Device and method for determining analyte levels

• US 6,741,877 B1
• Filed: 01/21/2000
• Issued: 05/25/2004
• Est. Priority Date: 03/04/1997
• Status: Expired due to Term

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Updike, Stuart J., Rhodes, Rathbun K., Shults, Mark C.
• Primary Examiner(s): Nasser, Robert L.
• Assistant Examiner(s): Carter, Ryan
• Application Number:
  US09/489,588
• Time in Patent Office: 1,586 Days
• Field of Search: 600/309, 600/345, 600/347, 600/365-366, 600/573, 600/582, 600/584, 424/422-425
• US Class Current: 600/345
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

Devices and methods for determining analyte levels are described. The devices and methods allow for the implantation of analyte-monitoring devices, such as glucose monitoring devices, that result in the delivery of a dependable flow of blood to deliver sample to the implanted device. The devices comprise a unique microarchitectural arrangement in the sensor region that allows accurate data to be obtained over long periods of time.

Claims

1. A device for measuring glucose in a biological fluid, comprising:

a) a housing comprising an electronic circuit and at least two electrodes operatively connected to said electronic circuit; and

b) a sensor operably connected to said electrodes of said housing, said sensor comprising an apparatus for determining the amount of glucose in a biological sample, said glucose determining apparatus operably associated with said electrodes and comprising a membrane impregnated with an oxidase, a bioprotective membrane substantially impermeable to macrophages, said bioprotective membrane positioned more distal to said housing than said oxidase impregnated membrane, and an angiogenic layer, said angiogenic layer positioned more distal to said housing than said bioprotective membrane, wherein said sensor protrudes from said housing.

2. The biological fluid measuring device of claim 1, wherein the sensor further comprises a sensor interface dome.

3. The biological fluid measuring device of claim 1, wherein said membrane impregnated with oxidase comprises a resistance layer, an enzyme layer, an interference layer and an electrolyte layer.

4. The biological fluid measuring device of claim 3, wherein said resistance layer comprises a polymer membrane with a oxygen-to-glucose permeability ratio of approximately 200:

1.

5. The biological fluid measuring device of claim 3, wherein said interference layer comprises a hydrophobic membrane substantially permeable to hydrogen peroxide.

6. The biological fluid measuring device of claim 3, wherein said interference layer comprises a hydrophobic membrane substantially impermeable to chemical compositions having a molecular weight substantially greater than hydrogen peroxide.

7. The biological fluid measuring device of claim 3, wherein said electrolyte layer comprises a semipermeable hydrophilic coating.

8. The biological fluid measuring device of claim 7, wherein said electrolyte layer comprises a curable copolymer of a urethane polymer and a hydrophilic film-forming polymer.

9. The biological fluid measuring device of claim 1, wherein said bioprotective membrane comprises polypropylene, polysulphone, polytetrafluoroethylene, or poly(ethylene terephthalate).

10. The biological fluid measuring device of claim 1, wherein said bioprotective membrane further comprises pores having a diameter of about 0.4 μ

m.

11. The biological fluid measuring device of claim 1, wherein said angiogenic layer is selected from the group consisting of hydrophilic polyvinylidene fluoride, mixed cellulose esters, polyvinyl chloride, polypropylene, polysulphone and polymethacrylate.

12. The biological fluid measuring device of claim 1, further comprising c) a securing element for securing said device to biological tissue, said securing element composed of a material selected from the group consisting of polyester, polypropylene cloth, polytetrafluoroethylene felts and expanded polytetrafluoroethylene.

13. The biological fluid measuring device of claim 12, wherein said securing element comprises a polyester velour.

14. The biological fluid measuring device of claim 1, wherein said housing comprising said electronic circuit is filled with material comprising waxes and resins wherein said waxes and resins secure said electronic circuit within said housing.

15. The device of claim 1, wherein said sensor comprises an interface tip for communicating with the tissue of said host, said tip comprising a fixation domain adapted for substantial fixation of said tip in a foreign body capsule.

16. The device of claim 15, wherein said wherein said sensor tip fixation domain further comprises a capsular attachment layer.

17. The device of claim 16, wherein said capsular attachment layer comprises a porous implantable material.

18. The device of claim 16, wherein said capsular attachment layer comprises one of polyester, velour, expanded polytetrafluoroethylene, polytetrafluoroethylene felts, and polypropylene cloth.

19. The device of claim 16, wherein said capsular attachment layer comprises surgical grade polyester velour.

20. The device of claim 1, wherein said bioprotective membrane comprises polytetrafluoroethylene.

21. The device of claim 1, wherein said angiogenic membrane comprises polytetrafluoroethylene.

22. The device of claim 1, wherein said bioprotective membrane and said angiogenic layer are formed from a polytetrafluoroethylene.

23. The device of claim 1, wherein said bioprotective membrane comprises pores having diameter ranging from about 0.1 micron to about 1.0 micron.

24. The device of claim 1, wherein said bioprotective membrane comprises pores having diameter ranging from about 0.2 micron to about 0.5 micron.

25. The device of claim 1, wherein said electronic circuit operably connected to at least one of said electrodes is adapted for continuous, long-term operation.

26. The device of claim 1, wherein said housing further comprises an apparatus operatively connected to said electronic circuit for transmitting data to a location external to said device.

