Method of Calibrating an Analyte-Measurement Device, and Associated Methods, Devices and Systems

• US 20100292948A1
• Filed: 07/26/2010
• Published: 11/18/2010
• Est. Priority Date: 10/31/2003
• Status: Abandoned Application

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Inventors: Feldman, Benjamin J., McGarraugh, Geoffrey V.
• Application Number:
  US12/843,608
• Publication Number:
  US 20100292948A1
• Time in Patent Office: Days
• US Class Current: 702/104
• CPC Class Codes: A61B 5/0004 characterised by the type of physiological signal transmitted
• CPC Class Codes: A61B 5/0024 for multiple sensor units attached to the patient, e.g. using a body or personal area network
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• 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: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/6898 Portable consumer electronic devices, e.g. music players, telephones, tablet computers
• CPC Class Codes: A61B 5/7246 using correlation, e.g. template matching or determination of similarity
• CPC Class Codes: A61B 5/742 using visual displays A61B5/339 takes precedence
• CPC Class Codes: A61B 5/746 Alarms related to a physiological condition, e.g. details of setting alarm thresholds or avoiding false alarms alarms per se G08B
• CPC Class Codes: A61B 5/7475 User input or interface means, e.g. keyboard, pointing device, joystick

Abstract

The invention relates to a method for calibrating an analyte-measurement device that is used to evaluate a concentration of analyte in bodily fluid at or from a measurement site in a body. The method involves measuring a concentration, or calibration concentration, of an analyte in blood from an “off-finger” calibration site, and calibrating the analyte-measurement device based on that calibration concentration. The invention also relates to a device, system, or kit for measuring a concentration of an analyte in a body, which employs a calibration device for adjusting analyte concentration measured in bodily fluid based on an analyte concentration measured in blood from an “off-finger” calibration site.

Claims

1-22. -22. (canceled)

23. A method for calibrating a signal from a subcutaneous sensor, comprising:

obtaining a calibration measurement from a calibration sensor placed in contact with capillary blood from an off-finger calibration site within a body;

evaluating whether the calibration measurement is within a predetermined range of analyte concentration; and

determining that the calibration measurement is suitable for use in converting an analyte signal from the subcutaneous sensor into an analyte concentration if the calibration measurement is within the predetermined range,

wherein the subcutaneous sensor comprises a working electrode, the working electrode comprising an analyte responsive enzyme and a mediator, wherein at least one of the analyte-responsive enzyme and the mediator is chemically bonded to a polymer disposed on the working electrode.

24. The method of claim 23, wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the polymer.

25. The method of claim 24, wherein at least one of the analyte-responsive enzyme and the mediator forms one or more of carbon-carbon, carbon-nitrogen, or metal-carbon covalent bonds with the polymer.

26. The method of claim 24, wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the polymer through a linker moiety.

27. The method of claim 24, wherein the mediator is covalently bonded to the polymer through one or more ligands of the mediator.

28. The method of claim 27, wherein the one or more ligands comprises a substituted or unsubstituted heterocyclic nitrogen-containing moiety.

29. The method of claim 24, wherein one or more ligands of the mediator are substituents of the polymer backbone.

30. The method of claim 24, wherein the analyte-responsive enzyme is covalently bonded to the polymer through one or more side chains of the enzyme.

31. The method of claim 30, wherein the one or more side chains of the analyte-responsive enzyme is selected from the group consisting of substituted or unsubstituted amines, alcohols, thiols, phenols, imidazoles, indols, and carboxylic acids.

32. The method of claim 24, wherein one or more side chains of the analyte-responsive enzyme are substituents of the polymer backbone.

33. The method of claim 23, wherein the polymer is crosslinked.

34. The method of claim 33, wherein at least one of the analyte-responsive enzyme and the mediator is crosslinked with the polymer.

35. The method of claim 34, wherein at least one of the analyte-responsive enzyme and the mediator is crosslinked with the polymer through one or more crosslinking agents.

36. The method of claim 35, wherein the one or more crosslinking agents is selected from the group consisting of substituted or unsubstituted epoxides, aldehydes, imidoesters, N-hydroxysuccinimide esters, carbodiimides, cyanuric chloride, tetrachlorobenzoquinone, benzoquinone and tetracyanoquinodimethane.

37. The method of claim 34, wherein one or more ligands of the mediator are crosslinkers of the polymer.

38. The method of claim 34, wherein one or more side chains of the analyte-responsive enzyme are crosslinkers of the polymer.

39. The method of claim 23, wherein the polymer forms a coordination complex with the mediator.

40. The method of claim 39, wherein one or more nitrogen-containing moieties of the polymer forms a coordination complex with a metal of the mediator.

41. The method of claim 23, wherein the mediator is ionically bonded to the polymer.

42. The method of claim 41, wherein the polymer comprises at least one positively charged moiety and the mediator comprises at least one negatively charged moiety.

43. The method of claim 41, wherein the polymer comprises at least one negatively charged moiety and the mediator comprises at least one positively charged moiety.

