Transducer for microfluid handling system

• US 6,575,020 B1
• Filed: 05/03/2000
• Issued: 06/10/2003
• Est. Priority Date: 05/03/1999
• Status: Expired due to Fees

• Current Assignee: Aktieselskabet AF 3/12 2003, Nanonord A/S
• Original Assignee: Cantion A/S
• Inventors: Jensenius, Tove Maria Henriette, de Charmoy Grey, Hasin Francois, Boisen, Anja, Thaysen, Jacob
• Primary Examiner(s): Larkin, Daniel S.
• Assistant Examiner(s): CYGAN, MICHAEL T
• Application Number:
  US09/563,331
• Time in Patent Office: 1,133 Days
• Field of Search: 73/240.6, 73/310.6, 73/530.1, 73/542.3, 73/542.4, 73/542.5, 73/542.6, 73/542.7, 73/543.8, 73/544.1, 73/544.2, 73/614.5, 73/616.1, 73/617.8, 73/617.9
• US Class Current: 73/54.23
• CPC Class Codes: G01N 11/00 Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties
• CPC Class Codes: G01N 11/16 by measuring damping effect upon oscillatory body
• CPC Class Codes: G01N 2035/00237 Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2291/0215 Mixtures of three or more gases, e.g. air
• CPC Class Codes: G01N 2291/0224 Mixtures of three or more liquids
• CPC Class Codes: G01N 2291/0255 (Bio)chemical reactions, e.g. on biosensors
• CPC Class Codes: G01N 2291/0256 Adsorption, desorption, surface mass change, e.g. on biosensors
• CPC Class Codes: G01N 2291/02818 Density, viscosity
• CPC Class Codes: G01N 2291/0427 Flexural waves, plate waves, e.g. Lamb waves, tuning fork, cantilever
• CPC Class Codes: G01N 29/022 Fluid sensors based on microsensors, e.g. quartz crystal-microbalance [QCM], surface acoustic wave [SAW] devices, tuning forks, cantilevers, flexural plate wave [FPW] devices microdevices per se B81B
• CPC Class Codes: G01N 29/036 by measuring frequency or resonance of acoustic waves
• CPC Class Codes: G01N 29/222 Constructional or flow details for analysing fluids optoacoustic fluid cells G01N29/2425
• CPC Class Codes: G01N 29/30 Arrangements for calibrating or comparing, e.g. with standard objects
• CPC Class Codes: G01N 9/002 using variation of the resonant frequency of an element vibrating in contact with the material submitted to analysis G01N9/34 takes precedence

Abstract

The present invention relates to integrated micro-cantilevers, micro-bridges or micro-membranes in micro-liquid handling systems. Such micro-liquid handling systems provide novel detection mechanisms for monitoring the physical, chemical and biological properties of fluids in such systems. The present invention further relates to micro-cantilever, micro-bridge or micro-membrane type sensors having integrated readout. Such constructions allow laminated flows of different liquids to flow in a channel without mixing, which opens up for new type of experiments and which reduces noise related to the liquid movement. The present invention even further relates to sensors having adjacent or very closely spaced micro-cantilevers, micro-bridges or micro-membranes which can be exposed to different chemical environments at the same time.

Claims

1. A sensor for detecting the presence of a substance in a liquid, said sensor comprising:

means for handling the liquid, said handling means comprising an interaction chamber of micrometer dimensions, an inlet and an outlet,

a first flexible member having a surface, said surface holding a substance, wherein the surface holding the substance is at least partly positioned inside the interaction chamber so that at least part of the substance is exposed to the liquid, and

means for detecting a mechanical parameter associated with the first flexible member, said mechanical parameter being related to the presence of the substance in the liquid;

wherein the interaction chamber, inlet and outlet of said means for handling are arranged to establish laminar flow across said first flexible member.

2. A sensor according to claim 1, wherein the first flexible member comprises a cantilever having a first and a second end, wherein the first end is attached to the interaction chamber.

3. A sensor according to claim 1, wherein the first flexible member comprises a bridge having a first and a second end, wherein the first and second ends are attached to the interaction chamber.

