Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberUSRE43399 E1
Publication typeGrant
Application numberUS 12/139,305
Publication dateMay 22, 2012
Filing dateJun 13, 2008
Priority dateJul 25, 2003
Fee statusPaid
Also published asEP1649260A2, EP1649260A4, US7074307, US20050115832, US20120228134, US20140001042, WO2005012873A2, WO2005012873A3
Publication number12139305, 139305, US RE43399 E1, US RE43399E1, US-E1-RE43399, USRE43399 E1, USRE43399E1
InventorsPeter C. Simpson, James R. Petisce, Victoria E. Carr-Brendel, James H. Brauker
Original AssigneeDexcom, Inc.
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Electrode systems for electrochemical sensors
US RE43399 E1
Abstract
The present invention relates generally to systems and methods for improved electrochemical measurement of analytes. The preferred embodiments employ electrode systems including an analyte-measuring electrode for measuring the analyte or the product of an enzyme reaction with the analyte and an auxiliary electrode configured to generate oxygen and/or reduce electrochemical interferants. Oxygen generation by the auxiliary electrode advantageously improves oxygen availability to the enzyme and/or counter electrode; thereby enabling the electrochemical sensors of the preferred embodiments to function even during ischemic conditions. Interferant modification by the auxiliary electrode advantageously renders them substantially non-reactive at the analyte-measuring electrode, thereby reducing or eliminating inaccuracies in the analyte signal due to electrochemical interferants.
Images(5)
Previous page
Next page
Claims(152)
1. An electrochemical sensor for determining a presence or a concentration of an analyte in a fluid, the sensor comprising:
a membrane system comprising an enzyme, wherein the enzyme reacts with the analyte;
an electroactive surface comprising a working electrode, the working electrode comprising a conductive material and configured to measure a product of the reaction of the enzyme with the analyte; and
an auxiliary electrode comprising a conductive material and configured to generate oxygen, wherein the auxiliary electrode is situated such that the oxygen generated diffuses to the enzyme or to the electroactive surface, wherein the auxiliary electrode comprises a polymer, wherein the polymer is situated on a surface of the auxiliary electrode, and wherein the polymer comprises a material that is directly impermeable to glucose but is permeable to oxygen.
2. The electrochemical sensor of claim 1, wherein the auxiliary electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.
3. The electrochemical sensor of claim 1, wherein the auxiliary electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.
4. The electrochemical sensor of claim 1, wherein the polymer comprises a material that is permeable to interfering species.
5. The electrochemical sensor of claim 4, wherein the polymer comprises a material having a molecular weight that allows transport therethrough of oxygen, urate, ascorbate, and acetaminophen.
6. The electrochemical sensor of claim 1, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.
7. The electrochemical sensor of claim 1, wherein the auxiliary electrode is configured to electrochemically modify an electrochemical interferant interferent to render the electrochemical interferent substantially electrochemically non-reactive at the working electrode.
8. The electrochemical sensor of claim 7, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.1 V.
9. The electrochemical sensor of claim 1, configured for measuring a concentration of glucose in a fluid.
10. The electrochemical sensor of claim 1, configured for insertion into a subcutaneous tissue of a host.
11. The electrochemical sensor of claim 1, configured for implantation into a subcutaneous tissue of a host.
12. The electrochemical sensor of claim 1, configured for measuring a concentration of glucose substantially without an oxygen deficit.
13. An electrochemical sensor for determining a presence or a concentration of an analyte in a fluid, the sensor comprising:
a membrane system comprising an enzyme, wherein the enzyme reacts with the analyte;
an electroactive surface comprising a working electrode, the working electrode comprising a conductive material and configured to measure a product of the reaction of the enzyme with the analyte; and
an auxiliary electrode comprising a conductive material and configured to generate oxygen, wherein the auxiliary electrode is situated such that the oxygen generated diffuses to the enzyme or to the electroactive surface, wherein the auxiliary electrode comprises a polymer, wherein the polymer is directly situated on a surface of the auxiliary electrode, and wherein the polymer comprises a material that is impermeable to glucose but is permeable to oxygen and permeable to interfering species.
14. The electrochemical sensor of claim 13, wherein the polymer comprises a material having a molecular weight that blocks glucose and allows transport therethrough of oxygen, urate, ascorbate, and acetaminophen.
15. The electrochemical sensor of claim 13, wherein the auxiliary electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.
16. The electrochemical sensor of claim 13, wherein the auxiliary electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.
17. The electrochemical sensor of claim 13, wherein the polymer comprises a material having a molecular weight that allows transport therethrough of urate, ascorbate, and acetaminophen.
18. The electrochemical sensor of claim 13, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.
19. The electrochemical sensor of claim 13, wherein the auxiliary electrode is configured to electrochemically modify an electrochemical interferant interferent to render the electrochemical interferent substantially electrochemically non-reactive at the working electrode.
20. The electrochemical sensor of claim 19, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.1 V.
21. The electrochemical sensor of claim 13, configured for measuring a concentration of glucose in a fluid.
22. The electrochemical sensor of claim 13, configured for insertion into a subcutaneous tissue of a host.
23. The electrochemical sensor of claim 13, configured for implantation into a subcutaneous tissue of a host.
24. The electrochemical sensor of claim 13, configured for measuring a concentration of glucose substantially without an oxygen deficit.
25. An electrochemical sensor for determining a presence or a concentration of an analyte in a fluid, the sensor comprising:
a membrane system comprising an enzyme, wherein the enzyme reacts with the analyte;
an electroactive surface comprising a working electrode, the working electrode comprising a conductive material and configured to measure a product of the reaction of the enzyme with the analyte; and
an auxiliary electrode comprising a conductive material and configured to modify an electrochemical interferant interferent such that the electrochemical interferent is rendered substantially electrochemically non-reactive at the working electrode, wherein the auxiliary electrode comprises a polymer, wherein the polymer is situated on a surface of the auxiliary electrode, and wherein the polymer comprises a material that is impermeable to glucose but is permeable to oxygen.
26. The electrochemical sensor of claim 25, wherein the auxiliary electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.
27. The electrochemical sensor of claim 25, wherein the auxiliary electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.
28. The electrochemical sensor of claim 25, wherein the polymer comprises a material that is permeable to an electrochemical interferant interferent.
29. The electrochemical sensor of claim 25, wherein the polymer comprises a material that is impermeable to glucose but is permeable to oxygen and interferants interferents.
30. The electrochemical sensor of claim 25, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.1V.
31. The electrochemical sensor of claim 25, wherein the auxiliary electrode is configured to generate oxygen.
32. The electrochemical sensor of claim 31, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.
33. The electrochemical sensor of claim 25, configured for measuring a concentration of glucose in a fluid.
34. The electrochemical sensor of claim 25, configured for insertion into a subcutaneous tissue of a host.
35. The electrochemical sensor of claim 25, configured for implantation into a subcutaneous tissue of a host.
36. The electrochemical sensor of claim 25, configured for measuring a concentration of glucose substantially without an oxygen deficit.
37. The electrochemical sensor of claim 25, wherein the auxiliary electrode is configured to generate oxygen.
38. The electrochemical sensor of claim 37, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.
39. An electrochemical sensor for determining a presence or a concentration of an analyte in a fluid, the sensor comprising:
a membrane system comprising an enzyme, wherein the enzyme reacts with the analyte;
an electroactive surface comprising a working electrode, the working electrode comprising a conductive material and configured to measure a product of the reaction of the enzyme with the analyte; and
an auxiliary electrode comprising a conductive material and configured to modify an electrochemical interferant interferent such that the electrochemical interferent is rendered substantially electrochemically non-reactive at the working electrode, wherein the auxiliary electrode comprises a polymer, wherein the polymer is situated on a surface of the auxiliary electrode, and wherein the polymer comprises a material having a molecular weight that blocks glucose and allows transport therethrough of oxygen, urate, ascorbate, and acetaminophen.
40. The electrochemical sensor of claim 39, wherein the auxiliary electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.
41. The electrochemical sensor of claim 39, wherein the auxiliary electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.
42. The electrochemical sensor of claim 39, wherein the polymer comprises a material that is permeable to an electrochemical interferant interferent.
43. The electrochemical sensor of claim 39, wherein the polymer comprises a material that is permeable to interferants interferents.
44. The electrochemical sensor of claim 39, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.1V.
45. The electrochemical sensor of claim 39, wherein the auxiliary electrode is configured to generate oxygen.
46. The electrochemical sensor of claim 45, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.
47. The electrochemical sensor of claim 39, configured for measuring a concentration of glucose in a fluid.
48. The electrochemical sensor of claim 39, configured for insertion into a subcutaneous tissue of a host.
49. The electrochemical sensor of claim 39, configured for implantation into a subcutaneous tissue of a host.
50. The electrochemical sensor of claim 39, configured for measuring a concentration of glucose substantially without an oxygen deficit.
51. An electrochemical sensor for measuring a concentration of an analyte in a biological fluid, the sensor comprising:
a membrane system comprising an enzyme configured to react with the analyte;
an electroactive surface comprising a working electrode, the working electrode comprising a conductive material and configured to measure a product of the reaction of the enzyme with the analyte; and
an auxiliary electrode comprising a conductive material and configured to generate oxygen, wherein the auxiliary electrode is situated such that the oxygen generated diffuses to the enzyme or to the electroactive surface, wherein the auxiliary electrode comprises a polymer, wherein the polymer is situated on a surface of the auxiliary electrode, and wherein the polymer comprises a material that is permeable or impermeable to glucose but is permeable to oxygen, and wherein the sensor is configured such that the auxiliary electrode is located between the electroactive surface of the working electrode and the biological fluid being measured.
52. The electrochemical sensor of claim 51, wherein the auxiliary electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.
53. The electrochemical sensor of claim 51, wherein the auxiliary electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.
54. The electrochemical sensor of claim 51, wherein the polymer comprises a material having a molecular weight that allows transport therethrough of oxygen, urate, ascorbate, and acetaminophen.
55. The electrochemical sensor of claim 51, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.
56. The electrochemical sensor of claim 51, wherein the auxiliary electrode is configured to electrochemically modify an electrochemical interferent to render the electrochemical interferent substantially electrochemically non-reactive at the working electrode.
57. The electrochemical sensor of claim 56, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.1 V.
58. The electrochemical sensor of claim 51, configured for measuring a concentration of glucose in a fluid.
59. The electrochemical sensor of claim 51, configured for measuring a concentration of glucose substantially without an oxygen deficit.
60. An electrochemical sensor for measuring a concentration of an analyte in a biological fluid, the sensor comprising:
a membrane system comprising an enzyme configured to react with the analyte;
an electroactive surface comprising a working electrode, the working electrode comprising a conductive material and configured to measure a product of the reaction of the enzyme with the analyte; and
an auxiliary electrode comprising a conductive material and configured to generate oxygen, wherein the auxiliary electrode is situated at a location directly between the electroactive surface and the biological fluid being measured such that the oxygen generated diffuses to the enzyme or to the electroactive surface, wherein the auxiliary electrode comprises a polymer, wherein the polymer is directly situated on a surface of the auxiliary electrode, and wherein the polymer comprises a material that is permeable or impermeable to glucose but is permeable to oxygen and permeable to one or more interfering species.
61. The electrochemical sensor of claim 60, wherein the polymer comprises a material having a molecular weight that blocks glucose and allows transport therethrough of oxygen, urate, ascorbate, and acetaminophen.
62. The electrochemical sensor of claim 60, wherein the auxiliary electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.
63. The electrochemical sensor of claim 60, wherein the auxiliary electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.
64. The electrochemical sensor of claim 60, wherein the polymer comprises a material having a molecular weight that allows transport therethrough of urate, ascorbate, and acetaminophen.
65. The electrochemical sensor of claim 60, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.
66. The electrochemical sensor of claim 60, wherein the auxiliary electrode is configured to electrochemically modify an electrochemical interferent to render the electrochemical interferent substantially electrochemically non-reactive at the working electrode.
67. The electrochemical sensor of claim 66, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.1 V.
68. The electrochemical sensor of claim 60, configured for measuring a concentration of glucose in a fluid.
69. The electrochemical sensor of claim 60, configured for insertion into a subcutaneous tissue of a host.
70. The electrochemical sensor of claim 60, configured for implantation into a subcutaneous tissue of a host.
71. The electrochemical sensor of claim 60, configured for measuring a concentration of glucose substantially without an oxygen deficit.
72. An electrochemical sensor for determining a presence or a concentration of an analyte in a fluid, the sensor comprising:
a membrane system comprising an enzyme configured to react with the analyte;
an electroactive surface comprising a working electrode, the working electrode comprising a conductive material and configured to measure a product of the reaction of the enzyme with the analyte; and
an auxiliary electrode comprising a conductive material and configured to modify an electrochemical interferent such that the electrochemical interferent is rendered substantially electrochemically non-reactive at the working electrode, wherein the auxiliary electrode comprises a polymer, wherein the polymer is situated on a surface of the auxiliary electrode such that at least a portion of the polymer is located more distal to the electroactive surface than the auxiliary electrode, and wherein the polymer comprises a material that is permeable or impermeable to glucose but is permeable to oxygen.
73. The electrochemical sensor of claim 72, wherein the auxiliary electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.
74. The electrochemical sensor of claim 72, wherein the auxiliary electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.
75. The electrochemical sensor of claim 72, wherein the polymer comprises a material that is permeable to an electrochemical interferent.
76. The electrochemical sensor of claim 72, wherein the polymer comprises a material that is impermeable to glucose but is permeable to oxygen and interferents.
77. The electrochemical sensor of claim 72, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.1 V.
78. The electrochemical sensor of claim 72, wherein the auxiliary electrode is configured to generate oxygen.
79. The electrochemical sensor of claim 78, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.
80. The electrochemical sensor of claim 72, configured for measuring a concentration of glucose in a fluid.
81. The electrochemical sensor of claim 72, configured for insertion into a subcutaneous tissue of a host.
82. The electrochemical sensor of claim 72, configured for implantation into a subcutaneous tissue of a host.
83. The electrochemical sensor of claim 72, configured for measuring a concentration of glucose substantially without an oxygen deficit.
84. The electrochemical sensor of claim 72, wherein the auxiliary electrode is configured to generate oxygen.
85. The electrochemical sensor of claim 84, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.
86. An electrochemical sensor for determining a presence or a concentration of an analyte in a fluid, the sensor comprising:
a membrane system comprising an enzyme configured to react with the analyte;
an electroactive surface comprising a working electrode, the working electrode comprising a conductive material and configured to measure a product of the reaction of the enzyme with the analyte; and
an auxiliary electrode comprising a conductive material and configured to modify an electrochemical interferent such that the electrochemical interferent is rendered substantially electrochemically non-reactive at the working electrode, wherein the auxiliary electrode located within or adjacent to a membrane system such that at least a portion of the membrane system is located more distal to the electroactive surface than the auxiliary electrode, and wherein the membrane system comprises a polymer comprising a material having a molecular weight that allows transport therethrough of oxygen, urate, ascorbate, and acetaminophen.
87. The electrochemical sensor of claim 86, wherein the auxiliary electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.
88. The electrochemical sensor of claim 86, wherein the auxiliary electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.
89. The electrochemical sensor of claim 86, wherein the polymer comprises a material that is permeable to an electrochemical interferent.
90. The electrochemical sensor of claim 86, wherein the polymer comprises a material that is permeable to interferents.
91. The electrochemical sensor of claim 86, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.1 V.
92. The electrochemical sensor of claim 86, wherein the auxiliary electrode is configured to generate oxygen.
93. The electrochemical sensor of claim 92, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.
94. The electrochemical sensor of claim 86, configured for measuring a concentration of glucose in a fluid.
95. The electrochemical sensor of claim 86, configured for insertion into a subcutaneous tissue of a host.
96. The electrochemical sensor of claim 86, configured for implantation into a subcutaneous tissue of a host.
97. The electrochemical sensor of claim 86, configured for measuring a concentration of glucose substantially without an oxygen deficit.
98. An electrochemical sensor for measuring a concentration of an analyte in a biological fluid in a host, the sensor comprising:
a membrane system comprising: a cell impermeable domain configured to contact a biological fluid in a host and an enzyme domain comprising enzyme, wherein the enzyme reacts with the analyte;
a working electrode comprising a conductive material and configured to measure a product of the reaction of the enzyme with the analyte; and
an auxiliary electrode located within or adjacent to the membrane system and comprising a conductive material and configured to modify an electrochemical interferent such that the electrochemical interferent is rendered substantially electrochemically non-reactive at the working electrode.
99. The sensor of claim 98, configured for measuring a concentration of glucose in a host.
100. The sensor of claim 98, configured for insertion into contact with a subcutaneous tissue of a host.
101. The sensor of claim 98, configured for communication with the intravascular system of a host.
102. The sensor of claim 98, configured for continuous measurement of the analyte in a host.
103. The sensor of claim 98, further comprising a potentiostat operably connected to the working electrode.
104. The sensor of claim 103, wherein the potentiostat enables continuous measurement of the analyte in a host.
105. The sensor of claim 98, further comprising sensor electronics operably connected to the working electrode, wherein the sensor electronics are configured to transmit data to a receiver.
106. The sensor of claim 105, wherein the sensor electronics comprise an RF transceiver configured to wirelessly transmit the data to a receiver.
107. The sensor of claim 98, wherein the membrane system is configured to limit diffusion of the analyte there through.
108. The sensor of claim 107, wherein the membrane system further comprises a resistance domain configured to limit diffusion of the analyte there through.
109. The sensor of claim 98, wherein the membrane system is configured to limit or block one or more interfering species there through.
110. The sensor of claim 109, wherein the membrane system further comprises an interference domain configured to limit or block the one or more interfering species there through.
111. The sensor of claim 109, wherein the membrane system further comprises an electrolyte domain configured to provide the hydrophilicity at the working electrode.
112. The sensor of claim 98, wherein the membrane system is configured to provide a hydrophilicity at the working electrode.
113. The sensor of claim 98, wherein the cell impermeable domain is located more distal from the working electrode than any other domain of the membrane system such that the cell impermeable domain directly contacts the host when placed into contact with the host's dermis, subcutaneous tissue and/or intravascular system.
114. The sensor of claim 98, wherein the auxiliary electrode is located within the cell impermeable domain.
115. The sensor of claim 98, wherein the auxiliary electrode is located between the cell impermeable domain and the enzyme domain.
116. An electrochemical sensor for continuous measurement of a concentration of an analyte in an in vivo biological environment, the sensor comprising:
a membrane comprising an outermost layer configured for protection of the sensor from the biological environment, wherein the membrane further comprises an enzyme configured to react with the analyte;
a working electrode comprising a conductive material and configured to measure a product of the reaction of the enzyme with the analyte; and
an auxiliary electrode located within or adjacent to the membrane and comprising a conductive material, wherein the auxiliary electrode is configured to modify an electrochemical interferent such that the electrochemical interferent is rendered substantially electrochemically non-reactive at the working electrode.
117. The sensor of claim 116, configured for measuring a concentration of glucose in a host.
118. The sensor of claim 116, configured for insertion into contact with a subcutaneous tissue of a host.
119. The sensor of claim 116, configured for communication with the intravascular system of a host.
120. The sensor of claim 116, further comprising a potentiostat operably connected to the working electrode.
121. The sensor of claim 120, wherein the potentiostat enables continuous measurement of the analyte in a host.
122. The sensor of claim 116, further comprising sensor electronics operably connected to the working electrode, wherein the sensor electronics are configured to transmit data to a receiver.
123. The sensor of claim 122, wherein the sensor electronics comprise an RF transceiver configured to wirelessly transmit the data to a receiver.
124. The sensor of claim 116, wherein the membrane is configured to limit diffusion of the analyte there through.
125. The sensor of claim 124, wherein the membrane further comprises a resistance domain configured to limit diffusion of the analyte there through.
126. The sensor of claim 116, wherein the membrane is configured to limit or block one or more interfering species there through.
127. The sensor of claim 126, wherein the membrane further comprises an interference domain configured to limit or block the one or more interfering species there through.
128. The sensor of claim 116, wherein the membrane is configured to provide a hydrophilicity at the working electrode.
129. The sensor of claim 128, wherein the membrane further comprises an electrolyte domain configured to provide the hydrophilicity at the working electrode.
130. The sensor of claim 116, wherein the cell impermeable domain is located more distal from the working electrode than any other domain of the membrane such that the cell impermeable domain directly contacts the host when placed into contact with the host's dermis, subcutaneous tissue and/or intravascular system.
131. The sensor of claim 116, wherein the auxiliary electrode is located within the outermost layer.
132. The sensor of claim 116, wherein the auxiliary electrode is located between the outermost layer and the enzyme.
133. An electrochemical sensor for measuring a concentration of an analyte in a biological fluid, the sensor comprising:
a membrane system comprising an enzyme configured to react with an analyte;
an electroactive surface comprising a working electrode, the working electrode comprising a conductive material and configured to measure a product of a reaction of the enzyme with the analyte; and
an auxiliary electrode comprising a conductive material and configured to generate oxygen, wherein the auxiliary electrode is situated such that the oxygen generated diffuses to the enzyme or to the electroactive surface, wherein the auxiliary electrode comprises a polymer, wherein the polymer is situated on a surface of the auxiliary electrode, wherein the polymer comprises a material that is permeable or impermeable to glucose but is permeable to oxygen, and wherein the sensor is configured such that the auxiliary electrode is located between the electroactive surface of the working electrode and a biological fluid in which a concentration of the analyte is being measured;
wherein the sensor is configured for insertion or implantation into a subcutaneous tissue of a host.
134. The electrochemical sensor of claim 133, wherein the auxiliary electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.
135. The electrochemical sensor of claim 133, wherein the auxiliary electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.
136. The electrochemical sensor of claim 133, wherein the polymer comprises a material that is permeable to interfering species.
137. The electrochemical sensor of claim 136, wherein the polymer comprises a material having a molecular weight that allows transport therethrough of oxygen, urate, ascorbate, and acetaminophen.
138. The electrochemical sensor of claim 133, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.
139. The electrochemical sensor of claim 133, wherein the auxiliary electrode is configured to electrochemically modify an electrochemical interferent to render the electrochemical interferent substantially electrochemically non-reactive at the working electrode.
140. The electrochemical sensor of claim 139, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.1 V.
141. The electrochemical sensor of claim 133, configured for measuring a concentration of glucose in a fluid.
142. The electrochemical sensor of claim 133, configured for measuring a concentration of glucose substantially without an oxygen deficit.
143. An electrochemical sensor for measuring a concentration of an analyte in a biological fluid, the sensor comprising:
a membrane system comprising an enzyme configured to react with an analyte;
an electroactive surface comprising a working electrode, the working electrode comprising a conductive material and configured to measure a product of a reaction of the enzyme with the analyte; and
an auxiliary electrode comprising a conductive material and configured to generate oxygen, wherein the auxiliary electrode is situated such that the oxygen generated diffuses to the enzyme or to the electroactive surface, wherein the auxiliary electrode comprises a polymer, wherein the polymer is situated on a surface of the auxiliary electrode, wherein the polymer comprises a material that is permeable or impermeable to glucose but is permeable to oxygen, wherein the polymer comprises a material that is permeable to interfering species, and wherein the sensor is configured such that the auxiliary electrode is located between the electroactive surface of the working electrode and a biological fluid in which a concentration of the analyte is being measured.
144. The electrochemical sensor of claim 143, wherein the auxiliary electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.
145. The electrochemical sensor of claim 143, wherein the auxiliary electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.
146. The electrochemical sensor of claim 143, wherein the polymer comprises a material that is permeable to interfering species.
147. The electrochemical sensor of claim 146, wherein the polymer comprises a material having a molecular weight that allows transport therethrough of oxygen, urate, ascorbate, and acetaminophen.
148. The electrochemical sensor of claim 143, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.
149. The electrochemical sensor of claim 143, wherein the auxiliary electrode is configured to electrochemically modify an electrochemical interferent to render the electrochemical interferent substantially electrochemically non-reactive at the working electrode.
150. The electrochemical sensor of claim 149, wherein the auxiliary electrode is configured to be set at a potential of at least about +0.1 V.
151. The electrochemical sensor of claim 143, configured for measuring a concentration of glucose in a fluid.
152. The electrochemical sensor of claim 143, configured for measuring a concentration of glucose substantially without an oxygen deficit.
Description
RELATED APPLICATION

This application claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 60/490,007, filed Jul. 25, 2003, the contents of which are hereby incorporated by reference in their entirety.