44. The method of claim 23, wherein the polymer is chemically bonded to the surface of the working electrode.

45. The method of claim 23, wherein the polymer forms a sensing layer membrane on the surface of the working electrode.

46. The method of claim 45, wherein the sensing layer membrane is formed in situ on the working electrode.

47. The method of claim 46, wherein the sensing layer membrane is formed in situ on the working electrode by crosslinking the polymer on the working electrode.

48. The method of claim 45 wherein the working electrode further comprises a mass transport limiting membrane disposed over the sensing layer membrane.

49. The method of claim 23, wherein the analyte-responsive enzyme is a glucose-responsive enzyme.

50. The method of claim 23, wherein the analyte-responsive enzyme is glucose dehydrogenase (GDH) or glucose oxidase (GOx).

51. The method of claim 23, wherein the analyte-responsive enzyme further comprises an enzyme cofactor.

52. The method of claim 51, wherein the enzyme cofactor is flavin adenine dinucleotide.

53. The method of claim 23, wherein the mediator comprises ruthenium or osmium.

54. The method of claim 23, wherein the analyte is glucose and the predetermined range is from about 60 mg/dL to about 350 mg/dL.

55. The method of claim 23, wherein the analyte is glucose.

56. The method of claim 23, wherein the calibration site is located in an arm of the body.

57. The method of claim 23, wherein the calibration site is located in a leg of the body.

58. The method of claim 23, wherein the subcutaneous sensor is located in an arm of the body.

59. The method of claim 23, wherein the subcutaneous sensor is located in the abdomen of the body.

60. The method of claim 23, wherein the subcutaneous sensor is located in one region of the body and the calibration site is located in another region of the body.

61. The method of claim 23, wherein each of the subcutaneous sensor and the calibration site is located in substantially one region of the body.

62. The method of claim 23, wherein the subcutaneous sensor is sufficient for electrochemically determining a concentration of an analyte.

63. The method of claim 23, wherein the obtaining the calibration measurement comprises determining the calibration measurement electrochemically or optically.

64. The method of claim 23, wherein the obtaining the calibration measurement comprises determining the calibration measurement from 1 microliter of blood or less.

65. The method of claim 23, wherein the obtaining the calibration measurement comprises determining the calibration measurement from 0.5 microliter of blood or less.

66. The method of claim 23, wherein the obtaining the calibration measurement comprises determining the calibration measurement from 0.2 microliter of blood or less.

67. The method of claim 23, further comprising, prior to the obtaining the calibration measurement, rubbing a surface of the body adjacent the calibration site.

68. The method of claim 67, wherein the rubbing comprises rubbing sufficient to enhance mobility of fluid at the calibration site.

69. The method of claim 23, wherein the evaluating is other than manual.

70. The method of claim 23, wherein the obtaining the calibration measurement comprises determining the calibration measurement within five minutes after the subcutaneous sensor is inserted at a measurement site.

71. The method of claim 23, wherein the obtaining the calibration measurement comprises determining the calibration measurement within one hour after the subcutaneous sensor is inserted at a measurement site.

72. The method of claim 23, wherein the obtaining the calibration measurement comprises determining the calibration measurement within three hours after the subcutaneous sensor is inserted at a measurement site.

73. The method of claim 23, wherein the obtaining the calibration measurement comprises determining the calibration measurement within about twenty-four hours after the subcutaneous sensor is inserted at a measurement site.

74. The method of claim 23, further comprising obtaining at least one analyte signal from the subcutaneous sensor.

75. The method of claim 74, further comprising evaluating the analyte signal based on a predetermined range for a rate of change in analyte concentration over a predetermined period.

76. The method of claim 75, wherein the analyte is glucose and the predetermined range is up to 2 mg/dL per minute in any direction.

77. The method of claim 75, further comprising repeating the obtaining an analyte signal, obtaining a calibration measurement or evaluating, or any combination thereof, until the analyte signal, the calibration measurement or both are suitable for use in converting an analyte signal from the subcutaneous sensor into an analyte concentration.

78. The method of claim 75, further comprising, when the analyte signal, the calibration measurement or both are suitable for use in converting an analyte signal from the subcutaneous sensor into an analyte concentration, determining a sensitivity based on a ratio of the analyte signal and the calibration measurement.

79. The method of claim 78, further comprising converting an analyte signal from the analyte sensor to an analyte concentration based on the sensitivity.

80. The method of claim 23, wherein the subcutaneous sensor and the calibration sensor are physically or wirelessly associated.

81. An in vivo analyte sensor calibration system, comprising:

an in vivo analyte sensor, at least a portion of the sensor subcutaneously positioned to generate one or more signals, wherein the analyte sensor comprises a working electrode, the working electrode comprising an analyte-responsive enzyme and a mediator, wherein at least one of the analyte-responsive enzyme and the mediator is chemically bonded to a polymer disposed on the working electrode;

a calibration sensor configured to be placed in contact with a blood sample from an off-finger calibration site to provide a calibration measurement; and

a calibration device in signal communication with one or more of the in vivo analyte sensor or the calibration sensor to calibrate the in vivo analyte sensor by determining whether a quality of the calibration measurement is suitable for calibration, and converting the one or more signals from the in vivo analyte sensor into a corresponding one or more analyte concentration values using the calibration measurement.