4. A sensor according to claim 1, wherein the first flexible member forms part of a boundary defining the interaction chamber.

5. A sensor according to claim 1, wherein the detecting means for detecting the mechanical parameter associated with the first flexible member comprises a piezoresistive element, said piezoresistive element being an integral part of the first flexible member.

6. A sensor according to claim 1, wherein the detecting means for detecting the mechanical parameter associated with the first flexible member comprises a laser, an optical element and a position sensitive photo detector.

7. A sensor according to claim 5, wherein the piezoresistive element forms part of a balanced bridge, such as a Wheatstone bridge.

8. A sensor according to claim 1 further comprising an actuator for moving the flexible member relative to the interaction chamber.

9. A sensor according to claim 8, wherein the actuator comprises a piezoelectric element.

10. A sensor according to claim 8, wherein the actuator comprises means for providing an electrostatic induced movement of the flexible member.

11. A sensor according to claim 8, wherein the actuator comprises means for providing a magnetic induced movement of the flexible member.

12. A sensor according to claim 8, wherein the actuator comprises means for providing a thermal induced movement of the flexible member.

13. A sensor according to claim 1, wherein the handling means is fabricated in a material selected from the group consisting of metals, glasses, polymers or semiconductor materials, such as silicon.

14. A sensor according to claim 1, wherein the substance being held by the surface of the first flexible member is selected from the group consisting of metals, polymers, biochemical molecules or micro-biochemical structures.

15. A sensor according to claim 1, further comprising

a second flexible member being at least partly positioned inside the interaction chamber so that at least part of the second flexible member is exposed to the fluid, and

means for detecting a mechanical parameter associated with the second flexible member.

16. A sensor according to claim 15, wherein the detecting means comprises a piezoresistive element, said piezoresistive element being an integral part of the second flexible member, and wherein the piezoresistive element forms part of a balanced bridge, such as a Wheatstone bridge.

17. The sensor of claim 1 wherein said interaction chamber is between 50 and 500 μ

M in at least one of width or depth dimensions.

18. The sensor of claim 1 wherein said means for detecting detects a stress change in said first flexible member.

19. The sensor of claim 1 wherein said mechanical parameter sensed by said means for detecting is a static parameter related to stress in said flexible member.

20. A sensor for detecting the presence of a substance in a liquid, said sensor comprising:

means for handling the liquid, said handling means comprising an interaction chamber of micrometer dimensions, an inlet and an outlet,

a first flexible member having a surface, said surface holding a substance, wherein the surface holding the substance is at least partly positioned inside the interaction chamber so that at least part of the substance is exposed to the liquid, and

means for detecting a mechanical parameter associated with the first flexible member, said mechanical parameter being related to the presence of the substance in the liquid, wherein the detecting means form an integral part of the first flexible member;

wherein the interaction chamber, inlet and outlet of said means for handling are arranged to establish laminar flow across said first flexible member.

21. A sensor according to claim 20, wherein the first flexible member comprises a cantilever having a first and a second end, wherein the first end is attached to the interaction chamber.

22. A sensor according to claim 20, wherein the detecting means for detecting the mechanical parameter associated with the first flexible member comprises a piezoresistive element.

23. A sensor according to claim 22, wherein the piezoresistive element forms part of a balanced bridge, such as a Wheatstone bridge.

24. A sensor according to claim 21 further comprising an actuator for moving the second end of the cantilever relative to the interaction chamber.

25. A sensor according to claim 24, wherein the actuator comprises a piezoelectric element, said piezoelectric element being an integral part of the cantilever.

26. A sensor according to claim 20, wherein the handling means is fabricated in a material selected from the group consisting of metals, glasses, polymers or semiconductor materials, such as silicon.

27. A sensor according to claim 20, wherein the substance being held by the surface of the first flexible member is selected from the group consisting of metals, polymers, biochemical molecules or micro-biochemical structures.

28. A sensor according to claim 20, further comprising

a second flexible member being at least partly positioned inside the interaction chamber so that at least part of the second flexible member is exposed to the fluid, and

means for detecting a mechanical parameter associated with the second flexible member.

