Biosensor and method of making

• US 20050103624A1
• Filed: 06/18/2004
• Published: 05/19/2005
• Est. Priority Date: 10/04/1999
• Status: Abandoned Application

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Inventors: Diebold, Eric R., Hill, Brian S., Bhullar, Raghbir S., Walling, Paul Douglas, Surridge, Nigel
• Application Number:
  US10/871,937
• Publication Number:
  US 20050103624A1
• Time in Patent Office: Days
• US Class Current: 204/403.10
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: H05K 1/0393 Flexible materials H05K1/038 takes precedence; specific organic compositions are classified in H05K1/0313 and subgroups
• CPC Class Codes: H05K 3/027 the conductive material being removed by irradiation, e.g. by photons, alpha or beta particles
• CPC Class Codes: Y10T 29/49117 Conductor or circuit manufacturing
• CPC Class Codes: Y10T 29/49155 Manufacturing circuit on or in base
• CPC Class Codes: Y10T 29/49156 with selective destruction of conductive paths

Abstract

An electrochemical biosensor with electrode elements that possess smooth, high-quality edges. These smooth edges define gaps between electrodes, electrode traces and contact pads. Due to the remarkable edge smoothness achieved with the present invention, the gaps can be quite small, which provides marked advantages in terms of test accuracy, speed and the number of different functionalities that can be packed into a single biosensor. Further, the present invention provides a novel biosensor production method in which entire electrode patterns for the inventive biosensors can be formed all at one, in nanoseconds—without regard to the complexity of the electrode patterns or the amount of conductive material that must be ablated to form them.

Claims

1. A biosensor, comprising:

a base substrate having first and second electrode elements formed thereon;

the first and second electrode elements having first and second respective edges defining a gap therebetween, the gap having a width and a length;

the first edge being spaced from a first theoretical line by a first distance that varies along the length of the gap, the first theoretical line defining a desired shape and placement of the first edge, wherein the standard deviation of the first distance is less than about 6 μ

m over the entire length of the gap;

a reagent at least partially covering the base substrate; and

one or more layers overlying and adhered to the base substrate, the one or more layers cooperating to form a sample-receiving chamber and a cover for the biosensor, at least a portion of the reagent and an electrode being positioned in the chamber.

2. The biosensor of claim 1, wherein the standard deviation of the first distance is less than about 2 μ

m.

3. The biosensor of claim 1, wherein the standard deviation of the first distance is less than about 1 μ

m.

4. The biosensor of claim 1, wherein the second edge is spaced from a second theoretical line by a second distance that varies along the length of the gap, the second theoretical line defining a desired shape and placement of the second edge, wherein the standard deviation of the second distance is less than about 6 μ

m over the entire length of the gap.

5. The biosensor of claim 4, wherein the standard deviation of both the first distance and the second distance is less than about 2 μ

m.

6. The biosensor of claim 4, wherein the standard deviation of both the first distance and the second distance is less than about 1 μ

m.

7. The biosensor of claim 1, wherein the gap width is about 250 μ

m or less.

8. The biosensor of claim 1, wherein the gap width is less than about 50 μ

m.

9. The biosensor of claim 1, wherein the gap width is less than about 20 μ

m.

10. The biosensor of claim 1, wherein the electrode elements are formed by broad field laser ablation.

11. The biosensor of claim 1, wherein the first and second electrode elements comprise a first electrode set, one of the electrodes of the set being the electrode positioned in the sample receiving chamber.

12. The biosensor of claim 11, further comprising a second electrode set formed on the base substrate, the second electrode set having a different feature size than the first electrode set.

13. The biosensor of claim 1, wherein the first and second electrode elements comprise first and second electrode traces.

14. The biosensor of claim 1, wherein the first and second electrode elements comprise first and second contact pads.

15. The biosensor of claim 1, wherein the length of the gap is at least 0.1 mm.

16. The biosensor of claim 1, wherein the length of the gap is at least 1 mm.

17. The biosensor of claim 1, wherein the length of the gap is at least 1 cm.

18. The biosensor of claim 1, wherein the length of the gap is at least one third the length of the biosensor.

19. The biosensor of claim 1, wherein the length of the gap is at least one half the length of the biosensor.

20. The biosensor of claim 1, wherein the gap is positioned within the sample receiving chamber.

21. The biosensor of claim 1, wherein the electrode elements comprise contact pads and the gap extends between the contact pads.