27. The device of claim 26, wherein said data transmitting apparatus comprises radiotelemetry.

28. The device of claim 1, wherein said device is wholly implantable.

29. The device of claim 28, wherein said device is sized and configured for being wholly implantable subcutaneously.

30. The device of claim 1, wherein said housing is substantially oval-shaped.

31. A wholly implantable glucose monitoring device, comprising:

a) a housing of size and configuration for whole implantation into a host; and

b) a sensor supported by said housing for communication with tissue of said host, said sensor comprising (i) a member for determining the amount of glucose in biological fluid of said host, and (ii) a bioprotective member disposed more distal to said housing than said glucose determining member and comprising a bioprotective membrane that is substantially impermeable to macrophages and permeable to glucose and oxygen; and

c) a member for securing the device to biological tissue of said host, said securing member cooperatively associated with said housing, and wherein said securing member comprises poly(ethylene terephthalate).

32. An implantable glucose monitoring device of claim 31, wherein said bioprotective membrane comprises pores, said pores having diameters ranging from about 0.1 micron to about 1.0 micron.

33. An implantable glucose monitoring device of claim 31, wherein said bioprotective membrane comprises polytetrafluoroethylene.

34. An implantable glucose monitoring device of claim 31, wherein said glucose determining member comprises a membrane containing glucose oxidase, said glucose oxidase-containing membrane positioned more proximal to said housing than said bioprotective member.

35. The device of claim 34, wherein said oxidase impregnated membrane comprises a single homogeneous structure.

36. The device of claim 35, wherein said glucose oxidase impregnated membrane comprises a resistance layer, and enzyme layer, an interference layer and an electrolyte layer.

37. The device of claim 36, wherein said resistance layer restricts the transport of glucose therethrough.

38. The device of claim 37, wherein said resistance layer comprises a polymer membrane with a oxygen-to-glucose permeability ratio of approximately 200:

1.

39. The device of claim 36, wherein said interference layer comprises a hydrophobic membrane substantially permeable to hydrogen peroxide.

40. The device of claim 39, wherein said interference layer comprises a hydrophobic membrane substantially impermeable to chemical compositions having a molecular weight substantially greater than hydrogen peroxide.

41. The device of claim 37, wherein said electrolyte layer comprises a semipermeable hydrophilic coating.

42. The device of claim 41, wherein said electrolyte layer comprises a curable copolymer of a urethane polymer and a hydrophilic film-forming polymer.

43. An implantable glucose monitoring device of claim 31, wherein said device further comprises at least two electrodes supported by said housing and operably connected to said sensor.

44. An implantable glucose monitoring device of claim 43, wherein said device further comprises electronic circuitry operably connected to at least one of said electrodes and adapted for long-term operation.

45. The device of claim 44, wherein said housing comprising said electronic circuitry is filled with material comprising waxes and resins wherein said waxes and resins secure said electronic circuit within said housing.

46. The device of claim 44, wherein said housing further comprises an apparatus operatively connected to said electronic circuitry for transmitting data to a location external to said device.

47. The device of claim 46, wherein said data transmitting apparatus comprises radiotelemetry.

50. The device of claim 31, wherein said sensor comprises an interface tip for communicating with the tissue of said host, said tip comprising a fixation domain adapted for substantial fixation of said tip in a foreign body capsule.

51. The device of claim 50, wherein said wherein said fixation domain further comprises a capsular attachment layer.

52. The device of claim 51, wherein said capsular attachment layer comprises a porous implantable material.

53. The device of claim 51, wherein said capsular attachment layer comprises one of polyester, velour, expanded polytetrafluoroethylene, polytetrafluoroethylene felts, and polypropylene cloth.

54. The device of claim 51, wherein said capsular attachment layer comprises surgical grade polyester velour.

55. The device of claim 31, further comprising an angiogenic layer positioned more distal to said housing than said bioprotective membrane.

56. The device of claim 55, wherein said angiogenic layer comprises one of hydrophilic polyvinylidene fluoride, mixed cellulose esters, polyvinyl chloride, polypropylene, polysulphone and polymethacrylate.

57. The device of claim 55, wherein said angiogenic layer comprises polytetrafluoroethylene.

58. The device of claim 55, wherein said bioprotective and angiogenic layers are formed from a polytetrafluoroethylene.

59. The device of claim 31, wherein said bioprotective membrane comprises one of polypropylene, polysulphone, polytetrafluoro ethylene, and poly(ethylene terephthalate).

60. The device of claim 31, wherein said device is sized and configured for being wholly implantable subcutaneously.

61. The device of claim 31, wherein said housing is substantially oval-shaped.

62. The device of claim 31, wherein said sensor further comprises a sensor interface dome that protrudes from said housing.

48. An implantable glucose monitoring device of claim 48, said housing comprising a cavity contained therewithin.

49. An implantable glucose monitoring device of claim 48, wherein said sensor is within said housing cavity.

63. A biological fluid measuring device, comprising:

(a) a housing comprising an electronic circuit and at least two electrodes operably connected to said electronic circuit; and

(b) a sensor operably connected to said electrodes of said housing, said sensor comprising (i) a bioprotective membrane, and (ii) an angiogenic layer said angiogenic layer positioned more distal to said housing than said bioprotective membrane, wherein said angiogenic layer comprises polytetrafluoroethylene.

64. The biological fluid measuring device of claim 63, wherein said bioprotective membrane is substantially impermeable to macrophages.

65. The biological fluid measuring devise of claim 63, wherein said bioprotective membrane comprises pores, said pores having diameters ranging from about 0.1 micron to about 1.0 micron.

66. The biological fluid measuring device of claim 63, wherein said bioprotective membrane comprises polytetrafluoroethylene.

