage.

13. The system of claim 12 comprising a priming pump.

14. The system of claim 12 comprising an immiscible fluid removal pump.

15. A system for generating sample droplets comprising

a variable height dispensing port;

at least one sample acquisition stage located at a higher level than the dispensing port; and

a droplet generator in fluid communication with the variable height dispensing port and the at least one sample acquisition stage, and

a vessel for collecting the sample droplet dispensed from the port, the vessel configured to contain a carrier fluid for receiving and protecting the sample droplet;

wherein the dispensing port is positioned below the level of the sample acquisition stage to create a siphoning effect, and wherein the droplet generator comprises an immiscible fluid for producing a sample droplet wrapped in an immiscible fluid.

16. The system of claim 15 wherein the system comprises at least one robotic system.

17. The system of claim 15 wherein the droplet generator is configured to wrap a droplet in the immiscible fluid.

18. The system of claim 15 wherein the distance between the sample acquisition stage and the dispensing port vary.