Use of microfluidic systems in the electrochemical detection of target analytes

• US 7,534,331 B2
• Filed: 01/25/2005
• Issued: 05/19/2009
• Est. Priority Date: 04/21/1999
• Status: Expired due to Term

• Current Assignee: Roche Molecular Systems (Roche Holding AG)
• Original Assignee: Osmetech Technology Inc. (Roche Holding AG)
• Inventors: Kayyem, Jon Faiz
• Primary Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US11/043,515
• Publication Number:
  US 20050211559A1
• Time in Patent Office: 1,575 Days
• Field of Search: 20440301-40315, 204/411, 204/412, 205/777.5, 205/778, 205/792
• US Class Current: 204/411
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• 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 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0611 duck bill valves
• CPC Class Codes: B01L 2400/0633 with moving parts
• CPC Class Codes: B01L 2400/0638 membrane valves, flap valves
• CPC Class Codes: B01L 2400/0677 phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
• 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: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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 3/502738 : characterised by integrated valves microvalves F16K99/0001
• 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 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B01L 7/525 : with physical movement of samples between temperature zones
• CPC Class Codes: B01L 9/527 : for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 35/00 : Methods or apparatus for measurement or analysis of nanostructures
• CPC Class Codes: B82Y 40/00 : Manufacture or treatment of nanostructures
• CPC Class Codes: C12Q 1/6813 : Hybridisation assays
• CPC Class Codes: C12Q 1/6825 : Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 2563/113 : the label being electroactive, e.g. redox labels
• CPC Class Codes: C12Q 2565/629 : being a microfluidic device
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2610/00 : Assays involving self-assembled monolayers [SAMs]
• CPC Class Codes: G01N 27/3275 : Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction
• CPC Class Codes: G01N 27/3276 : being a hybridisation with immobilised receptors using a FET type sensor G01N27/4145; concerning the hybridisation C12Q1/68
• CPC Class Codes: G01N 27/447 : using electrophoresis
• CPC Class Codes: G01N 27/4473 : by electric means
• CPC Class Codes: G01N 27/44752 : Controlling the zeta potential, e.g. by wall coatings
• CPC Class Codes: G01N 27/44791 : Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 33/5302 : Apparatus specially adapted for immunological test procedures
• CPC Class Codes: G01N 33/5438 : Electrodes
• CPC Class Codes: G01N 33/54386 : Analytical elements

Abstract

The invention relates generally to methods and apparatus for conducting analyses, particularly microfluidic devices for the detection of target analytes.

Claims

1. A microfluidic device for the detection of a target analyte in a fluid sample comprising:

a) a solid support member;

b) a sealing inlet port;

c) a detection chamber formed in said support member;

d) a plurality of detection electrodes positioned in said detection chamber, each comprising a binding ligand; and

,

e) a microchannel formed in said support member coupled to and extending between said detection chamber and said sealing inlet port.

3. The device according to claims 1 or 2, further comprising a pump for inducing flow of a sample through said microfluidic device.

4. The device according to claims 1 or 2 further comprising a means for mixing a sample, said means positioned within said microchannel.

5. A device according to claim 3 or 4, wherein at least one of said detection electrodes comprises a planar conductive electrode.

6. A device according to claim 5, further comprising a reference electrode.

7. A device according to claim 3 or 4, wherein said detection electrode comprises gold.

8. A device according to claim 7, further comprising a reference electrode.

9. A device according to claim 3 or 4, further comprising a processor coupled to said detection electrodes and configured to receive an output signal.

10. A device according to claim 9, further comprising a reference electrode.

11. A device according to claim 3 or 4, further comprising an AC voltage source capable of delivering a DC offset voltage to said electrodes.

12. A device according to claim 11, further comprising a reference electrode.

13. A device according to claim 3 or 4, wherein said binding ligand is a nucleic acid.

14. A device according to claim 13, further comprising a reference electrode.

15. A device according to claim 3 or 4, further comprising a reference electrode.

18. A device according to claim 1, 2, 16, or 17, wherein at least one of said detection electrodes comprises a planar conductive electrode.