67. The biological fluid measuring device of claim 63, further comprising (c) a member for securing said device to biological tissue, and securing member associated with said housing.

68. The biological fluid measuring device of claim 67, wherein said securing member comprises poly(ethylene terephthalate).

69. The biological fluid measuring device of claim 63, wherein said sensor further comprises a member for determining the amount of glucose in a biological sample.

70. The biological fluid measuring device of claim 69, wherein said glucose determining member comprises a membrane containing glucose oxidase, said glucose oxidase-containing membrane positioned more proximal to said housing than said bioprotective membrane.

71. The device of claim 70, wherein said glucose oxidase-containing membrane comprises a resistance layer, and enzyme layer, an interference layer and an electrolyte layer.

72. The device of claim 71, wherein said resistance layer restricts the transport of glucose therethrough.

73. The device of claim 71, wherein said resistance layer comprises a polymer membrane with a oxygen-to-glucose permeability ratio of approximately 200:

1.

74. The device of claim 71, wherein said interference layer comprises a hydrophobic membrane substantially permeable to hydrogen peroxide.

75. The device of claim 74, wherein said interference layer comprises a hydrophobic membrane substantially impermeable to chemical compositions having a molecular weight substantially greater than hydrogen peroxide.

76. The device of claim 74, wherein said electrolyte layer comprises a semipermeable hydrophilic coating.

77. The device of claim 76, wherein said electrolyte layer comprises a curable copolymer of a urethane polymer and a hydrophilic film-forming polymer.

78. The device of claim 70, wherein said glucose oxidase-containing membrane comprises a single homogeneous structure.

79. The device of claim 67, wherein said securing member comprises one of polyester, polypropylene cloth, polytetrafluoroethylene felts and expanded polytetrafluoroethylene.

80. The device of claim 67, wherein said securing member comprises a polyester velour.

81. The device of claim 63, wherein said housing comprising said electronic circuit is filled with material comprising waxes and resins wherein said waxes and resins secure said electronic circuit within said housing.

82. The device of claim 81, wherein said data transmitting apparatus comprises radiotelemetry.

83. The device of claim 63, wherein said sensor further comprises an interface tip for communicating with the tissue of said host, said tip comprising a fixation domain adapted for substantial fixation of said tip in a foreign body capsule.

84. The device of claim 83, wherein said wherein said sensor tip fixation domain further comprises a capsular attachment layer.

85. The device of claim 84, wherein said capsular attachment layer comprises a porous implantable material.

86. The device of claim 84, wherein said capsular attachment layer comprises one of polyester, velour, expanded polytetrafluoroethylene, polytetrafluoroethylene felts, and polypropylene cloth.

87. The device of claim 84, wherein said capsular attachment layer comprises surgical grade polyester velour.

88. The device of claim 63, wherein said bioprotective membrane comprises one of polypropylene, polysulphone, polytetrafluoroethylene, and poly(ethylene terephthalate).

89. The device of claim 63, wherein said electronic circuit operably connected to said at least two electrodes is adapted for long-term operation.

90. The device of claim 63, wherein said device is wholly implantable.

91. The device of claim 90, wherein said device is sized and configured for being wholly implantable subcutaneously.

92. The device of claim 63, wherein said housing is substantially oval-shaped.

93. The device of claim 63, wherein said sensor further comprises a sensor interface dome that protrudes from said housing.

94. A device for measuring glucose in a tissue of a host comprising:

a wholly implantable device comprising a sensor having an interface tip for communicating with the tissue of said host, said tip comprising a fixation domain adapted for substantial fixation of said tip in a foreign bode capsule, wherein said sensor tip fixation domain comprises a capsular attachment layer on said sensor, and wherein said sensor tip fixation domain further comprises an angiogenic layer on said sensor.

95. The device of claim 94, wherein said wholly implantable device is sized and configured for being wholly implanted subcutaneously.

96. The device of claim 94, wherein said capsular attachment layer comprises surgical grade polyester velour.

97. The device of claim 94, further comprising a securing element for securing said device to biological tissue.

98. The device of claim 97, wherein said securing element comprises one of polyester, polypropylene cloth, polytetrafluoroethylene felts and expanded polytetrafluoroethylene.

99. The device of claim 98, wherein said securing element comprises a polyester velour.

100. The device of claim 94, wherein said capsular attachment layer comprises a porous implantable material.

101. The device of claim 94, wherein said capsular attachment layer comprises one of polyester, velour, expanded polytetrafluoroethylene, polytetrafluoroethylene felts, and polypropylene cloth.

102. The device of claim 94, wherein said angiogenic layer comprises one of hydrophilic polyvinylidene fluoride, mixed cellulose esters, polyvinyl chloride, polypropylene, polysulphone and polymethacrylate.

103. The device of claim 94, wherein said angiogenic layer comprises polytetrafluoroethylene.

104. The device of claim 94, further comprising a bioprotective membrane substantially impermeable to macrophages, said bioprotective membrane located proximal to said angiogenic layer.

105. The device of claim 106, wherein said bioprotective membrane comprises polytetrafluoroethylene.

106. The device of claim 104, wherein said bioprotective and angiogenic layers are formed from a polytetrafluoroethylene.

107. The device of claim 104, wherein said bioprotective membrane comprises pores having diameter ranging from about 0.1 micron to about 1.0 micron.

108. The device of claim 104, wherein said bioprotective membrane comprises pores having diameter ranging from about 0.2 micron to about 0.5 micron.

109. The device of claim 104, wherein said bioprotective membrane comprises one of polypropylene, polysulphone, polytetrafluoroethylene, and poly(ethylene terephthalate).