29. A sensor according to claim 28, wherein the detecting means comprises a piezoresistive element, said piezoresistive element being an integral part of the second flexible member, and wherein the piezoresistive element forms part of a balanced bridge, such as a Wheatstone bridge.

30. The sensor of claim 20 wherein said interaction chamber is between 50 and 500 μ

M in a t least one of width or depth dimensions.

31. The sensor of claim 20 wherein said means for detecting detects a stress change in said first flexible member.

32. The sensor of claim 20 wherein said mechanical parameter sensed by said means for detecting is a static parameter related to stress in said flexible member.

33. A sensor for detecting the presence of a substance in a liquid, said sensor comprising:

means for handling the liquid, said handling means comprising an interaction chamber of micrometer dimensions, an inlet and an outlet,

a first flexible member having a surface, said surface holding a substance, wherein the surface holding the substance is at least partly positioned inside the interaction chamber so that at least part of the substance is exposed to the liquid, and wherein the first flexible member forms an integral part of the handling means, and

means for detecting a mechanical parameter associated with the first flexible member, said mechanical parameter being related to the presence of the substance in a liquid,

wherein the interaction chamber, inlet and outlet of said means for handling are arranged to establish laminar flow across said first flexible member.

34. A sensor according to claim 33, wherein the first flexible member comprises a cantilever having a first and a second end, wherein the first end is attached to the interaction chamber.

35. A sensor according to claim 33, wherein the detecting means for detecting the mechanical parameter associated with the first flexible member comprises a piezoresistive element, said piezoresistive element being an integral part of the first flexible member.

36. A sensor according to claim 35, wherein the piezoresistive element forms part of a balanced bridge, such as a Wheatstone bridge.

37. A sensor according to claim 33 further comprising an actuator for moving the second end of the cantilever relative to the interaction chamber.

38. A sensor according to claim 37, wherein the actuator comprises a piezoelectric element, said piezoelectric element being an integral part of the cantilever.

39. A sensor according to claim 33, wherein the handling means is fabricated in a material selected from the group consisting of metals, glasses, polymers or semiconductor materials, such as silicon, and wherein the interaction chamber is of micrometer dimensions.

40. A sensor according to claim 33, wherein the substance being held by the surface of the first flexible member is selected from the group consisting of metals, polymers, biochemical molecules or micro-biochemical structures.

41. A sensor according to claim 33, further comprising:

a second flexible member being at least partly positioned inside the interaction chamber so that at least part of the second flexible member is exposed to the liquid, and

means for detecting a mechanical parameter associated with the second flexible member.

42. A sensor according to claim 41, wherein the second flexible member detecting means comprises a second piezoresistive element, said second piezoresistive element being an integral part of the second flexible member, and wherein the second piezoresistive element forms part of a balanced bridge, such as a Wheatstone bridge.

43. The sensor of claim 33 wherein said interaction chamber is between 50 and 500 μ

M in at least one of width or depth dimensions.

44. The sensor of claim 33 wherein said means for detecting detects a stress change in said first flexible member.

45. The sensor of claim 33 wherein said mechanical parameter sensed by said means for detecting is a static parameter related to stress in said flexible member.

49. A sensor according to claim 33, wherein the substance being held by the surface of the first flexible member is selected from the group consisting of metals, polymers, biochemical molecules or micro-biochemical structures.

46. A sensor for detecting the presence of a substance in a liquid, said sensor comprising:

means for handling the liquid, said handling means comprising an interaction chamber of micrometer dimensions, an inlet and an outlet and being fabricated in a material selected from the group consisting of metals, glasses, polymers, or semiconductor materials, such as silicon,

a first flexible member comprising a cantilever having a first and a second end, wherein the first end is attached to the interaction chamber, said cantilever having a surface, said surface holding a substance, wherein the surface holding the substance is at least partly positioned inside the interaction chamber so that at least part of the substance is exposed to the liquid, and wherein fabrication of the first flexible member is part of fabrication of the handling means,

means for detecting a mechanical parameter associated with the first flexible member, said mechanical parameter being related to the presence of the substance in the liquid;

wherein the interaction chamber, inlet and outlet of said means for handling are arranged to establish laminar flow across said first flexible member.