FIELD OF THE INVENTION

The present invention relates generally to systems and methods for improving electrochemical sensor performance.

BACKGROUND OF THE INVENTION

Electrochemical sensors are useful in chemistry and medicine to determine the presence or concentration of a biological analyte. Such sensors are useful, for example, to monitor glucose in diabetic patients and lactate during critical care events.

Diabetes mellitus is a disorder in which the pancreas cannot create sufficient insulin (Type I or insulin dependent) and/or in which insulin is not effective (Type 2 or non-insulin dependent). In the diabetic state, the victim suffers from high blood sugar, which causes an array of physiological derangements (kidney failure, skin ulcers, or bleeding into the vitreous of the eye) associated with the deterioration of small blood vessels. A hypoglycemic reaction (low blood sugar) is induced by an inadvertent overdose of insulin, or after a normal dose of insulin or glucose-lowering agent accompanied by extraordinary exercise or insufficient food intake.

Conventionally, a diabetic person carries a self-monitoring blood glucose (SMBG) monitor, which typically comprises uncomfortable finger pricking methods. Due to the lack of comfort and convenience, a diabetic will normally only measure his or her glucose level two to four times per day. Unfortunately, these time intervals are spread apart so far that the diabetic will likely find out too late, sometimes incurring dangerous side effects, of a hyperglycemic or hypoglycemic condition. It is not only unlikely that a diabetic will take a timely SMBG value, but additionally the diabetic will not know if their blood glucose value is going up (higher) or down (lower) based on conventional methods.

Consequently, a variety of transdermal and implantable electrochemical sensors are being developed for continuously detecting and/or quantifying blood glucose values. Many implantable glucose sensors suffer from complications within the body and provide only short-term or less-than-accurate working of blood glucose. Similarly, transdermal sensors have problems in accurately working and reporting back glucose values continuously over extended periods of time. Some efforts have been made to obtain blood glucose data from implantable devices and retrospectively determine blood glucose trends for analysis; however these efforts do not aid the diabetic in determining real-time blood glucose information. Some efforts have also been made to obtain blood glucose data from transdermal devices for prospective data analysis, however similar problems have occurred.

SUMMARY OF THE PREFERRED EMBODIMENTS

In contrast to the prior art, the sensors of preferred embodiments advantageously generate oxygen to allow the sensor to function at sufficient oxygen levels independent of the oxygen concentration in the surrounding environment. In another aspect of the preferred embodiments, systems and methods for modifying electrochemical interferants are provided.

Accordingly, in a first embodiment, an electrochemical sensor for determining a presence or a concentration of an analyte in a fluid is provided, the sensor comprising a membrane system comprising an enzyme, wherein the enzyme reacts with the analyte; an electroactive surface comprising a working electrode, the working electrode comprising a conductive material and configured to measure a product of the reaction of the enzyme with the analyte; and an auxiliary electrode comprising a conductive material and configured to generate oxygen, wherein the auxiliary electrode is situated such that the oxygen generated diffuses to the enzyme or to the electroactive surface.

In an aspect of the first embodiment, the auxiliary electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.

In an aspect of the first embodiment, the auxiliary electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.

In an aspect of the first embodiment, the auxiliary electrode comprises a polymer, wherein the polymer is situated on a surface of the auxiliary electrode.

In an aspect of the first embodiment, the polymer comprises a material that is impermeable to glucose but is permeable to oxygen.

In an aspect of the first embodiment, the polymer comprises a material that is impermeable to glucose but is permeable to oxygen and permeable to interfering species.

In an aspect of the first embodiment, the polymer comprises a material having a molecular weight that blocks glucose and allows transport therethrough of oxygen, urate, ascorbate, and acetaminophen.

In an aspect of the first embodiment, the polymer comprises a material that is permeable to glucose and oxygen.

In an aspect of the first embodiment, the polymer comprises a material that is permeable to glucose, oxygen, and interfering species.

In an aspect of the first embodiment, the polymer comprises a material having a molecular weight that allows transport therethrough of oxygen, glucose, urate, ascorbate, and acetaminophen.

In an aspect of the first embodiment, the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.

In an aspect of the first embodiment, the auxiliary electrode is configured to electrochemically modify an electrochemical interferant to render the electrochemical interferent substantially electrochemically non-reactive at the working electrode.

In an aspect of the first embodiment, the auxiliary electrode is configured to be set at a potential of at least about +0.1 V.

In a second embodiment, an electrochemical sensor for determining a presence or a concentration of an analyte in a fluid is provided, the sensor comprising a membrane system comprising an enzyme, wherein the enzyme reacts with the analyte; an electroactive surface comprising a working electrode, the working electrode comprising a conductive material and configured to measure a product of the reaction of the enzyme with the analyte; and an auxiliary electrode comprising a conductive material and configured to modify an electrochemical interferant such that the electrochemical interferent is rendered substantially electrochemically non-reactive at the working electrode.

In an aspect of the second embodiment, the auxiliary electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.

In an aspect of the second embodiment, the auxiliary electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.

In an aspect of the second embodiment, the auxiliary electrode comprises a polymer, wherein the polymer is situated on a surface of the auxiliary electrode.

In an aspect of the second embodiment, the polymer comprises a material that is permeable to an electrochemical interferant.

In an aspect of the second embodiment, the polymer comprises a material that is impermeable to glucose but is permeable to oxygen.

In an aspect of the second embodiment, the polymer comprises a material that is impermeable to glucose but is permeable to oxygen and interferants.

In an aspect of the second embodiment, the polymer comprises a material having a molecular weight that blocks glucose and allows transport therethrough of oxygen, urate, ascorbate, and acetaminophen.

In an aspect of the second embodiment, the polymer comprises a material that is permeable to glucose and oxygen.

In an aspect of the second embodiment, the polymer comprises a material that is permeable to glucose, oxygen, and interferants.

In an aspect of the second embodiment, the polymer comprises a material having a molecular weight that allows transport therethrough of oxygen, glucose, urate, ascorbate, and acetaminophen.

In an aspect of the second embodiment, the auxiliary electrode is configured to be set at a potential of at least about +0.1V.

In an aspect of the second embodiment, the auxiliary electrode is configured to generate oxygen.

In an aspect of the second embodiment, the auxiliary electrode is configured to be set at a potential of at least about +0.6 V.

In a third embodiment, an electrochemical sensor is provided comprising an electroactive surface configured to measure an analyte; and an auxiliary interferant-modifying electrode configured to modify an electrochemical interferant such that the electrochemical interferant is rendered substantially non-reactive at the electroactive surface.

In an aspect of the third embodiment, the auxiliary interferant-modifying electrode comprises a conductive material selected from the group consisting of a conductive metal, a conductive polymer, and a blend of a conductive metal and a conductive polymer.

In an aspect of the third embodiment, the auxiliary interferant-modifying electrode comprises a form selected from the group consisting of a mesh, a grid, and a plurality of spaced wires.

In an aspect of the third embodiment, the auxiliary interferant-modifying electrode comprises a polymer, wherein the polymer is situated on a surface of the auxiliary interferant-modifying electrode.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an exploded perspective view of one exemplary embodiment of a implantable glucose sensor.

FIG. 2 is a block diagram that illustrates sensor electronics in one exemplary embodiment.

FIG. 3 is a graph that shows a raw data stream obtained from a glucose sensor without an auxiliary electrode of the preferred embodiments.

FIG. 4 is a side schematic illustration of a portion of an electrochemical sensor of the preferred embodiments, showing an auxiliary electrode placed proximal to the enzyme domain within a membrane system.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The following description and examples illustrate some exemplary embodiments of the disclosed invention in detail. Those of skill in the art will recognize that there are numerous variations and modifications of this invention that are encompassed by its scope. Accordingly, the description of a certain exemplary embodiment should not be deemed to limit the scope of the present invention.

Definitions

In order to facilitate an understanding of the preferred embodiments, a number of terms are defined below.

The term “analyte” as used herein is a broad term and is used in its ordinary sense, including, without limitation, to refer to a substance or chemical constituent in a biological fluid (for example, blood, interstitial fluid, cerebral spinal fluid, lymph fluid or urine) that can be analyzed. Analytes can include naturally occurring substances, artificial substances, metabolites, and/or reaction products. In some embodiments, the analyte for measurement by the sensing regions, devices, and methods is glucose. However, other analytes are contemplated as well, including but not limited to acarboxyprothrombin; acylcarnitine; adenine phosphoribosyl transferase; adenosine deaminase; albumin; alpha-fetoprotein; amino acid profiles (arginine (Krebs cycle), histidine/urocanic acid, homocysteine, phenylalanine/tyrosine, tryptophan); andrenostenedione; antipyrine; arabinitol enantiomers; arginase; benzoylecgonine (cocaine); biotinidase; biopterin; c-reactive protein; carnitine; carnosinase; CD4; ceruloplasmin; chenodeoxycholic acid; chloroquine; cholesterol; cholinesterase; conjugated 1-β hydroxy-cholic acid; cortisol; creatine kinase; creatine kinase MM isoenzyme; cyclosporin A; d-penicillamine; de-ethylchloroquine; dehydroepiandrosterone sulfate; DNA (acetylator polymorphism, alcohol dehydrogenase, alpha 1-antitrypsin, cystic fibrosis, Duchenne/Becker muscular dystrophy, glucose-6-phosphate dehydrogenase, hemoglobin A, hemoglobin S, hemoglobin C, hemoglobin D, hemoglobin E, hemoglobin F, D-Punjab, beta-thalassemia, hepatitis B virus, HCMV, HIV-1, HTLV-1, Leber hereditary optic neuropathy, MCAD, RNA, PKU, Plasmodium vivax, sexual differentiation, 21-deoxycortisol); desbutylhalofantrine; dihydropteridine reductase; diptheria/tetanus antitoxin; erythrocyte arginase; erythrocyte protoporphyrin; esterase D; fatty acids/acylglycines; free β-human chorionic gonadotropin; free erythrocyte porphyrin; free thyroxine (FT4); free tri-iodothyronine (FT3); fumarylacetoacetase; galactose/gal-1-phosphate; galactose-1-phosphate uridyltransferase; gentamicin; glucose-6-phosphate dehydrogenase; glutathione; glutathione perioxidase; glycocholic acid; glycosylated hemoglobin; halofantrine; hemoglobin variants; hexosaminidase A; human erythrocyte carbonic anhydrase I; 17-alpha-hydroxyprogesterone; hypoxanthine phosphoribosyl transferase; immunoreactive trypsin; lactate; lead; lipoproteins ((a), B/A-1, β); lysozyme; mefloquine; netilmicin; phenobarbitone; phenytoin; phytanic/pristanic acid; progesterone; prolactin; prolidase; purine nucleoside phosphorylase; quinine; reverse tri-iodothyronine (rT3); selenium; serum pancreatic lipase; sissomicin; somatomedin C; specific antibodies (adenovirus, anti-nuclear antibody, anti-zeta antibody, arbovirus, Aujeszky's disease virus, dengue virus, Dracunculus medinensis, Echinococcus granulosus, Entamoeba histolytica, enterovirus, Giardia duodenalisa, Helicobacter pylori, hepatitis B virus, herpes virus, HIV-1, IgE (atopic disease), influenza virus, Leishmania donovani, leptospira, measles/mumps/rubella, Mycobacterium leprae, Mycoplasma pneumoniae, Myoglobin, Onchocerca volvulus, parainfluenza virus, Plasmodium falciparum, poliovirus, Pseudomonas aeruginosa, respiratory syncytial virus, rickettsia (scrub typhus), Schistosoma mansoni, Toxoplasma gondii, Trepenoma pallidium, Trypanosoma cruzi/rangeli, vesicular stomatis virus, Wuchereria bancrofti, yellow fever virus); specific antigens (hepatitis B virus, HIV-1); succinylacetone; sulfadoxine; theophylline; thyrotropin (TSH); thyroxine (T4); thyroxine-binding globulin; trace elements; transferrin; UDP-galactose-4-epimerase; urea; uroporphyrinogen I synthase; vitamin A; white blood cells; and zinc protoporphyrin. Salts, sugar, protein, fat, vitamins and hormones naturally occurring in blood or interstitial fluids can also constitute analytes in certain embodiments. The analyte can be naturally present in the biological fluid or endogenous, for example, a metabolic product, a hormone, an antigen, an antibody, and the like. Alternatively, the analyte can be introduced into the body or exogenous, for example, a contrast agent for imaging, a radioisotope, a chemical agent, a fluorocarbon-based synthetic blood, or a drug or pharmaceutical composition, including but not limited to insulin; ethanol; cannabis (marijuana, tetrahydrocannabinol, hashish); inhalants (nitrous oxide, amyl nitrite, butyl nitrite, chlorohydrocarbons, hydrocarbons); cocaine (crack cocaine); stimulants (amphetamines, methamphetamines, Ritalin, Cylert, Preludin, Didrex, PreState, Voranil, Sandrex, Plegine); depressants (barbituates, methaqualone, tranquilizers such as Valium, Librium, Miltown, Serax, Equanil, Tranxene); hallucinogens (phencyclidine, lysergic acid, mescaline, peyote, psilocybin); narcotics (heroin, codeine, morphine, opium, meperidine, Percocet, Percodan, Tussionex, Fentanyl, Darvon, Talwin, Lomotil); designer drugs (analogs of fentanyl, meperidine, amphetamines, methamphetamines, and phencyclidine, for example, Ecstasy); anabolic steroids; and nicotine. The metabolic products of drugs and pharmaceutical compositions are also contemplated analytes. Analytes such as neurochemicals and other chemicals generated within the body can also be analyzed, such as, for example, ascorbic acid, uric acid, dopamine, noradrenaline, 3-methoxytyramine (3MT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5HT), and 5-hydroxyindoleacetic acid (FHIAA).

The terms “operable connection,” “operably connected,” and “operably linked” as used herein are broad terms and are used in their ordinary sense, including, without limitation, one or more components linked to another component(s) in a manner that allows transmission of signals between the components. For example, one or more electrodes can be used to detect the amount of analyte in a sample and convert that information into a signal; the signal can then be transmitted to a circuit. In this case, the electrode is “operably linked” to the electronic circuitry.

The term “host” as used herein is a broad term and is used in its ordinary sense, including, without limitation, mammals, particularly humans.

The term “sensor,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, the portion or portions of an analyte-monitoring device that detects an analyte. In one embodiment, the sensor includes an electrochemical cell that has a working electrode, a reference electrode, and optionally a counter electrode passing through and secured within the sensor body forming an electrochemically reactive surface at one location on the body, an electronic connection at another location on the body, and a membrane system affixed to the body and covering the electrochemically reactive surface. During general operation of the sensor, a biological sample (for example, blood or interstitial fluid), or a portion thereof, contacts (directly or after passage through one or more membranes or domains) an enzyme (for example, glucose oxidase); the reaction of the biological sample (or portion thereof) results in the formation of reaction products that allow a determination of the analyte level in the biological sample.

The term “signal output,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, an analog or digital signal directly related to the measured analyte from the analyte-measuring device. The term broadly encompasses a single point, or alternatively, a plurality of time spaced data points from a substantially continuous glucose sensor, which comprises individual measurements taken at time intervals ranging from fractions of a second up to, for example, 1, 2, or 5 minutes or longer.

The term “electrochemical cell,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, a device in which chemical energy is converted to electrical energy. Such a cell typically consists of two or more electrodes held apart from each other and in contact with an electrolyte solution. Connection of the electrodes to a source of direct electric current renders one of them negatively charged and the other positively charged. Positive ions in the electrolyte migrate to the negative electrode (cathode) and there combine with one or more electrons, losing part or all of their charge and becoming new ions having lower charge or neutral atoms or molecules; at the same time, negative ions migrate to the positive electrode (anode) and transfer one or more electrons to it, also becoming new ions or neutral particles. The overall effect of the two processes is the transfer of electrons from the negative ions to the positive ions, a chemical reaction.

The term “potentiostat,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, an electrical system that controls the potential between the working and reference electrodes of a three-electrode cell at a preset value independent of resistance changes between the electrodes. It forces whatever current is necessary to flow between the working and counter electrodes to keep the desired potential, as long as the cell voltage and current do not exceed the compliance limits of the potentiostat.

The terms “electrochemically reactive surface” and “electroactive surface” as used herein are broad terms and are used in their ordinary sense, including, without limitation, the surface of an electrode where an electrochemical reaction takes place. In one example, a working electrode measures hydrogen peroxide produced by the enzyme catalyzed reaction of the analyte being detected reacts creating an electric current (for example, detection of glucose analyte utilizing glucose oxidase produces H2O2 as a by product, H2O2 reacts with the surface of the working electrode producing two protons (2H+), two electrons (2e) and one molecule of oxygen (O2) which produces the electronic current being detected). In the case of the counter electrode, a reducible species, for example, O2 is reduced at the electrode surface in order to balance the current being generated by the working electrode.

The term “sensing region” as used herein is a broad term and is used in its ordinary sense, including, without limitation, the region of a monitoring device responsible for the detection of a particular analyte. The sensing region generally comprises a non-conductive body, a working electrode, a reference electrode, and optionally a counter electrode passing through and secured within the body forming electrochemically reactive surfaces on the body and an electronic connective means at another location on the body, and a multi-domain membrane system affixed to the body and covering the electrochemically reactive surface.

The terms “raw data stream” and “data stream,” as used herein, are broad terms and are used in their ordinary sense, including, without limitation, an analog or digital signal directly related to the measured an analyte from an analyte sensor. In one example, the raw data stream is digital data in “counts” converted by an A/D converter from an analog signal (for example, voltage or amps) representative of a analyte concentration. The terms broadly encompass a plurality of time spaced data points from a substantially continuous analyte sensor, which comprises individual measurements taken at time intervals ranging from fractions of a second up to, for example, 1, 2, or 5 minutes or longer.

The term “counts,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, a unit of measurement of a digital signal. In one example, a raw data stream measured in counts is directly related to a voltage (for example, converted by an A/D converter), which is directly related to current from the working electrode. In another example, counter electrode voltage measured in counts is directly related to a voltage.

The terms “electrical potential” and “potential” as used herein, are broad terms and are used in their ordinary sense, including, without limitation, the electrical potential difference between two points in a circuit which is the cause of the flow of a current.

The term “ischemia,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, local and temporary deficiency of blood supply due to obstruction of circulation to a part (for example, a sensor). Ischemia can be caused by mechanical obstruction (for example, arterial narrowing or disruption) of the blood supply, for example.

The term “system noise,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, unwanted electronic or diffusion-related noise which can include Gaussian, motion-related, flicker, kinetic, or other white noise, for example.

The terms “signal artifacts” and “transient non-glucose related signal artifacts that have a higher amplitude than system noise,” as used herein, are broad terms and are used in their ordinary sense, including, without limitation, signal noise that is caused by substantially non-glucose reaction rate-limiting phenomena, such as ischemia, pH changes, temperature changes, pressure, and stress, for example. Signal artifacts, as described herein, are typically transient and characterized by a higher amplitude than system noise.

The term “low noise,” as used herein, is a broad term and is used in its ordinary sense, including, without limitation, noise that substantially decreases signal amplitude.

The terms “high noise” and “high spikes,” as used herein, are broad terms and are used in their ordinary sense, including, without limitation, noise that substantially increases signal amplitude.

The phrase “distal to” as used herein is a broad term and is used in its ordinary sense, including, without limitation, the spatial relationship between various elements in comparison to a particular point of reference. For example, some embodiments of a device include a membrane system having a cell disruptive domain and a cell impermeable domain. If the sensor is deemed to be the point of reference and the cell disruptive domain is positioned farther from the sensor, then that domain is distal to the sensor.

The phrase “proximal to” as used herein is a broad term and is used in its ordinary sense, including, without limitation, the spatial relationship between various elements in comparison to a particular point of reference. For example, some embodiments of a device include a membrane system having a cell disruptive domain and a cell impermeable domain. If the sensor is deemed to be the point of reference and the cell impermeable domain is positioned nearer to the sensor, then that domain is proximal to the sensor.

The terms “interferants” and “interfering species,” as used herein, are broad terms and are used in their ordinary sense, including, but not limited to, effects and/or species that interfere with the measurement of an analyte of interest in a sensor to produce a signal that does not accurately represent the analyte measurement. In one example of an electrochemical sensor, interfering species are compounds with an oxidation potential that overlaps with the analyte to be measured.

As employed herein, the following abbreviations apply: Eq and Eqs (equivalents); mEq (milliequivalents); M (molar); mM (millimolar) μM (micromolar); N (Normal); mol (moles); mmol (millimoles); μmol (micromoles); nmol (nanomoles); g (grams); mg (milligrams); μg (micrograms); Kg (kilograms); L (liters); mL (milliliters); dL (deciliters); μL (microliters); cm (centimeters); mm (millimeters); μm (micrometers); nm (nanometers); h and hr (hours); min. (minutes); s and sec. (seconds); ° C. (degrees Centigrade).

Overview

The preferred embodiments relate to the use of an electrochemical sensor that measures a concentration of an analyte of interest or a substance indicative of the concentration or presence of the analyte in fluid. In some embodiments, the sensor is a continuous device, for example a subcutaneous, transdermal, or intravascular device. In some embodiments, the device can analyze a plurality of intermittent blood samples.