110. The device of claim 94, further comprising a membrane impregnated with an oxidase located proximal to said angiogenic layer.

111. The device of claim 110, wherein said oxidase impregnated membrane comprises a resistance layer, and enzyme layer an interference layer and an electrolyte layer.

112. The device of claim 111, wherein said resistance layer restricts the transport of glucose therethrough.

113. The device of claim 112, wherein said resistance layer comprises a polymer membrane with a oxygen-to-glucose permeability ratio of approximately 200:

1.

114. The device of claim 111, wherein said interference layer comprises a hydrophobic membrane substantially permeable to hydrogen peroxide.

115. The device of claim 114, wherein said interference layer comprises a hydrophobic membrane substantially impermeable to chemical compositions having a molecular weight substantially greater than hydrogen peroxide.

116. The device of claim 111, wherein said electrolyte layer comprises a semipermeable hydrophilic coating.

117. The device of claim 116, wherein said electrolyte layer comprises a curable copolymer of a urethane polymer and a hydrophilic film-forming polymer.

118. The device of claim 111, wherein said enzyme layer contains glucose oxidase.

119. The device of claim 110, wherein said oxidase impregnated membrane comprises a single homogeneous structure.

120. The device of claim 94, further comprising a housing that has an electronic circuit and at least two electrodes operatively connected to said electronic circuit, wherein said sensor is operably connected to said electrodes of said housing.

121. The device of claim 120, wherein said housing comprising said electronic circuit is filled with material comprising waxes and resins wherein said waxes and secure said electronic circuit within said housing.

122. The device of claim 120, wherein said electronic circuit operably connected to at least one of said electrodes is adapted for long-term operation.

123. The device of claim 120, wherein said housing further comprises an apparatus operatively connected to said electronic circuit for transmitting data to a location external to said device.

124. The device of claim 123, wherein said data transmitting apparatus comprises radiotelemetry.

125. The device of claim 94, wherein said device is sized and configured for being wholly implantable subcutaneously.

126. The device of claim 94, wherein said housing is substantially oval-shaped.

127. The device of claim 94, wherein said sensor interface tip comprises a dome configuration.

128. The device of claim 127, wherein said sensor interface tip protrudes from said housing.

129. An implantable device for subcutaneous monitoring of glucose levels, comprising a housing and a sensor comprising an angiogenic layer for promoting adequate microcirculatory delivery of glucose and oxygen to said sensor, wherein said sensor further comprises a capsular attachment layer.

130. The device of claim 129, wherein said implantable device is sized and configured for being wholly implanted subcutaneously.

131. The device of claim 129, further comprising a securing element for securing said device to biological tissue.

132. The device of claim 131, wherein said securing element comprises one of polyester, polypropylene cloth, polytetrafluoroethylene felts and expanded polytetrafluoroethylene.

133. The device of claim 132, wherein said securing element comprises a polyester velour.

134. The device of claim 129, wherein said angiogenic layer comprises one of hydrophilic polyvinylidene fluoride, mixed cellulose esters, polyvinyl chloride, polypropylene, polysulphone and polymethacrylate.

135. The device of claim 129, wherein said angiogenic layer comprises polytetrafluoroethylene.

136. The device of claim 129 further comprising a bioprotective membrane substantially impermeable to macrophages, said bioprotective membrane located proximal to said angiogenic layer.

137. The device of claim 136, wherein said bioprotective membrane comprises polytetrafluoroethylene.

138. The device of claim 136, wherein said bioprotective and angiogenic layers are formed from a polytetrafluoroethylene.

139. The device of claim 136, wherein said bioprotective membrane comprises pores having diameter ranging from about 0.1 micron to about 1.0 micron.

140. The device of claim 136, wherein said bioprotective membrane comprises pores having diameter ranging from about 0.2 micron to about 0.5 micron.

141. The device of claim 136, wherein said bioprotective membrane comprises one of polypropylene, polysulphone, polytetrafluoroethylene, and poly(ethylene terephthalate).

142. The device of claim 129, said sensor further comprising a membrane impregnated with an oxidase.

143. The device of claim 142, wherein said oxidase impregnated membrane comprises a resistance layer, and enzyme layer, an interference layer and an electrolyte layer.

144. The device of claim 142, wherein said oxidase impregnated membrane comprises a single homogeneous structure.

145. The device of claim 143, wherein said resistance layer restricts the transport of glucose therethrough.

146. The device of claim 145, wherein said resistance layer comprises a polymer membrane with a oxygen-to-glucose permeability ratio of approximately 200:

1.

147. The device of claim 143, wherein said interference layer comprises a hydrophobic membrane substantially permeable to hydrogen peroxide.

148. The device of claim 143, wherein said interference layer comprises a hydrophobic membrane substantially impermeable to chemical compositions having a molecular weight substantially greater than hydrogen peroxide.

149. The device of claim 143, wherein said electrolyte layer comprises a semipermeable hydrophilic coating.

150. The device of claim 143, wherein said electrolyte layer comprises a curable copolymer of a urethane polymer and a hydrophilic film-forming polymer.

151. The device of claim 143, wherein said enzyme layer contains glucose oxidase.

152. The device of claim 129, wherein said housing comprises an electronic circuit and at least two electrodes operatively connected to said electronic circuit, and wherein said sensor is operably connected to said electrodes of said housing.

153. The device of claim 152, wherein said housing comprising said electric circuit is filled with material comprising waxes and resins wherein said waxes and resins secure said electronic circuit within said housing.

