Biosensor membranes composed of polymers containing heterocyclic nitrogens

• US 20050241957A1
• Filed: 07/01/2005
• Published: 11/03/2005
• 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 7,670,470 B2
• Time in Patent Office: Days
• US Class Current: 205/777.500
• 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 wish such membranes are also described.

Claims

1-89. -89. (canceled)

90. A crosslinked membrane for use in an analytical sensor, comprising:

a polymer having the formula;

wherein the solid horizontal line represents a polymer backbone;

A is an alkyl substituted with a water-soluble constituent;

D is selected from phenylalkyl, alkoxystyrene, hydroxyalkyl, alkoxyalkyl, alkoxycarbonylalkyl, a poly(ethylene glycol)-containing constituent, and a polyhydroxyl-containing constituent; and

each of n, l, p and q is independently a positive number.

91. The membrane of claim 90, wherein A is negatively charged.

92. The membrane of claim 90, wherein A is selected from a sulfonate, a carboxylate, and a phosphate.

93. The membrane of claim 90, wherein A is selected from sulfopropyl, sulfobutyl, carboxypropyl, and carboxypentyl.

94. The membrane 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.

95. The membrane of claim 94, wherein L is substituted with an aryl, alkoxy, alkenyl, alkynyl, —

F, —

Cl, —

OH, aldehyde, ketone, ester, or amide.

96. The membrane of claim 90, wherein D is styrene or C1-C18 alkyl methacrylate.

97. The membrane of claim 90, wherein an average molecular weight of the polymer is above about 50,000.

98. The membrane of claim 90, wherein an average molecular weight of the polymer is above about 50,000 to about 200,000.

99. The membrane of claim 90, wherein the polymer further comprises a B-containing copolymer such that the polymer has the formula:

100. The membrane of claim 99, wherein B is selected from a chelator, a negatively charged constituent, a hydrophobic hydrocarbon constituent, a hydrophilic hydroxyl or polyhydroxy constituent, a silicon polymer, and a poly(ethylene glycol).

101. The membrane of claim 99, wherein B is a poly(ethylene glycol) having a molecular weight of from about 100 to about 20,000.

102. The membrane of claim 99, wherein B is a poly(ethylene glycol) having a molecular weight of from about 200 to about 2000.

103. The membrane of claim 99, wherein [n/(n+m+l+p)]×

100% is from about 1% to about 25%.

104. The membrane of claim 99, wherein [m/(n+m+l+p)]×

100% is from about 1% to about 15%.

105. The membrane of claim 99, wherein [l/(n+m+l+p)]×

100% is from about 20% to about 90%.

106. The membrane of claim 99, wherein [p/(n+m+l+p)]×

100% is from about 1% to about 50%.

107. The membrane of claim 90, wherein at least one heterocyclic nitrogen constituent of the polymer is independently selected from pyridine, imidazole, oxazole, thiazole, pyrazole, and any derivative thereof.

108. The membrane of claim 90 sufficient to limit a flux of glucose or lactate thereacross.

109. The membrane of claim 90 sufficient to limit a flux of glucose or lactate thereacross in vivo.

110. An electrochemical sensor, comprising:

a working electrode comprising;

a sensing layer in contact with a conductive material of the electrode;

a membrane disposed over the sensing layer, the membrane comprising a polymer having the formula;

wherein the solid horizontal line represents a polymer backbone;

A is an alkyl substituted with a water-soluble constituent;

D is selected from phenylalkyl, alkoxystyrene, hydroxyalkyl, alkoxyalkyl, alkoxycarbonylalkyl, a poly(ethylene glycol)-containing constituent, and a polyhydroxyl-containing constituent; and

each of n, l, p and q is independently a positive number; and

a counter electrode in electrochemical communication with the working electrode.