The sensor uses any known method, including invasive, minimally invasive, and non-invasive sensing techniques, to provide an output signal indicative of the concentration of the analyte of interest. The sensor is of the type that senses a product or reactant of an enzymatic reaction between an analyte and an enzyme in the presence of oxygen as a measure of the analyte in vivo or in vitro. Such a sensor typically comprises a membrane surrounding the enzyme through which a bodily fluid passes and in which an analyte within the bodily fluid reacts with an enzyme in the presence of oxygen to generate a product. The product is then measured using electrochemical methods and thus the output of an electrode system functions as a measure of the analyte. In some embodiments, the sensor can use an amperometric, coulometric, conductimetric, and/or potentiometric technique for measuring the analyte. In some embodiments, the electrode system can be used with any of a variety of known in vitro or in vivo analyte sensors or monitors.

FIG. 1 is an exploded perspective view of one exemplary embodiment of an implantable glucose sensor 10 that utilizes an electrode system 16. In this exemplary embodiment, a body with a sensing region 14 includes an electrode system (16a to 16c), also referred to as the electroactive sensing surface, and sensor electronics, which are described in more detail with reference to FIG. 2.

In this embodiment, the electrode system 16 is operably connected to the sensor electronics (FIG. 2) and includes electroactive surfaces (including two-, three- or more electrode systems), which are covered by a membrane system 18. The membrane system 18 is disposed over the electroactive surfaces of the electrode system 16 and provides one or more of the following functions: 1) protection of the exposed electrode surface from the biological environment (cell impermeable domain); 2) diffusion resistance (limitation) of the analyte (resistance domain); 3) a catalyst for enabling an enzymatic reaction (enzyme domain); 4) limitation or blocking of interfering species (interference domain); and/or 5) hydrophilicity at the electrochemically reactive surfaces of the sensor interface (electrolyte domain), for example, such as described in co-pending U.S. patent application Ser. No. 10/838,912, filed May 3, 2004 and entitled “IMPLANTABLE ANALYTE SENSOR,” the contents of which are incorporated herein by reference in their entirety. The membrane system can be attached to the sensor body by mechanical or chemical methods such as described in co-pending U.S. patent application Ser. No. 10/885,476, filed Jul. 6, 2004 and entitled, “SYSTEMS AND METHODS FOR MANUFACTURE OF AN ANALYTE-MEASURING DEVICE INCLUDING A MEMBRANE SYSTEM” and U.S. patent application Ser. No. 10/838,912 filed May 3, 2004 and entitled, “IMPLANTABLE ANALYTE SENSOR”, which are incorporated herein by reference in their entirety.

In the embodiment of FIG. 1, the electrode system 16 includes three electrodes (working electrode 16a, counter electrode 16b, and reference electrode 16c), wherein the counter electrode is provided to balance the current generated by the species being measured at the working electrode. In the case of a glucose oxidase based glucose sensor, the species measured at the working electrode is H2O2. Glucose oxidase, GOX, catalyzes the conversion of oxygen and glucose to hydrogen peroxide and gluconate according to the following reaction:
GOX+Glucose+O2→Gluconate+H2O2+reduced GOX

The change in H2O2 can be monitored to determine glucose concentration because for each glucose molecule metabolized, there is a proportional change in the product H2O2. Oxidation of H2O2 by the working electrode is balanced by reduction of ambient oxygen, enzyme generated H2O2, or other reducible species at the counter electrode. The H2O2 produced from the glucose oxidase reaction further reacts at the surface of working electrode and produces two protons (2H+), two electrons (2e−), and one oxygen molecule (O2). In such embodiments, because the counter electrode utilizes oxygen as an electron acceptor, the most likely reducible species for this system are oxygen or enzyme generated peroxide. There are two main pathways by which oxygen can be consumed at the counter electrode. These pathways include a four-electron pathway to produce hydroxide and a two-electron pathway to produce hydrogen peroxide. In addition to the counter electrode, oxygen is further consumed by the reduced glucose oxidase within the enzyme domain. Therefore, due to the oxygen consumption by both the enzyme and the counter electrode, there is a net consumption of oxygen within the electrode system. Theoretically, in the domain of the working electrode there is significantly less net loss of oxygen than in the region of the counter electrode. In some embodiments, there is a close correlation between the ability of the counter electrode to maintain current balance and sensor function.

In general, in electrochemical sensors wherein an enzymatic reaction depends on oxygen as a co-reactant, depressed function or inaccuracy can be experienced in low oxygen environments, for example in vivo. Subcutaneously implanted devices are especially susceptible to transient ischemia that can compromise device function; for example, because of the enzymatic reaction required for an implantable amperometric glucose sensor, oxygen must be in excess over glucose in order for the sensor to effectively function as a glucose sensor. If glucose becomes in excess, the sensor turns into an oxygen sensitive device. In vivo, glucose concentration can vary from about one hundred times or more that of the oxygen concentration. Consequently, one limitation of prior art enzymatic-based electrochemical analyte sensors can be caused by oxygen deficiencies, which is described in more detail with reference to FIG. 3.

FIG. 2 is a block diagram that illustrates sensor electronics in one exemplary embodiment; one skilled in the art appreciates however that a variety of sensor electronics configurations can be implemented with the preferred embodiments. In this embodiment, a potentiostat 20 is shown, which is operatively connected to electrode system 16 (FIG. 1) to obtain a current value, and includes a resistor (not shown) that translates the current into voltage. The A/D converter 21 digitizes the analog signal into “counts” for processing. Accordingly, the resulting raw data signal in counts is directly related to the current measured by the potentiostat.

A microprocessor 22 is the central control unit that houses EEPROM 23 and SRAM 24, and controls the processing of the sensor electronics. The alternative embodiments can utilize a computer system other than a microprocessor to process data as described herein. In some alternative embodiments, an application-specific integrated circuit (ASIC) can be used for some or all the sensor's central processing. EEPROM 23 provides semi-permanent storage of data, storing data such as sensor ID and necessary programming to process data signals (for example, programming for data smoothing such as described elsewhere herein). SRAM 24 is used for the system's cache memory, for example for temporarily storing recent sensor data.

The battery 25 is operatively connected to the microprocessor 22 and provides the necessary power for the sensor. In one embodiment, the battery is a Lithium Manganese Dioxide battery, however any appropriately sized and powered battery can be used. In some embodiments, a plurality of batteries can be used to power the system. Quartz crystal 26 is operatively connected to the microprocessor 22 and maintains system time for the computer system.

The RF Transceiver 27 is operably connected to the microprocessor 22 and transmits the sensor data from the sensor to a receiver. Although a RF transceiver is shown here, some other embodiments can include a wired rather than wireless connection to the receiver. In yet other embodiments, the sensor can be transcutaneously connected via an inductive coupling, for example. The quartz crystal 28 provides the system time for synchronizing the data transmissions from the RF transceiver. The transceiver 27 can be substituted with a transmitter in one embodiment.

Although FIGS. 1 and 2 and associated text illustrate and describe an exemplary embodiment of an implantable glucose sensor, the electrode systems of the preferred embodiments described below can be implemented with any known electrochemical sensor, including U.S. Pat. No. 6,001,067 to Shults et al.; U.S. Pat. No. 6,702,857 to Brauker et al.; U.S. Pat. No. 6,212,416 to Ward et al.; U.S. Pat. No. 6,119,028 to Schulman et al; U.S. Pat. No. 6,400,974 to Lesho; U.S. Pat. No. 6,595,919 to Berner et al.; U.S. Pat. No. 6,141,573 to Kurnik et al.; U.S. Pat. No. 6,122,536 to Sun et al.; European Patent Application EP 1153571 to Varall et al.; U.S. Pat. No. 6,512,939 to Colvin et al.; U.S. Pat. No. 5,605,152 to Slate et al.; U.S. Pat. No. 4,431,004 to Bessman et al.; U.S. Pat. No. 4,703,756 to Gough et al.; U.S. Pat. No. 6,514,718 to Heller et al; to U.S. Pat. No. 5,985,129 to Gough et al.; WO Patent Application Publication No. 2004/021877 to Caduff; U.S. Pat. No. 5,494,562 to Maley et al.; U.S. Pat. No. 6,120,676 to Heller et al.; and U.S. Pat. No. 6,542,765 to Guy et al., co-pending U.S. patent application Ser. No. 10/838,912 filed May 3, 2004 and entitled, “IMPLANTABLE ANALYTE SENSOR”; U.S. patent application Ser. No. 10/789,359 filed Feb. 26, 2004 and entitled, “INTEGRATED DELIVERY DEVICE FOR A CONTINUOUS GLUCOSE SENSOR”; “OPTIMIZED SENSOR GEOMETRY FOR AN IMPLANTABLE GLUCOSE SENSOR”; U.S. application Ser. No. 10/633,367 filed Aug. 1, 2003 entitled, “SYSTEM AND METHODS FOR PROCESSING ANALYTE SENSOR DATA,” the contents of each of which are incorporated herein by reference in their entirety.

FIG. 3 is a graph that depicts a raw data stream obtained from a prior art glucose sensor such as described with reference to FIG. 1. The x-axis represents time in minutes. The y-axis represents sensor data in counts. In this example, sensor output in counts is transmitted every 30-seconds. The raw data stream 30 includes substantially smooth sensor output in some portions, however other portions exhibit erroneous or transient non-glucose related signal artifacts 32. Particularly, referring to the signal artifacts 32, it is believed that effects of local ischemia on prior art electrochemical sensors creates erroneous (non-glucose) signal values due to oxygen deficiencies either at the enzyme within the membrane system and/or at the counter electrode on the electrode surface.

In one situation, when oxygen is deficient relative to the amount of glucose, then the enzymatic reaction is limited by oxygen rather than glucose. Thus, the output signal is indicative of the oxygen concentration rather than the glucose concentration, producing erroneous signals. Additionally, when an enzymatic reaction is rate-limited by oxygen, glucose is expected to build up in the membrane because it is not completely catabolized during the oxygen deficit. When oxygen is again in excess, there is also excess glucose due to the transient oxygen deficit. The enzyme rate then speeds up for a short period until the excess glucose is catabolized, resulting in spikes of non-glucose related increased sensor output. Accordingly, because excess oxygen (relative to glucose) is necessary for proper sensor function, transient ischemia can result in a loss of signal gain in the sensor data.

In another situation, oxygen deficiency can be seen at the counter electrode when insufficient oxygen is available for reduction, which thereby affects the counter electrode in that it is unable to balance the current coming from the working electrode. When insufficient oxygen is available for the counter electrode, the counter electrode can be driven in its electrochemical search for electrons all the way to its most negative value, which could be ground or 0.0 V, which causes the reference to shift, reducing the bias voltage, such is as described in more detail below. In other words, a common result of ischemia a drop off in sensor current as a function of glucose concentration (for example, lower sensitivity). This happens because the working electrode no longer oxidizes all of the H2O2 arriving at its surface because of the reduced bias. In some extreme circumstances, an increase in glucose can produce no increase in current or even a decrease in current.

In some situations, transient ischemia can occur at high glucose levels, wherein oxygen can become limiting to the enzymatic reaction, resulting in a non-glucose dependent downward trend in the data. In some situations, certain movements or postures taken by the patient can cause transient signal artifacts as blood is squeezed out of the capillaries resulting in local ischemia and causing non-glucose dependent signal artifacts. In some situations, oxygen can also become transiently limited due to contracture of tissues around the sensor interface. This is similar to the blanching of skin that can be observed when one puts pressure on it. Under such pressure, transient ischemia can occur in both the epidermis and subcutaneous tissue. Transient ischemia is common and well tolerated by subcutaneous tissue. However, such ischemic periods can cause an oxygen deficit in implanted devices that can last for many minutes or even an hour or longer.

Although some examples of the effects of transient ischemia on a prior art glucose sensor are described above, similar effects can be seen with analyte sensors that use alternative catalysts to detect other analytes, for example, amino acids (amino acid oxidase), alcohol (alcohol oxidase), galactose (galactose oxidase), lactate (lactate oxidase), cholesterol (cholesterol oxidase), or the like.

Another problem with conventional electrochemical sensors is that they can electrochemically react not only with the analyte to be measured (or by-product of the enzymatic reaction with the analyte), but additionally can react with other electroactive species that are not intentionally being measured (for example, interfering species), which causes an increase in signal strength due to these “interfering species”. In other words, interfering species are compounds with an oxidation or reduction potential that overlaps with the analyte to be measured (or the by-product of the enzymatic reaction with the analyte). For example, in a conventional amperometric glucose oxidase-based glucose sensor wherein the sensor measures hydrogen peroxide, interfering species such as acetaminophen, ascorbate, and urate are known to produce inaccurate signal strength when they are not properly controlled.

Some conventional glucose sensors utilize a membrane system that blocks at least some interfering species, such as ascorbate and urate. In some such systems, at least one layer of the membrane system includes a porous structure that has a relatively impermeable matrix with a plurality of “micro holes” or pores of molecular dimensions, such that transfer through these materials is primarily due to passage of species through the pores (for example, the layer acts as a microporous barrier or sieve blocking interfering species of a particular size). In other such systems, at least one layer of the membrane system defines a permeability that allows selective dissolution and diffusion of species as solutes through the layer. Unfortunately, it is difficult to find membranes that are satisfactory or reliable in use, especially in vivo, which effectively block all interferants and/or interfering species in some embodiments.

Electrochemical Sensors of the Preferred Embodiments

In one aspect of the preferred embodiments, an electrochemical sensor is provided with an auxiliary electrode configured to generate oxygen in order to overcome the effects of transient ischemia. In another aspect of the preferred embodiments, an electrochemical sensor is provided with an auxiliary electrode configured to electrochemically modify (for example, oxidize or reduce) electrochemical interferants to render them substantially non-electroactively reactive at the electroactive sensing surface(s) in order to overcome the effects of interferants on the working electrode.

It is known that oxygen can be generated as a product of electrochemical reactions occurring at a positively charged electrode (for example, set at about +0.6 to about +1.2 V or more). One example of an oxygen producing reaction is the electrolysis of water, which creates oxygen at the anode (for example, the working electrode). In the exemplary electrochemical glucose sensor, glucose is converted to hydrogen peroxide by reacting with glucose oxidase and oxygen, after which the hydrogen peroxide is oxidized at the working electrode and oxygen is generated therefrom. It is noted that one challenge to generating oxygen electrochemically in this way is that while an auxiliary electrode does produce excess oxygen, the placement of the auxiliary electrode in proximity to the analyte-measuring working electrode can cause oxidation of hydrogen peroxide at the auxiliary electrode, resulting in reduced signals at the working electrode. It is also known that many electrochemical interferants can be reduced at a potential of from about +0.1V to +1.2V or more; for example, acetaminophen is reduced at a potential of about +0.4 V.

Accordingly, the sensors of preferred embodiments place an auxiliary electrode above the electrode system 16, or other electroactive sensing surface, thereby reducing or eliminating the problem of inaccurate signals as described above.

FIG. 4 is a side schematic illustration of a portion of the sensing region of an electrochemical sensor of the preferred embodiments, showing an auxiliary electrode between the enzyme and the outside solution while the working (sensing) electrode is located below the enzyme and further from the outside solution. Particularly, FIG. 4 shows an external solution 12, which represents the bodily or other fluid to which the sensor is exposed in vivo or in vitro.

The membrane system 18 includes a plurality of domains (for example, cell impermeable domain, resistance domain, enzyme domain, and/or other domains such as are described in U.S. Published Patent Application 2003/0032874 to Rhodes et al. and copending U.S. patent application Ser. No. 10/885,476, filed Jul. 6, 2004 and entitled, “SYSTEMS AND METHODS FOR MANUFACTURE OF AN ANALYTE-MEASURING DEVICE INCLUDING A MEMBRANE SYSTEM”, the contents of which are incorporated herein by reference in their entireties) is located proximal to the external solution and finctions to transport fluids necessary for the enzymatic reaction, while protecting inner components of the sensor from harsh biohazards, for example. Although each domain is not independently shown, the enzyme 38 is shown disposed between an auxiliary electrode 36 and the working electrode 16a in the illustrated embodiment.

Preferably, the auxiliary electrode 36 is located within or adjacent to the membrane system 18, for example, between the enzyme and other domains, although the auxiliary electrode can be placed anywhere between the electroactive sensing surface and the outside fluid. The auxiliary electrode 36 is formed from known working electrode materials (for example, platinum, palladium, graphite, gold, carbon, conductive polymer, or the like) and has a voltage setting that produces oxygen (for example, from about +0.6 V to +1.2 V or more) and/or that electrochemically modifies (for example, reduces) electrochemical interferants to render them substantially non-reactive at the electroactive sensing surface(s) (for example, from about +0.1 V to +1.2 V or more). The auxiliary electrode can be a mesh, grid, plurality of spaced wires or conductive polymers, or other configurations designed to allow analytes to penetrate therethrough.

In the aspect of the preferred embodiments wherein the auxiliary electrode 36 is configured to generate oxygen, the oxygen generated from the auxiliary electrode 36 diffuses upward and/or downward to be utilized by the enzyme 38 and/or the counter electrode (depending on the placement of the auxiliary electrode). Additionally, the analyte (for example, glucose) from the outside solution (diffuses through the auxiliary electrode 36) reacts with the enzyme 38 and produces a measurable product (for example, hydrogen peroxide). Therefore, the product of the enzymatic reaction diffuses down to the working electrode 16a for accurate measurement without being eliminated by the auxiliary electrode 36.

In one alternative embodiment, the auxiliary electrode 36 can be coated with a polymeric material, which is impermeable to glucose but permeable to oxygen. By this coating, glucose will not electroactively react at the auxiliary electrode 36, which can otherwise cause at least some of the glucose to pre-oxidize as it passes through the auxiliary electrode 36 (when placed above the enzyme), which can prevent accurate glucose concentration measurements at the working electrode in some sensor configurations. In one embodiment, the polymer coating comprises silicone, however any polymer that is selectively permeable to oxygen, but not glucose, can be used. The auxiliary electrode 16 can be coated by any known process, such as dip coating or spray coating, after which is can be blown, blotted, or the like to maintain spaces within the electrode for glucose transport.

In another alternative embodiment, the auxiliary electrode 36 can be coated with a polymeric material that is permeable to glucose and oxygen and can be placed between the enzyme and the outside fluid. Consequently, the polymeric coating will cause glucose from the outside fluid to electroactively react at the auxiliary electrode 36, thereby limiting the amount of glucose that passes into the enzyme 38, and thus reducing the amount of oxygen necessary to successfully react with all available glucose in the enzyme. The polymeric material can function in place of or in combination with the resistance domain in order to limit the amount of glucose that passes through the membrane system. This embodiment assumes a stoichiometric relationship between glucose oxidation and decreased sensor signal output, which can be compensated for by calibration in some sensor configurations. Additionally, the auxiliary electrode generates oxygen, further reducing the likelihood of oxygen becoming a rate-limiting factor in the enzymatic reaction and/or at the counter electrode, for example.

In another aspect of the preferred embodiments, the auxiliary electrode 36 is configured to electrochemically modify (for example, oxidize or reduce) electrochemical interferants to render them substantially non-reactive at the electroactive sensing surface(s). In these embodiments, which can be in addition to or alternative to the above-described oxygen-generating embodiments, a polymer coating is chosen to selectively allow interferants (for example, urate, ascorbate, and/or acetaminophen such as described in U.S. Pat. No. 6,579,690 to Bonnecaze, et al.) to pass through the coating and electrochemically react with the auxiliary electrode, which effectively pre-oxidizes the interferants, rendering them substantially non-reactive at the working electrode 16a. In one exemplary embodiment, silicone materials can be synthesized to allow the transport of oxygen, acetaminophen and other interferants, but not allow the transport of glucose. In some embodiments, the polymer coating material can be chosen with a molecular weight that blocks glucose and allows the transport of oxygen, urate, ascorbate, and acetaminophen. In another exemplary embodiment, silicone materials can be synthesized to allow the transport of oxygen, glucose, acetaminophen, and other interferants. In some embodiments, the polymer coating material is chosen with a molecular weight that allows the transport of oxygen, glucose, urate, ascorbate, and acetaminophen. The voltage setting necessary to react with interfering species depends on the target electrochemical interferants, for example, from about +0.1 V to about +1.2 V. In some embodiments, wherein the auxiliary electrode is set at a potential of from about +0.6 to about +1.2 V, both oxygen-generation and electrochemical interferant modification can be achieved. In some embodiments, wherein the auxiliary electrode is set at a potential below about +0.6 V, the auxiliary electrode will function mainly to electrochemically modify interferants, for example.

Therefore, the sensors of preferred embodiments reduce or eliminate oxygen deficiency problems within electrochemical sensors by producing oxygen at an auxiliary electrode located above the enzyme within an enzyme-based electrochemical sensor. Additionally or alternatively, the sensors of preferred embodiments reduce or eliminate interfering species problems by electrochemically reacting with interferants at the auxiliary electrode rendering them substantially non-reactive at the working electrode.