22. The biosensor of claim 1, wherein the electrode elements comprise electrode traces and the gap extends between the electrode traces.

23. The biosensor of claim 1, wherein the electrode elements comprise a working electrode and a counter electrode and the gap extends between the working electrode and the counter electrode.

24. The biosensor of claim 23, wherein the gap extends across the sample receiving chamber.

25. A biosensor, comprising:

a base substrate having first and second electrode elements formed thereon;

the first and second electrode elements having first and second respective edges defining a gap therebetween, the gap having a width and a length;

the first edge being spaced from a first theoretical line by a first distance that varies along the length of the gap, the first theoretical line defining a desired shape and placement of the first edge, wherein the first distance is less than about 6 μ

m over the entire length of the gap;

a reagent at least partially covering the base substrate; and

one or more layers overlying and adhered to the base substrate, the one or more layers cooperating to form a sample-receiving chamber and a cover for the biosensor, at least a portion of the reagent layer and an electrode being positioned in the chamber.

26. The biosensor of claim 25, wherein the first distance is less than about 2 μ

m.

27. The biosensor of claim 25, wherein the first distance is less than about 1 μ

m.

28. The biosensor of claim 25, wherein the second edge is spaced from a second theoretical line by a second distance that varies along the length of the gap, the second theoretical line defining a desired shape and placement of the second edge, wherein the second distance is less than about 6 μ

m over the entire length of the gap.

29. The biosensor of claim 28, wherein the first distance and the second distance are both less than about 4 μ

m.

30. The biosensor of claim 28, wherein the first distance and the second distance are both less than about 2 μ

m.

31. The biosensor of claim 25, wherein the electrode elements are formed by broad field laser ablation.

32. The biosensor of claim 25, wherein the first and second electrode elements comprise an electrode set, one of the electrodes of the set being the electrode positioned in the sample receiving chamber.

33. The biosensor of claim 32, further comprising a second electrode set formed on the base substrate, the second electrode set having a different feature size than the first electrode set.

34. The biosensor of claim 25, wherein the first and second electrode elements comprise first and second electrode traces.

35. The biosensor of claim 25, wherein the first and second electrode elements comprise first and second contact pads.

36. A method of making a biosensor comprising the following steps:

providing a base substrate having a layer of electrically conductive material thereon;

removing a portion of the conductive material to form first and second electrode elements on the base substrate having first and second respective edges defining a gap therebetween, the gap having a width and a length;

the first edge being spaced from a first theoretical line by a first distance that varies along the length of the gap, the first theoretical line defining a desired shape and placement of the first edge, wherein the standard deviation of the first distance is less than about 6 μ

m over the entire length of the gap;

providing a reagent at least partially covering the base; and

adhering one or more layers to the base, the one or more layers cooperating to form a sample-receiving chamber and a cover for the biosensor, at least a portion of the reagent and an electrode being positioned within the chamber.

37. The method of claim 36, further comprising removing at least 10% of the conductive material.

38. The method of claim 36, further comprising removing at least 50% of the conductive material.

39. The method of claim 36, further comprising removing at least 90% of the conductive material.

40. The method of claim 36, wherein the electrically conductive material is removed by broad field laser ablation.

41. The method of claim 36, wherein the first and second electrode elements comprise a first electrode set.

42. The method of claim 41, further comprising forming a second electrode set on the base substrate having a feature size different from the first electrode set, one of the electrodes of the first electrode set being the electrode positioned within the sample receiving chamber and one of the electrodes of the second electrode set being positioned in the sample receiving chamber.

43. The method of claim 36, wherein the standard deviation is less than about 2 μ

m.

44. The method of claim 36, wherein the standard deviation is less than about 1 μ

m.

45. The method of claim 36, further comprising forming the electrode elements in less than about 0.25 seconds.

46. The method of claim 36, further comprising forming the electrode elements in less than about 50 nanoseconds.

47. The method of claim 36, further comprising forming the electrode elements in less than about 25 nanoseconds.

48. The method of claim 36, wherein the step of adhering the one or more layers to the base comprises laminating a spacing layer having a void that defines the perimeter of the sample receiving chamber over the base substrate and laminating a covering layer over the spacing layer.

49. The method of claim 48, further comprising forming a vent opening in the covering layer that communicates with the sample receiving chamber.