47. A sensor according to claim 46, wherein the detecting means for detecting the mechanical parameter associated with the first flexible member comprises a piezoresistive element, said piezoresistive element being an integral part of the first flexible member.

48. A sensor according to claim 46, further comprising an actuator for moving the second end of the cantilever relative to the interaction chamber.

50. A sensor according to claim 46, further comprising:

a second flexible member being at least partly positioned inside the interaction chamber so that at least part of the second flexible member is exposed to the liquid, and

means for detecting a mechanical parameter associated with the second flexible member.

51. A sensor according to claim 50, wherein the detecting means comprises a piezoresistive element, said piezoresistive element being an integral part of the second flexible member, and wherein the piezoresistive element forms part of a balanced bridge, such as a Wheatstone bridge.

52. The sensor of claim 46 wherein said interaction chamber is between 50 and 500 μ

M in at least one of width or depth dimensions.

53. The sensor of claim 46 wherein said mechanical parameter sensed by said means for detecting is a static parameter related to stress in said flexible member.

87. The method of claim 53 wherein said static mechanical parameter is a stress change in the first flexible member.

88. The sensor of claim 46 wherein said means for detecting detects a stress change in said first flexible member.

54. A sensor for detecting the presence of a first and a second substance in a liquid, said sensor comprising:

means for handling the liquid, said handling means comprising an interaction chamber of micrometer dimensions, an inlet and an outlet,

a first flexible member having a surface, said surface holding a first substance, wherein the surface holding the first substance is at least partly positioned inside the interaction chamber so that at least part of the first substance is exposed to the liquid,

a second flexible member having a surface, said surface holding a second substance, wherein the surface holding the second substance is at least partly positioned inside the interaction chamber so that at least part of the second substance is exposed to the liquid,

a first detecting means for detecting a first mechanical parameter associated with the first flexible member, said first mechanical parameter being related to the presence of the first substance in the liquid, and

a second detecting means for detecting a second mechanical parameter associated with the second flexible member, said second mechanical parameter being related to the presence of the second substance in the liquid;

wherein the interaction chamber, inlet and outlet of said means for handling are arranged to establish laminar flow across said first and second flexible members.

55. A sensor according to claim 54, wherein each of the first and second flexible members comprises a cantilever having a first and a second end, wherein the first end is attached to the interaction chamber.

56. A sensor according to claim 54, wherein each of the first and second flexible members comprises a bridge having a first and a second end, wherein the first and second ends are attached to the interaction chamber.

57. A sensor according to claim 54, wherein each of the first and second flexible members forms part of a boundary defining the interaction chamber.

58. A sensor according to claim 54, wherein the first detecting means comprises a piezoresistive element, said piezoresistive element being an integral part of the first flexible member.

59. A sensor according to claim 54, wherein the second detecting means comprises a piezoresistive element, said piezoresistive element being an integral part of the second flexible member.

60. A sensor according to claim 58, wherein each of the piezoresistive elements forms part of a balanced bridge, such as a Wheatstone bridge.

61. A sensor according to claim 54 further comprising actuators for moving the first and second flexible members relative to the interaction chamber.

62. A sensor according to claim 61, wherein the actuators comprise piezoelectric elements, said piezoelectric elements being an integral part of the cantilevers.

63. A sensor according to claim 61, wherein the actuators comprise means for providing an electrostatic induced movement of the second end of the cantilevers.

64. A sensor according to claim 61, wherein the actuators comprise means for providing a magnetic induced movement of the second end of the cantilevers.

65. A sensor according to claim 61, wherein the actuators comprise means for providing a thermal induced movement of the second end of the cantilevers.

66. A sensor according to claim 54, wherein the handling means is fabricated in a material selected from the group consisting of metals, glasses, polymers or semiconductor materials, such as silicon.

67. A sensor according to claim 54, wherein the substances being held by the surface of the first and second flexible members are selected from the group consisting of metals, polymers, biochemical molecules or micro-biochemical structures.

68. The sensor of claim 54 wherein said interaction chamber is between 50 and 500 μ

M in at least one of width or depth dimensions.