154. The device of claim 152, wherein said electronic circuit operably connected to at least one of said electrodes is adapted for long-term operation.

155. The device of claim 129, wherein said housing comprises an apparatus operatively connected to said electronic circuit for transmitting data to a location external to said device.

156. The device of claim 155, wherein said data transmitting apparatus comprises radiotelemetry.

157. The device of claim 129, wherein said device is sized and configured for being wholly implantable subcutaneously.

158. The device of claim 129, wherein said housing is substantially oval-shaped.

159. The device of claim 129, wherein said sensor comprises an interface tip that has a dome configuration.

160. The device of claim 159, wherein said interface tip protrudes from said housing.

161. A device for measuring glucose in a biological fluid, comprising:

a) a housing comprising an electronic circuit and at least two electrodes operatively connected to said electronic circuit; and

b) a sensor operably connected to said electrodes of said housing, said sensor comprising an apparatus for determining the amount of glucose in a biological sample, said glucose determining apparatus operably associated with said electrodes and comprising a membrane impregnated with an oxidase, a bioprotective membrane substantially impermeable to macrophages, said bioprotective membrane positioned more distal to said housing than said oxidase impregnated membrane, and an angiogenic layer positioned more distal to said housing than said bioprotective membrane, wherein the sensor further comprises a sensor interface dome.

162. The device of claim 161, further comprising c) a securing element for securing said device to biological tissue.

163. The device of claim 162, wherein said securing element comprises one of polyester, polypropylene cloth, polytetrafluoroethylene felts and expanded polytetrafluoroethylene.

164. The device of claim 162, wherein said securing element comprises a polyester velour.

165. The device of claim 161, wherein said sensor interface dome comprises an interface tip for communicating with the tissue of said host, said tip comprising a fixation domain adapted for substantial fixation of said tip in a foreign body capsule.

166. The device of claim 165, wherein said wherein said fixation domain further comprises a capsular attachment layer.

167. The device of claim 166, wherein said capsular attachment layer comprises a porous implantable material.

168. The device of claim 166, wherein said capsular attachment layer comprises one of polyester, velour, expanded polytetrafluoroethylene, polytetrafluoroethylene felts, and polypropylene cloth.

169. The device of claim 166, wherein said capsular attachment layer comprises surgical grade polyester velour.

170. The device of claim 161, wherein said angiogenic layer comprises one of hydrophilic polyvinylidene fluoride, and mixed cellulose esters.

171. The device of claim 161, wherein said angiogenic layer comprises one of polyvinyl chloride, polypropylene, polysulphone, and polymethacrylate.

172. The device of claim 161, wherein said bioprotective membrane comprises polytetrafluoroethylene.

173. The device of claim 161, wherein said angiogenic layer comprises polytetrafluoroethylene.

174. The device of claim 161, wherein said bioprotective and angiogenic layers are formed from a polytetrafluoroethylene.

175. The device of claim 161, wherein said bioprotective membrane comprises pores having diameter ranging from about 0.1 micron to about 1.0 micron.

176. The device of claim 161, wherein said bioprotective membrane comprises pores having diameter ranging forming about 0.2 micron to about 0.5 micron.

177. The device of claim 161, wherein said bioprotective membrane comprises one of polypropylene, polysulphone, polytetrafluoroethylene, and poly(ethylene terephthalate).

178. The device of claim 161, wherein said oxidase impregnated membrane comprises a single homogeneous structure.

179. The device of claim 161, wherein said oxidase impregnated membrane comprises a resistance layer, and enzyme layer, an interference layer and an electrolyte layer.

180. The device of claim 179, wherein said resistance layer restricts the transport of glucose therethrough.

181. The device of claim 179, wherein said resistance layer comprises a polymer membrane with a oxygen-to-glucose permeability ratio of approximately 200:

1.

182. The device of claim 179, wherein said interference layer comprises a hydrophobic membrane substantially permeable to hydrogen peroxide.

183. The device of claim 179, wherein said interference layer comprises a hydrophobic membrane substantially impermeable to chemical compositions having a molecular weight substantially greater than hydrogen peroxide.

184. The device of claim 179, said electrolyte layer comprises a semipermeable hydrophilic coating.

185. The device of claim 184, wherein said electrolyte layer comprises a curable copolymer of a urethane polymer and a hydrophilic film-forming polymer.

186. The device of claim 179, wherein said enzyme layer contains glucose oxidase.

187. The device of claim 161, wherein said housing comprising said electronic circuit is filled with material comprising waxes and resins wherein said waxes and resins secure said electronic circuit within said housing.

188. The device of claim 161, wherein said electronic circuit operably connected to at least one of said electrodes is adapted for long-term operation.

189. The device of claim 161, wherein said housing further comprises an apparatus operatively connected to said electronic circuit for transmitting data to a location external to said device.

190. The device of claim 189, wherein said data transmitting apparatus comprises radiotelemetry.

191. The device of claim 161, wherein said device is wholly implantable.

192. The device of claim 191, wherein said device is sized and configured for being wholly implantable subcutaneously.

193. The device of claim 161, wherein said housing is substantially oval-shaped.

194. The device of claim 161, wherein said sensor interface dome protrudes from said housing.

254. The device of claim 180, wherein said device is sized and configured for being wholly implantable subcutaneously.

195. A device for measuring glucose in a biological fluid, comprising:

a) a housing comprising an electronic circuit and at least two electrodes operatively connected to said electronic circuit; and

b) a sensor operably connected to said electrodes of said housing, said sensor comprising an apparatus for determining the amount of glucose in a biological sample, said glucose determining apparatus operably associated with said electrodes and comprising a membrane impregnated with an oxidase, a bioprotective membrane substantially impermeable to macrophages, said bioprotective membrane positioned more distal to said housing than said oxidase impregnated membrane, and an angiogenic layer positioned more distal to said housing than said bioprotective membrane, wherein said membrane impregnated with oxidase comprises a resistance layer, and enzyme layer, an interference layer and an electrolyte layer.

