DUAL ELECTRODE SYSTEM FOR A CONTINUOUS ANALYTE SENSOR

• US 20080083617A1
• Filed: 10/01/2007
• Published: 04/10/2008
• Est. Priority Date: 10/04/2006
• Status: Active Grant

Abstract

Disclosed herein are systems and methods for a continuous analyte sensor, such as a continuous glucose sensor. One such system utilizes first and second working electrodes to measure additional analyte or non-analyte related signal. Such measurements may provide a background and/or sensitivity measurement(s) for use in processing sensor data and may be used to trigger events such as digital filtering of data or suspending display of data.

Claims

1. A continuous glucose sensor, the sensor comprising:

a first working electrode comprising a first electroactive surface disposed beneath an active enzymatic portion of a sensor membrane, wherein the first working electrode is configured to generate a first signal having a first noise component related to a noise-causing species; and

a second working electrode comprising a second electroactive surface disposed beneath an inactive-enzymatic or a non-enzymatic portion of the sensor membrane, wherein the second working electrode is configured to generate a second signal having a second noise component related to the noise-causing species;

wherein the first electroactive surface and the second electroactive surface are each dimensioned to integrate at least one signal generated by a plurality of local point sources that produce the noise-causing species, such that the first noise component and the second noise component are substantially equivalent.

2. The sensor of claim 1, wherein at least one dimension of each of the first electroactive surface and second electroactive surface is greater than a sum of diameters of about 10 average human cells.

3. The sensor of claim 1, wherein at least one dimension of each of the first electroactive surface and second electroactive surface is greater than about 500 μ

m.

4. The sensor of claim 1, wherein each of the first electroactive surface and second electroactive surface is configured and arranged to integrate noise detected about a circumference of the sensor.

5. The sensor of claim 1, wherein the noise-causing species comprises at least one member selected from the group consisting of externally produced H₂O₂, urea, lactic acid, phosphates, citrates, peroxides, amino acids, amino acid precursors, amino acid break-down products, nitric oxide, NO-donors, NO-precursors, reactive oxygen species, compounds having electroactive acidic, amine or sulfhydryl groups, acetaminophen, ascorbic acid, dopamine, ephedrine, ibuprofen, L-dopa, methyldopa, salicylate, tetracycline, tolazamide, tolbutamide, and triglycerides.

6. The sensor of claim 5, wherein the noise-causing species is non-constant.

7. The sensor of claim 1, wherein the first electroactive surface and second electroactive surface are spaced at a distance that allows noise caused by a local point source that produces noise-causing species to be measured equivalently at the first electroactive surface and the second electroactive surface.

8. The sensor of claim 1, wherein the first electroactive surface and second electroactive surface are spaced at a distance less than a crosstalk diffusion distance of a measured species.

9. The sensor of claim 8, wherein the measured species comprises H₂O₂ produced in the active enzymatic portion of the sensor membrane.

10. The sensor of claim 8, further comprising a physical diffusion barrier configured and arranged to physically block crosstalk from the active enzymatic portion of the sensor membrane to the second electroactive surface by at least 50%.

11. The sensor of claim 10, wherein the physical diffusion barrier is configured and arranged to physically block an amount of the measured species diffusing from the active enzymatic portion of the membrane to the second electroactive surface, such that there is substantially no signal associated with crosstalk measured at the second working electrode.

12. The sensor of claim 1, further comprising a physical diffusion barrier comprising a discontinuous portion of a membrane disposed between the first electroactive surface and the second electroactive surface.

13. The sensor of claim 12, wherein the physical diffusion barrier comprises a first barrier layer formed on the first working electrode and a second barrier layer formed on the second working electrode, wherein the first barrier layer and the second barrier layer are each independently formed.

14. The sensor of claim 12, wherein the physical diffusion barrier comprises a first resistance domain formed on the first working electrode and a second resistance domain formed on the second working electrode, and the sensor membrane further comprises a third resistance domain disposed continuously over the first and second resistance domains, wherein the first resistance domain and the second resistance domain are configured and arranged to attenuate diffusion of the measurable species from the active enzymatic portion of the sensor to the second electroactive surface by at least 2-fold, and the third resistance domain is configured such that a sensitivity of each of the first signal and the second signal is substantially equivalent.

15. The sensor of claim 14, wherein the physical diffusion barrier is configured and arranged to attenuate the diffusion of the measured species by at least 10-fold.