Methods and devices that are suitable for use in conjunction with aspects of the preferred embodiments are disclosed in co-pending U.S. patent application Ser. No. 10/842,716, filed May 10, 2004 and entitled, “MEMBRANE SYSTEMS INCORPORATING BIOACTIVE AGENTS”; co-pending U.S. patent application Ser. No. 10/838,912 filed May 3, 2004 and entitled, “IMPLANTABLE ANALYTE SENSOR”; U.S. patent application Ser. No. 10/789,359 filed Feb. 26, 2004 and entitled, “INTEGRATED DELIVERY DEVICE FOR A CONTINUOUS GLUCOSE SENSOR”; U.S. application Ser. No. 10/685,636 filed Oct. 28, 2003 and entitled, “SILICONE COMPOSITION FOR MEMBRANE SYSTEM”; U.S. application Ser. No. 10/648,849 filed Aug. 22, 2003 and entitled, “SYSTEMS AND METHODS FOR REPLACING SIGNAL ARTIFACTS IN A GLUCOSE SENSOR DATA STREAM”; U.S. application Ser. No. 10/646,333 filed Aug. 22, 2003 entitled, “OPTIMIZED SENSOR GEOMETRY FOR AN IMPLANTABLE GLUCOSE SENSOR”; U.S. application Ser. No. 10/647,065 filed Aug. 22, 2003 entitled, “POROUS MEMBRANES FOR USE WITH IMPLANTABLE DEVICES”; U.S. application Ser. No. 10/633,367 filed Aug. 1, 2003 entitled, “SYSTEM AND METHODS FOR PROCESSING ANALYTE SENSOR DATA”; U.S. Pat. No. 6,702,857 entitled “MEMBRANE FOR USE WITH IMPLANTABLE DEVICES”; U.S. application Ser. No. 09/916,711 filed Jul. 27, 2001 and entitled “SENSOR HEAD FOR USE WITH IMPLANTABLE DEVICE”; U.S. application Ser. No. 09/447,227 filed Nov. 22, 1999 and entitled “DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS”; U.S. application Ser. No. 10/153,356 filed May 22, 2002 and entitled “TECHNIQUES TO IMPROVE POLYURETHANE MEMBRANES FOR IMPLANTABLE GLUCOSE SENSORS”; U.S. application Ser. No. 09/489,588 filed Jan. 21, 2000 and entitled “DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS”; U.S. application Ser. No. 09/636,369 filed Aug. 11, 2000 and entitled “SYSTEMS AND METHODS FOR REMOTE MONITORING AND MODULATION OF MEDICAL DEVICES”; and U.S. application Ser. No. 09/916,858 filed Jul. 27, 2001 and entitled “DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS,” as well as issued patents including U.S. Pat. No. 6,001,067 issued Dec. 14, 1999 and entitled “DEVICE AND METHOD FOR DETERMINING ANALYTE LEVELS”; U.S. Pat. No. 4,994,167 issued Feb. 19, 1991 and entitled “BIOLOGICAL FLUID MEASURING DEVICE”; and U.S. Pat. No. 4,757,022 filed Jul. 12, 1988 and entitled “BIOLOGICAL FLUID MEASURING DEVICE”; U.S. application Ser. No. 60/489,615 filed Jul. 23, 2003 and entitled “ROLLED ELECTRODE ARRAY AND ITS METHOD FOR MANUFACTURE”; U.S. application Ser. No. 60/490,010 filed Jul. 25, 2003 and entitled “INCREASING BIAS FOR OXYGEN PRODUCTION IN AN ELECTRODE ASSEMBLY”; U.S. application Ser. No. 60/490,009 filed Jul. 25, 2003 and entitled “OXYGEN ENHANCING ENZYME MEMBRANE FOR ELECTROCHEMICAL SENSORS”; U.S. application Ser. No. 60/490,007 filed Jul. 25, 2003 and entitled “OXYGEN-GENERATING ELECTRODE FOR USE IN ELECTROCHEMICAL SENSORS”; U.S. application Ser. No. 10/896,637 filed Jul. 21, 2004 and entitled “ROLLED ELECTRODE ARRAY AND ITS METHOD FOR MANUFACTURE”; U.S. application Ser. No. 10/896,772 filed Jul. 21, 2004 and entitled “INCREASING BIAS FOR OXYGEN PRODUCTION IN AN ELECTRODE SYSTEM”; U.S. application Ser. No. 10/896,639 filed Jul. 21, 2004 and entitled “OXYGEN ENHANCING MEMBRANE SYSTEMS FOR IMPLANTABLE DEVICES”; U.S. application Ser. No. 10/897,377 filed Jul. 21, 2004 and entitled “ELECTROCHEMICAL SENSORS INCLUDING ELECTRODE SYSTEMS WITH INCREASED OXYGEN GENERATION”. The foregoing patent applications and patents are incorporated herein by reference in their entireties.

All references cited herein are incorporated herein by reference in their entireties. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and/or take precedence over any such contradictory material.

The term “comprising” as used herein is synonymous with “including,” “containing,” or “characterized by,” and is inclusive or open-ended and does not exclude additional, unrecited elements or method steps.

All numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding approaches.