196. The device of claim 195, further comprising c) a securing element for securing said device to biological tissue.

197. The device of claim 196, wherein said securing element comprises one of polyester, polypropylene cloth, polytetrafluoroethylene felts and expanded polytetrafluoroethylene.

198. The device of claim 196, wherein said securing element comprises a polyester velour.

199. The device of claim 196, wherein said sensor comprises an interface tip for communicating with the tissue of said host, said tip comprising a fixation domain adapted for substantial fixation of said tip in a foreign body capsule.

200. The device of claim 199, wherein said wherein said fixation domain further comprises a capsular attachment layer.

201. The device of claim 200, wherein said capsular attachment layer comprises a porous implantable material.

202. The device of claim 200, wherein said capsular attachment layer comprises one of polyester, velour, expanded polytetrafluoroethylene, polytetrafluoroethylene felts, and polypropylene cloth.

203. The device of claim 200, wherein said capsular attachment layer comprises surgical grade polyester velour.

204. The device of claim 195, wherein said angiogenic layer comprises one of hydrophilic polyvinylidene fluoride, mixed cellulose esters, polyvinyl chloride, polypropylene, polysulphone and polymethacrylate.

205. The device of claim 195, wherein said bioprotective membrane comprises polytetrafluoroethylene.

206. The device of claim 195, wherein said angiogenic layer comprises polytetrafluoroethylene.

207. The device of claim 195, wherein said bioprotective and angiogenic layers are formed from a polytetrafluoroethylene.

208. The device of claim 195, wherein said bioprotective membrane comprises pores having diameter ranging from about 0.1 micron to about 1.0 micron.

209. The device of claim 208, wherein said bioprotective membrane comprises pores having diameter ranging from about 0.2 micron to about 0.5 micron.

210. The device of claim 195, wherein said bioprotective membrane comprises one of polypropylene, polysulphone, polytetrafluoroethylene, and poly(ethylene terephthalate).

211. The device of claim 195, wherein said resistance layer restricts the transport of glucose therethrough.

212. The device of claim 211, wherein said resistance layer comprises a polymer membrane with a oxygen-to-glucose permeability ratio of approximately 200:

1.

213. The device of claim 195, wherein said interference layer comprises a hydrophobic membrane substantially permeable to hydrogen peroxide.

214. The device of claim 213, wherein said interference layer comprises a hydrophobic membrane substantially impermeable to chemical compositions having a molecular weight substantially greater than hydrogen peroxide.

215. The device of claim 195, wherein said electrolyte layer comprises a semipermeable hydrophilic coating.

216. The device of claim 215, wherein said electrolyte layer comprises a curable copolymer of a urethane polymer and a hydrophilic film-forming polymer.

217. The device of claim 195, wherein said enzyme layer contains glucose oxidase.

218. The device of claim 195, wherein said housing comprising said electronic circuit is filled with material comprising waxes and resins wherein said waxes and resins secure said electric circuit within said housing.

219. The device of claim 195, wherein said electronic circuit operably connected to at least one of said electrodes is adapted for long-term operation.

220. The device of claim 195, wherein said housing further comprises an apparatus operatively connected to said electronic circuit for transmitting data to a location external to said device.

221. The device of claim 220, wherein said data transmitting apparatus comprises radiotelemetry.

222. The device of claim 195, wherein said device is wholly implantable.

223. The device of claim 222, said device is sized and configured for being wholly implantable subcutaneously.

224. The device of claim 195, wherein said housing is substantially oval-shaped.

225. The device of claim 195, wherein said sensor further comprises a sensor interface dome that protrudes from said housing.

226. A device for measuring glucose in a biological fluid, comprising:

a) a housing comprising an electronic circuit and at least two electrodes operatively connected to said electronic circuit;

b) a sensor operably connected to said electrodes of said housing, said sensor comprising an apparatus for determining the amount of glucose in a biological sample, said glucose determining apparatus operably associated with said electrodes and comprising a membrane impregnated with an oxidase, a bioprotective membrane substantially impermeable to macrophages, said bioprotective membrane positioned more distal to said housing than said oxidase impregnated membrane, and an angiogenic layer positioned more distal to said housing than said bioprotective membrane,

c) a securing element for securing said device to biological tissue, said securing element composed of a material selected from the group consisting of polyester, polypropylene cloth, polytetrafluoroethylene felts and expanded polytetrafluoroethylene.

227. The device of claim 226, wherein said securing element comprises a polyester velour.

228. The device of claim 226, wherein said sensor comprises an interface tip for communicating with the tissue of said host, said tip comprising a fixation domain adapted for substantial fixation of said tip in a foreign body capsule.

229. The device of claim 228, wherein said wherein said fixation domain further comprises a capsular attachment layer.

230. The device of claim 229, wherein said capsular attachment layer comprises a porous implantable material.

231. The device of claim 229, wherein said capsular attachment layer comprises one of polyester, velour, expanded polytetrafluoroethylene, polytetrafluoroethylene felts, and polypropylene cloth.

