Enzyme Stabilizing Agent for Continuous Glucose Sensor Membrane

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Solution Overview

Problem

Enzymatic glucose sensors face performance issues under low oxygen conditions and are sensitive to temperature and pH, leading to increased manufacturing costs and reduced throughput due to the need for restricted curing temperatures to preserve enzymatic activity.

Innovation Solution

A sensing membrane comprising an enzyme domain with a hydrophilic polymer, such as poly-N-vinylpyrrolidone, and a base polymer like polyurethane, along with a cross-linking agent, which enhances thermal stability and pH tolerance, and includes a zwitterionic enzyme stabilizing agent to reduce enzyme degradation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If polymer membrane curing is conducted at high temperatures to reduce curing time and increase throughput, then productivity improves, but enzyme degradation occurs which reduces sensor reliability

Engineering Contradiction:
Improvecuring throughputVSAvoidenzymatic activity
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent introduces a stabilizing agent that modifies the thermal stability parameter of the enzyme, allowing the curing process to occur at higher temperatures without enzyme degradation. This enables the membrane curing to be conducted at temperatures that reduce curing time while maintaining enzymatic activity through the protective effect of the stabilizing agent.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The stabilizing agent acts as an intermediary substance between the enzyme and the high-temperature curing environment. It mediates the interaction by protecting the enzyme from thermal damage while allowing the curing process to proceed, thus resolving the contradiction between high-temperature processing and enzyme preservation.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If the sensor operates under low oxygen conditions, then glucose sensitivity is improved, but sensor signal decreases due to oxygen dependency

Engineering Contradiction:
Improveglucose sensitivityVSAvoidsensor signal
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The stabilizing agent modifies the operational parameters of the enzyme system, enhancing its performance under low oxygen conditions. This allows the sensor to maintain reliable signal output while operating in low oxygen environments, thereby improving glucose sensitivity without sacrificing signal reliability.

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If the pH range is expanded to increase adaptability, then sensor versatility improves, but enzyme degradation increases which reduces reliability

Engineering Contradiction:
ImprovepH rangeVSAvoidenzymatic activity
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The stabilizing agent alters the pH stability parameters of the enzyme, enabling it to maintain activity across a broader pH range. This allows the sensor to be used in diverse pH environments without enzyme degradation, thus expanding adaptability while preserving reliability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The stabilizing agent serves as an intermediary that protects the enzyme from pH-induced degradation. It mediates between the enzyme and varying pH conditions, allowing the sensor to operate across an expanded pH range while maintaining enzymatic activity and reliability.

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 solution improves sensor performance under low oxygen conditions, increases thermal and pH stability, and reduces manufacturing time and costs by maintaining enzymatic activity and extending the usable pH range.

Implementation Method 1

a hydrophilic polymer which makes up from about 5 wt. % to about 30 wt. % of the enzyme domain

Methodology Applied
Scientific EffectHydrophilic polymer stabilization:

Implementation Method 2

includes a zwitterionic enzyme stabilizing agent to reduce enzyme degradation

Methodology Applied
Scientific EffectZwitterionic stabilization:

Implementation Method 3

along with a cross-linking agent, which enhances thermal stability and pH tolerance

Methodology Applied
Scientific EffectCross-linking:

Data Source

PatentUS20240277268A1Membrane for continuous analyte sensors
Publication Date: 2024.08.22 DEXCOM INC
  • US20240277268A1 patent drawing
  • US20240277268A1 patent drawing
  • US20240277268A1 patent drawing

AI summary

Devices are presented for measurement of an analyte concentration. The devices comprise: a sensor configured to generate a signal indicative of a concentration of an analyte; and a sensing membrane located over the sensor. The sensing membrane comprises an enzyme domain comprising an enzyme, a base polymer, and a hydrophilic polymer which makes up from about 5 wt. % to about 30 wt. % of the enzyme domain.