16. The sensor of claim 14, wherein the sensitivities of the first signal and the second signals are within 20% of each other.

17. A continuous glucose sensor configured for insertion into a host and for detecting glucose in the host, the sensor comprising:

a first working electrode comprising a first electroactive surface disposed beneath an active enzymatic portion of a sensor membrane, wherein the first working electrode is configured to generate a first signal having a first noise component related to a noise-causing species;

a second working electrode comprising a second electroactive surface disposed beneath an inactive-enzymatic or a non-enzymatic portion of the sensor membrane, wherein the second working electrode is configured to generate a second signal having a second noise component related to the noise-causing species; and

a physical diffusion barrier;

wherein the first electroactive surface and the second electroactive surface are spaced at a distance that allows noise caused by a local point source that produces noise-causing species to be measured substantially equivalently at the first electroactive surface and the second electroactive surface.

18. The sensor of claim 17, wherein the sensor membrane has a thickness, and wherein the distance between the first electroactive surface and the second electroactive surface is less than about twice the thickness of the sensor membrane.

19. The sensor of claim 18, wherein the thickness of the sensor membrane is less than about 80 microns.

20. The sensor of claim 17, wherein the distance between the first electroactive surface and the second electroactive surface is less than or equal to about a crosstalk diffusion distance of a measurable species.

21. The sensor of claim 20, wherein the measurable species comprises H₂O₂ produced in the active enzymatic portion of the sensor membrane.

22. The sensor of claim 17, wherein the noise-causing species comprises at least one member selected from the group consisting of externally produced H₂O₂, urea, lactic acid, phosphates, citrates, peroxides, amino acids, amino acid precursors, amino acid break-down products, nitric oxide, NO-donors, NO-precursors, reactive oxygen species, compounds having electroactive acidic, amine or sulfhydryl groups, acetaminophen, ascorbic acid, dopamine, ephedrine, ibuprofen, L-dopa, methyldopa, salicylate, tetracycline, tolazamide, tolbutamide, and triglycerides.

23. The sensor of claim 17, wherein the active enzymatic portion of the membrane is configured to produce a measurable species, and wherein the physical diffusion barrier is configured and arranged to physically block at least some diffusion of the measurable species from the active enzymatic portion of the membrane to the second electroactive surface.

24. The sensor of claim 23, wherein the physical diffusion barrier is configured and arranged to physically block at least 50% of the measurable species diffusing from the active enzymatic portion of the membrane to the second electroactive surface, such that there is substantially no signal associated with crosstalk measured at the second working electrode.

25. The sensor of claim 23, wherein the measurable species comprises H₂O₂ produced in the active enzymatic portion of the sensor membrane.

26. The sensor of claim 17, wherein the physical diffusion barrier comprises a discontinuous portion of the membrane disposed between the first electroactive surface and the second electroactive surface.

27. The sensor of claim 17, wherein the physical diffusion barrier comprises a first barrier layer formed on the first electrode and a second barrier layer formed on the second electrode, wherein each of the first barrier layer and the second barrier layer is independently formed.

28. The sensor of claim 17, wherein the physical diffusion barrier comprises a first resistance domain formed on the first electrode and a second resistance domain formed on the second electrode, and wherein the first resistance domain and the second resistance domain are configured and arranged to attenuate diffusion of the measurable species from the active enzymatic portion of the membrane to the second electroactive surface by at least 2-fold.

29. The sensor of claim 28, wherein the physical diffusion barrier is configured and arranged to attenuate the diffusion of the measurable species by at least 10-fold.

30. The sensor of claim 28, wherein the sensor membrane further comprises a third resistance domain disposed continuously over the first electroactive surface and the second electroactive surface, wherein the third resistance domain is configured such that a sensitivity of each of the first signal and the second signal is substantially equivalent.

31. The sensor of claim 17, further comprising an insulator configured to insulate the first working electrode from the second working electrode, wherein the sensor membrane is the insulator.

32. The sensor of claim 17, wherein the first electroactive surface and the second electroactive surface are each dimensioned to integrate noise caused by a plurality of local point sources that produce noise-causing species in vivo.

33. The sensor of claim 32, wherein the first electroactive surface and the second electroactive surface are each sized in at least one dimension such that each of the first noise component and second noise component can be integrated across the dimension.

