Mediator-Functionalized Sensor Polymers for Low-Interference Glucose Detection

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Solution Overview

Problem

Conventional electrochemical analyte sensors, such as amperometric glucose sensors, are prone to interference from electroactive species that generate spurious signals, leading to inaccurate measurements due to overlapping oxidation or reduction potentials with the analyte or its by-products.

Innovation Solution

Incorporation of enzyme mediators, like Amine Reactive Phenazine Ethosulphate (AR-PES), into analyte sensor materials to facilitate electron transfer at lower operating potentials, reducing interference from interfering species and maintaining accurate analyte signal detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional amperometric sensors use high electrical potentials to detect analyte signals, then the analyte detection sensitivity is improved, but interfering species generate spurious signals causing measurement inaccuracy

Engineering Contradiction:
Improveanalyte detection accuracyVSAvoidinterference from electroactive species
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent introduces enzyme mediators (such as phenazine ethosulfate, ferrocene, or quinone derivatives) as intermediary substances that facilitate electron transfer between the enzyme-analyte reaction and the electrode. These mediators operate at lower potentials (below 300 mV) compared to conventional direct detection methods, thereby enabling analyte signal detection while avoiding the oxidation or reduction of interfering electroactive species that occur at higher potentials. The mediator acts as a shuttle, accepting electrons from the enzymatic reaction and delivering them to the electrode surface at a potential where interferents remain electrochemically inactive.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the electrical potential parameter from high potentials (around 535 mV in conventional sensors) to low potentials (below 300 mV, preferably between -200 mV and +100 mV). This parameter change is achieved by coupling the enzyme to a mediator that has a suitable redox potential, allowing the sensor to operate in a potential window where the analyte can be detected but interfering species do not undergo electrochemical reactions. This parameter modification fundamentally resolves the contradiction by decoupling detection sensitivity from high potential requirements.

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If enzyme mediators are coupled to amine functional polymers to enable low potential operation, then interference rejection is improved, but the device complexity increases

Engineering Contradiction:
Improveinterference rejectionVSAvoidsensor material composition
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent employs composite materials consisting of amine-functional polymers (such as polylysine, polyacrylamide, or chitosan) covalently coupled to enzyme mediators. This composite structure provides multiple benefits: the polymer matrix offers structural support and facilitates mediator presentation to the electrode, while the mediator enables low-potential electron transfer. The composite nature of this material combination allows the sensor to achieve both interference rejection and functional efficiency without requiring entirely new device architectures.

Inventive Principle:
Principle #40Composite materials

3Power

If conventional sensors operate at high potentials to ensure analyte signal strength, then signal detection capability is improved, but the operating potential range overlaps with interferent oxidation/reduction potentials

Engineering Contradiction:
Improvesignal strengthVSAvoidoverlapping electrochemical reactions
Core Design Contradiction:
PowerVSObject-affected harmful factors

Solution Approach 1:

The mediator serves as an intermediary that decouples signal generation from high potential requirements. The enzyme-catalyzed reaction generates electrons that are transferred to the mediator at low potential, and the mediator subsequently transfers these electrons to the electrode. This two-step process maintains strong signal generation while operating in a potential window free from interferent reactions, effectively resolving the overlap problem.

Inventive Principle:
Principle #24Intermediary (Mediator)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The use of enzyme mediators allows sensors to operate at lower electrical potentials, effectively distinguishing between true analyte signals and interfering species, ensuring accurate glucose detection even in the presence of interferents, and maintaining sensor functionality post-sterilization.

Implementation Method 1

mediators as well as coenzymes including flavin adenine dinucleotide 'FAD' (e.g., for use with glucose dehydrogenase enzymes) and nicotinamide adenine dinucleotide 'NAD' (e.g., for use with 3-hydroxybutyrate dehydrogenases)... facilitate the transfer electrons from enzyme/analyte reactions to sensor electrodes

Methodology Applied
Scientific EffectElectron transfer: Redox Reactions

Implementation Method 2

a polymer functionalized with an agent selected to mediate reactivity of the enzyme with the analyte

Methodology Applied
Scientific EffectEnzyme reactivity: Enzyme

Data Source

PatentUS12522853B2Enzyme mediator functionalized polymers for use with analyte sensors
Publication Date: 2026.01.13 MEDTRONIC MINIMED INC
  • US12522853B2 patent drawing
  • US12522853B2 patent drawing
  • US12522853B2 patent drawing

AI summary

Embodiments of the invention provide amperometric analyte sensors having elements selected to optimize enzymatic activities associated with such sensors including polymers functionalized with enzymatic mediators as well as methods for making and using such sensors. While embodiments of the invention can be used in a variety of contexts, typical embodiments of the invention include glucose or ketone sensors used in the management of diabetes.