The above description discloses several methods and materials of the present invention. This invention is susceptible to modifications in the methods and materials, as well as alterations in the fabrication methods and equipment. Such modifications will become apparent to those skilled in the art from a consideration of this disclosure or practice of the invention disclosed herein. Consequently, it is not intended that this invention be limited to the specific embodiments disclosed herein, but that it cover all modifications and alternatives coming within the true scope and spirit of the invention as embodied in the attached claims.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US1564641Apr 10, 1922Dec 8, 1925Chicago Miniature Lamp WorksDetector for wireless systems
US2402306Oct 7, 1943Jun 18, 1946Turkel HenryRetaining guard guide for needles
US3210578Jan 12, 1962Oct 5, 1965Westinghouse Electric CorpMultispeed motor connector
US3381371Sep 27, 1965May 7, 1968Sanders Associates IncMethod of constructing lightweight antenna
US3775182Feb 25, 1972Nov 27, 1973Du PontTubular electrochemical cell with coiled electrodes and compressed central spindle
US3826244Jul 20, 1973Jul 30, 1974Us Health Education & WelfareThumbtack microelectrode and method of making same
US3838033Aug 31, 1972Sep 24, 1974Hoffmann La RocheEnzyme electrode
US3933593Aug 9, 1972Jan 20, 1976Beckman Instruments, Inc.Rate sensing batch analysis method
US3982530Apr 22, 1975Sep 28, 1976Egon StorchPenial appliance
US4052754Jul 14, 1976Oct 11, 1977Homsy Charles AImplantable structure
US4067322Jan 28, 1976Jan 10, 1978Johnson Joseph HDisposable, pre-gel body electrodes
US4197840Sep 29, 1976Apr 15, 1980Bbc Brown Boveri & Company, LimitedPermanent magnet device for implantation
US4240889Jan 24, 1979Dec 23, 1980Toyo Boseki Kabushiki KaishaEnzyme electrode provided with immobilized enzyme membrane
US4255500Mar 29, 1979Mar 10, 1981General Electric CompanyVibration resistant electrochemical cell having deformed casing and method of making same
US4324257Feb 25, 1980Apr 13, 1982U.S. Philips CorporationDevice for the transcutaneous measurement of the partial oxygen pressure in blood
US4374013 *Mar 3, 1981Feb 15, 1983Enfors Sven OlofOxygen stabilized enzyme electrode
US4378016Jul 15, 1981Mar 29, 1983Biotek, Inc.Artificial endocrine gland containing hormone-producing cells
US4388166May 15, 1982Jun 14, 1983Tokyo Shibaura Denki Kabushiki KaishaElectrochemical measuring apparatus provided with an enzyme electrode
US4402694Jul 16, 1981Sep 6, 1983Biotek, Inc.Body cavity access device containing a hormone source
US4418148Nov 5, 1981Nov 29, 1983Miles Laboratories, Inc.Multilayer enzyme electrode membrane
US4431004Oct 27, 1981Feb 14, 1984Bessman Samuel PImplantable glucose sensor
US4431507 *Jan 12, 1982Feb 14, 1984Matsushita Electric Industrial Co., Ltd.Enzyme electrode
US4442841Apr 30, 1981Apr 17, 1984Mitsubishi Rayon Company LimitedElectrode for living bodies
US4477314Jul 20, 1983Oct 16, 1984Siemens AktiengesellschaftMethod for determining sugar concentration
US4484987May 19, 1983Nov 27, 1984The Regents Of The University Of CaliforniaMethod and membrane applicable to implantable sensor
US4494950Jan 19, 1982Jan 22, 1985The Johns Hopkins UniversityPlural module medication delivery system
US4545382Oct 22, 1982Oct 8, 1985Genetics International, Inc.Sensor for components of a liquid mixture
US4571292Aug 12, 1982Feb 18, 1986Case Western Reserve UniversityApparatus for electrochemical measurements
US4578215Aug 12, 1983Mar 25, 1986Micro-Circuits CompanyElectrical conductivity-enhancing and protecting material
US4650547Dec 20, 1985Mar 17, 1987The Regents Of The University Of CaliforniaMethod and membrane applicable to implantable sensor
US4655880Aug 1, 1983Apr 7, 1987Case Western Reserve UniversityApparatus and method for sensing species, substances and substrates using oxidase
US4671288Jun 13, 1985Jun 9, 1987The Regents Of The University Of CaliforniaElectrochemical cell sensor for continuous short-term use in tissues and blood
US4672970Jul 29, 1985Jun 16, 1987Mitsubishi Rayon Company, Ltd.Electrode for living body
US4680268Sep 18, 1985Jul 14, 1987Children's Hospital Medical CenterImplantable gas-containing biosensor and method for measuring an analyte such as glucose
US4685463Apr 3, 1986Aug 11, 1987Williams R BruceDevice for continuous in vivo measurement of blood glucose concentrations
US4703756May 6, 1986Nov 3, 1987The Regents Of The University Of CaliforniaComplete glucose monitoring system with an implantable, telemetered sensor module
US4711245May 7, 1984Dec 8, 1987Genetics International, Inc.Sensor for components of a liquid mixture
US4721677May 7, 1987Jan 26, 1988Children's Hospital Medical CenterImplantable gas-containing biosensor and method for measuring an analyte such as glucose
US4726381Jun 4, 1986Feb 23, 1988Solutech, Inc.Dialysis system and method
US4750496Jan 28, 1987Jun 14, 1988Xienta, Inc.Method and apparatus for measuring blood glucose concentration
US4757022Nov 19, 1987Jul 12, 1988Markwell Medical Institute, Inc.Biological fluid measuring device
US4763658Jul 29, 1987Aug 16, 1988Solutech, Inc.Dialysis system 2nd method
US4776944Sep 1, 1987Oct 11, 1988Jiri JanataChemical selective sensors utilizing admittance modulated membranes
US4781798May 8, 1987Nov 1, 1988The Regents Of The University Of CaliforniaTransparent multi-oxygen sensor array and method of using same
US4786657Jul 2, 1987Nov 22, 1988Minnesota Mining And Manufacturing CompanyPolyurethanes and polyurethane/polyureas crosslinked using 2-glyceryl acrylate or 2-glyceryl methacrylate
US4795542Apr 24, 1986Jan 3, 1989St. Jude Medical, Inc.Electrochemical concentration detector device
US4813424Dec 23, 1987Mar 21, 1989University Of New MexicoLong-life membrane electrode for non-ionic species
US4822336Mar 4, 1988Apr 18, 1989Ditraglia JohnBlood glucose level sensing
US4858615Jul 29, 1988Aug 22, 1989Sentron V.O.F.Catheter sensor and memory unit
US4861830Jun 22, 1987Aug 29, 1989Th. Goldschmidt AgPolymer systems suitable for blood-contacting surfaces of a biomedical device, and methods for forming
US4871440Jul 6, 1988Oct 3, 1989Daiken Industries, Ltd.Biosensor
US4883057Sep 9, 1986Nov 28, 1989Research Foundation, The City University Of New YorkCathodic electrochemical current arrangement with telemetric application
US4886740May 28, 1986Dec 12, 1989Imperial Chemical Industries PlcEnzyme-electrode sensor with organosilane treated membrane
US4890620Feb 17, 1988Jan 2, 1990The Regents Of The University Of CaliforniaTwo-dimensional diffusion glucose substrate sensing electrode
US4890621Jan 19, 1988Jan 2, 1990Northstar Research Institute, Ltd.Continuous glucose monitoring and a system utilized therefor
US4909908Oct 27, 1988Mar 20, 1990Pepi RossElectrochemical cncentration detector method
US4919141Jan 4, 1988Apr 24, 1990Institute fur Diabetestechnologie Gemeinnutzige Forschungs- und Entwicklungsgesellschaft mbHImplantable electrochemical sensor
US4927407Jun 19, 1989May 22, 1990Regents Of The University Of MinnesotaCardiac assist pump with steady rate supply of fluid lubricant
US4953552Apr 21, 1989Sep 4, 1990Demarzo Arthur PBlood glucose monitoring system
US4955861Apr 21, 1988Sep 11, 1990Therex Corp.Dual access infusion and monitoring system
US4970145Jan 20, 1988Nov 13, 1990Cambridge Life Sciences PlcImmobilized enzyme electrodes
US4973320Aug 2, 1988Nov 27, 1990Firma Carl FreudenbergTissue-compatible medical device and method for manufacturing the same
US4974929Mar 28, 1990Dec 4, 1990Baxter International, Inc.Fiber optical probe connector for physiologic measurement devices
US4975175Jun 15, 1989Dec 4, 1990Isao KarubeMiniaturized oxygen electrode and miniaturized biosensor and production process thereof
US4992794Oct 10, 1989Feb 12, 1991Texas Instruments IncorporatedTransponder and method for the production thereof
US4994167Jul 7, 1988Feb 19, 1991Markwell Medical Institute, Inc.Biological fluid measuring device
US5030333Oct 14, 1986Jul 9, 1991Children's Hospital Medical CenterPolarographic method for measuring both analyte and oxygen with the same detecting electrode of an electroenzymatic sensor
US5034112May 16, 1989Jul 23, 1991Nissan Motor Company, Ltd.Device for measuring concentration of nitrogen oxide in combustion gas
US5050612Sep 12, 1989Sep 24, 1991Matsumura Kenneth NDevice for computer-assisted monitoring of the body
US5063081Aug 15, 1990Nov 5, 1991I-Stat CorporationMethod of manufacturing a plurality of uniform microfabricated sensing devices having an immobilized ligand receptor
US5089112Jan 11, 1990Feb 18, 1992Associated Universities, Inc.Electrochemical biosensor based on immobilized enzymes and redox polymers
US5140985Oct 21, 1991Aug 25, 1992Schroeder Jon MNoninvasive blood glucose measuring device
US5155149Oct 10, 1991Oct 13, 1992Boc Health Care, Inc.Silicone polyurethane copolymers containing oxygen sensitive phosphorescent dye compounds
US5165407Apr 9, 1991Nov 24, 1992The University Of KansasImplantable glucose sensor
US5171689Apr 18, 1989Dec 15, 1992Matsushita Electric Industrial Co., Ltd.Solid state bio-sensor
US5183549Jan 26, 1990Feb 2, 1993Commtech International Management CorporationMulti-analyte sensing electrolytic cell
US5190041Dec 27, 1991Mar 2, 1993Palti Yoram ProfSystem for monitoring and controlling blood glucose
US5198771Sep 3, 1991Mar 30, 1993Transducer Research, Inc.Potentiostatic apparatus and methods
US5200051Nov 7, 1989Apr 6, 1993I-Stat CorporationWholly microfabricated biosensors and process for the manufacture and use thereof
US5202261Nov 18, 1991Apr 13, 1993Miles Inc.Conductive sensors and their use in diagnostic assays
US5212050Aug 15, 1990May 18, 1993Mier Randall MMethod of forming a permselective layer
US5242835Jul 21, 1992Sep 7, 1993Radiometer A/SMethod and apparatus for determining the concentration of oxygen
US5249576Oct 24, 1991Oct 5, 1993Boc Health Care, Inc.Universal pulse oximeter probe
US5250439Dec 14, 1992Oct 5, 1993Miles Inc.Use of conductive sensors in diagnostic assays
US5266179Jul 19, 1991Nov 30, 1993Matsushita Electric Industrial Co., Ltd.Quantitative analysis method and its system using a disposable sensor
US5281319Jun 29, 1992Jan 25, 1994Agency Of Industrial Science And TechnologyCarbon micro-sensor electrode and method for preparing it
US5282848Apr 19, 1993Feb 1, 1994Meadox Medicals, Inc.Self-supporting woven vascular graft
US5284140Feb 11, 1992Feb 8, 1994Eli Lilly And CompanyAcrylic copolymer membranes for biosensors
US5286364Mar 29, 1991Feb 15, 1994Rutgers UniversitySurface-modified electochemical biosensor
US5298144Sep 15, 1992Mar 29, 1994The Yellow Springs Instrument Company, Inc.Chemically wired fructose dehydrogenase electrodes
US5299571Jan 22, 1993Apr 5, 1994Eli Lilly And CompanyApparatus and method for implantation of sensors
US5307263Nov 17, 1992Apr 26, 1994Raya Systems, Inc.Modular microprocessor-based health monitoring system
US5310469Dec 31, 1991May 10, 1994Abbott LaboratoriesBiosensor with a membrane containing biologically active material
US5312361Aug 10, 1992May 17, 1994Zadini Filiberto PAutomatic cannulation device
US5322063Oct 4, 1991Jun 21, 1994Eli Lilly And CompanyHydrophilic polyurethane membranes for electrochemical glucose sensors
US5330634Aug 28, 1992Jul 19, 1994Via Medical CorporationCalibration solutions useful for analyses of biological fluids and methods employing same
US5337747Jan 7, 1993Aug 16, 1994Frederic NeftelImplantable device for estimating glucose levels
US5352348Nov 3, 1992Oct 4, 1994Nova Biomedical CorporationMethod of using enzyme electrode
US5352351Jun 8, 1993Oct 4, 1994Boehringer Mannheim CorporationBiosensing meter with fail/safe procedures to prevent erroneous indications
US5354449Jan 2, 1992Oct 11, 1994Band David MpH electrode
US5372133Feb 3, 1993Dec 13, 1994N.V. Nederlandsche Apparatenfabriek NedapImplantable biomedical sensor device, suitable in particular for measuring the concentration of glucose
US5384028Aug 27, 1993Jan 24, 1995Nec CorporationBiosensor with a data memory
US5387327Oct 19, 1992Feb 7, 1995Duquesne University Of The Holy GhostImplantable non-enzymatic electrochemical glucose sensor
US5390671Mar 15, 1994Feb 21, 1995Minimed Inc.Transcutaneous sensor insertion set
US5391250Mar 15, 1994Feb 21, 1995Minimed Inc.Method of fabricating thin film sensors
US5411647Jan 25, 1994May 2, 1995Eli Lilly And CompanyTechniques to improve the performance of electrochemical sensors
US5411866Mar 30, 1993May 2, 1995National Research Council Of CanadaMethod and system for determining bioactive substances
US5425717Aug 12, 1993Jun 20, 1995The Kendall CompanyEpidural catheter system utilizing splittable needle
US5428123Apr 23, 1993Jun 27, 1995The Polymer Technology GroupCopolymers and non-porous, semi-permeable membrane thereof and its use for permeating molecules of predetermined molecular weight range
US5431160Nov 9, 1993Jul 11, 1995University Of New MexicoMiniature implantable refillable glucose sensor and material therefor
US5438984Mar 30, 1993Aug 8, 1995Sudor PartnersApparatus and method for the collection of analytes on a dermal patch
US5462645Sep 21, 1992Oct 31, 1995Imperial College Of Science, Technology & MedicineDialysis electrode device
US5466575Sep 10, 1992Nov 14, 1995I-Stat CorporationProcess for the manufacture of wholly microfabricated biosensors
US5469846Sep 27, 1994Nov 28, 1995Duquesne University Of The Holy GhostImplantable non-enzymatic electrochemical glucose sensor
US5474552Jun 27, 1994Dec 12, 1995Cb-Carmel Biotechnology Ltd.Implantable drug delivery pump
US5476094Nov 15, 1993Dec 19, 1995Eli Lilly And CompanyAcrylic copolymer membranes for biosensors
US5476776Jul 15, 1994Dec 19, 1995University Of New MexicoImmobilized enzymes for use in an electrochemical sensor
US5482008Sep 11, 1992Jan 9, 1996Stafford; Rodney A.Electronic animal identification system
US5482473May 9, 1994Jan 9, 1996Minimed Inc.Flex circuit connector
US5486776Sep 29, 1994Jan 23, 1996Xilinx, Inc.Antifuse-based programmable logic circuit
US5494562Jun 27, 1994Feb 27, 1996Ciba Corning Diagnostics Corp.Electrochemical sensors
US5496453Oct 12, 1994Mar 5, 1996Kyoto Daiichi Kagaku Co., Ltd.Biosensor and method of quantitative analysis using the same
US5497772Nov 19, 1993Mar 12, 1996Alfred E. Mann Foundation For Scientific ResearchGlucose monitoring system
US5502396Sep 21, 1994Mar 26, 1996Asulab S.A.Measuring device with connection for a removable sensor
US5507288May 3, 1995Apr 16, 1996Boehringer Mannheim GmbhAnalytical system for monitoring a substance to be analyzed in patient-blood
US5508509Nov 30, 1993Apr 16, 1996Minnesota Mining And Manufacturing CompanySensing elements and methods for uniformly making individual sensing elements
US5531878May 13, 1993Jul 2, 1996The Victoria University Of ManchesterSensor devices
US5564439Dec 27, 1994Oct 15, 1996George J. PichaInfusion device for soft tissue
US5568806Feb 16, 1995Oct 29, 1996Minimed Inc.Transcutaneous sensor insertion set
US5569186Apr 25, 1994Oct 29, 1996Minimed Inc.Closed loop infusion pump system with removable glucose sensor
US5569462Mar 31, 1995Oct 29, 1996Baxter International Inc.Methods for enhancing vascularization of implant devices
US5571395Nov 4, 1994Nov 5, 1996Goldstar Co., Ltd.Breath alcohol analyzer using a biosensor
US5575930Oct 6, 1993Nov 19, 1996Tietje-Girault; JordisMethod of making gas permeable membranes for amperometric gas electrodes
US5582184Oct 11, 1994Dec 10, 1996Integ IncorporatedInterstitial fluid collection and constituent measurement
US5582497Jun 27, 1994Dec 10, 1996Wing Labo Co., Ltd.Automatic warehouse system
US5593852Sep 1, 1994Jan 14, 1997Heller; AdamSubcutaneous glucose electrode
US5605152Jul 18, 1994Feb 25, 1997Minimed Inc.Optical glucose sensor
US5607565Mar 27, 1995Mar 4, 1997Coulter CorporationApparatus for measuring analytes in a fluid sample
US5611900Jul 20, 1995Mar 18, 1997Michigan State UniversityMicrobiosensor used in-situ
US5624537Sep 20, 1994Apr 29, 1997The University Of British Columbia - University-Industry Liaison OfficeBiosensor and interface membrane
US5628890Sep 27, 1995May 13, 1997Medisense, Inc.Electrochemical sensor
US5640954May 5, 1995Jun 24, 1997Pfeiffer; ErnstMethod and apparatus for continuously monitoring the concentration of a metabolyte
US5653863May 9, 1996Aug 5, 1997Bayer CorporationMethod for reducing bias in amperometric sensors
US5660163May 18, 1995Aug 26, 1997Alfred E. Mann Foundation For Scientific ResearchGlucose sensor assembly
US5665222Oct 11, 1995Sep 9, 1997E. Heller & CompanySoybean peroxidase electrochemical sensor
US5676820Feb 3, 1995Oct 14, 1997New Mexico State University Technology Transfer Corp.Remote electrochemical sensor
US5682884Jul 27, 1994Nov 4, 1997Medisense, Inc.Strip electrode with screen printing
US5686829May 18, 1995Nov 11, 1997Metrohm AgVoltammetric method and apparatus
US5703359Jul 29, 1996Dec 30, 1997Leybold Inficon, Inc.Composite membrane and support assembly
US5704354Jun 23, 1995Jan 6, 1998Siemens AktiengesellschaftElectrocatalytic glucose sensor
US5706807Oct 11, 1996Jan 13, 1998Applied Medical ResearchSensor device covered with foam membrane
US5707502Jul 12, 1996Jan 13, 1998Chiron Diagnostics CorporationSensors for measuring analyte concentrations and methods of making same
US5711861Nov 22, 1995Jan 27, 1998Ward; W. KennethDevice for monitoring changes in analyte concentration
US5735273Sep 12, 1995Apr 7, 1998Cygnus, Inc.Chemical signal-impermeable mask
US5741330Jun 7, 1995Apr 21, 1998Baxter International, Inc.Close vascularization implant material
US5741634Jun 6, 1995Apr 21, 1998A & D Company LimitedThrowaway type chemical sensor
US5746898Nov 12, 1992May 5, 1998Siemens AktiengesellschaftElectrochemical-enzymatic sensor
US5749832Jan 28, 1993May 12, 1998The Victoria University Of ManchesterMonitoring systems
US5756632Jun 2, 1995May 26, 1998The Polymer Technology GroupSystems for premeating molecules of predetermined molecular weight range
US5776324May 17, 1996Jul 7, 1998Encelle, Inc.Electrochemical biosensors
US5777060Sep 26, 1996Jul 7, 1998Minimed, Inc.Silicon-containing biocompatible membranes
US5791344Jan 4, 1996Aug 11, 1998Alfred E. Mann Foundation For Scientific ResearchPatient monitoring system
US5795453Jan 23, 1996Aug 18, 1998Gilmartin; Markas A. T.Electrodes and metallo isoindole ringed compounds
US5795774Jul 10, 1997Aug 18, 1998Nec CorporationBiosensor
US5800420Dec 19, 1996Sep 1, 1998Elan Medical Technologies LimitedAnalyte-controlled liquid delivery device and analyte monitor
US5807375Nov 2, 1995Sep 15, 1998Elan Medical Technologies LimitedAnalyte-controlled liquid delivery device and analyte monitor
US5820622Dec 18, 1996Oct 13, 1998Elan Medical Technologies LimitedAnalyte-controlled liquid delivery device and analyte monitor
US5833603Mar 13, 1996Nov 10, 1998Lipomatrix, Inc.Implantable biosensing transponder
US5837454Jun 7, 1995Nov 17, 1998I-Stat CorporationProcess for the manufacture of wholly microfabricated biosensors
US5840148Jun 30, 1995Nov 24, 1998Bio Medic Data Systems, Inc.Method of assembly of implantable transponder
US5851197Feb 5, 1997Dec 22, 1998Minimed Inc.Injector for a subcutaneous infusion set
US5863400Apr 12, 1995Jan 26, 1999Usf Filtration & Separations Group Inc.Electrochemical cells
US5879373Dec 22, 1995Mar 9, 1999Boehringer Mannheim GmbhSystem and method for the determination of tissue properties
US5882494Aug 28, 1995Mar 16, 1999Minimed, Inc.Polyurethane/polyurea compositions containing silicone for biosensor membranes
US5895235Mar 25, 1996Apr 20, 1999Em Microelectronic-Marin SaProcess for manufacturing transponders of small dimensions
US5914026Jan 6, 1997Jun 22, 1999Implanted Biosystems Inc.Implantable sensor employing an auxiliary electrode
US5928130Mar 16, 1998Jul 27, 1999Schmidt; BrunoApparatus and method for implanting radioactive seeds in tissue
US5944661Apr 16, 1997Aug 31, 1999Giner, Inc.Potential and diffusion controlled solid electrolyte sensor for continuous measurement of very low levels of transdermal alcohol
US5954643Jun 9, 1997Sep 21, 1999Minimid Inc.Insertion set for a transcutaneous sensor
US5954954Jun 20, 1997Sep 21, 1999Suprex CorporationMethod and apparatus for determination of analyte concentration
US5957854Dec 5, 1997Sep 28, 1999Besson; MarcusWireless medical diagnosis and monitoring equipment
US5963132Oct 11, 1996Oct 5, 1999Avid Indentification Systems, Inc.Encapsulated implantable transponder
US5964993Dec 19, 1996Oct 12, 1999Implanted Biosystems Inc.Glucose sensor
US5965380Jan 12, 1999Oct 12, 1999E. Heller & CompanySubcutaneous glucose electrode
US5972199Feb 11, 1997Oct 26, 1999E. Heller & CompanyElectrochemical analyte sensors using thermostable peroxidase
US5985129Apr 28, 1992Nov 16, 1999The Regents Of The University Of CaliforniaMethod for increasing the service life of an implantable sensor
US5989409Sep 11, 1995Nov 23, 1999Cygnus, Inc.Method for glucose sensing
US5999848Sep 12, 1997Dec 7, 1999Alfred E. Mann FoundationDaisy chainable sensors and stimulators for implantation in living tissue
US6001067Mar 4, 1997Dec 14, 1999Shults; Mark C.Device and method for determining analyte levels
US6011984Nov 21, 1996Jan 4, 2000Minimed Inc.Detection of biological molecules using chemical amplification and optical sensors
US6013113Mar 6, 1998Jan 11, 2000Wilson Greatbatch Ltd.Slotted insulator for unsealed electrode edges in electrochemical cells
US6030827Jan 23, 1998Feb 29, 2000I-Stat CorporationMicrofabricated aperture-based sensor
US6049727Apr 3, 1998Apr 11, 2000Animas CorporationImplantable sensor and system for in vivo measurement and control of fluid constituent levels
US6051389Nov 7, 1997Apr 18, 2000Radiometer Medical A/SEnzyme sensor
US6059946Apr 13, 1998May 9, 2000Matsushita Electric Industrial Co., Ltd.Biosensor
US6066083Nov 27, 1998May 23, 2000Syntheon LlcImplantable brachytherapy device having at least partial deactivation capability
US6066448 *Mar 6, 1996May 23, 2000Meso Sclae Technologies, Llc.Multi-array, multi-specific electrochemiluminescence testing
US6081735Jul 3, 1997Jun 27, 2000Masimo CorporationSignal processing apparatus
US6081736Oct 20, 1997Jun 27, 2000Alfred E. Mann FoundationImplantable enzyme-based monitoring systems adapted for long term use
US6083710Jun 16, 1999Jul 4, 2000E. Heller & CompanyElectrochemical analyte measurement system
US6088608Oct 20, 1997Jul 11, 2000Alfred E. Mann FoundationElectrochemical sensor and integrity tests therefor
US6093156Dec 2, 1997Jul 25, 2000Abbott LaboratoriesMethod and apparatus for obtaining blood for diagnostic tests
US6093172Dec 31, 1997Jul 25, 2000Minimed Inc.Injector for a subcutaneous insertion set
US6117290Jul 24, 1998Sep 12, 2000Pepex Biomedical, LlcSystem and method for measuring a bioanalyte such as lactate
US6119028Oct 20, 1997Sep 12, 2000Alfred E. Mann FoundationImplantable enzyme-based monitoring systems having improved longevity due to improved exterior surfaces
US6120676Jun 4, 1999Sep 19, 2000Therasense, Inc.Method of using a small volume in vitro analyte sensor
US6121009Jul 16, 1999Sep 19, 2000E. Heller & CompanyElectrochemical analyte measurement system
US6122536Jul 8, 1996Sep 19, 2000Animas CorporationImplantable sensor and system for measurement and control of blood constituent levels
US6134461Mar 4, 1998Oct 17, 2000E. Heller & CompanyElectrochemical analyte
US6141573Aug 4, 1998Oct 31, 2000Cygnus, Inc.Chemical signal-impermeable mask
US6144869May 11, 1999Nov 7, 2000Cygnus, Inc.Monitoring of physiological analytes
US6144871Mar 26, 1999Nov 7, 2000Nec CorporationCurrent detecting sensor and method of fabricating the same
US6162611Jan 3, 2000Dec 19, 2000E. Heller & CompanySubcutaneous glucose electrode
US6175752Apr 30, 1998Jan 16, 2001Therasense, Inc.Analyte monitoring device and methods of use
US6189536Apr 15, 1999Feb 20, 2001Medtronic Inc.Method for protecting implantable devices
US6212416May 22, 1998Apr 3, 2001Good Samaritan Hospital And Medical CenterDevice for monitoring changes in analyte concentration
US6233471May 11, 1999May 15, 2001Cygnus, Inc.Signal processing for measurement of physiological analysis