232. The device of claim 229, wherein said capsular attachment layer comprises surgical grade polyester velour.

233. The device of claim 226, wherein said angiogenic layer comprises one of hydrophilic polyvinylidene fluoride, mixed cellulose esters, polyvinyl chloride, polypropylene, polysulphone and polymethacrylate.

234. The device of claim 226, wherein said bioprotective membrane comprises polytetrafluoroethylene.

235. The device of claim 226, wherein said angiogenic layer comprises polytetrafluoroethylene.

236. The device of claim 226, wherein said bioprotective and angiogenic layers are formed from a polytetrafluoroethylene.

237. The device of claim 226, wherein said bioprotective membrane comprises pores having diameter ranging from about 0.1 micron to about 1.0 micron.

238. The device of claim 226, wherein said bioprotective membrane comprises pores having diameter ranging from about 0.2 micron to about 0.5 micron.

239. The device of claim 226, wherein said bioprotective membrane comprises one of polypropylene, polysulphone, polytetrafluoroethylene, and poly(ethylene terephthalate).

240. The device of claim 226, wherein said oxidase impregnated membrane comprises a resistance layer, and enzyme layer, an interference layer and an electrolyte layer.

241. The device of claim 226, wherein said oxidase impregnated membrane comprises a single homogeneous structure.

242. The device of claim 240, wherein said resistance layer restricts the transport of glucose therethrough.

243. The device of claim 240, wherein said resistance layer comprises a polymer membrane with a oxygen-to-glucose permeability ratio of approximately 200:

1.

244. The device of claim 240, wherein said interference layer comprises a hydrophobic membrane substantially permeable to hydrogen peroxide.

245. The device of claim 240, wherein said interference layer comprises a hydrophobic membrane substantially impermeable to chemical compositions having a molecular weight substantially greater than hydrogen peroxide.

246. The device of claim 240, wherein said electrolyte layer comprises a semipermeable hydrophilic coating.

247. The device of claim 246, wherein said electrolyte layer comprises a curable copolymer of a urethane polymer and a hydrophilic film-forming polymer.

248. The device of claim 240, wherein said enzyme layer contains glucose oxidase.

249. The device of claim 226, wherein said housing comprising said electronic circuit is filled with material comprising waxes and resins wherein said waxes and resins secure said electronic circuit within said housing.

250. The device of claim 226, wherein said electronic circuit operably connected to at least one of said electrodes is adapted for long-term operation.

251. The device of claim 226, wherein said housing further comprises an apparatus operatively connected to said electronic circuit for transmitting data to a location external to said device.

252. The device of claim 251, wherein said data transmitting apparatus comprised radiotelemetry.

253. The device of claim 226, wherein said device is wholly implantable.

255. The device of claim 229, wherein said housing is substantially oval-shaped.

256. The device of claim 226, wherein said sensor further comprises a sensor interface dome that protrudes from said housing.

257. A biological fluid measuring device, comprising:

a) a housing comprising an electronic circuit and at least two electrodes operably connected to said electronic circuit; and

b) a sensor operably connected to said electrodes of said housing, said sensor comprising (i) a bioprotective membrane, and (ii) an angiogenic layer, said angiogenic layer positioned more distal to said housing than said bioprotective membrane; and

c) a member for securing said device to biological tissue, and securing member associated with said housing.

258. The device of claim 257, wherein said securing element comprises one of a material selected from the group consisting of polyester, polypropylene cloth, polytetrafluoroethylene felts and expanded polytetrafluoroethylene.

259. The device of claim 258, wherein said securing element comprises a polyester velour.

260. The device of claim 257, wherein said sensor comprises an interface tip for communicating with the tissue of said host, said tip comprising a fixation domain adapted for substantial fixation of said tip in a foreign body capsule.

261. The device of claim 260, wherein said wherein said fixation domain further comprises a capsular attachment layer.

262. The device of claim 261, wherein said capsular attachment layer comprises a porous implantable material.

263. The device of claim 261, wherein said capsular attachment layer comprises one of polyester, velour, expanded polytetramethylene, polytetrafluoroethylene felts, and polypropylene cloth.

264. The device of claim 261, wherein said capsular attachment layer comprises surgical grade polyester velour.

265. The device of claim 257, wherein said angiogenic layer comprises one of hydrophilic polyvinylidene fluoride, mixed cellulose esters, polyvinyl chloride, polypropylene, polysulphone and polymethacrylate.

266. The device of claim 257, wherein said bioprotective membrane comprises polytetrafluoroethylene.

267. The device of claim 257, wherein said angiogenic layer comprises polytetrafluoroethylene.

268. The device of claim 257, wherein said bioprotective and angiogenic layers are formed from a polytetrafluoroethylene.

269. The device of claim 257, wherein said bioprotective membrane comprises pores having diameter ranging from about 0.1 micron to about 1.0 micron.

270. The device of claim 257, wherein said bioprotective membrane comprises pores having diameter ranging from about 0.2 micron to about 0.5 micron.

271. The device of claim 257, wherein said bioprotective membrane comprises one of polypropylene, polysulphone, polytetrafluoroethylene, and poly(ethylene terephthalate).

272. The device of claim 257, wherein said oxidase impregnated membrane comprises a resistance layer, and enzyme layer, an interference layer and an electrolyte layer.

273. The device of claim 272, wherein said oxidase impregnated membrane comprises a single homogeneous structure.

274. The device of claim 272, wherein said resistance layer restricts the transport of glucose therethrough.

275. The device of claim 274, wherein said resistance layer comprises a polymer membrane with a oxygen-to-glucose permeability ratio of approximately 200:

1.