34. The sensor of claim 33, wherein the dimension is greater than a sum of diameters of about 10 average human cells.

35. The sensor of claim 17, wherein each of the first electroactive surface and the second electroactive surface is dimensioned such that each of the first noise component and the second noise component is substantially equivalent.

36. A sensor configured and arranged for insertion into a host and for continuously detecting glucose in the host, the sensor comprising:

a first working electrode configured to generate a first signal having a first noise component related to a noise-causing species, the first working electrode having a first electroactive surface having a first surface area; and

a second working electrode configured to generate a second signal having a second noise component related to the noise-causing species, the second working electrode having a second electroactive surface having a second surface area;

wherein the first working electrode and the second working electrode are configured and arranged to integrate the first noise component and the second noise component about a circumference of the sensor.

37. The sensor of claim 36, wherein the noise-causing species comprises at least one member selected from the group consisting of externally produced H₂O₂, urea, lactic acid, phosphates, citrates, peroxides, amino acids, amino acid precursors, amino acid break-down products, nitric oxide, NO-donors, NO-precursors, reactive oxygen species, compounds having electroactive acidic, amine or sulfhydryl groups, acetaminophen, ascorbic acid, dopamine, ephedrine, ibuprofen, L-dopa, methyldopa, salicylate, tetracycline, tolazamide, tolbutamide, and triglycerides.

38. The sensor of claim 36, wherein the noise-causing species is non-constant.

39. The sensor of claim 36, wherein the first surface area and the second surface area are each dimensioned to integrate noise caused by a plurality of local point sources that produce noise-causing species in vivo.

40. The sensor of claim 36, wherein the first surface area and the second surface area are each sized in at least one dimension such that each of the first noise component and the second noise component can be integrated across the dimension.

41. The sensor of claim 40, wherein the dimension is greater than a sum of diameters of about 10 average human cells.

42. The sensor of claim 40, wherein the dimension is greater than about 500 μ

m.

43. The sensor of claim 36, wherein the first surface area and the second surface area are each dimensioned such that each of the first noise component and the second noise component is substantially equivalent.

44. The sensor of claim 40, wherein the first surface area and the second surface area are each dimensioned such that each of the first noise component and the second noise component is equivalent to ±

10%.

45. The sensor of claim 36, wherein the first electroactive surface and the second electroactive surface are spaced a distance that allows noise caused by a local point source that produces noise-causing species to be measured equivalently at the first electroactive surface and the second electroactive surface.

46. The sensor of claim 36, wherein the first electroactive surface is disposed beneath an active enzymatic portion of a sensor membrane and the second electroactive surface is disposed beneath at least one of an inactive enzymatic or a non-enzymatic portion of the sensor membrane, and wherein the first electroactive surface and the second electroactive surface are spaced a distance less than about a crosstalk distance of a measurable species produced in the active enzymatic portion of the sensor membrane.

47. The sensor of claim 46, wherein the measurable species comprises H₂O₂.

48. The sensor of claim 46, wherein the crosstalk distance comprises a maximum distance the measurable species can diffuse from the active enzymatic portion of the sensor membrane to the second electroactive surface, and thereby cause a measurable signal on the second working electrode.

49. The sensor of claim 46, further comprising a physical diffusion barrier.

50. The sensor of claim 49, wherein the physical diffusion barrier comprises a first barrier layer formed on the first working electrode and a second barrier layer formed on the second working electrode, wherein each of the first barrier layer and the second barrier layer is independently formed.

51. The sensor of claim 49, wherein the physical diffusion barrier comprises a first resistance domain formed on the first working electrode and a second resistance domain formed on the second working electrode, and wherein the first resistance domain and the second resistance domain are configured and arranged to attenuate diffusion of the measurable species from the active enzymatic portion of the membrane to the second electroactive surface by at least 2-fold.

52. The sensor of claim 51, wherein the physical diffusion barrier is configured and arranged to attenuate the diffusion of the measurable species by at least 10-fold.

53. The sensor of claim 51, wherein the sensor membrane further comprises a third resistance domain disposed continuously over the first resistance domain and the second resistance domain, wherein the third resistance domain is configured such that a sensitivity of each of the first signal and the second signal is substantially equivalent.

54. The sensor of claim 36, further comprising an insulator configured to insulate the first working electrode from the second working electrode, wherein the sensor membrane is the insulator.