19. A device according to claim 18, wherein said detection electrode comprises gold.

20. A device according to claim 19, further comprising a reference electrode.

21. A device according to claim 18, further comprising a processor coupled to said detection electrodes and configured to receive an output signal.

22. A device according to claim 21, further comprising a reference electrode.

23. A device according to claim 18, further comprising an AC voltage source capable of delivering a DC offset voltage to said electrodes.

24. A device according to claim 23, further comprising a reference electrode.

25. A device according to claim 18, wherein said binding ligand is a nucleic acid.

26. A device according to claim 25, further comprising a reference electrode.

27. A device according to claim 18, further comprising a reference electrode.

28. A device according to claim 1, 2, 16, or 17, wherein said detection electrode comprises gold.

29. A device according to claim 28, further comprising a processor coupled to said detection electrodes and configured to receive an output signal.

30. A device according to claim 29, further comprising a reference electrode.

31. A device according to claim 28, further comprising an AC voltage source capable of delivering a DC offset voltage to said electrodes.

32. A device according to claim 31, further comprising a reference electrode.

33. A device according to claim 28, wherein said binding ligand is a nucleic acid.

34. A device according to claim 33, further comprising a reference electrode.

35. A device according to claim 28, further comprising a reference electrode.

36. A device according to claim 1, 2, 16, or 17, further comprising a processor coupled to said detection electrodes and configured to receive an output signal.

37. A device according to claim 36, further comprising an AC voltage source capable of delivering a DC offset voltage to said electrodes.

38. A device according to claim 37, further comprising a reference electrode.

39. A device according to claim 36, wherein said binding ligand is a nucleic acid.

40. A device according to claim 39, further comprising a reference electrode.

41. A device according to claim 36, further comprising a reference electrode.

42. A device according to claim 1, 2, 16, or 17, further comprising an AC voltage source capable of delivering a DC offset voltage to said electrodes.

43. A device according to claim 42, wherein said binding ligand is a nucleic acid.

44. A device according to claim 43, further comprising a reference electrode.

45. A device according to claim 42, further comprising a reference electrode.

46. A device according to claim 1, 2, 16, or 17, wherein said binding ligand is a nucleic acid.

47. A device according to claim 46, further comprising a reference electrode.

48. A device according to claim 1, 2, 16 or 17, further comprising a reference electrode.

2. A microfluidic device for the detection of a target analyte in a fluid sample comprising:

a) a solid support member;

b) a sample inlet port;

c) a detection chamber formed in said support member;

d) a plurality of detection electrodes positioned in said detection chamber, each comprising a binding ligand;

e) a microchannel formed in said support member coupled to and extending between said detection chamber and said sample inlet port; and

,

f) a valve, positioned within said microchannel.

16. A microfluidic device for the detection of a target analyte in a fluid sample comprising:

a) a solid support;

b) a sample inlet port;

c) a detection chamber formed in said support member;

d) a plurality of detection electrodes positioned in said detection chamber, each comprising a binding ligand;

e) a first microchannel formed in said support member coupled to and extending between said detection chamber and said sample inlet port;

f) a pump for inducing the flow of a sample through said microfluidic device; and

,

g) a second microchannel formed in said support member coupled to and extending between said detection chamber and said pump.

17. A microfluidic device for the detection of a target analyte in a fluid sample comprising:

a) a solid support;

b) a sample inlet port;

c) a detection chamber formed in said support member;

d) a plurality of detection electrodes positioned in said detection chamber, each comprising a binding ligand;

e) a first microchannel formed in said support member coupled to and extending between said detection chamber and said sample inlet port;

f) a mixing chamber for mixing a sample; and

g) a second microchannel formed in said support member coupled to and extending between said detection chamber and said mixing chamber.