US6248067Feb 5, 1999Jun 19, 2001Minimed Inc.Analyte sensor and holter-type monitor system and method of using the same
US6256522Aug 17, 1995Jul 3, 2001University Of Pittsburgh Of The Commonwealth System Of Higher EducationSensors for continuous monitoring of biochemicals and related method
US6259937Jun 19, 1998Jul 10, 2001Alfred E. Mann FoundationImplantable substrate sensor
US6264825 *Jun 23, 1999Jul 24, 2001Clinical Micro Sensors, Inc.Binding acceleration techniques for the detection of analytes
US6268161Sep 30, 1998Jul 31, 2001M-Biotech, Inc.Biosensor
US6274285Nov 12, 1999Aug 14, 2001Agfa-Gevaert NvRadiation-sensitive recording material for the production of driographic offset printing plates
US6275717Jun 23, 1998Aug 14, 2001Elan Corporation, PlcDevice and method of calibrating and testing a sensor for in vivo measurement of an analyte
US6284478Dec 4, 1996Sep 4, 2001E. Heller & CompanySubcutaneous glucose electrode
US6285897Apr 7, 1999Sep 4, 2001Endonetics, Inc.Remote physiological monitoring system
US6293925Dec 18, 1998Sep 25, 2001Minimed Inc.Insertion device for an insertion set and method of using the same
US6294281Nov 30, 1998Sep 25, 2001Therasense, Inc.Biological fuel cell and method
US6300002Aug 16, 1999Oct 9, 2001Moltech Power Systems, Inc.Notched electrode and method of making same
US6309526Aug 26, 1999Oct 30, 2001Matsushita Electric Industrial Co., Ltd.Biosensor
US6325979Oct 15, 1997Dec 4, 2001Robert Bosch GmbhDevice for gas-sensoring electrodes
US6329161Sep 22, 2000Dec 11, 2001Therasense, Inc.Subcutaneous glucose electrode
US6343225Sep 14, 1999Jan 29, 2002Implanted Biosystems, Inc.Implantable glucose sensor
US6356776Aug 16, 2000Mar 12, 2002Cygnus, Inc.Device for monitoring of physiological analytes
US6360888Feb 10, 2000Mar 26, 2002Minimed Inc.Glucose sensor package system
US6366794Nov 19, 1999Apr 2, 2002The University Of ConnecticutGeneric integrated implantable potentiostat telemetry unit for electrochemical sensors
US6368141Jul 2, 1999Apr 9, 2002Vanantwerp Nannette M.Insertion set for a transcutenous sensor with cable connector lock mechanism
US6368274May 8, 2000Apr 9, 2002Medtronic Minimed, Inc.Reusable analyte sensor site and method of using the same
US6400974Jun 29, 2000Jun 4, 2002Sensors For Medicine And Science, Inc.Implanted sensor processing system and method for processing implanted sensor output
US6407195Apr 25, 1996Jun 18, 20023M Innovative Properties CompanyTackified polydiorganosiloxane oligourea segmented copolymers and a process for making same
US6409674Sep 24, 1998Jun 25, 2002Data Sciences International, Inc.Implantable sensor with wireless communication
US6413393Jul 7, 1999Jul 2, 2002Minimed, Inc.Sensor including UV-absorbing polymer and method of manufacture
US6418332Feb 24, 2000Jul 9, 2002MinimedTest plug and cable for a glucose monitor
US6424847Feb 23, 2000Jul 23, 2002Medtronic Minimed, Inc.Glucose monitor calibration methods
US6442413May 15, 2000Aug 27, 2002James H. SilverImplantable sensor
US6447448Dec 30, 1999Sep 10, 2002Ball Semiconductor, Inc.Miniature implanted orthopedic sensors
US6454710Apr 11, 2001Sep 24, 2002Motorola, Inc.Devices and methods for monitoring an analyte
US6459917May 22, 2000Oct 1, 2002Ashok GowdaApparatus for access to interstitial fluid, blood, or blood plasma components
US6461496Oct 27, 1999Oct 8, 2002Therasense, Inc.Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator
US6466810Nov 28, 2000Oct 15, 2002Legacy Good Samaritan Hospital And Medical CenterImplantable device for monitoring changes in analyte concentration
US6484045Feb 10, 2000Nov 19, 2002Medtronic Minimed, Inc.Analyte sensor and method of making the same
US6484046Jul 10, 2000Nov 19, 2002Therasense, Inc.Electrochemical analyte sensor
US6498941Mar 9, 2000Dec 24, 2002Advanced Cardiovascular Systems, Inc.Catheter based probe and method of using same for detecting chemical analytes
US6510329Jan 24, 2001Jan 21, 2003Datex-Ohmeda, Inc.Detection of sensor off conditions in a pulse oximeter
US6512939Jun 27, 2000Jan 28, 2003Medtronic Minimed, Inc.Implantable enzyme-based monitoring systems adapted for long term use
US6514718Nov 29, 2001Feb 4, 2003Therasense, Inc.Subcutaneous glucose electrode
US6520326Oct 9, 2001Feb 18, 2003Medtronic Minimed, Inc.Glucose sensor package system
US6534711Apr 14, 1998Mar 18, 2003The Goodyear Tire & Rubber CompanyEncapsulation package and method of packaging an electronic circuit module
US6542765Mar 10, 1998Apr 1, 2003The Regent Of The University Of CaliforniaMethod for the iontophoretic non-invasive determination of the in vivo concentration level of an inorganic or organic substance
US6546268Jun 2, 2000Apr 8, 2003Ball Semiconductor, Inc.Glucose sensor
US6547839Jan 23, 2001Apr 15, 2003Skc Co., Ltd.Method of making an electrochemical cell by the application of polysiloxane onto at least one of the cell components
US6551496Mar 6, 2001Apr 22, 2003Ysi IncorporatedMicrostructured bilateral sensor
US6553241Aug 30, 2001Apr 22, 2003Mallinckrodt Inc.Oximeter sensor with digital memory encoding sensor expiration data
US6558320Jan 20, 2000May 6, 2003Medtronic Minimed, Inc.Handheld personal data assistant (PDA) with a medical device and method of using the same
US6558321Aug 11, 2000May 6, 2003Dexcom, Inc.Systems and methods for remote monitoring and modulation of medical devices
US6558351Jun 1, 2000May 6, 2003Medtronic Minimed, Inc.Closed loop system for controlling insulin infusion
US6560471Jan 2, 2001May 6, 2003Therasense, Inc.Analyte monitoring device and methods of use
US6565509Sep 21, 2000May 20, 2003Therasense, Inc.Analyte monitoring device and methods of use
US6579498Mar 22, 2000Jun 17, 2003David EgliseImplantable blood glucose sensor system
US6595919Feb 27, 2001Jul 22, 2003Cygnus, Inc.Device for signal processing for measurement of physiological analytes
US6612984Nov 28, 2000Sep 2, 2003Kerr, Ii Robert A.System and method for collecting and transmitting medical data
US6613379May 8, 2001Sep 2, 2003Isense Corp.Implantable analyte sensor
US6615078Apr 21, 2000Sep 2, 2003Cygnus, Inc.Methods and devices for removing interfering species
US6618934Jun 15, 2000Sep 16, 2003Therasense, Inc.Method of manufacturing small volume in vitro analyte sensor
US6642015Dec 29, 2000Nov 4, 2003Minimed Inc.Hydrophilic polymeric material for coating biosensors
US6654625Jun 16, 2000Nov 25, 2003Therasense, Inc.Mass transport limited in vivo analyte sensor
US6689265Mar 23, 2001Feb 10, 2004Therasense, Inc.Electrochemical analyte sensors using thermostable soybean peroxidase
US6699383May 28, 2002Mar 2, 2004Siemens AktiengesellschaftMethod for determining a NOx concentration
US6702857Jul 27, 2001Mar 9, 2004Dexcom, Inc.Membrane for use with implantable devices
US6721587Feb 15, 2002Apr 13, 2004Regents Of The University Of CaliforniaMembrane and electrode structure for implantable sensor
US6730200Apr 28, 2000May 4, 2004Abbott LaboratoriesElectrochemical sensor for analysis of liquid samples
US6737158Oct 30, 2002May 18, 2004Gore Enterprise Holdings, Inc.Porous polymeric membrane toughened composites
US6741877Jan 21, 2000May 25, 2004Dexcom, Inc.Device and method for determining analyte levels
US6743635Nov 1, 2002Jun 1, 2004Home Diagnostics, Inc.System and methods for blood glucose sensing
US6773565Jun 20, 2001Aug 10, 2004Kabushiki Kaisha RikenNOx sensor
US6784274Aug 6, 2002Aug 31, 2004Minimed Inc.Hydrophilic, swellable coatings for biosensors
US6793802Jan 4, 2001Sep 21, 2004Tyson Bioresearch, Inc.Biosensors having improved sample application and measuring properties and uses thereof
US6801041May 14, 2002Oct 5, 2004Abbott LaboratoriesSensor having electrode for determining the rate of flow of a fluid
US6802957Sep 28, 2001Oct 12, 2004Marine Biological LaboratorySelf-referencing enzyme-based microsensor and method of use
US6809507Dec 28, 2001Oct 26, 2004Medtronic Minimed, Inc.Implantable sensor electrodes and electronic circuitry
US6809653Dec 17, 1999Oct 26, 2004Medtronic Minimed, Inc.Telemetered characteristic monitor system and method of using the same
US6862465Jul 27, 2001Mar 1, 2005Dexcom, Inc.Device and method for determining analyte levels
US6881551Jan 28, 2003Apr 19, 2005Therasense, Inc.Subcutaneous glucose electrode
US6891317May 21, 2002May 10, 2005Sri InternationalRolled electroactive polymers
US6892085Nov 26, 2002May 10, 2005Medtronic Minimed, Inc.Glucose sensor package system
US6893552Oct 23, 2001May 17, 2005Arrowhead Center, Inc.Microsensors for glucose and insulin monitoring
US6895263May 8, 2002May 17, 2005Medtronic Minimed, Inc.Real time self-adjusting calibration algorithm
US6895265Jun 25, 2002May 17, 2005James H. SilverImplantable sensor
US6952604Dec 21, 2001Oct 4, 2005Becton, Dickinson And CompanyMinimally-invasive system and method for monitoring analyte levels
US6965791Mar 26, 2003Nov 15, 2005Sorenson Medical, Inc.Implantable biosensor system, apparatus and method
US6972080Jun 12, 2000Dec 6, 2005Matsushita Electric Industrial Co., Ltd.Electrochemical device for moving particles covered with protein
US7003336Feb 8, 2001Feb 21, 2006Medtronic Minimed, Inc.Analyte sensor method of making the same
US7008979Sep 27, 2002Mar 7, 2006Hydromer, Inc.Coating composition for multiple hydrophilic applications
US7033322Nov 8, 2001Apr 25, 2006Silver James HImplantable sensor
US7070580Apr 1, 2003Jul 4, 2006Unomedical A/SInfusion device and an adhesive sheet material and a release liner
US7078582Aug 21, 2001Jul 18, 20063M Innovative Properties CompanyStretch removable adhesive articles and methods
US7081195Dec 7, 2004Jul 25, 2006Dexcom, Inc.Systems and methods for improving electrochemical analyte sensors
US7110803Sep 9, 2003Sep 19, 2006Dexcom, Inc.Device and method for determining analyte levels
US7115884Oct 6, 1997Oct 3, 2006Trustees Of Tufts CollegeSelf-encoding fiber optic sensor
US7134999Aug 22, 2003Nov 14, 2006Dexcom, Inc.Optimized sensor geometry for an implantable glucose sensor
US7136689Jan 19, 2005Nov 14, 2006Dexcom, Inc.Device and method for determining analyte levels
US7153265Apr 22, 2002Dec 26, 2006Medtronic Minimed, Inc.Anti-inflammatory biosensor for reduced biofouling and enhanced sensor performance
US7166074Jun 2, 2003Jan 23, 2007Medtronic Minimed, Inc.Reusable analyte sensor site and method of using the same
US7192450Aug 22, 2003Mar 20, 2007Dexcom, Inc.Porous membranes for use with implantable devices
US7207974Feb 21, 2003Apr 24, 2007Medtronic Minimed, Inc.Insertion device for an insertion set and method of using the same
US7248906Dec 12, 2002Jul 24, 2007Danfoss A/SMethod and device for monitoring analyte concentration by optical detection
US7267665Dec 31, 2002Sep 11, 2007Medtronic Minimed, Inc.Closed loop system for controlling insulin infusion
US7279174May 8, 2003Oct 9, 2007Advanced Cardiovascular Systems, Inc.Stent coatings comprising hydrophilic additives
US20020042561Nov 30, 2001Apr 11, 2002Schulman Joseph H.Implantable sensor and integrity tests therefor
US20020084196Dec 28, 2001Jul 4, 2002Therasense, Inc.Small volume in vitro analyte sensor and methods
US20020099997Sep 28, 2001Jul 25, 2002Philippe PiretTurbocoding methods with a large minimum distance, and systems for implementing them
US20020119711Jan 4, 2002Aug 29, 2002Minimed, Inc.Insertion set for a transcutaneous sensor
US20020177763May 22, 2001Nov 28, 2002Burns David W.Integrated lancets and methods
US20020188185Jun 12, 2001Dec 12, 2002Borzu SohrabPercutaneous biological fluid sampling and analyte measurement devices and methods
US20030004457Jun 25, 2002Jan 2, 2003Andersson Stig O.Hypodermic implant device
US20030006669May 21, 2002Jan 9, 2003Sri InternationalRolled electroactive polymers
US20030009093Jun 25, 2002Jan 9, 2003Silver James H.Implantable sensor
US20030032874Jul 27, 2001Feb 13, 2003Dexcom, Inc.Sensor head for use with implantable devices
US20030036773Aug 2, 2002Feb 20, 2003Whitehurst Todd K.Systems and methods for treatment of coronary artery disease
US20030050546Jun 21, 2002Mar 13, 2003Desai Shashi P.Methods for improving the performance of an analyte monitoring system
US20030065254Oct 31, 2002Apr 3, 2003Alfred E. Mann Foundation For Scientific ResearchImplantable enzyme-based monitoring system having improved longevity due to improved exterior surfaces
US20030088166Nov 11, 2002May 8, 2003Therasense, Inc.Electrochemical analyte sensor
US20030097082Dec 23, 2002May 22, 2003Board Of Regents, The University Of Texas SystemMethods and apparatuses for navigating the subarachnoid space
US20030125613Dec 27, 2001Jul 3, 2003Medtronic Minimed, Inc.Implantable sensor flush sleeve
US20030130616Dec 31, 2002Jul 10, 2003Medtronic Minimed, Inc.Closed loop system for controlling insulin infusion
US20030134347Jan 28, 2003Jul 17, 2003Therasense, Inc.Subcutaneous glucose electrode
US20030138674Nov 14, 2002Jul 24, 2003Zeikus Gregory J.Electrochemical methods for generation of a biological proton motive force and pyridine nucleotide cofactor regeneration
US20030187338Apr 18, 2003Oct 2, 2003Therasense, Inc.Analyte monitoring device and methods of use
US20030199745May 14, 2003Oct 23, 2003Cygnus, Inc.Methods and devices for removing interfering species
US20030203498Nov 1, 2002Oct 30, 2003Home Diagnostics, Inc.System and methods for blood glucose sensing
US20030211050May 6, 2003Nov 13, 2003The Procter & Gamble CompanyCompositions comprising anionic functionalized polyorganosiloxanes for hydrophobically modifying surfaces and enhancing delivery of active agents to surfaces treated therewith
US20030211625Apr 1, 2003Nov 13, 2003Cohan Bruce E.Method and apparatus for non-invasive monitoring of blood substances using self-sampled tears
US20030225324Jun 3, 2002Dec 4, 2003Anderson Edward J.Noninvasive detection of a physiologic Parameter within a body tissue of a patient
US20030225437Apr 4, 2003Dec 4, 2003Ferguson Patrick J.Device for retaining material
US20030235817Mar 21, 2003Dec 25, 2003Miroslaw BartkowiakMicroprocessors, devices, and methods for use in analyte monitoring systems
US20040006263Feb 14, 2003Jan 8, 2004Anderson Edward J.Noninvasive detection of a physiologic parameter within a body tissue of a patient
US20040015063Dec 21, 2001Jan 22, 2004Denuzzio John D.Minimally-invasive system and method for monitoring analyte levels
US20040045879Sep 9, 2003Mar 11, 2004Dexcom, Inc.Device and method for determining analyte levels
US20040063167Jul 11, 2003Apr 1, 2004Peter KaastrupMinimising calibration problems of in vivo glucose sensors
US20040074785Oct 18, 2002Apr 22, 2004Holker James D.Analyte sensors and methods for making them
US20040078219Oct 21, 2002Apr 22, 2004Kimberly-Clark Worldwide, Inc.Healthcare networks with biosensors
US20040106857Nov 20, 2003Jun 3, 2004Regents Of The University Of CaliforniaMembrane and electrode structure for implantable sensor
US20040106859Nov 24, 2003Jun 3, 2004James SayAnalyte monitoring device and methods of use
US20040111017Nov 25, 2003Jun 10, 2004Therasense, Inc.Mass transport limited in vivo analyte sensor
US20040133164Nov 5, 2003Jul 8, 2004Funderburk Jeffery V.Sensor inserter device and methods of use
US20040138543Oct 27, 2003Jul 15, 2004Russell Geoffrey A.Assembly of single use sensing elements
US20040143173Jun 2, 2003Jul 22, 2004Medtronic Minimed, Inc.Reusable analyte sensor site and method of using the same
US20040167801Feb 16, 2004Aug 26, 2004James SayAnalyte monitoring device and methods of use
US20040173472Sep 28, 2001Sep 9, 2004Marine Biological LaboratorySelf-referencing enzyme-based microsensor and method of use
US20040176672Jan 15, 2004Sep 9, 2004Silver James H.Implantable, retrievable, thrombus minimizing sensors
US20040180391Oct 10, 2003Sep 16, 2004Miklos GratzlSliver type autonomous biosensors
US20040219664Jun 7, 2004Nov 4, 2004Therasense, Inc.Electrodes with multilayer membranes and methods of using and making the electrodes
US20040224001May 8, 2003Nov 11, 2004Pacetti Stephen D.Stent coatings comprising hydrophilic additives
US20040234575Apr 15, 2003Nov 25, 2004Roland HorresMedical products comprising a haemocompatible coating, production and use thereof
US20040236200Nov 24, 2003Nov 25, 2004James SayAnalyte monitoring device and methods of use
US20040242982Sep 6, 2002Dec 2, 2004Tetsuya SakataMeasuring instrument, installation body, and density measurer
US20040254433Jun 12, 2003Dec 16, 2004Bandis Steven D.Sensor introducer system, apparatus and method
US20050027180Aug 1, 2003Feb 3, 2005Goode Paul V.System and methods for processing analyte sensor data
US20050027181Aug 1, 2003Feb 3, 2005Goode Paul V.System and methods for processing analyte sensor data
US20050027182Dec 31, 2003Feb 3, 2005Uzair SiddiquiSystem for monitoring physiological characteristics
US20050027463Aug 1, 2003Feb 3, 2005Goode Paul V.System and methods for processing analyte sensor data
US20050031689May 10, 2004Feb 10, 2005Dexcom, Inc.Biointerface membranes incorporating bioactive agents
US20050033132May 14, 2004Feb 10, 2005Shults Mark C.Analyte measuring device
US20050038332Jun 3, 2004Feb 17, 2005Frank SaidaraSystem for monitoring physiological characteristics
US20050043598Aug 22, 2003Feb 24, 2005Dexcom, Inc.Systems and methods for replacing signal artifacts in a glucose sensor data stream
US20050051427Jul 21, 2004Mar 10, 2005Brauker James H.Rolled electrode array and its method for manufacture
US20050051440Jul 21, 2004Mar 10, 2005Simpson Peter C.Electrochemical sensors including electrode systems with increased oxygen generation
US20050054909Jul 21, 2004Mar 10, 2005James PetisceOxygen enhancing membrane systems for implantable devices
US20050056551Jun 28, 2002Mar 17, 2005Cranfield UniversityElectrochemical detection of analytes
US20050056552Jul 21, 2004Mar 17, 2005Simpson Peter C.Increasing bias for oxygen production in an electrode system
US20050070770Dec 12, 2002Mar 31, 2005Holger DiracMethod and device for monitoring analyte concentration by optical detection
US20050077584Dec 6, 2004Apr 14, 2005Uhland Scott A.Hermetically sealed microchip reservoir devices
US20050090607Oct 28, 2003Apr 28, 2005Dexcom, Inc.Silicone composition for biocompatible membrane
US20050096519Aug 2, 2004May 5, 2005Denuzzio John D.Minimally-invasive system and method for monitoring analyte levels
US20050103625Dec 22, 2004May 19, 2005Rathbun RhodesSensor head for use with implantable devices
US20050112169Aug 22, 2003May 26, 2005Dexcom, Inc.Porous membranes for use with implantable devices
US20050115832Jul 21, 2004Jun 2, 2005Simpson Peter C.Electrode systems for electrochemical sensors
US20050121322Jan 24, 2005Jun 9, 2005Therasense, Inc.Analyte monitoring device and methods of use
US20050143635Dec 3, 2004Jun 30, 2005Kamath Apurv U.Calibration techniques for a continuous analyte sensor
US20050176136Nov 16, 2004Aug 11, 2005Dexcom, Inc.Afinity domain for analyte sensor
US20050177036Dec 22, 2004Aug 11, 2005Shults Mark C.Device and method for determining analyte levels
US20050181012Jan 11, 2005Aug 18, 2005Sean SaintComposite material for implantable device
US20050182451Jan 11, 2005Aug 18, 2005Adam GriffinImplantable device with improved radio frequency capabilities
US20050183954Apr 19, 2005Aug 25, 2005Hitchcock Robert W.Implantable biosensor system, apparatus and method
US20050192557Feb 26, 2004Sep 1, 2005DexcomIntegrated delivery device for continuous glucose sensor
US20050197554Feb 28, 2005Sep 8, 2005Michael PolchaComposite thin-film glucose sensor
US20050211571Jun 23, 2003Sep 29, 2005Jurgen SchuleinElectrochemical detection method and device
US20050215871Dec 7, 2004Sep 29, 2005Feldman Benjamin JAnalyte sensor, and associated system and method employing a catalytic agent
US20050242479May 3, 2004Nov 3, 2005Petisce James RImplantable analyte sensor
US20050245795May 3, 2004Nov 3, 2005Dexcom, Inc.Implantable analyte sensor
US20050245799May 3, 2004Nov 3, 2005Dexcom, Inc.Implantable analyte sensor
US20050258037Apr 21, 2003Nov 24, 2005Kiamars HajizadehElectrochemical sensor
US20050261563May 20, 2004Nov 24, 2005Peter ZhouTransducer for embedded bio-sensor using body energy as a power source
US20050272989Jun 4, 2004Dec 8, 2005Medtronic Minimed, Inc.Analyte sensors and methods for making and using them
US20060003398Jul 15, 2005Jan 5, 2006Therasense, Inc.Subcutaneous glucose electrode
US20060015020Jul 6, 2004Jan 19, 2006Dexcom, Inc.Systems and methods for manufacture of an analyte-measuring device including a membrane system
US20060015024Mar 10, 2005Jan 19, 2006Mark BristerTranscutaneous medical device with variable stiffness
US20060016700Jun 21, 2005Jan 26, 2006Dexcom, Inc.Transcutaneous analyte sensor
US20060019327Mar 10, 2005Jan 26, 2006Dexcom, Inc.Transcutaneous analyte sensor
US20060020186Mar 10, 2005Jan 26, 2006Dexcom, Inc.Transcutaneous analyte sensor
US20060020187Mar 10, 2005Jan 26, 2006Dexcom, Inc.Transcutaneous analyte sensor
US20060020189Mar 10, 2005Jan 26, 2006Dexcom, Inc.Transcutaneous analyte sensor
US20060020191Mar 10, 2005Jan 26, 2006Dexcom, Inc.Transcutaneous analyte sensor
US20060020192Mar 10, 2005Jan 26, 2006Dexcom, Inc.Transcutaneous analyte sensor
US20060036139Mar 10, 2005Feb 16, 2006Dexcom, Inc.Transcutaneous analyte sensor
US20060036140Mar 10, 2005Feb 16, 2006Dexcom, Inc.Transcutaneous analyte sensor
US20060036141Mar 10, 2005Feb 16, 2006Dexcom, Inc.Transcutaneous analyte sensor
US20060036142Mar 10, 2005Feb 16, 2006Dexcom, Inc.Transcutaneous analyte sensor
US20060036143Mar 10, 2005Feb 16, 2006Dexcom, Inc.Transcutaneous analyte sensor
US20060036144Jun 21, 2005Feb 16, 2006Dexcom, Inc.Transcutaneous analyte sensor
US20060036145Jun 21, 2005Feb 16, 2006Dexcom, Inc.Transcutaneous analyte sensor
US20060078908Jun 7, 2005Apr 13, 2006Pitner James BMultianalyte sensor
US20060079740Nov 16, 2005Apr 13, 2006Silver James HSensors for detecting substances indicative of stroke, ischemia, or myocardial infarction
US20060142651Feb 22, 2006Jun 29, 2006Mark BristerAnalyte sensor
US20060155180Feb 22, 2006Jul 13, 2006Mark BristerAnalyte sensor
US20060177379Dec 30, 2005Aug 10, 2006Soheil AsgariComposition comprising an agent providing a signal, an implant material and a drug
US20060183871Apr 14, 2006Aug 17, 2006Ward Robert SBiosensor membrane material
US20060183984Feb 22, 2006Aug 17, 2006Dobbles J MAnalyte sensor
US20060183985Feb 22, 2006Aug 17, 2006Mark BristerAnalyte sensor
US20060189856Apr 25, 2006Aug 24, 2006James PetisceOxygen enhancing membrane systems for implantable devices
US20060195029Jan 17, 2006Aug 31, 2006Shults Mark CLow oxygen in vivo analyte sensor
US20060198864May 3, 2006Sep 7, 2006Mark ShultsBiointerface membranes incorporating bioactive agents
US20060200019Apr 25, 2006Sep 7, 2006James PetisceOxygen enhancing membrane systems for implantable devices
US20060200020May 2, 2006Sep 7, 2006Mark BristerTranscutaneous analyte sensor
US20060200022May 2, 2006Sep 7, 2006Brauker James HOptimized sensor geometry for an implantable glucose sensor
US20060200970May 2, 2006Sep 14, 2006Mark BristerTranscutaneous analyte sensor
US20060204536May 3, 2006Sep 14, 2006Mark ShultsBiointerface membranes incorporating bioactive agents
US20060211921May 2, 2006Sep 21, 2006Brauker James HOptimized sensor geometry for an implantable glucose sensor
US20060222566Jan 18, 2006Oct 5, 2006Brauker James HTranscutaneous analyte sensor
US20060224108May 2, 2006Oct 5, 2006Brauker James HOptimized sensor geometry for an implantable glucose sensor
US20060229512Jan 18, 2006Oct 12, 2006Petisce James RCellulosic-based interference domain for an analyte sensor
US20060235285May 2, 2006Oct 19, 2006Mark BristerTranscutaneous analyte sensor
US20060258761Apr 14, 2006Nov 16, 2006Robert BoockSilicone based membranes for use in implantable glucose sensors
US20060263839May 10, 2006Nov 23, 2006Isense CorporationCombined drug delivery and analyte sensor apparatus
US20060270922May 23, 2006Nov 30, 2006Brauker James HAnalyte sensor
US20060270923May 23, 2006Nov 30, 2006Brauker James HAnalyte sensor
US20060275857May 16, 2006Dec 7, 2006Kjaer ThomasEnzyme sensor with a cover membrane layer covered by a hydrophilic polymer
US20060275859May 16, 2006Dec 7, 2006Kjaer ThomasEnzyme sensor including a water-containing spacer layer
