MICROFLUIDIC ANALYSIS SYSTEM

• US 20100092987A1
• Filed: 11/12/2009
• Published: 04/15/2010
• Est. Priority Date: 09/05/2003
• Status: Abandoned Application

• Current Assignee: Stokes Bio Ltd. (Perspecta, Inc.)
• Original Assignee: Stokes Bio Ltd. (Perspecta, Inc.)
• Inventors: Dalton, Tara, Davies, Mark
• Application Number:
  US12/617,286
• Publication Number:
  US 20100092987A1
• Time in Patent Office: Days
• US Class Current: 435/6.14
• 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: 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 2200/141 Preventing contamination, tampering
• 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 3/502776 specially adapted for focusing or laminating flows
• CPC Class Codes: B01L 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: B01L 7/525 with physical movement of samples between temperature zones
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• 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

A microfluidic analysis system (1) performs polymerase chain reaction (PCR) analysis on a bio sample. In a centrifuge (6) the sample is separated into DNA and RNA constituents. The vortex is created by opposing flow of a silicon oil primary carrier fluid effecting circulation by viscous drag. The bio sample exits the centrifuge enveloped in the primary carrier fluid. This is pumped by a flow controller (7) to a thermal stage (9). The thermal stage (9) has a number of microfluidic devices (70) each having thermal zones (71, 72, 73) in which the bio sample is heated or cooled by heat conduction to/from a thermal carrier fluid and the primary carrier fluid. Thus, the carrier fluids envelope the sample, control its flowrate, and control its temperature without need for moving parts at the micro scale.

Claims

1-20. -20. (canceled)

21. A method for analyzing a sample, the method comprising:

flowing sample droplets enveloped in an immiscible carrier fluid to an analysis stage; and

analyzing the flowing droplets at the analysis stage, wherein the sample droplets do not contact a surface of the analysis stage.

22. The method according to claim 21, wherein the sample comprises nucleic acid molecules

23. The method according to claim 22, wherein prior to analyzing, the method further comprises amplifying the nucleic acid molecules.

24. The method according to claim 23, wherein amplifying is by a polymerase chain reaction.

25. The method according to claim 21, wherein analyzing comprises optically detecting fluorescent tags on molecules in the sample.

26. The method according to claim 21, wherein flowing is continuously flowing.

27. The method according to claim 21, wherein the carrier fluid is a biologically non-reactive fluid.

28. The method according to claim 27, wherein the biologically non-reactive fluid is silicone oil.

29. A method of diagnosing cancer in a subject, the method comprising:

flowing sample droplets enveloped in an immiscible carrier fluid to an analysis stage, wherein the sample droplets comprise nucleic acid molecules, at least some of which are suspected of having mutations that are indicative of a cancer;

amplifying the nucleic acid molecules in the droplets;

hybridizing labeled probes to the nucleic acid molecules in the droplets, wherein the probes are specific for the mutations indicative of the cancer; and

detecting the labeled nucleic acids in the droplets at the analysis stage, wherein the droplets do not contact a surface of the analysis stage.

30. The method according to claim 29, wherein amplifying is by the polymerase chain reaction.

31. The method according to claim 29 wherein the labeled probes are fluorescently labeled probes.

32. The method according to claim 29, wherein flowing is continuously flowing.

33. The method according to claim 29, wherein the carrier fluid is a biologically non-reactive fluid.

34. The method according to claim 33, wherein the biologically non-reactive fluid is silicone oil.

35. A biological sample analysis system, the system comprising:

an analysis stage comprising an inlet and an outlet, wherein the inlet receives a flow of sample droplets enveloped in an immiscible carrier fluid, wherein the droplets do not contact a surface of the analysis stage and the droplets are analyzed as they flow to the outlet of the stage.

36. The system according to claim 35, further comprising a thermal cycling stage configured such that the enveloped droplets flow through the thermal cycling stage prior to reaching the inlet of the analysis stage.

37. The system according to claim 36, further comprising a sample preparation stage fluidly coupled to the analysis stage.

38. The system according to claim 35, wherein the flow is a continuous flow.

39. The method according to claim 35, wherein the carrier fluid is a biologically non-reactive fluid.

40. The method according to claim 39, wherein the biologically non-reactive fluid is silicone oil.