Analyte Sensor Membrane Segmentation for Interference Blocking

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Solution Overview

Problem

Conventional electrochemical glucose sensors face challenges in accurately measuring glucose levels due to interference from substances like acetaminophen, ascorbic acid, and uric acid, leading to inaccurate signal responses and delayed detection of hyperglycemic or hypoglycemic conditions in diabetic patients.

Innovation Solution

An electrochemical analyte sensor with a membrane system that includes a hydrophilic electrode domain and an interference domain comprising cellulosic derivatives, such as cellulose acetate or cellulose acetate butyrate, to block the passage of interfering substances, allowing for accurate glucose measurement by reducing equivalent glucose signal responses of interferents to less than 60 mg/dL.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional electrochemical sensors are used to measure glucose, then the sensor can detect electroactive species, but interfering species such as acetaminophen, ascorbic acid, and uric acid cause inaccurate glucose signal amplitude

Engineering Contradiction:
Improveglucose measurement accuracyVSAvoidinterference from electroactive species
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The membrane system is divided into multiple functional domains: a first domain with high oxygen permeability for rapid break-in, a second domain (interference domain) with cellulosic derivatives that blocks interfering species, and a third domain with enzyme layer for glucose detection. This segmentation allows each domain to perform its specific function optimally while working together as a integrated system.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different regions of the membrane system have tailored properties: the first domain has high oxygen permeability for rapid equilibration, the second domain has selective permeability to block interferents while allowing glucose passage, and the third domain contains immobilized enzyme for catalysis. Each local region is optimized for its specific function to resolve the contradiction between detection accuracy and interference rejection.

Inventive Principle:
Principle #3Local quality

2Measurement precision

If the sensor uses a multi-domain membrane system with interference blocking, then measurement accuracy improves, but device complexity increases

Engineering Contradiction:
Improveglucose measurement accuracyVSAvoidmembrane system structure
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

Multiple functional requirements are merged into a single integrated membrane system that combines oxygen permeability, interference blocking, and enzyme immobilization capabilities in one cohesive structure. This merging reduces the need for separate components while achieving multiple functions simultaneously, thus improving accuracy without proportionally increasing complexity.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The membrane system uses composite material structures combining different polymers and cellulosic derivatives with distinct properties in a single integrated membrane. This allows the system to achieve high oxygen permeability, interferent blocking, and enzyme immobilization simultaneously within one component rather than requiring multiple separate layers or devices.

Inventive Principle:
Principle #40Composite materials

3Loss of time

If the sensor is designed for rapid break-in (less than 2 hours), then timely glucose monitoring is achieved, but the membrane must allow rapid analyte transport which may reduce selectivity

Engineering Contradiction:
Improvebreak-in timeVSAvoidsignal accuracy
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The membrane is segmented into domains with different permeability characteristics: the first domain has high oxygen permeability for rapid break-in, while the second domain provides selective interference blocking. This segmentation allows rapid analyte transport for quick break-in while maintaining selectivity for accurate measurement.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The membrane system optimizes physical parameters such as oxygen permeability and porosity in different domains to achieve rapid analyte transport for fast break-in, while simultaneously maintaining selective permeability properties for interferent blocking, thus resolving the contradiction between speed and accuracy.

Inventive Principle:
Principle #35Parameter changes

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 sensor enables rapid break-in and accurate glucose monitoring in vivo, providing timely and reliable data for diabetic patients, reducing the risk of dangerous glycemic events by effectively filtering out interfering substances and enhancing the sensitivity and specificity of glucose measurements.

Implementation Method 1

an interference domain comprising cellulosic derivatives, such as cellulose acetate or cellulose acetate butyrate, to block the passage of interfering substances

Methodology Applied
Scientific EffectPhysical barrier blocking: Filter (physical)

Implementation Method 2

a hydrophilic electrode domain and an interference domain

Methodology Applied
Scientific EffectHydrophilic transport: Permeation

Implementation Method 3

an analyte (or a species derived from it) that is electro-active generates a detectable signal at an electrode

Methodology Applied
Scientific EffectElectrochemical reaction: Redox Reactions

Implementation Method 4

an enzyme is provided that reacts with the analyte to be measured, and the byproduct of the reaction is qualified or quantified at the electrode

Methodology Applied
Scientific EffectEnzymatic catalysis: Enzyme

Implementation Method 5

hydrogen peroxide, which is then quantified by amperometric measurement (for example, change in electrical current) through a polarized electrode

Methodology Applied
Scientific EffectAmperometric detection: Conduction (electrical)

Data Source

PatentEP2004796B1Membranes for an analyte sensor
Publication Date: 2015.04.08 DEXCOM INC
  • EP2004796B1 patent drawingFigure 1
  • EP2004796B1 patent drawingFigure 2
  • EP2004796B1 patent drawingFigure 3

AI summary

The present invention relates generally to devices for measuring an analyte in a host. More particularly, the present invention relates to devices for measurement of glucose in a host that incorporate a hydrophilic electrode domain and/or a cellulosic-based interference domain.