55. A continuous glucose sensor configured and arranged for insertion into a host and for detecting glucose in the host, the sensor comprising:

a first working electrode comprising a first electroactive surface disposed beneath an active enzymatic portion of a sensor membrane, wherein the first electroactive surface is configured to measure a measurable species;

a second working electrode comprising a second electroactive surface disposed beneath at least one of an inactive enzymatic portion of the sensor membrane and a non-enzymatic portion of the sensor membrane, wherein the second electroactive surface is configured to measure said measurable species, and wherein the first electroactive surface and the second electroactive surface are spaced within a crosstalk distance of the measurable species; and

a physical diffusion barrier disposed between the first working electrode and the second working electrode, wherein the physical diffusion barrier is configured and arranged such that there is substantially no signal associated with crosstalk.

56. The sensor of claim 55, wherein the noise-causing species comprises at least one member selected from the group consisting of externally produced H₂O₂, urea, lactic acid, phosphates, citrates, peroxides, amino acids, amino acid precursors, amino acid break-down products, nitric oxide, NO-donors, NO-precursors, reactive oxygen species, compounds having electroactive acidic, amine or sulfhydryl groups, acetaminophen, ascorbic acid, dopamine, ephedrine, ibuprofen, L-dopa, methyldopa, salicylate, tetracycline, tolazamide, tolbutamide, and triglycerides.

57. The sensor of claim 56, wherein the noise-causing species is non-constant.

58. The sensor of claim 56, wherein the measurable species is H₂O₂ produced in an active enzymatic portion of a sensor membrane.

59. The sensor of claim 56, wherein the crosstalk distance is a maximum distance the measurable species can diffuse between the active enzymatic portion of the membrane and the second working electrode, and be detected as crosstalk.

60. The sensor of claim 56, wherein the first electroactive surface has a first area and the second electroactive surface has a second area;

wherein the first area and the second area are dimensioned such that the first noise component and the second noise component are substantially equivalent.

61. The sensor of claim 60, wherein at least one dimension of each of the first area and the second area is greater than a sum of diameters of about 10 average human cells.

62. The sensor of claim 60, wherein at least one dimension of each of the first area and the second area is greater than about 500 μ

m.

63. The sensor of claim 60, wherein the first area and the second area are each configured and arranged to integrate noise caused by a plurality of local point sources that produce noise-causing species in vivo.

64. The sensor of claim 60, wherein the first area and the second area are each configured and arranged to integrate noise detected about a circumference of the sensor.

65. The sensor of claim 55, wherein the physical diffusion barrier comprises a discontinuous portion of the membrane disposed between the first electroactive surface and the second electroactive surface.

66. The sensor of claim 55, wherein the physical diffusion barrier comprises a first barrier layer formed on the first working electrode and a second barrier layer formed on the second working electrode, wherein the first barrier layer and the second barrier layer are independently formed.

67. The sensor of claim 55, wherein the physical diffusion barrier comprises a first resistance domain formed on the first working electrode and a second resistance domain formed on the second working electrode, and wherein the first resistance domain and the second resistance domain are configured and arranged to attenuate diffusion of the measurable species from the active enzymatic portion of the membrane to the second electroactive surface by at least 2-fold.

68. The sensor of claim 67, wherein the physical diffusion barrier is configured and arranged to attenuate the diffusion of the measurable species by at least 10-fold.

69. The sensor of claim 67, wherein the sensor membrane further comprises a third resistance domain disposed continuously over the first resistance domain and the second resistance domain, wherein the third resistance domain is configured such that a sensitivity of each of the first signal and the second signal is substantially equivalent.

70. The sensor of claim 55, further comprising an insulator configured to insulate the first working electrode from the second working electrode, wherein the sensor membrane is the insulator.

71. The sensor of claim 55, wherein the first electroactive surface and the second electroactive surface are spaced a distance that allows noise caused by a local point source that produces noise-causing species to be measured equivalently at the first electroactive surface and the second electroactive surface.

72. A continuous glucose sensor configured and arranged for insertion into a host for and detecting glucose in the host, the sensor comprising:

a first working electrode comprising a first resistance domain, wherein the first working electrode is configured to generate a first signal having a first noise component related to a noise-causing species;

a second working electrode comprising a second resistance domain, wherein the second working electrode is configured to generate a second signal having a second noise component related to the noise-causing species; and

a third resistance domain disposed continuously over the first resistance domain and the second resistance domain.