276. The device of claim 272, wherein said interference layer comprises a hydrophobic membrane substantially permeable to hydrogen peroxide.

277. The device of claim 276, wherein said interference layer comprises a hydrophobic membrane substantially impermeable to chemical compositions having a molecular weight substantially greater than hydrogen peroxide.

278. The device of claim 272, wherein said electrolyte layer comprises a semipermeable hydrophilic coating.

279. The device of claim 278, wherein said electrolyte layer comprises a curable copolymer of a urethane polymer and a hydrophilic film-forming polymer.

280. The device of claim 272, wherein said enzyme layer contains glucose oxidase.

281. The device of claim 257, wherein said housing comprising said electronic circuit is filled with material comprising waxes and resins wherein said waxes and resins secure said electronic circuit within said housing.

282. The device of claim 257, wherein said electronic circuit operably connected to at least one of said electrodes is adapted for long-term operation.

283. The device of claim 257, wherein said housing further comprises an apparatus operatively connected to said electronic circuit for transmitting data to a location external to said device.

284. The device of claim 283, wherein said data transmitting apparatus comprises radiotelemetry.

285. The device of claim 284, wherein said device is wholly implantable.

286. The device of claim 285, wherein said device is sized and configured for being wholly implantable subcutaneously.

287. The device of claim 257, wherein said housing is substantially oval-shaped.

288. The device of claim 257, wherein said sensor further comprises a sensor interface dome that protrudes from said housing.

289. A device for measuring glucose in a tissue of a host comprising a wholly implantable device comprising a sensor comprising an interface tip for communicating with the tissue of said host, said tip comprising a fixation domain adapted for substantial fixation of said tip in a foreign body capsule, wherein said sensor tip fixation domain further comprises a capsular attachment layer made from surgical grade polyester velour on said sensor.

290. The device of claim 289, further comprising a securing element for securing said device to biological tissue.

291. The device of claim 290, wherein said securing element comprises one of polyester, polypropylene cloth, polytetrafluoroethylene felts and expanded polytetrafluoroethylene.

292. The device of claim 291, wherein said securing element comprises a polyester velour.

293. The device of claim 289, wherein said sensor tip fixation domain further comprises an angiogenic layer on said sensor.

294. The device of claim 293, wherein said angiogenic layer comprises one of hydrophilic polyvinylidene fluoride, mixed cellulose esters, polyvinyl chloride, polypropylene, polysulphone and polymethacrylate.

295. The device of claim 293, wherein said angiogenic layer comprises polytetrafluoroethylene.

296. The device of claim 289, further comprising a bioprotective membrane substantially impermeable to macrophages, said bioprotective membrane located proximal to said angiogenic layer.

297. The device of claim 296, wherein said bioprotective membrane comprises polytetrafluoroethylene.

298. The device of claim 296, wherein said bioprotective and angiogenic layers are formed from a polytetrafluoroethylene.

299. The device of claim 296, wherein said bioprotective membrane comprises pores having diameter ranging from about 0.1 micron to about 1.0 micron.

300. The device of claim 296, wherein said bioprotective membrane comprises pores having diameter ranging from about 0.2 micron to about 0.5 micron.

301. The device of claim 296, wherein said bioprotective membrane comprises one of polypropylene, polysulphone, polytetrafluoroethylene, and poly(ethylene terephthalate).

302. The device of claim 301, said sensor further comprising a membrane impregnated with an oxidase.

303. The device of claim 302, wherein said oxidase impregnated membrane comprises a resistance layer, and enzyme layer, an interference layer and an electrolyte layer.

304. The device of claim 302, wherein said oxidase impregnated membrane comprises a single homogeneous structure.

305. The device of claim 303, wherein said resistance layer restricts the transport of glucose therethrough.

306. The device of claim 303, wherein said resistance layer comprises a polymer membrane with a oxygen-to-glucose permeability ratio of approximately 200:

1.

307. The device of claim 303, wherein said interference layer comprises a hydrophobic membrane substantially permeable to hydrogen peroxide.

308. The device of claim 307, said interference layer comprises a hydrophobic membrane substantially impermeable to chemical compositions having a molecular weight substantially greater than hydrogen peroxide.

309. The device of claim 303, wherein said electrolyte layer comprises a semipermeable hydrophilic coating.

310. The device of claim 309, wherein said electrolyte layer comprises a curable copolymer of a urethane polymer and a hydrophilic film-forming polymer.

311. The device of claim 303, wherein said enzyme layer contains glucose oxidase.

312. The device of claim 289, comprising a housing that has an electronic circuit and at least two electrodes operatively connected to said electronic circuit, wherein said sensor is operably connected to said electrodes of said housing.

313. The device of claim 312, wherein said housing comprising said electronic circuit is filled with material comprising waxes and resins wherein said waxes and resins secure said electronic circuit within said housing.

314. The device of claim 312 wherein said electronic circuit operably connected to at least one of said electrodes is adapted for long-term operation.

315. The device of claim 312, wherein said housing further comprises an apparatus operatively connected to said electronic circuit for transmitting data to a location external to said device.

316. The device of claim 315, wherein said data transmitting apparatus comprises radiotelemetry.

317. The device of claim 289, wherein said device is sized and configured for being wholly implantable subcutaneously.

318. The device of claim 289, wherein said housing is substantially oval-shaped.

319. The device of claim 289, wherein said sensor interface tip comprises a dome configuration.

320. The device of claim 289, wherein said sensor interface tip protrudes from said housing.