69. The sensor of claim 54 wherein said means for detecting detects a stress change in at least one of said first and second flexible members.

70. The sensor of claim 54 wherein said mechanical parameter sensed by said first and second detecting means are a static parameters related to stress in said first and second flexible members.

71. A sensor for detecting the presence of a first and a second substrate in a moving laminated liquid, said laminated fluid comprising, in a cross section perpendicular to a direction of movement, a first and a second region, said sensor in comprising:

means for handling the laminated liquid, said handling means comprising an interaction chamber, an inlet and an outlet, wherein the interaction chamber, inlet and outlet of said means for handling are arranged to establish laminar flow of the moving laminated liquid including said first and second regions;

a first flexible member having a surface, said surface holding a first substance, wherein the surface holding the first substance is at least partly positioned inside the interaction chamber so that at least part of the first substance is exposed to the first region of the laminated liquid,

a second flexible member having a surface, said surface holding a second substance, wherein the surface holding the second substance is at least partly positioned inside the interaction chamber so that at least part of the second substance is exposed to the second region of the laminated liquid,

means for detecting a first mechanical parameter associated with the first flexible member, said first mechanical parameter being related to the presence of the first substance in the first region of the liquid, and

means for detecting a second mechanical parameter associated with the second flexible member, said second mechanical parameter being related to the presence of the second substance in the second region of the liquid.

72. A sensor according to claim 71, wherein the detecting means for detecting the first mechanical parameter associated with the first flexible member comprises a piezoresistive element, said piezoresistive element being an integral part of the first flexible member.

73. A sensor according to claim 72, wherein the detecting means for detecting the second mechanical parameter associated with the second flexible member comprises a piezoresistive element, said piezoresistive element being an integral part of the second flexible member.

74. A sensor according to claim 71, wherein the detecting means for detecting the first and second mechanical parameters associated with the first and second flexible member, respectively, comprises a laser, an optical element and a position sensitive photo detector.

75. A sensor according to claim 71, further comprising a first actuator for moving part of the first flexible element relative to the handling means.

76. A sensor according to claim 75, wherein the first actuator comprises a piezoelectric element, said piezoelectric element being an integral part of the first flexible member.

77. A sensor according to claim 71, further comprising a second actuator for moving part of the second flexible element relative to the handling means.

78. A sensor according to claim 77, wherein the second actuator comprises a piezoelectric element, said piezoelectric element being an integral part of the second flexible member.

79. A sensor according to claim 71, wherein the handling means is fabricated in a material selected from the group consisting of metals, glasses, polymers or semiconductor materials, such as silicon.

80. A sensor according to claim 71, wherein the substances being held by the surface of the first and second flexible members are selected from the group consisting of metals, polymers, biochemical molecules or micro-biochemical structures.

81. The sensor of claim 71 wherein said interaction chamber is between 50 and 500 μ

M in at least one of width or depth dimensions.

82. The sensor of claim 71 wherein said means for detecting detects a stress change in at least one of said first and second flexible members.

83. The sensor of claim 71 wherein said mechanical parameter sensed by said means for detecting first and second mechanical parameters are static parameters related to stress in said first and second flexible members.

84. The sensor of claim 83 wherein first and second fluid regions are introduced into said interaction chamber and maintained separate from each other by the laminar flow therein;

said first and second flexible members are each disposed in one of said first and second laminar fluid flow regions.

85. The sensor of claim 71 wherein said first and second mechanical parameters are static parameters.

86. A method for detecting the presence of a substance in a liquid using a sensor including,

an interaction chamber of micrometer dimensions having an inlet and an outlet through which a liquid to be sensed is supplied, and

at least one cantilevered sensor having a first flexible member provided with a surface reacting to the presence of a substance to be measured, said first flexible member being provided at least partially within said interaction chamber, the method comprising:

introducing the liquid to be sampled to the interaction camber via the inlet and outlet of said interaction chamber so that a laminar flow is established across said first flexible member;

detecting a static mechanical parameter associated with said first flexible member related to the presence of the substance to be measured; and

correlating said mechanical parameter to the presence of the substance.