Glucose Sensor Barrier Layer for Protein Interference

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Solution Overview

Problem

Boronic acid-based glucose sensors face interference from glycated proteins and high molecular weight endogenous materials, which hinder accurate glucose detection in body fluids.

Innovation Solution

A glucose sensor with a hydrophilic, polymeric barrier layer that is permeable to glucose but restricts the passage of proteins and glycated proteins, utilizing a semipermeable membrane with in situ polymerization of hydrophilic and negatively charged monomers to control pore size and enhance selectivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a boronic acid receptor is used for glucose sensing, then glucose detection capability is achieved, but interference from glycated proteins and high molecular weight endogenous materials occurs

Engineering Contradiction:
Improveglucose detection accuracyVSAvoidprotein interference
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The sensor system is segmented into distinct functional layers: a sensing region containing the boronic acid/fluorophore chemistry and a barrier layer containing the semipermeable membrane. This segmentation allows the sensing region to maintain high glucose detection precision while the barrier layer selectively blocks protein interferents, resolving the contradiction between detection capability and interference resistance.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A barrier layer acting as an intermediary component is introduced between the sample environment and the sensing region. This intermediary layer selectively permits glucose passage while blocking glycated proteins and high molecular weight endogenous materials, thereby protecting the boronic acid receptor from interference while maintaining glucose detection accuracy.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If the barrier layer restricts protein passage, then protein interference is eliminated, but glucose permeability must be maintained

Engineering Contradiction:
Improveprotein interferenceVSAvoidglucose permeability
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The barrier layer employs a semipermeable membrane with specifically engineered porous structure. The pore size and distribution are controlled to create size-based selectivity: pores are sufficiently large to allow glucose molecules to pass freely but small enough to exclude glycated proteins and high molecular weight endogenous materials. This porous structure simultaneously achieves protein restriction and glucose permeability, resolving the contradiction between eliminating interference and maintaining reliable glucose detection.

Inventive Principle:
Principle #31Porous materials

3Measurement precision

If a semipermeable membrane is used to block proteins, then selectivity is improved, but manufacturing complexity increases due to in situ polymerization process

Engineering Contradiction:
Improvemolecular selectivityVSAvoidmembrane fabrication
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The semipermeable membrane is pre-formed with appropriate porous structure before being applied to the sensing region. The in situ polymerization process then fills the pores with hydrophilic polymer to establish the selective barrier properties. This preliminary formation of the membrane structure separates the mechanical support function from the selective barrier function, simplifying the overall manufacturing process while achieving the required molecular selectivity.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The in situ polymerization process enables precise control of the barrier layer's physical and chemical parameters, including pore size, polymer crosslinking density, and hydrophilicity. By adjusting polymerization conditions such as monomer concentration, initiator amount, and reaction time, the membrane's selectivity characteristics can be optimized to achieve optimal protein blocking while maintaining glucose permeability, thereby managing manufacturing complexity through parameter control.

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 barrier layer effectively prevents protein interference, improving the accuracy and sensitivity of glucose detection by allowing glucose to pass while blocking larger molecules, thereby enhancing the sensor's response time and stability in bodily fluids.

Implementation Method 1

a hydrophilic, polymeric, glucose-permeable barrier layer comprising a semipermeable membrane which is provided on at least a part of the sensing region

Methodology Applied
Scientific EffectSemipermeable membrane filtration: Semipermeable Membrane

Implementation Method 2

a hydrophilic polymer and/or a negatively charged polymer is present within the pores of the membrane

Methodology Applied
Scientific EffectElectrostatic repulsion: Ion Repulsion/Attraction

Implementation Method 3

A hydrophilic and/or negatively charged polymer is present within the pores of the membrane. This is achieved via in situ polymerisation

Methodology Applied
Scientific EffectHydrophilic interaction: Hydrophile

Implementation Method 4

initiating polymerisation; wherein the sensor is adapted so that glucose enters the sensing region of the sensor through said barrier layer

Methodology Applied
Scientific EffectPolymerisation: Photopolymerisation

Data Source

PatentEP2537034B1Barrier layer for glucose sensor
Publication Date: 2019.01.02 BAXTER HEALTHCARE SA
  • EP2537034B1 patent drawingFigure 1~1a
  • EP2537034B1 patent drawingFigure 2~3
  • EP2537034B1 patent drawingFigure 4

AI summary

An optical glucose sensor comprising: a sensing region comprising a boronic acid receptor for binding to glucose and a fluorophore associated with said receptor; an optical waveguide for directing incident light onto the sensing region; and a hydrophilic, polymeric, glucose-permeable barrier layer which is provided on at least a part of the sensing region; wherein the sensor is adapted so that glucose enters the sensing region of the sensor through said barrier layer.