73. The sensor of claim 72, wherein the noise-causing species comprises at least one member selected from the group consisting of externally produced H₂O₂, urea, lactic acid, phosphates, citrates, peroxides, amino acids, amino acid precursors, amino acid break-down products, nitric oxide, NO-donors, NO-precursors, reactive oxygen species, compounds having electroactive acidic, amine or sulfhydryl groups, acetaminophen, ascorbic acid, dopamine, ephedrine, ibuprofen, L-dopa, methyldopa, salicylate, tetracycline, tolazamide, tolbutamide, and triglycerides.

74. The sensor of claim 72, wherein the noise-causing species is non-constant.

75. The sensor of claim 72, wherein the first signal comprises a first sensitivity and the second signal comprises a second sensitivity, and wherein the third resistance domain is configured such that the first sensitivity and the second sensitivity are substantially equivalent.

76. The sensor of claim 75, wherein the first sensitivity and the second sensitivity are equivalent to ±

10%.

77. The sensor of claim 72, wherein each of the first resistance domain and the second resistance domain is independently formed on the first working electrode and the second working electrode, respectively.

78. The sensor of claim 72, wherein the first working electrode comprises a first electroactive surface and a first membrane portion disposed thereon, the first membrane portion comprising an active enzymatic enzyme domain and the first resistance domain, and wherein the second working electrode comprises a second electroactive surface and a second membrane portion disposed thereon, the second membrane portion comprising at least one of an inactive enzymatic portion or a non-enzymatic portion and the second resistance domain.

79. The sensor of claim 78, wherein the active enzymatic enzyme domain is configured to generate a measurable species.

80. The sensor of claim 79, wherein the measurable species comprises H₂O₂ produced in the active enzymatic portion of the sensor membrane.

81. The sensor of claim 78, further comprising a physical diffusion barrier, wherein physical diffusion barrier comprises the first resistance domain and the second resistance domain.

82. The sensor of claim 81, wherein the physical diffusion barrier is configured and arranged to attenuate diffusion of the measurable species from the active enzymatic enzyme domain to the second electroactive surface by at least 2-fold.

83. The sensor of claim 82, wherein the diffusion is attenuated by at least 10-fold.

84. The sensor of claim 81, wherein the physical diffusion barrier is configured and arranged to physically block some crosstalk from the active enzymatic enzyme domain to the second electroactive surface.

85. The sensor of claim 81, wherein the physical diffusion barrier is configured and arranged to physically block an amount of a measurable species diffusing from the active enzymatic enzyme domain to the second electroactive surface, such that there is substantially no signal associated with crosstalk measured at the second working electrode.

86. The sensor of claim 81, wherein the physical diffusion barrier comprises a first barrier layer formed on the first working electrode and a second barrier layer formed on the second working electrode, wherein each of the first barrier layer and the second barrier layer is independently formed.

87. The sensor of claim 79, wherein the first electroactive surface and the second electroactive surface are spaced closer together than a crosstalk distance.

88. The sensor of claim 87, wherein the crosstalk distance comprises a distance less than a maximum distance the measurable species can diffuse, and generate a signal associated with crosstalk.

89. The sensor of claim 79, wherein the first electroactive surface and the second electroactive surface are spaced a distance that allows noise caused by a local point source that produces noise-causing species to be measured equivalently at the first and second electroactive surfaces.

90. The sensor of claim 79, wherein each of the first electroactive surface and the second electroactive surface is configured and arranged to integrate the signal caused by a plurality of local point sources that produce noise-causing species in vivo such that the first noise component and the second noise component are substantially equivalent.

91. The sensor of claim 79, wherein the first electroactive surface and the second electroactive surface are configured and arranged to integrate signals detected about a circumference of the sensor.

92. The sensor of claim 79, wherein the first electroactive surface and the second electroactive surface are each sized in at least one dimension such that the first noise component and the second noise component can be integrated across the dimension.

93. The sensor of claim 79, wherein the dimension of each of the first electroactive surface and the second electroactive surface is greater than a sum of diameters of about 10 average human cells.

94. The sensor of claim 93, wherein the dimension of each of the first electroactive surface and the second electroactive surface is greater than about 500 μ

m.