Temperature-insensitive membrane materials and analyte sensors containing the same
Inventors
Bommakanti, Balasubrahmanya S. • LaTour, John V. • Hoss, Udo • Ouyang, Tianmei • Le, Phu • Sandhu, Gary • WALLIS, Kevin
Assignees
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Publication Number
US-12662577-B2
Publication Date
2026-06-23
Expiration Date
Abstract
Membranes permeable to an analyte may overlay the active sensing region of a sensor to limit the analyte flux and improve the response linearity of the sensor. Temperature variation of the analyte permeability can be problematic in some instances. Polymeric membrane compositions having limited variation in analyte permeability as a function of temperature may comprise: a polymer backbone comprising one or more side chains that comprise a heterocycle; and an amine-free polyether arm appended, via an alkyl spacer or a hydroxy-functionalized alkyl spacer, to the heterocycle of at least a portion of the one or more side chains.
Core Innovation
Temperature-dependent analyte permeability is identified as a problem for in vivo analyte sensors, because it complicates calibration of analyte concentration measurements. The disclosed approach uses a polymeric membrane overcoating that overlays an enzyme sensing region to limit analyte flux. This membrane is designed to provide temperature-insensitive analyte permeability behavior so sensor response can remain stable across a temperature range.
The polymeric membrane material comprises a polymer backbone with one or more side chains that include a heterocycle, where at least a portion of the side-chain heterocycles are functionalized with an amine-free polyether arm. The amine-free polyether arm is appended via an alkyl spacer or a hydroxy-functionalized alkyl spacer to the heterocycle of the side chains. The polyether arm structure is defined by Formula 13 using parameters w, x, y, and z.
The disclosure further expands the membrane polymer architecture with optional structural features, including additional sulfonate-containing arms and/or crosslinkers that can include first and second portions bonded to respective polymer backbones. Example membrane compositions include heterocycle-containing polymers such as poly(4-vinylpyridine-co-styrene). In sensor implementations, the membrane is positioned over sensing regions that include an analyte-responsive enzyme and a counter electrode, for measuring analyte concentration in bodily fluid.
For temperature-insensitive performance, the sensor signal is reported to exhibit less than 2% variation across 17°C to 42°C at constant glucose concentration. The disclosed membrane-enabled sensor is also associated with biocompatibility targets using tests referenced as ISO 10993-1, and with additional test summaries including cytotoxicity score thresholds and other safety-related endpoints.
Claims Coverage
The partial disclosure includes three independent claims (clm-00001, clm-00014, clm-00015). Each claim focuses on a different inventive aspect: an in vivo analyte sensor architecture with a defined heterocycle/amine-free polyether arm membrane, and two related membrane-composition making routes defined by Formula 14 or Formula 15 precursors.
Temperature-insensitive membrane in an in vivo analyte sensor
An in vivo analyte sensor having a below-skin working electrode with at least one sensing region, where each sensing region comprises an analyte-responsive enzyme, a counter electrode, and a polymeric membrane overcoating the sensing region, the polymeric membrane material including a polymer backbone with heterocycle side chains and an amine-free polyether arm appended via an alkyl spacer or a hydroxy-functionalized alkyl spacer, the amine-free polyether arm having a structure of Formula 13 with w, x, and z ranges.
Reacting heterocyclic-nitrogen polymer with a Formula 14 amine-free polyether arm precursor
A method of making a polymeric membrane composition by reacting a polymer comprising one or more side chains with a heterocyclic or heteroaromatic nitrogen atom with an amine-free polyether arm precursor comprising a structure of Formula 14, wherein x, y, and z fall within specified ranges, A1 is an alkyl group having between about 2 and about 20 carbon atoms, and X is a halide.
Reacting heterocyclic-nitrogen polymer with a Formula 15 amine-free polyether arm precursor
A method of making a polymeric membrane composition by reacting a polymer comprising one or more side chains with a heterocyclic or heteroaromatic nitrogen atom with an amine-free polyether arm precursor comprising a structure of Formula 15, wherein x, y, and z fall within specified ranges, and A2 is an alkyl group having between 1 and about 10 carbon atoms.
Across the independent claims, the core inventive coverage centers on an in vivo analyte sensor in which sensing-region membranes are formed from heterocycle-bearing polymer backbones functionalized with amine-free polyether arms defined by Formula 13, and methods for making related polymeric membrane compositions by reacting heterocyclic or heteroaromatic nitrogen-containing polymers with amine-free polyether arm precursors defined by Formula 14 or Formula 15.
Stated Advantages
Temperature-insensitive analyte permeability behavior enabling less than 2% sensor signal variation across 17°C to 42°C at constant glucose concentration.
Biocompatibility targets are addressed, including cytotoxicity score 2 or below and an ISO 10993-1 reference.
Safety-related test summaries are reported, including hemolysis index ≤2, and Ames test (mutagenicity), with additional irritation/implantation-related endpoints referenced.
Documented Applications
In vivo analyte sensing in bodily fluid using a sensor having sensing regions with an enzyme and a polymeric membrane overcoating, with example analyte monitoring including glucose (and lactate is referenced via a lactate-responsive enzyme dependent claim family member).
Glucose monitoring with an analyte sensor signal reported to have less than 2% variation across 17°C to 42°C when glucose concentration is constant.
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