US20060289307Aug 24, 2005Dec 28, 2006University Of South FloridaEpoxy Enhanced Polymer Membrane to Increase Durability of Biosensors
US20070007133Mar 29, 2006Jan 11, 2007Andre MangSensor with increased biocompatibility
US20070027384Oct 4, 2006Feb 1, 2007Mark BristerDual electrode system for a continuous analyte sensor
US20070027385Oct 4, 2006Feb 1, 2007Mark BristerDual electrode system for a continuous analyte sensor
US20070032717Oct 4, 2006Feb 8, 2007Mark BristerDual electrode system for a continuous analyte sensor
US20070032718Oct 10, 2006Feb 8, 2007Shults Mark CDevice and method for determining analyte levels
US20070038044Jun 1, 2006Feb 15, 2007Dobbles J MAnalyte sensor
US20070045902May 23, 2006Mar 1, 2007Brauker James HAnalyte sensor
US20070093704Oct 4, 2006Apr 26, 2007Mark BristerDual electrode system for a continuous analyte sensor
US20070135698Dec 13, 2005Jun 14, 2007Rajiv ShahBiosensors and methods for making and using them
US20070163880Mar 1, 2007Jul 19, 2007Dexcom, Inc.Analyte sensor
US20070173709Jan 17, 2007Jul 26, 2007Petisce James RMembranes for an analyte sensor
US20070173710Jan 17, 2007Jul 26, 2007Petisce James RMembranes for an analyte sensor
US20070173711Sep 23, 2005Jul 26, 2007Medtronic Minimed, Inc.Sensor with layered electrodes
US20070197889Feb 22, 2006Aug 23, 2007Mark BristerAnalyte sensor
US20070203966Mar 23, 2007Aug 30, 2007Dexcom, Inc.Transcutaneous analyte sensor
US20070208246Apr 11, 2007Sep 6, 2007Brauker James HTranscutaneous analyte sensor
US20070213611Mar 27, 2007Sep 13, 2007Simpson Peter CDual electrode system for a continuous analyte sensor
US20070215491Apr 3, 2007Sep 20, 2007Abbott Diabetes Care, Inc.Subcutaneous Glucose Electrode
US20070218097Apr 3, 2007Sep 20, 2007Abbott Diabetes Care, Inc.Subcutaneous Glucose Electrode
US20070227907Apr 4, 2006Oct 4, 2007Rajiv ShahMethods and materials for controlling the electrochemistry of analyte sensors
US20070232879May 3, 2007Oct 4, 2007Mark BristerTranscutaneous analyte sensor
US20070235331May 18, 2007Oct 11, 2007Dexcom, Inc.Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise
US20070259217May 1, 2007Nov 8, 2007The Penn State Research FoundationMaterials and configurations for scalable microbial fuel cells
US20070275193Feb 14, 2005Nov 29, 2007Desimone Joseph MFunctional Materials and Novel Methods for the Fabrication of Microfluidic Devices
US20070299385Sep 6, 2007Dec 27, 2007Microchips, Inc.Device for the controlled exposure of reservoir-based sensors
US20080021666Oct 1, 2007Jan 24, 2008Dexcom, Inc.System and methods for processing analyte sensor data
US20080027301Nov 1, 2006Jan 31, 2008Ward W KennethAnalyte sensing and response system
US20080033269Oct 29, 2005Feb 7, 2008San Medi Tech (Huzhou) Co., Ltd.Catheter-free implantable needle biosensor
US20080034972Aug 10, 2006Feb 14, 2008The Regents Of The University Of CaliforniaMembranes with controlled permeability to polar and apolar molecules in solution and methods of making same
US20080045824Jun 14, 2007Feb 21, 2008Dexcom, Inc.Silicone composition for biocompatible membrane
US20080154101Sep 27, 2007Jun 26, 2008Faquir JainImplantable Biosensor and Methods of Use Thereof
US20080188731Apr 11, 2008Aug 7, 2008Dexcom, Inc.Transcutaneous analyte sensor
US20080194935Apr 11, 2008Aug 14, 2008Dexcom, Inc.Transcutaneous analyte sensor
US20080194938Apr 17, 2008Aug 14, 2008Dexcom, Inc.Transcutaneous medical device with variable stiffness
US20080208025May 1, 2008Aug 28, 2008Dexcom, Inc.Low oxygen in vivo analyte sensor
US20080214915Apr 11, 2008Sep 4, 2008Dexcom, Inc.Transcutaneous analyte sensor
US20080214918Apr 28, 2008Sep 4, 2008Dexcom, Inc.Dual electrode system for a continuous analyte sensor
US20080242961Jun 11, 2008Oct 2, 2008Dexcom, Inc.Transcutaneous analyte sensor
US20080262334Jun 30, 2008Oct 23, 2008Animas Technologies, Llc.Method and device for predicting physiological values
US20080296155May 1, 2008Dec 4, 2008Dexcom, Inc.Low oxygen in vivo analyte sensor
US20080306368Aug 21, 2008Dec 11, 2008Dexcom, Inc.System and methods for processing analyte sensor data
US20090012379Aug 20, 2008Jan 8, 2009Dexcom, Inc.System and methods for processing analyte sensor data
US20090045055Oct 28, 2008Feb 19, 2009Dexcom, Inc.Sensor head for use with implantable devices
US20090062633Nov 4, 2008Mar 5, 2009Dexcorn, Inc.Implantable analyte sensor
US20090076356Nov 3, 2008Mar 19, 2009Dexcom, Inc.Dual electrode system for a continuous analyte sensor
US20090076360Sep 13, 2007Mar 19, 2009Dexcom, Inc.Transcutaneous analyte sensor
US20090099436Dec 15, 2008Apr 16, 2009Dexcom, Inc.Dual electrode system for a continuous analyte sensor
US20090124879Jan 14, 2009May 14, 2009Dexcom, Inc.Transcutaneous analyte sensor
US20090143660Dec 5, 2008Jun 4, 2009Dexcom, Inc.Transcutaneous analyte sensor
USRE31916Apr 29, 1981Jun 18, 1985Becton Dickinson & CompanyElectrochemical detection cell
EP0098592A2Jul 5, 1983Jan 18, 1984Fujisawa Pharmaceutical Co., Ltd.Portable artificial pancreas
EP0127958B1May 8, 1984Mar 11, 1992MediSense, Inc.Sensor electrode systems
EP0284518B1Mar 25, 1988Oct 7, 1992Isao KarubeMiniaturized oxygen electrode and miniaturized biosensor and production process thereof
EP0320109A1Nov 2, 1988Jun 14, 1989MediSense, Inc.Improved sensing system
EP0353328A1Aug 3, 1988Feb 7, 1990Dräger Nederland B.V.A polarographic-amperometric three-electrode sensor
EP0390390A1Mar 19, 1990Oct 3, 1990Associated Universities, Inc.Electrochemical biosensor based on immobilized enzymes and redox polymers
EP0396788A1May 8, 1989Nov 14, 1990Dräger Nederland B.V.Process and sensor for measuring the glucose content of glucosecontaining fluids
EP0476980B1Sep 17, 1991Apr 9, 1997Fujitsu LimitedOxygen electrode and process for the production thereof
EP0534074B1Jul 15, 1992Mar 6, 1996Institut für Diabetestechnologie Gemeinnützige Forschungs - und Entwicklungsgesellschaft mbHMethod and instrument for testing the concentration of body fluid constituents
EP0535898B1Sep 28, 1992Feb 5, 1997Eli Lilly And CompanyHydrophilic polyurethane membranes for electrochemical glucose sensors
EP0539625A1Oct 28, 1991May 5, 1993Dräger Medical Electronics B.V.Electrochemical sensor for measuring the glucose content of glucose containing fluids
EP0817809B1Mar 25, 1996Jul 31, 2002Medtronic MiniMed, Inc.Homogenous polymer compositions containing silicone for biosensor membranes
EP0838230B1Oct 22, 1997Sep 17, 2003Terumo Kabushiki KaishaGuide wire
EP0967788A2Feb 10, 1999Dec 29, 1999Hewlett-Packard CompanyDynamic generation of multi-resolution and tile-based images from flat compressed images
EP1153571A1May 3, 2001Nov 14, 2001A. Menarini Industrie Farmaceutiche Riunite S.R.L.Apparatus for measurement and control of the content of glucose, lactate or other metabolites in biological fluids
FR2656423A1 Title not available
FR2760962B1 Title not available
GB1442303A Title not available
JP62083649A Title not available
JP62083849A Title not available
JP63067560A Title not available
WO2001068901A2Mar 16, 2001Sep 20, 2001Roche Diagnostics GmbhImplantable analyte sensor
WO2001088524A1May 10, 2001Nov 22, 2001Therasense IncElectrodes with multilayer membranes and methods of using and making the electrodes
WO2004021877A1Sep 4, 2002Mar 18, 2004Andreas CaduffMethod and device for measuring glucose
Non-Patent Citations
Reference
1Aalders et al. 1991. Development of a wearable glucose sensor; studies in healthy volunteers and in diabetic patients. The International Journal of Artificial Organs 14(2):102-108.
2Abe et al. 1992. Characterization of glucose microsensors for intracellular measurements. Anal. Chem. 64(18):2160-2163.
3Abel et al. 1984. Experience with an implantable glucose sensor as a prerequisite of an artificial beta cell, Biomed. Biochim. Acta 43(5):577-584.
4Abel, P. U.; von Woedtke, T. Biosensors for in vivo glucose measurement: can we cross the experimental stage. Biosens Bioelectron 2002, 17, 1059-1070.
5Armour, et al. Dec. 1990. Application of Chronic Intravascular Blood Glucose Sensor in Dogs. Diabetes 39:1519-1526.
6Asberg et al. 2003. Hydrogels of a Conducting Conjugated Polymer as 3-D Enzyme Electrode. Biosensors Bioelectronics. pp. 199-207.
7Atanasov et al. 1994. Biosensor for continuous glucose monitoring. Biotechnology and Bioengineering 43:262-266.
8Atanasov et al. 1997. Implantation of a refillable glucose monitoring-telemetry device. Biosens Bioelectron 12:669-680.
9Aussedat, et al. 1997. A user-friendly method for calibrating a subcutaneous glucose sensor-based hypoglycaemic alarm. Biosensors & Bioelectronics 12(11):1061-1071.
10Baker et al. 1993. Dynamic concentration challenges for biosensor characterization. Biosensors & Bioelectronics, 8:433-441.
11Baker, et al. 1996. Dynamic delay and maximal dynamic error in continuous biosensors. Anal Chem 68(8):1292-1297.
12Bani Amer, M. M. 2002. An accurate amperometric glucose sensor based glucometer with eliminated cross-sensitivity. J Med Eng Technol 26(5):208-213.
13Bard et al. 1980. Electrochemical Methods. John Wiley & Sons, pp. 173-175.
14Beach et al. 1999. Subminiature implantable potentiostat and modified commercial telemetry device for remote glucose monitoring. IEEE Transactions on Instrumentation and Measurement 48(6):1239-1245.
15Bellucci et al. Jan. 1986. Electrochemical behaviour of graphite-epoxy composite materials (GECM) in aqueous salt solutions, Journal of Applied Electrochemistry, 16(1):15-22.
16Bessman et al., Progress toward a glucose sensor for the artificial pancreas, Proceedings of a Workshop on Ion-Selective Microelectrodes, Jun. 4-5, 1973, Boston, MA, 189-197.
17Bindra et al. 1989. Pulsed amperometric detection of glucose in biological fluids at a surface-modified gold electrode. Anal Chem, 61:2566-2570.
18Bindra et al. 1991. Design and in Vitro Studies of a Needle-Type Glucose Senso for Subcutaneous Monitoring. Anal. Chem 63:1692-96.
19Bisenberger et al. 1995. A triple-step potential waveform at enzyme multisensors with thick-film gold electrodes for detection of glucose and sucrose. Sensors and Actuators, B 28:181-189.
20Bode, B. W. 2000. Clinical utility of the continuous glucose monitoring system. Diabetes Technol Ther, 2(Suppl 1):S35-41.
21Bott, A. 1998. Electrochemical methods for the determination of glucose. Current Separations, 17(1)25-31.
22Bott, A. W. 1997. A comparison of cyclic voltammetry and cyclic staircase voltammetry. Current Separations, 16(1):23-26.
23 *Bott, A.W. 1997. A Comparison of cyclic voltammetry and staircase voltammetry. Current Separations, 16(1):23-26.
24Bowman,et al. 1986. The packaging of implantable integrated sensors. IEEE Trans Biomed Eng BME33(2):248-255.
25Brooks, et al. "Development of an on-line glucose sensor for fermentation monitoring," Biosensors, 3:45-56 (1987/88).
26CAI et al. 2004. A wireless, remote query glucose biosensor based on a pH-sensitive polymer. Anal Chem 76(4):4038-4043.
27Campanella et al. 1993. Biosensor for direct determination of glucose and lactate in undiluted biological fluids. Biosensors & Bioelectronics 8:307-314.
28Cass et al. "Ferrocene-mediated enzyme electrodes for amperometric determination of glucose," Anal. Chem., 36:667-71 (1984).
29Cassidy et al., Apr. 1993. Novel electrochemical device for the detection of cholesterol or glucose, Analyst, 118:415-418.
30Chen et al. 2006. A noninterference polypyrrole glucose biosensor. Biosensors and Bioelectronics 22:639-643.
31Chia et al. 2004. Glucose sensors: toward closed loop insulin delivery. Endocrinol Metab Clin North Am 33:175-95.
32Choleau et al. 2002. Calibration of a subcutaneo amperometric glucose sensor. Part 1. Effect of measurement uncertainties on the determination of sensor sensitivity and background current. Biosensors and Bioelectronics, 17:641-646.
33Choleau, et al. 2002. Calibration of a subcutaneous amperometric glucose sensor implanted for 7 days in diabetic patients. Part 2. Superiority of the one-point calibration method. Biosensors and Bioelectronics 17:647-654.
34Claremont et al. Jul. 1986. Potentially-implantable, ferrocene-mediated glucose sensor. J. Biomed. Eng. 8:272-274.
35Clark et al. 1981. One-minute electrochemical enzymic assay for cholesterol in biological materials, Clin. Chem. 27(12):1978-1982.
36Clark et al. 1987. Configurational cyclic voltammetry: increasing the specificity and reliablity of implanted electrodes, IEEE/Ninth Annual Conference of the Engineering in Medicine and Biology Society, pp. 0782-0783.
37Clark et al. 1988. Long-term stability of electroenzymatic glucose sensors implanted in mice. Trans Am Soc Artif Intern Organs 34:259-265.
38CLSI. Performance metrics for continuous interstitial glucose monitoring; approved guideline, CLSI document POCT05-A. Wayne, PA: Clinical and Laboratory Standards Institute: 2008 28(33), 72 pp.
39Csoregi et al., 1994. Design, characterization, and one-point in vivo calibration of a subcutaneously implanted glucose electrode. Anal Chem. 66(19):3131-3138.
40Danielsson et al. 1988. Enzyme thermistors, Methods in Enzymology, 137:181-197.
41Davies, et al. 1992. Polymer membranes in clinical sensor applications. I. An overview of membrane function, Biomaterials, 13(14):971-978.
42Davis et al. 1983. Bioelectrochemical fuel cell and sensor based on a quinoprotein, alcohol dehydrogenase. Enzyme Microb. Technol., vol. 5, September, 383-388.
43Dixon et al. 2002. Characterization in vitro and in vivo of the oxygen dependence of an enzyme/polymer biosensor for monitoring brain glucose. Journal of Neuroscience Methods, 119:135-142.
44Durliat et al. 1976. Spectrophotometric and electrochemical determinations of L(+)-lactate in blood by use of lactate dehydrogenase from yeast, Clin. Chem. 22(11):1802-1805.
45El Deheigy et al. 1986. Optimization of an implantable coated wire glucose sensor. J. Biomed Eng. 8: 121-129.
46Fare et al. 1998. Functional characterization of a conducting polymer-based immunoassay system. Biosensors & Bioelectronics 13(3-4):459-470.
47Feldman et al. 2003. A continuous glucose sensor based on wired enzyme technology—results from a 3-day trial in patients with type 1 diabetes. Diabetes Technol Ther 5(5):769-779.
48Fischer et al. 1989. Oxygen Tension at the Subcutaneous Implantation Site of Glucose Sensors. Biomed. Biochem 11/12:965-972.
49Fischer et al. 1995. Hypoglycaemia-warning by means of subcutaneous electrochemical glucose sensors: an animal study, Horm. Metab. Rese. 27:53.
50Frohnauer, et al. 2001. Graphical human insulin time-activity profiles using standardized definitions. Diabetes Technology & Therapeutics 3(3):419-429.
51Frost, et al. 2002. Implantable chemical sensors for real-time clinical monitoring: Progress and challenges. Current Opinion in Chemical Biology 6:633-641.
52Ganesh et al., Evaluation of the VIA® blood chemistry monitor for glucose in healthy and diabetic volunteers, Journal of Diabetese Science and Technology, 2(2):182-193, Mar. 2008.
53Gilligan et al. Feasibility of continuous long-term glucose monitoring from a subcutaneous glucose sensor in humans. Diabetes Technol. Ther. 2004, 6, 378-386.
54Gilligan, B. C.; Shults, M.; Rhodes, R. K.; Jacobs, P. G.; Brauker, J. H.; Pintar, T. J.; Updike, S. J. Feasibility of continuo long-term glucose monitoring from a subcutaneous glucose sensor in humans. Diabetes Technol. Ther. 2004, 6, 378-386.
55Godsland, et al. 2001. Maximizing the Success Rate of Minimal Model Insulin Sensitivity Measurement in Humans: The Importance of Basal Glucose Levels. The Biochemical Society and the Medical Research Society, 1-9.
56Hall et al. 1998. Electrochemical oxidation of hydrogen peroxide at platinum electrodes. Part 1. An adsorption-controlled mechanism. Electrochimica Acta, 43(5-6):579-588.
57Hall et al. 1998. Electrochemical oxidation of hydrogen peroxide at platinum electrodes. Part II: Effect of potential. Electrochimica Acta; 43(14-15):2015-2024.
58Hall et al. 1999. Electrochemical oxidation of hydrogen peroxide at platinum electrodes. Part III: Effect of temperature. Electrochimica Acta, 44:2455-2462.
59Hall et al. 1999. Electrochemical oxidation of hydrogen peroxide at platinum electrodes. Part IV: Phosphate buffer dependence. Electrochimica Acta, 44:4573-4582.
60Hall et al. 2000. Electrochemical oxidation of hydrogen peroxide at platinum electrodes. Part V: Inhibition by chloride. Electrochimica Acta, 45:3573-3579.
61Hashiguchi et al. (1994). "Development of a miniaturized glucose monitoring system by combining a needle-type glucose sensor with microdialysis sampling method: Long-term subcutaneous tissue glucose monitoring in ambulatory diabetic patients," Diabetes Care, 17(5): 387-396.
62Heller, "Electrical wiring of redox enzymes," Acc. Chem. Res., 23:128-134 (1990).
63Heller, A. 1992. Electrical Connection of Enzyme Redox Centers to Electrodes. J. Phys. Chem. 96:3579-3587.
64Heller, A. 2003. Plugging metal connectors into enzymes. Nat Biotechnol 21:631-2.
65Heller, A. Implanted electrochemical glucose sensors for the management of diabetes. Annu Rev Biomed Eng 1999, 1, 153-175.
66Hicks, 1985. In Situ Monitoring, Clinical Chemistry, 31(12):1931-1935.
67Hitchman, M. L. 1978. "Measurement of Dissolved Oxygen." In Elving et al. (Eds.). Chemical Analysis, vol. 49, Chap. 3, pp. 34-49, 59-123. New York: John Wiley & Sons.
68Hu, et al. 1993. A needle-type enzyme-based lactate sensor for in vivo monitoring, Analytica Chimica Acta, 281:503-511.
69Huang et al. Electrochemical Generation of Oxygen. 1: The Effects of Anions and Cations on Hydrogen Chemisorption and Aniodic Oxide Film Formation on Platinum Electrode. 2: The Effects of Anions and Cations on Oxygen Generation on Platinum Electrode, pp. 1-116, Aug. 1975.
70IPRP for PCT/US04/024178 filed Jul. 21, 2004.
71ISR and WO for PCT/US04/024178 filed Jul. 21, 2004.
72Jablecki et al. 2000. Simulations of the frequency response of Implantable glucose sensors. Analytical Chemistry, 72:1853-1859.
73Jaremko et al. 1998. Advances toward the implantable artificial pancreas for treatment of diabetes. Diabetes Care, 21(3):444-450.
74Jensen et al. 1997. Fast wave forms for pulsed electrochemical detection of glucose by incorporation of reductive desorption of oxidation products. Analytical Chemistry, 69(9):1776-1781.
75Johnson (1991). "Reproducible electrodeposition of biomolecules for the fabrication of miniature electroenzymatic biosensors," Sensors and Actuators B, 5:85-89.
76Johnson et al. 1992. In vivo evaluation of an electroenzymatic glucose sensor implanted in subcutaneous tissue. Biosensors & Bioelectronics, 7:709-714.
77Kacaniklic, May-Jun. 1994. Electroanalysis, 6(5-6):381-390.
78Kang et al. In vitro and short-term in vivo characteristics of a Kel-F thin film modified glucose sensor. Anal Sci 2003, 19, 1481-1486.
79Kang, S. K.; Jeong, R.A.; Park, S.; Chung, T. D.; Park, S.; Kim, H.C. In vitro and short-term in vivo characteristics of a Kel-F thin film modified glucose sensor. Anal Sci 2003, 19, 1481-1486.
80Karube et al. 1993. Microbiosensors for acetylcholine and glucose. Biosensors & Bioelectronics 8:219-228.
81Kawagoe et al. 1991. Enzyme-modified organic conducting salt microelectrode, Anal. Chem. 63:2961-2965.
82Keedy et al. 1991. Determination of urate in undiluted whole blood by enzyme electrode. Biosensors & Bioelectronics, 6: 491-499.
83Kerner et al. 1988. A potentially implantable enzyme electrode for amperometric measurement of glucose, Horm Metab Res Suppl. 20:8-13.
84Kerner, et al. "The function of a hydrogen peroxide-detecting electroenzymatic glucose electrode is markedly impaired in human sub-cutaneous tissue and plasma," Biosensors & Bioelectronics, 8:473-482 (1993).
85Ko, Wen H. 1985. Implantable Sensors for Closed-Loop Prosthetic Systems, Futura Pub. Co., Inc., Mt. Kisco, NY, Chapter 15:197-210.
86Kondo et al. 1982. A miniature glucose sensor, implantable in the blood stream. Diabetes Care. 5(3):218-221.
87Koschinsky, et al. 1998. New approach to technical and clinical evaluation of devices for self-monitoring of blood glucose. Diabetes Care 11(8): 619-619.
88Koudelka et al. 1989. In vivo response of microfabricated glucose sensors to glycemia changes in normal rats. Biomed Biochim Acta 48(11-12):953-956.
89Koudelka et al. 1991. In-vivo behaviour of hypodermically implanted microfabricated glucose sensors. Biosensors & Bioelectronics 6:31-36.
90Kraver et al. A mixed-signal sensor interface microinstrument. Sensors and Actuators A: Physical 2001, 91, 266-277.
91Kraver, K.; Gutha, M. R.; Strong, T.; Bird, P.; Cha, G.; Hoeld, W., Brown, R. A mixed-signal sensor interface microinstrument. Sensors and Actuators A: Physical 2001, 91, 266-277.
92LaCourse et al. 1993. Optimization of waveforms for pulsed amperometric detection of carbohydrates based on pulsed voltammetry. Analytical Chemistry, 65:50-52.
93Lerner et al. 1984. An implantable electrochemical glucose sensor. Ann. N. Y. Acad. Sci., 428:263-278.
94Leypoldt et al. 1984. Model of a two-substrate enzyme electrode for glucose. Anal. Chem., 56:2896-2904.
95Linke et al. 1994. Amperometric biosensor for in vivo glucose sensing based on glucose oxidase immobilized in a redox hydrogel. Biosensors & Bioelectronics 9:151-158.
96Lowe, 1984. Biosensors, Trends in Biotechnology, 2(3):59-65.
97Luong et al. 2004. Solubilization of Multiwall Carbon Nanotubes by 3-Aminopropyltriethoxysilane Towards the Fabrication of Electrochemical Biosensors with Promoted Electron Transfer. Electronanalysis 16(1-2):132-139.
98Maidan et al. 1992. Elimination of Electrooxidizable Interferent-Produced Currents in Amperometric Biosensors, Analytical Chemistry, 64:2889-2896.
99Makale et al. 2003. Tissue window chamber system for validation of implanted oxygen sensors. Am. J. Physiol. Heart Circ. Physiol. 284:H2288-2294.
100Mascini et al. 1989. Glucose electrochemical probe with extended linearity for whole blood. J Pharm Biomed Anal 7(12): 1507-1512.
101Mastrototaro, et al. "An electroenzymatic glucose sensor fabricated on a flexible substrate," Sensors and Actuators B, 5:139-44 (1991).
102Matthews et al. 1988. An amperometric needle-type glucose sensor testing in rats and man. Diabetic Medicine 5:248-252.
103McGrath et al. The use of differential measurements with a glucose biosensor for interference compensation during glucose determinations by flow injection analysis. Biosens Bioelectron 1995, 10, 937-943.
104McGrath, M. J.; Iwuoha, E. I.; Diamond, D.; Smyth, M. R. The use of differential measurements with a glucose biosensor for interference compensation during glucose determinations by flow injection analysis. Biosens Bioelectron 1995, 10, 937-943.
105McKean, et al. Jul. 7, 1988. A Telemetry Instrumentation System for Chronically Implanted Glucose and Oxygen Sensors. Transactions on Biomedical Engineering 35:526-532.
106Memoli et al. A comparison between different immobilised glucoseoxidase-based electrodes. J Pharm Biomed Anal 2002, 29, 1045-1052.
107Moatti-Sirat et al., Reduction of acetaminophen interference in glucose sensors by a composite Nafion membrane: demonstration in rats and man, Diabetologia 37(6):610-616, Jun. 1994.
108Moatti-Sirat, D, et al. 1992. Evaluating in vitro and in vivo the interference of ascorbate and acetaminophen on glucose detection by a needle-type glucose sensor. Biosensors and Bioelectronics 7:345-352.
109Morff et al. 1990. Microfabrication of reproducible, economical, electroenzymatic glucose sensors, Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 12(2):0483-0484.
110Mosbach et al. 1975. Determination of heat changes in the proximity of immobilized enzymes with an enzyme termistor and its use for the assay of metobolites, Biochim. Biophys. Acta. (Enzymology), 403:256-265.
111Motonaka et al. 1993. Determination of cholesteral and cholesteral ester with novel enzyme microsensors, Anal. Chem. 65:3258-3261.
112Mowery et al. 2000. Preparation and characterization of hydrophobic polymeric films that are thromboresistant via nitric oxide release. Biomaterials 21:9-21.
113Murphy, et al. 1992. Polymer membranes in clinical sensor applications. II. The design and fabrication of permselective hydrogels for electrochemical devices, Biomaterials, 13(14):979-990.
