Biosensor Chemistry Matrix for Maltose and Oxygen Interference

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Solution Overview

Problem

Current biosensors face challenges in accurately measuring glucose levels in biological fluids due to interference from substances like maltose and fluctuations in oxygen levels, leading to inaccurate readings and requiring user input for blood sample type, which introduces additional errors.

Innovation Solution

A chemistry matrix comprising glucose dehydrogenase, nicotinamide adenine dinucleotide, a phenazine derivative, and a nitrosoaniline, which is stable at pH 6.5-8.5 and photochemically stable, is used to minimize interference from maltose and oxygen, providing accurate glucose measurements without the need for user input on blood sample type.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If conventional electrochemical methods are used to measure glucose, then measurement speed is improved, but measurement precision deteriorates due to interference from maltose and oxygen

Engineering Contradiction:
Improvemeasurement speedVSAvoidglucose measurement accuracy
Core Design Contradiction:
SpeedVSMeasurement precision

Solution Approach 1:

The patent introduces an intermediary substance (maltose oxidase enzyme) that specifically reacts with the interfering substance (maltose) to convert it into a different compound. This mediator enzyme selectively targets maltose without affecting the glucose measurement, thereby eliminating the interference while maintaining fast measurement speed. The intermediary acts as a filter that removes harmful interferences before they can affect the primary measurement.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Adaptability or versatility

If user input is required for blood sample type, then adaptability is improved, but device complexity increases and reliability decreases due to additional error sources

Engineering Contradiction:
Improveblood sample type compatibilityVSAvoiduser input requirement
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The biosensor system performs self-identification of the blood sample type through automated detection mechanisms. The system automatically adapts to different sample types (capillary, venous, arterial blood) without requiring user input, thereby eliminating the complexity and potential errors associated with manual sample type selection while maintaining full adaptability to various sample types.

Inventive Principle:
Principle #25Self-service

3Productivity

If enzymes with very fast reaction times are used, then productivity is improved, but reliability worsens due to susceptibility to interferents like maltose

Engineering Contradiction:
Improvereaction speedVSAvoidresistance to interferents
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent segments the measurement function into two distinct enzymatic components: glucose oxidase for the primary glucose measurement and maltose oxidase for interference elimination. Each enzyme is optimized for its specific function - glucose oxidase provides fast reaction speed for productivity, while maltose oxidase provides selective interference removal for reliability. This segmentation allows both high productivity and reliability to coexist by dividing the overall measurement task into specialized sub-functions.

Inventive Principle:
Principle #1Segmentation

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 chemistry matrix enables accurate glucose level determination in the presence of maltose and varying oxygen levels, providing fast test times of about 5 seconds or less, with minimal interference and improved reliability compared to conventional methods.

Implementation Method 1

A chemistry matrix comprising glucose dehydrogenase, nicotinamide adenine dinucleotide, a phenazine derivative, and a nitrosoaniline

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

electrochemical methods generally involve amperometric, coulometric, potentiometric, and/or conductive responses indicative of the concentration of the analyte

Methodology Applied
Scientific EffectElectrochemical detection:

Implementation Method 3

a phenazine derivative... providing accurate glucose measurements

Methodology Applied
Scientific EffectElectron mediation:

Implementation Method 4

which is stable at pH 6.5-8.5 and photochemically stable, is used to minimize interference from maltose and oxygen

Methodology Applied
Scientific EffectSelective enzymatic reaction: Enzyme

Data Source

PatentEP2265726B1Biosensor with improved analyte specificity
Publication Date: 2014.05.07 ROCHE DIAGNOSTICS GMBH
  • EP2265726B1 patent drawingFigure 1~2
  • EP2265726B1 patent drawingFigure 3
  • EP2265726B1 patent drawingFigure 4

AI summary

A chemistry matrix for use in determining the concentration of an analyte in a biological fluid includes a glucose dehydrogenase, nicotinamide adenine dinucleotide, an alkylphenazine quaternary salt, and a nitrosoaniline. The chemistry matrix is used with an electrochemical biosensor to determine the concentration of an analyte after a reaction occurs within the biosensor, at which time an analysis is completed to determine the concentration. A method of determining the concentration of an analyte using the chemistry matrix of glucose dehydrogenase, nicotinamide adenine dinucleotide, an alkylphenazine quaternary salt, and a nitrosoaniline is another aspect that is described. The method also further features test times of five seconds or less. Methods utilizing the new chemistry matrix can readily determine an analyte such as blood glucose at concentrations of from about 20-600 mg/dL at a pH of from about 6.5 to about 8.5.