82. The system of claim 81, wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the polymer.

83. The system of claim 82, wherein at least one of the analyte-responsive enzyme and the mediator forms one or more of carbon-carbon, carbon-nitrogen, or metal-carbon covalent bonds with the polymer.

84. The system of claim 82, wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the polymer through a linker moiety.

85. The system of claim 82, wherein the mediator is covalently bonded to the polymer through one or more ligands of the mediator.

86. The system of claim 85, wherein the one or more ligands comprises a substituted or unsubstituted heterocyclic nitrogen-containing moiety.

87. The system of claim 82, wherein one or more ligands of the mediator are substituents of the polymer backbone.

88. The system of claim 82, wherein the analyte-responsive enzyme is covalently bonded to the polymer through one or more side chains of the enzyme.

89. The system of claim 88, wherein the one or more side chains of the analyte-responsive enzyme is selected from the group consisting of substituted or unsubstituted amines, alcohols, thiols, phenols, imidazoles, indols, and carboxylic acids.

90. The system of claim 82, wherein one or more side chains of the analyte-responsive enzyme are substituents of the polymer backbone.

91. The system of claim 81, wherein the polymer is crosslinked.

92. The system of claim 91, wherein at least one of the analyte-responsive enzyme and the mediator is crosslinked with the polymer.

93. The system of claim 92, wherein at least one of the analyte-responsive enzyme and the mediator is crosslinked with the polymer through one or more crosslinking agents.

94. The system of claim 93, wherein the one or more crosslinking agents is selected from the group consisting of substituted or unsubstituted epoxides, aldehydes, imidoesters, N-hydroxysuccinimide esters, carbodiimides, cyanuric chloride, tetrachlorobenzoquinone, benzoquinone and tetracyanoquinodimethane.

95. The system of claim 92, wherein one or more ligands of the mediator are crosslinkers of the polymer.

96. The system of claim 92, wherein one or more side chains of the analyte-responsive enzyme are crosslinkers of the polymer.

97. The system of claim 91, wherein the polymer forms a coordination complex with the mediator.

98. The system of claim 97, wherein one or more nitrogen-containing moieties of the polymer forms a coordination complex with a metal of the mediator.

99. The system of claim 81, wherein the mediator is ionically bonded to the polymer.

100. The system of claim 99, wherein the polymer comprises at least one positively charged moiety and the mediator comprises at least one negatively charged moiety.

101. The system of claim 99, wherein the polymer comprises at least one negatively charged moiety and the mediator comprises at least one positively charged moiety.

102. The system of claim 81, wherein the polymer is chemically bonded to the surface of the working electrode.

103. The system of claim 81, wherein the polymer forms a sensing layer membrane on the surface of the working electrode.

104. The system of claim 103, wherein the sensing layer membrane is formed in situ on the working electrode.

105. The system of claim 104, wherein the sensing layer membrane is formed in situ on the working electrode by crosslinking the polymer on the working electrode.

106. The system of claim 103, wherein the working electrode further comprises a mass transport limiting membrane disposed over the sensing layer membrane.

107. The system of claim 81, wherein the analyte-responsive enzyme is a glucose-responsive enzyme.

108. The system of claim 81, wherein the analyte-responsive enzyme is glucose dehydrogenase (GDH) or glucose oxidase (GOx).

109. The system of claim 81, wherein the analyte-responsive enzyme further comprises an enzyme cofactor.

110. The system of claim 109, wherein the enzyme cofactor is flavin adenine dinucleotide.

111. The system of claim 81, wherein the mediator comprises ruthenium or osmium.

112. The system of claim 81, wherein the calibration device evaluates whether the calibration measurement is within a predetermined range of an analyte concentration to determine whether the quality of the calibration measurement is suitable for calibration.

113. The system of claim 112, wherein the predetermined range comprises about 60 mg/dL to about 350 mg/dL.

114. The system of claim 81, wherein the calibration site is an arm.

115. The system of claim 81, wherein the calibration site is an abdomen.

116. The system of claim 81, wherein the blood sample for the calibration measurement is 1 microliter or less.

117. The system of claim 81, wherein the blood sample for the calibration measurement is 0.5 microliters or less.

118. The system of claim 81, wherein the blood sample for the calibration measurement is 0.2 microliters or less.

119. The system of claim 81, wherein the calibration device determines sensitivity based on the calibration measurement when the calibration measurement is determined to be suitable.

120. The system of claim 81, wherein the calibration device evaluates the quality of the one or more signals.

121. The system of claim 120, wherein the quality of the generated one or more signals is based on evaluating a rate of change of the one or more signals from the in vivo analyte sensor.

122. The system of claim 120, wherein the calibration device determines sensitivity based on the evaluated quality of the one or more signals from the in vivo analyte sensor.

123. The system of claim 81, wherein the calibration sensor is an in vitro sensor.

124. The system of claim 123, wherein the in vitro sensor is a test strip.

125. The system of claim 81, wherein the calibration sensor is an in vivo calibration sensor.

126. The system of claim 81, wherein the in vivo analyte sensor is a transcutaneous sensor.