114Myler et al. 2002. Ultra-thin-polysiloxane-film-composite membranes for the optimisation of amperometric oxidase enzyme electrodes. Biosens Bioelectron 17:35-43.
115Neuburger et al. 1987. Pulsed amperometric detection of carbohydrates at gold electrodes with a two-step potential waveform. Anal. Chem., 59:150-154.
116Office Action dated Apr. 10, 2007 in U.S. Appl. 11/077,714.
117Office Action dated Apr. 10, 2007 in U.S. Appl. No. 11/077,715.
118Office Action dated Apr. 11, 2007 in U.S. Appl. No. 10/896,639.
119Office Action dated Apr. 12, 2010 in U.S. Appl. No. 11/333,837.
120Office Action dated Apr. 16, 2009 in U.S. Appl. 11/077,714.
121Office Action dated Apr. 21, 2008 in U.S. Appl. No. 11/077,643.
122Office Action dated Apr. 27, 2010 in U.S. Appl. No. 11/078,232.
123Office Action dated Apr. 4, 2006 in U.S. Appl. No. 09/447,227.
124Office Action dated Apr. 6, 2006 in U.S. Appl. No. 10/896,639.
125Office Action dated Apr. 6, 2009 in U.S. Appl. No. 11/077,883.
126Office Action dated Aug. 1, 2006 in U.S. Appl. No. 09/447,227.
127Office Action dated Aug. 11, 2008 in U.S. Appl. No. 11/360,819.
128Office Action dated Aug. 15, 2001 in U.S. Appl. No. 09/447,227.
129Office Action dated Aug. 22, 2006 in U.S. Appl. No. 10/896,639.
130Office Action dated Dec. 11, 2008 in U.S. Appl. No. 09/447,227.
131Office Action dated Dec. 12, 2007 in U.S. Appl. No. 11/543,707.
132Office Action dated Dec. 14, 2005 in U.S. Appl. No. 10/896,772.
133Office Action dated Dec. 23, 2004 in U.S. Appl. No. 09/916,711.
134Office Action dated Dec. 24, 2008 in U.S. Appl. No. 10/885,476.
135Office Action dated Dec. 26, 2007 in U.S. Appl. No. 11/021,046.
136Office Action dated Dec. 26, 2008 in U.S. Appl. No. 11/360,819.
137Office Action dated Dec. 3, 2008 in U.S. Appl. No. 11/675,063.
138Office Action dated Dec. 30, 2008 in U.S. Appl. No. 11/034,343.
139Office Action dated Dec. 7, 1998 in U.S. Appl. No. 08/811,473.
140Office Action dated Feb. 10, 2009 in U.S. Appl. No. 11/077,713.
141Office Action dated Feb. 11, 2004 in U.S. Appl. No. 09/916,711.
142Office Action dated Feb. 14, 2006 in U.S. Appl. No. 09/916,711.
143Office Action dated Feb. 19, 2010 in U.S. Appl. No. 11/675,063.
144Office Action dated Feb. 23, 2009 in U.S. Appl. No. 11/439,630.
145Office Action dated Feb. 23, 2010 in U.S. Appl. No. 12/113,508.
146Office Action dated Feb. 24, 2006 in U.S. Appl. No. 10/646,333.
147Office Action dated Feb. 4, 2009 in U.S. Appl. No. 11/021,046.
148Office Action dated Feb. 9, 2006 in U.S. Appl. No. 10/897,312.
149Office Action dated Jan. 10, 2008 in U.S. Appl. 11/077,714.
150Office Action dated Jan. 11, 2005 in U.S. Appl. No. 10/896,772.
151Office Action dated Jan. 15, 2008 in U.S. Appl. No. 11/034,344.
152Office Action dated Jan. 16, 2003 in U.S. Appl. No. 09/447,227.
153Office Action dated Jan. 17, 2002 in U.S. Appl. No. 09/447,227.
154Office Action dated Jan. 20, 2010 in U.S. Appl. No. 11/077,713.
155Office Action dated Jan. 22, 2009 in U.S. Appl. No. 11/692,154.
156Office Action dated Jan. 22, 2010 in U.S. Appl. No. 11/439,630.
157Office Action dated Jan. 23, 2008 in U.S. Appl. No. 09/447,227.
158Office Action dated Jan. 26, 2009 in U.S. Appl. No. 11/078,230.
159Office Action dated Jan. 27, 2006 in U.S. Appl. No. 11/007,635.
160Office Action dated Jan. 28, 2008 in U.S. Appl. No. 11/077,715.
161Office Action dated Jan. 29, 2009, in U.S. Appl. No. 11/360,252.
162Office Action dated Jan. 3, 2008 in U.S. Appl. No. 11/157,746.
163Office Action dated Jan. 30, 2007 in U.S. Appl. No. 11/077,763.
164Office Action dated Jan. 7, 2009 in U.S. Appl. No. 11/157,365.
165Office Action dated Jul. 1, 2005 in U.S. Appl. No. 09/916,711.
166Office Action dated Jul. 10, 2008 in U.S. Appl. No. 11/034,343.
167Office Action dated Jul. 10, 2008 in U.S. Appl. No. 11/077,759.
168Office Action dated Jul. 15, 2002 in U.S. Appl. No. 09/447,227.
169Office Action dated Jul. 16, 2008 in U.S. Appl. No. 10/838,912.
170Office Action dated Jul. 17, 2007 in U.S. Appl. No. 09/447,227.
171Office Action dated Jul. 19, 2005 in U.S. Appl. No. 10/896,772.
172Office Action dated Jul. 23, 2004 in U.S. Appl. No. 09/916,711.
173Office Action dated Jul. 26, 2007 in U.S. Appl. No. 11/077,715.
174Office Action dated Jul. 27, 2007 in U.S. Appl. 11/077,714.
175Office Action dated Jul. 9, 2003 in U.S. Appl. No. 09/447,227.
176Office Action dated Jun. 10, 2009 in U.S. Appl. No. 11/675,063.
177Office Action dated Jun. 12, 2008 in U.S. Appl. No. 09/447,227.
178Office Action dated Jun. 19, 2008 in U.S. Appl. No. 11/021,162.
179Office Action dated Jun. 23, 2008 in U.S. Appl. No. 11/021,046.
180Office Action dated Jun. 24, 2008 in U.S. Appl. No. 11/077,883.
181Office Action dated Jun. 24, 2010 in U.S. Appl. No. 12/113,724.
182Office Action dated Jun. 26, 2008 in U.S. Appl. No. 11/157,365.
183Office Action dated Jun. 29, 2009 in U.S. Appl. No. 11/333,837.
184Office Action dated Jun. 30, 2008 in U.S. Appl. No. 11/078,230.
185Office Action dated Jun. 30, 2008 in U.S. Appl. No. 11/360,252.
186Office Action dated Jun. 6, 2005 in U.S. Appl. No. 10/646,333.
187Office Action dated Mar. 11, 2009 in U.S. Appl. No. 11/077,643.
188Office Action dated Mar. 11, 2010 in U.S. Appl. No. 11/280,672.
189Office Action dated Mar. 14, 2007 in U.S. Appl. No. 10/695,636.
190Office Action dated Mar. 24, 2008 in U.S. Appl. No. 10/838,912.
191Office Action dated Mar. 31, 2008 in U.S. Appl. No. 11/077,759.
192Office Action dated Mar. 4, 2009 in U.S. Appl. No. 10/991,353.
193Office Action dated Mar. 5, 2009 in U.S. Appl. No. 10/896,637.
194Office Action dated Mar. 5, 2009 in U.S. Appl. No. 11/078,232.
195Office Action dated Mar. 9, 2007 in U.S. Appl. No. 09/447,227.
196Office Action dated May 1, 2008 in U.S. Appl. No. 11/157,746.
197Office Action dated May 11, 2006 in U.S. Appl. No. 10/897,377.
198Office Action dated May 12, 2008 in U.S. Appl. No. 11/077,715.
199Office Action dated May 17, 2007 in U.S. Appl. No. 11/077,759.
200Office Action dated May 22, 2006 in U.S. Appl. No. 10/896,772.
201Office Action dated May 5, 2008 in U.S. Appl. No. 11/077,713.
202Office Action dated May 5, 2008 in U.S. Appl. No. 11/078,232.
203Office Action dated Nov. 1, 2007 in U.S. Appl. No. 11/034,343.
204Office Action dated Nov. 12, 2008 in U.S. Appl. No. 11/078,232.
205Office Action dated Nov. 12, 2008, 2008 in U.S. Appl. No. 11/077,715.
206Office Action dated Nov. 28, 2003 in U.S. Appl. No. 09/447,227.
207Office Action dated Nov. 28, 2008 in U.S. App. No. 11/333,837.
208Office Action dated Nov. 28, 2008 in U.S. App. No. 11/360,250.
209Office Action dated Oct. 1, 2008 in U.S. Appl. No. 11/077,643.
210Office Action dated Oct. 11, 2006 in U.S. Appl. 11/077,714.
211Office Action dated Oct. 18, 2005 in U.S. Appl. No. 10/897,377.
212Office Action dated Oct. 29, 2009 in U.S. Appl. No. 11/280,672.
213Office Action dated Oct. 31, 2006 in U.S. Appl. No. 11/077,715.
214Office Action dated Oct. 5, 2007 in U.S. Appl. No. 10/896,639.
215Office Action dated Oct. 8, 2008 in U.S. Appl. No. 10/896,637.
216Office Action dated Oct. 9, 2007 in U.S. Appl. No. 11/077,883.
217Office Action dated Sep. 12, 2008 in U.S. Appl. No. 10/991,353.
218Office Action dated Sep. 16, 2008 in U.S. Appl. 11/077,714.
219Office Action dated Sep. 18, 2007 in U.S. Appl. No. 11/078,230.
220Office Action dated Sep. 18, 2008 in U.S. Appl. No. 11/077,883.
221Office Action dated Sep. 18, 2008 in U.S. Appl. No. 11/439,630.
222Office Action dated Sep. 2, 2009 in U.S. Appl. No. 11/077,713.
223Office Action dated Sep. 2, 2009 in U.S. Appl. No. 11/078,072.
224Office Action dated Sep. 21, 2007 in U.S. Appl. No. 10/838,912.
225Office Action dated Sep. 22, 2004 in U.S. Appl. No. 10/646,333.
226Office Action dated Sep. 22, 2005 in U.S. Appl. No. 09/447,227.
227Office Action dated Sep. 23, 2005 in U.S. Appl. No. 10/896,639.
228Office Action dated Sep. 24, 2003 in U.S. Appl. No. 09/916,711.
229Office Action dated Sep. 5, 2006 in U.S. Appl. No. 09/916,711.
230Office Action dated Sep. 5, 2008 in U.S. Appl. No. 11/078,230.
231Office Action mailed Dec. 12, 2007 in U.S. Appl. No. 11/543,539.
232Office Action mailed Dec. 12, 2007 in U.S. Appl. No. 11/543,683.
233Office Action mailed Dec. 17, 2007 in U.S. Appl. No. 11/543,734.
234Office Action mailed Jun. 5, 2007 in U.S. Appl. No. 11/543,734.
235Office Action mailed Jun. 5, 2008 in U.S. Appl. No. 10/838,909.
236Office Action mailed Mar. 16, 2009 in U.S. Appl. No. 10/838,909.
237Office Action mailed May 18, 2007 in U.S. Appl. No. 11/543,683.
238Office Action mailed May 18, 2007 in U.S. Appl. No. 11/543,707.
239Office Action mailed May 23, 2007 in U.S. Appl. No. 11/543,539.
240Ohara et al. 1994. "Wired" enzyme electrodes for amperometric determination of glucose or lactate in the presence of interfering substances. Anal Chem 66:2451-2457.
241Okuda et al. 1971. Mutarotase effect on micro determinations of D-glucose and its anomers with β-D-glucose oxidase. Anal Biochem 43:312-315.
242Patel et al. 2003. Amperometric glucose sensors based on ferrocene containing polymeric electron transfer systems-a preliminary report. Biosens Bioelectron 18:1073-6.
243Pfeiffer, E.F. 1990. The glucose sensor: the missing link in diabetes therapy, Horm Metab Res Suppl. 24:154-164.
244Pickup et al. 1988. Progress towards in vivo glucose sensing with a ferrocene-mediated amperometric enzyme electrode. 34-36.
245Pickup et al. 1989. Potentially-implantable, amperometric glucose sensors with mediated electron transfer: improving the operating stability. Biosensors 4:109-119.
246Pickup et al. 1993. Developing glucose sensors for in vivo use. Elsevier Science Publishers Ltd (UK), TIBTECH vol. 11: 285-291.
247Pickup, et al. "Implantable glucose sensors: choosing the appropriate sensor strategy," Biosensors, 3:335-346 (1987/88).
248Pickup, et al. "In vivo molecular sensing in diabetes mellitus: an implantable glucose sensor with direct electron transfer," Diabetologia, 32:213-217 (1989).
249Pishko, et al. "Amperometric glucose microelectrodes prepared through immobilization of glucose oxidase in redox hydrogels," Anal. Chem., 63:2268-72 (1991).
250Poitout, et al. 1991. In Vitro and In Vivo Evaluation in Dogs of a Miniaturized Glucose Sensor, ASAIO Transactions, 37:M298-M300.
251Poitout, et al. 1993. A glucose monitoring system for on line estimation in man of blood glucose concentration using a miniaturized glucose sensor implanted in the subcutaneous tissue and a wearable control unit. Diabetologia 36:658-663.
252Postlethwaite et al. 1996. Interdigitated array electrode as an alternative to the rotated ring-disk electrode for determination of the reaction products of dioxygen reduction. Analytical Chemistry, 68:2951-2958.
253Prabhu et al. 1981. Electrochemical studies of hydrogen peroxide at a platinum disc electrode, Electrochimica Acta 26(6):725-729.
254Quinn et al. 1997. Biocompatible, glucose-permeable hydrogel for in situ coating of implantable biosensors. Biomaterials 18:1665-1670.
255Rabah et al., 1991. Electrochemical wear of graphite anodes during electrolysis of brine, Carbon, 29(2):165-171.
256Rebrin et al. 1992. Subcutaenous glucose monitoring by means of electrochemical sensors: fiction or reality? J. Biomed. Eng. 14:33-40.
257Rebrin, et al. "Automated feedback control of subcutaneous glucose concentration in diabetic dogs," Diabetologia, 32:573-76 (1989).
258Rhodes et al. 1994. Prediction of pocket-portable and implantable glucose enzyme electrode performance from combined species permeability and digital simulation analysis. Analytical Chemistry, 66(9):1520-1529.
259Rhodes, et al. 1994 Prediction of pocket-portable and implantable glucose enzyme electrode performance from combined species permeability and digital simulation analysis. Analytical Chemistry, 66(9):1520-1529.
260Sakakida et al. 1992. Development of Ferrocene-Mediated Needle-Type Glucose Sensor as a Measure of True Subcutaneous Tissue Glucose Concentrations. Artif. Organs Today 2(2):145-158.
261Sansen et al. 1985. "Glucose sensor with telemetry system." in Ko, W. H. (Ed.). Implantable Sensors for Closed Loop Prosthetic Systems. Chap. 12, pp. 167-175, Mount Kisco, NY: Futura Publishing Co.
262Sansen et al. 1990. A smart sensor for the voltammetric measurement of oxygen or glucose concentrations. Sensors and Actuators, B 1:298-302.
263Sansen, et al. 1990. A smart sensor for the voltammetric measurement of oxygen or glucose concentrations. Sensors and Actuators, B 1:298-302.
264Schmidt et al. 1993. Glucose concentration in subcutaneous extracellular space. Diabetes Care 16(5):695-700.
265Schmidtke et al., Measurement and modeling of the transient difference between blood and subcutaneous glucose concentrations in the rat after injection of insulin. Proc Natl Aced Sci U S A 1998, 95, 294-299.
266Schoemaker et al. 2003. The SCGM1 system: Subcutaneous continuous glucose monitoring based on microdialysis technique. Diabetes Technology & Therapeutics 5(4):599-608.
267Schoonen et al. 1990 Development of a potentially wearable glucose sensor for patients with diabetes mellitus: design and in-vitro evaluation. Biosensors & Bioelectronics 5:37-46.
268Schuler et al. 1999. Modified gas-permeable silicone rubber membranes for covalent immobilisation of enzymes and their use in biosensor development. Analyst 124:1181-1184.
269Selam, J. L. 1997. Management of diabetes with glucose sensors and implantable insulin pumps. From the dream of the 60s to the realities of the 90s. ASAIO J, 43:137-142.
270Shaw, et al. "In vitro testing of a simply constructed, highly stable glucose sensor suitable for implantation in diabetic patients," Biosensors & Bioelectronics, 6:401-406 (1991).
271Shichiri et al. 1982. Wearable artificial endocrine pancrease with needle-type glucose sensor. Lancet 2:1129-1131.
272Shichiri et al. 1985. Needle-type Glucose Sensor for Wearable Artificial Endocrine Pancreas in Implantable Sensors 197-210.
273Shichiri, et al. 1983. Glycaemic Control in Pancreatectomized Dogs with a Wearable Artificial Endocrine Pancreas. Diabetologia 24:179-184.
274Shichiri, et al. 1986. Telemetry Glucose Monitoring Device with Needle-Type Glucose Sensor: A Useful Tool for Blood Glucose Monitoring in Diabetic Individuals. Diabetes Care, Inc. 9(3):298-301.
275Shults, et al. 1994. A telemetry-instrumentation system for monitoring multiple subcutaneously implanted glucose sensors. IEEE Transactions on Biomedical Engineering 41(10):937-942.
276Sokol et al. 1980, Immobilized-enzyme rate-determination method for glucose analysis, Clin. Chem. 26(1):89-92.
277Stern et al., 1957. Electrochemical polarization: 1. A theoretical analysis of the shape of polarization curves, Journal of the Electrochemical Society, 104(1):56-63.
278Sternberg et al. 1988. Covalent enzyme coupling on cellulose acetate membranes for glucose sensor development. Anal. Chem. 69:2781-2786.
279Stokes. 1988. Polyether Polyurethanes: Biostable or Not? J. Biomat. Appl. 3:228-259.
280Thome et al. 1995. Can the decrease in subcutaneous glucose concentration precede the decrease in blood glucose level? Proposition for a push-pull kinetics hypothesis, Horm. Metab. Res. 27:53.
281Thomé-Duret et al. 1996. Modification of the sensitivity of glucose sensor implanted into subcutaneous tissue. Diabetes Metabolism, 22:174-178.
282Thome-Duret et al. 1996. Use of a subcutaneous glucose sensor to detect decreases in glucose concentration prior to observation in blood, Anal. Chem. 68:3822-3826.
283Thompson, et al., In Vivo Probes: Problems and Perspectives, Department of Chemistry, University of Toronto, Canada, pp. 255-261, 1986.
284Tierney et al. 2000. Effect of acetaminophen on the accuracy of glucose measurements obtained with the GlucoWatch biographer. Diabetes Technol Ther 2:199-207.
285Torjman et al., Glucose monitoring in acute care: technologies on the horizon, Journal of Deabetes Science and Technology, 2(2):178-181, Mar. 2008.
286Tse et al. 1987. Time-Dependent Inactivation of Immobilized Glucose Oxidase and Catalase. Biotechnol. Bioeng. 29:705-713.
287Turner and Pickup, "Diabetes mellitus: biosensors for research and management," Biosensors, 1:85-115 (1985).
288Turner, A.P.F. 1988. Amperometric biosensor based on mediator-modified electrodes. Methods in Enzymology 137:90-103.
289TURNERet al. 1984. Carbon Monoxide: Acceptor Oxidoreductase from Pseudomonas Thermocarboxydovorans Strain C2 and its use in a Carbon Monoxide Sensor. Analytica Chimica Acta, 163: 161-174.
290U.S. Appl. No. 09/447,227, filed Nov. 22, 2999.
291U.S. Appl. No. 10/838,658, filed May 3, 2004.
292U.S. Appl. No. 10/838,909, filed May 3, 2004.
293U.S. Appl. No. 10/838,912, filed May 3, 2004.
294U.S. Appl. No. 10/885,476, filed Jul. 6, 2004.
295U.S. Appl. No. 10/897,377, filed Jul. 21, 2004.
296Updike et al. 1967. The enzyme electrode. Nature, 214:986-988.
297Updike et al. 1988. Laboratory Evaluation of New Reusable Blood Glucose Sensor. Diabetes Care, 11:801-807.
298Updike et al. 2000. A subcutaneous glucose sensor with improved longevity, dynamic range, and stability of calibration. Diabetes Care 23(2):208-214.
299Updike, et al. 1979. Continuous glucose monitor based on an immobilized enzyme electrode detector. J Lab Clin Med, 93(4):518-527.
300Updike, et al. 1994 Enzymatic glucose sensor: Improved long-term performance in vitro and in vivo. ASAIO Journal, 40(2):157-163.
301Updike, et al. 1997. Principles of long-term fully impleated sensors with emphasis on radiotelemetric monitoring of blood glucose form inside a subcutaneous foreign body capsule (FBC). In Fraser, ed., Biosensors in the Body. New York. John Wiley & Sons, pp. 117-137.
302Vadgama, P. Nov. 1981. Enzyme electrodes as practical biosensors. Journal of Medical Engineering & Technology 5(6):293-298.
303Vadgama. 1988. Diffusion limited enzyme electrodes. NATO ASI Series: Series C, Math and Phys. Sci. 226:359-377.
304Velho et al. 1989. Strategies for calibrating a subcutaneous glucose sensor. Biomed Biochim Acta 48(11/12):957-964.
305Wagner, et al. 1998. Continuous amperometric monitoring of glucose in a brittle diabetic chimpanzee with a miniature subcutaneous electrode. Proc. Natl. Acad. Sci. A, 95:6379-6382.
306Wang et al. 1994. Highly Selective Membrane-Free, Mediator-Free Glucose Biosensor. Anal. Chem. 66:3600-3603.
307Wang et al. Improved ruggedness for membrane-based amperometric sensors using a pulsed amperometric method. Anal Chem 1997, 69, 4482-4489.
308Wang, X.; Pardue, H. L. Improved ruggedness for membrane-based amperometric sensors using a pulsed amperometric method. Anal Chem 1997, 69, 4482-4489.
309Ward et al. 2000. Rise in background current over time in a subcutaneous glucose sensor in the rabbit: Relevance to calibration and accuracy. Biosensors & Bioelectronics, 15:53-61.
310Ward et al. 2002. A new amperometric glucose microsensor: In vitro and short-term in vivo evaluation. Biosensors & Bioelectronics, 17:181-189.
311Ward et al. Understanding Spontaneous Output Fluctuations of an Amperometric Glucose Sensor: Effect of Inhalation Anesthesia and e of a Nonenzyme Containing Electrode. ASAIO Journal 2000, 540-546.
312Ward, et al. 1999. Assessment of chronically implanted subcutaneous glucose sensors in dogs: The effect of surrounding fluid masses. ASAIO Journal, 45:555-561.
313Ward, et al. 2000. Rise in background current over time in a subcutaneous glucose sensor in the rabbit: Relevance to calibration and accuracy. Biosensors & Bioelectronics, 15:53-61.
314Ward, et al. 2002. A new amperometric glucose microsensor: In vitro and short-term in vivo evaluation, Biosensors & Bioelectronics, 17:181-189.
315Ward, W. K.; Wood, M. D.; Troupe, J. E. Understanding Spontaneous Output Fluctuations of an Amperometric Glucose Sensor: Effect of Inhalation Anesthesia and e of a Nonenzyme Containing Electrode. ASAIO Journal 2000, 540-546.
316Wientjes, K. J. C. Development of a glucose sensor for diabetic patients. 2000.
317Wilkins et al. 1988. The coated wire electrode glucose sensor, Horm Metab Res Suppl., 20:50-55.
318Wilkins et al. 1995. Integrated implantable device for long-term glucose monitoring. Biosens. Bioelectron 10:485-494.
319Wilkins et al. Glucose monitoring: state of the art and future possibilities. Med Eng Phys 1995, 18, 273-288.
320Wilkins, et al. 1995. Integrated implantable device for long-term glucose monitoring. Biosens. Bioelectron., 10:485-494.
321Wilson et al. 1992. Progress toward the development of an implantable sensor for glucose. Clin. Chem., 38(9):1613-1617.
322 *Wilson, et al. 1992. Progress toward the development of an implantable sensor for glucose. Clin. Chem., 38(9):1613-1617.
323Wilson, et al. 2000. Enzyme-based biosensors for in vivo measurements. Chem. Rev., 100:2693-2704.
324Worsley et al., Measurement of glucose in blood with a phenylboronic acid optical sensor, Journal of Diabetes Science and Technology, 2(2):213-220, Mar. 2008.
325Wright et al., Bioelectrochemical dehalogenations via direct electrochemistry of poly(ethylene oxide)- modified myoglobin, Electrochemistry Communications 1 (1999) 603-611.
326Wu et al. 1999. In situ electrochemical oxygen generation with an immunoisolation device. Ann. N.Y. Acad. Sci., 875:105-125.
327Yamasaki, Yoshimitsu. Sep. 1984. The development of a needle-type glucose sensor for wearable artificial endocrine pancreas. Medical Journal of Osaka University 35(1-2):25-34.
328Yamasakiet al. 1989. Direct measurement of whole blood glucose by a needle-type sensor. Clinica Chimica Acta. 93:93-98.
329Yang et al (1996). "A glucose biosensor based on an oxygen electrode: In-vitro performances in a model buffer solution and in blood plasma," Biomedical Instrumentation & Technology, 30:55-61.
330Yang, et al. 2004. A Comparison of Physical Properties and Fuel Cell Performance of Nafion and Zirconium Phosphate/Nafion Composite Membranes. Journal Of Membrane Science 237:145-161.
331Yanget al. 1998. Development of needle-type glucose sensor with high selectivity. Science and Actuators B 46:249-256.
332Zamzow et al. 1990. Development and evaluation of a wearable blood glucose monitor, ASAIO Transactions; 36(3): pp. M588-M591.
333Zhang et al (1993). Electrochemical oxidation of H202 on Pt and Pt + Ir electrodes in physiological buffer and its applicability to H202-based biosensors. J. Electroanal. Chem., 345:253-271.
334Zhang et al. 1993. In vitro and in vivo evaluation of oxygen effects on a glucose oxidase based implantable glucose sensor. Analytica Chimica Acta, 281:513-520.
335Zhang et al. 1994. Elimination of the acetaminophen interference in an implantable glucose sensor. Analytical Chemistry 66(7):1183-1188.
336Zhang et al. 1994. Elimination of the acetaminophen interference in an implantable glucose sensor. Analytical Chemistry, 66(7):1183-1188.
337Zhu et al. (1994). "Fabrication and characterization of glucose sensors based on a microarray H202 electrode." Biosensors & Bioelectronics, 9: 295-300.
338Zhu et al. 2002. Planar amperometric glucose sensor based on glucose oxidase immobilized by chitosan film on prussian blue layer. Sensors, 2:127-136.
Classifications
U.S. Classification204/403.05, 204/403.11, 600/347, 600/345
International ClassificationA61B5/05, G01N27/327, G01N27/26, G01N27/416, G01N
Cooperative ClassificationA61B5/14865, A61B5/14532, C12Q1/001, G01N27/3274
European ClassificationG01N27/416, A61B5/1486B, A61B5/145G, C12Q1/00B
Legal Events
DateCodeEventDescription
Jun 17, 2008ASAssignment
Owner name: DEXCOM, INC., CALIFORNIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:SIMPSON, PETER C.;PETISCE, JAMES R.;CARR-BRENDEL, VICTORIA;AND OTHERS;SIGNING DATES FROM 20050103 TO 20050111;REEL/FRAME:021106/0346
Jul 15, 2010ASAssignment
Owner name: DEXCOM, INC., CALIFORNIA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:SIMPSON, PETER C.;PETISCE, JAMES R.;CARR-BRENDEL, VICTORIA;AND OTHERS;SIGNING DATES FROM 20050103 TO 20050111;REEL/FRAME:024693/0657
Oct 2, 2012CCCertificate of correction
Jan 13, 2014FPAYFee payment
Year of fee payment: 8