50. A method of forming a biosensor used to measure presence or concentration of an analyte in a fluid sample, comprising:

(a) providing an electrically conductive material on a base;

(b) removing a portion of the electrically conductive material by broad field laser ablation to form an electrode set on the base;

(c) providing a reagent at least partially covering the base; and

(d) adhering one or more layers to the base, the one or more layers cooperating to form a sample-receiving chamber and a cover for the biosensor, at least a portion of both the reagent layer and the electrode set being positioned in the chamber.

51. The method of claim 50, wherein the electrode set comprises first and second electrodes having first and second respective edges defining a gap therebetween, the gap having a width and a length, the first edge being spaced from a first theoretical line by a first distance that varies along the length of the gap, the first theoretical line defining a desired shape and placement of the first edge, wherein the standard deviation of the first distance is less than about 6 μ

m over the entire length of the gap.

52. The method of claim 51, wherein the standard deviation of the first distance is less than about 2 μ

m.

53. The method of claim 51, wherein the standard deviation of the first distance is less than about 1 μ

m.

54. The method of claim 51, wherein the electrode set comprises at least two electrode sets having different feature sizes.

55. The method of claim 50, wherein the electrode set comprises at least two electrode sets having different feature sizes.

56. The method of claim 50, wherein step (c) comprises at least partially covering the electrode set with the reagent.

57. The method of claim 50, further comprising removing at least 10% of the conductive material.

58. The method of claim 50, further comprising removing at least 50% of the conductive material.

59. The method of claim 50, further comprising removing at least 90% of the conductive material.

60. A method of forming a biosensor used to measure concentration of an analyte in a fluid sample, comprising:

(a) providing an electrically conductive material on a base;

(b) removing at least 10% of the electrically conductive material to form at least two electrode sets on the base, the electrode sets having different feature sizes;

(c) providing a reagent at least partially covering the base; and

(d) adhering one or more layers to the base, the one or more layers cooperating to form a sample-receiving chamber, at least a portion of one of the electrode sets being positioned in the chamber.

61. The method of claim 60, further comprising removing at least 50% of the conductive material.

62. The method of claim 60, further comprising removing at least 90% of the conductive material.

63. The method of claim 60, wherein the electrically conductive material is removed by broad field laser ablation.

64. The method of claim 60, wherein one of the electrode sets comprises first and second electrodes having first and second respective edges defining a gap therebetween, the gap having a width and a length, the first edge being spaced from a first theoretical line by a first distance that varies along the length of the gap, the first theoretical line defining a desired shape and placement of the first edge, wherein the standard deviation of the first distance is less than about 6 μ

m over the entire length of the gap.

65. The method of claim 64, wherein the standard deviation of the first distance is less than about 2 μ

m.

66. The method of claim 64, wherein the standard deviation of the first distance is less than about 1 μ

m.

67. The method of claim 60, wherein step (c) comprises at least partially covering the electrode set with the reagent.

68. A method of manufacturing a plurality of biosensors, comprising:

(a) providing a web of base substrate material having a metal conductive layer formed thereon;

(b) projecting an image of an electrode pattern onto the metal conductive layer with a laser apparatus, wherein an electrode pattern that corresponds to the image is formed by laser ablation on the web of base substrate material;

(c) moving one of the laser apparatus and the web of base substrate material and repeating step (b) a plurality of times to produce a plurality of the electrode patterns at spaced intervals along the web of base substrate material;

(d) depositing a reagent on the web of base substrate material and at least partially covering each electrode pattern of the plurality of electrode patterns with the reagent;

(e) laminating at least one web of a covering layer or a spacing layer over the web of base substrate material, thereby forming a cover and a sample-receiving chamber for each biosensor; and

(f) cutting through the at least one web of a covering layer or a spacing layer and the web of base substrate material to form the plurality of biosensors.

69. The method of claim 68, wherein the electrode pattern formed in step (b) comprises a complete electrode pattern for one of the biosensors, whereby the complete electrode pattern for each biosensor is formed in a single step.

70. The method of claim 68, wherein the electrode pattern formed in step (b) comprises a partial electrode pattern, the image comprises a plurality of the same or different images, and steps (b) and (c) are repeated until the plurality of electrode patterns comprises a plurality of complete electrode patterns, whereby each complete electrode pattern is formed in multiple steps.

