Biosensor Membranes Composed of Polymers Containing Heterocyclic Nitrogens

• US 20110017595A1
• Filed: 09/29/2010
• Published: 01/27/2011
• Est. Priority Date: 05/15/2001
• Status: Active Grant

• Current Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Diabetes Care Incorporated (Abbott Laboratories Incorporated)
• Inventors: Cho, Hyun, Mao, Fei
• Granted Patent: US 8,377,271 B2
• Time in Patent Office: Days
• US Class Current: 204/403.14
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• 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 5/6846 specially adapted to be brought in contact with an internal body part, i.e. invasive
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: C12Q 1/006 for glucose

Abstract

Novel membranes comprising various polymers containing heterocyclic nitrogen groups are described. These membranes are usefully employed in electrochemical sensors, such as amperometric biosensors. More particularly, these membranes effectively regulate a flux of analyte to a measurement electrode in an electrochemical sensor, thereby improving the functioning of the electrochemical sensor over a significant range of analyte concentrations. Electrochemical sensors equipped with such membranes are also described.

Claims

1-89. -89. (canceled)

90. A polymer complex comprising:

a first polymer comprising an analyte responsive enzyme and a mediator, wherein at least one of the analyte-responsive enzyme and the mediator is chemically bonded to the first polymer; and

a second polymer disposed on top and in contact with the first polymer, the second polymer comprising a polymer having the formula;

91. The polymer complex of claim 90, wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the first polymer.

92. The polymer complex of claim 91, 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 first polymer.

93. The polymer complex of claim 91, wherein at least one of the analyte-responsive enzyme and the mediator is covalently bonded to the first polymer through a linker moiety.

94. The polymer complex of claim 91, wherein the mediator is covalently bonded to the first polymer through one or more ligands of the mediator.

95. The polymer complex of claim 94, wherein the one or more ligands comprises a substituted or unsubstituted heterocyclic nitrogen-containing moiety.

96. The polymer complex of claim 94, wherein one or more ligands of the mediator are substituents of the first polymer backbone.

97. The polymer complex of claim 91, wherein the analyte-responsive enzyme is covalently bonded to the first polymer through one or more side chains of the enzyme.

98. The polymer complex of claim 97, 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.

99. The polymer complex of claim 97, wherein one or more side chains of the analyte-responsive enzyme are substituents of the first polymer backbone.

100. The polymer complex of claim 90, wherein the first polymer is crosslinked.

101. The polymer complex of claim 100, wherein at least one of the analyte-responsive enzyme and the mediator is crosslinked with the first polymer.

102. The polymer complex of claim 101, wherein at least one of the analyte-responsive enzyme and the mediator is crosslinked with the first polymer through one or more crosslinking agents.

103. The polymer complex of claim 102, 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.

104. The polymer complex of claim 100, wherein one or more ligands of the mediator are crosslinkers of the first polymer.

105. The polymer complex of claim 100, wherein one or more side chains of the analyte-responsive enzyme are crosslinkers of the first polymer.

106. The polymer complex of claim 90, wherein the first polymer forms a coordination complex with the mediator.

107. The polymer complex of claim 106, wherein one or more nitrogen-containing moieties of the first polymer forms a coordination complex with a metal of the mediator.

108. The polymer complex of claim 106, wherein the mediator is ionically bonded to the first polymer.

109. The polymer complex of claim 108, wherein the first polymer of comprises at least one positively charged moiety and the mediator comprises at least one negatively charged moiety.

110. The polymer complex of claim 108, wherein the first polymer comprises at least one negatively charged moiety and the mediator comprises at least one positively charged moiety.

111. The polymer complex of claim 90, wherein the analyte-responsive enzyme is a glucose-responsive enzyme.

112. The polymer complex of claim 111, wherein the analyte-responsive enzyme is glucose dehydrogenase (GDH) or glucose oxidase (GOx).

113. The polymer complex of claim 90, wherein the analyte-responsive enzyme further comprises an enzyme cofactor.

114. The polymer complex of claim 113, wherein the enzyme cofactor is flavin adenine dinucleotide.

115. The polymer complex of claim 90, wherein the mediator comprises ruthenium or osmium.

116. The polymer complex of claim 90, wherein A is negatively charged.

117. The polymer complex of claim 90, wherein A is selected from a sulfonate, a carboxylate, and a phosphate.

118. The polymer complex of claim 90, wherein A is selected from sulfopropyl, sulfobutyl, carboxypropyl, and carboxypentyl.

119. The polymer complex of claim 90, wherein A is of the formula L-G, where L is a C2-C12 linear or branched alkyl linker and G is a negatively charged carboxy or sulfonate.

120. The polymer complex of claim 119, wherein L is substituted with an aryl, alkoxy, alkenyl, alkynyl, —

F, —

Cl, —

OH, aldehyde, ketone, ester, or amide.

121. The polymer complex of claim 90, wherein D is styrene or C1-C18 alkyl methacrylate.

122. The polymer complex of claim 90, wherein an average molecular weight of the second polymer is above 50,000.

123. The polymer complex of claim 90, wherein an average molecular weight of the second polymer is above 200,000.

124. The polymer complex of claim 90, wherein at least one constituent of the second polymer is independently selected from pyridine, imidazole, oxazole, thiazole, pyrazole, and any derivative thereof.

125. The polymer complex of claim 90, where the second polymer is configured to limit a flux of glucose or lactate there across.

126. The polymer complex of claim 90, wherein the second polymer is formed in situ on top of the first polymer.

127. An electrochemical sensor, comprising:

a working electrode comprising a polymer complex, the polymer complex comprising;

a first polymer disposed on top and in contact with the working electrode, the first polymer comprising an analyte responsive enzyme and a mediator, wherein at least one of the analyte-responsive enzyme and the mediator is chemically bonded to the first polymer; and

a second polymer disposed on top and in contact with the first polymer, the second polymer comprising a polymer having the formula;