71. The method of claim 68, wherein step (c) comprises continuously moving the web of base substrate material.

72. The method of claim 68, wherein step (c) comprises moving the web of base substrate material in discrete increments.

73. The method of claim 68, wherein step (c) comprises moving the web of base substrate material at a rate of at least 10 meters per minute.

74. The method of claim 68, wherein the electrode pattern includes at least two electrode sets having different feature sizes.

75. The method of claim 68, wherein the electrode pattern comprises first and second electrodes having first and second respective edges defining a gap therebetween, the gap having a width and a length, the first edge being spaced from a first theoretical line by a first distance that varies along the length of the gap, the first theoretical line defining a desired shape and placement of the first edge, wherein the standard deviation of the first distance is less than about 6 μ

m over the entire length of the gap.

76. The method of claim 75, wherein the standard deviation is less than about 2 μ

m.

77. The method of claim 75, wherein the standard deviation is less than about 1 μ

m.

78. The method of claim 68, wherein the metal conductive layer comprises at least one member selected form the group consisting of gold, platinum, palladium and iridium.

79. The method of claim 68, wherein step (e) comprises:

laminating the spacing layer over the base substrate material, the spacing layer having a void that defines the perimeter of the chamber; and

laminating the covering layer over the spacing layer.

80. The method of claim 68, wherein each electrode pattern formed in step (b) is formed in less than 1 second.

81. The method of claim 68, wherein each electrode pattern formed in step (b) is formed in less than 0.25 second.

82. The method of claim 68, wherein each electrode pattern formed in step (b) is formed all at once.

83. The method of claim 68, wherein each electrode pattern formed in step (b) comprises the entire electrode pattern for one of the biosensors and each entire electrode pattern is formed all at once.

84. The method of claim 68, wherein the reagent is applied in a substantially continuous stripe.

85. The method of claim 68, wherein the electrode pattern is anisotropic.

86. The method of claim 68, wherein the electrode pattern is asymmetric.

87. The method of claim 68, wherein the electrode pattern formed in step (b) comprises a complete electrode pattern for one of the biosensors, whereby the complete electrode pattern for each biosensor is formed in a single step, the method further comprising forming the complete electrical patterns at a rate of at least 100 per minute.

88. The method of claim 87, wherein forming the electrode patterns comprises removing at least 20% of the metal conductive layer.

89. The method of claim 87, wherein forming the electrode patterns comprises removing at least 50% of the metal conductive layer.

90. The method of claim 87, wherein forming the electrode patterns comprises removing at least 90% of the metal conductive layer.

91. The method of claim 68, wherein the electrode pattern formed in step (b) comprises a complete electrode pattern for one of the biosensors, whereby the complete electrode pattern for each biosensor is formed in a single step, the method further comprising forming the complete electrical patterns at a rate of at least 1000 per minute.

92. The method of claim 91, wherein forming the electrode patterns comprises removing at least 20% of the metal conductive layer.

93. The method of claim 91, wherein forming the electrode patterns comprises removing at least 50% of the metal conductive layer.

94. The method of claim 91, wherein forming the electrode patterns comprises removing at least 90% of the metal conductive layer.

95. The method of claim 68, wherein the electrode pattern formed in step (b) comprises a complete electrode pattern for one of the biosensors, whereby the complete electrode pattern for each biosensor is formed in a single step, the method further comprising forming the complete electrical patterns at a rate of at least 2000 per minute.

96. The method of claim 95, wherein forming the electrode patterns comprises removing at least 20% of the metal conductive layer.

97. The method of claim 95, wherein forming the electrode patterns comprises removing at least 50% of the metal conductive layer.

98. The method of claim 95, wherein forming the electrode patterns comprises removing at least 90% of the metal conductive layer.

99. The method of claim 68, wherein the electrode pattern formed in step (b) comprises a complete electrode pattern for one of the biosensors, whereby the complete electrode pattern for each biosensor is formed in a single step, the method further comprising forming the complete electrical patterns at a rate of at least 3000 per minute.

100. The method of claim 99, wherein forming the electrode patterns comprises removing at least 20% of the metal conductive layer.

101. The method of claim 99, wherein forming the electrode patterns comprises removing at least 50% of the metal conductive layer.

102. The method of claim 99, wherein forming the electrode patterns comprises removing at least 90% of the metal conductive layer.