3-Phenylimino Phenothiazine Mediator Synthesis for Low Background Current

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Solution Overview

Problem

Existing electrochemical test sensors face challenges with high background current, leading to low signal-to-noise ratios and assay imprecision, particularly at lower glucose levels and high hematocrit sample levels, due to the use of mediators like ferricyanide, which are not adequately addressed by prior methods for forming 3-phenylimino-3H-phenothiazine or 3-phenyliminio-3H-phenoxazine derivatives.

Innovation Solution

A method is developed to produce and stabilize 3-phenylimino-3H-phenothiazine or 3-phenyliminio-3H-phenoxazine mediators with low background current, using specific reactants, solvents, and processing steps, including the use of sodium persulfate as a coupling agent, to enhance their stability and performance in electrochemical test sensors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If ferricyanide is used as a mediator in electrochemical test sensors, then the mediator can facilitate electron transfer, but the background current becomes high resulting in low signal-to-noise ratio and assay imprecision

Engineering Contradiction:
Improvesignal-to-noise ratioVSAvoidbackground current
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the chemical structure and properties of the mediator by synthesizing 3-phenylimino-3H-phenothiazine derivatives with specific molecular characteristics that result in low background current while maintaining electron transfer capability. This parameter change in mediator chemistry directly resolves the contradiction between reliable signal detection and harmful background current.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a stable but low-background mediator compound that can be easily synthesized and incorporated into the sensor. The mediator is designed to be chemically stable during storage yet active during the brief test period, effectively replacing problematic long-lasting high-background mediators like ferricyanide.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Productivity

If quicker sample test times are implemented (less than 10 seconds), then productivity increases, but it becomes difficult to burn off high background current before measurement

Engineering Contradiction:
Improvetest timeVSAvoidbackground current
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the temporal characteristics of the background current by using a mediator with inherently low background current that does not require extended burning-off time. This parameter change allows rapid testing without the interference of persistent background current, resolving the contradiction between quick test times and background current management.

Inventive Principle:
Principle #35Parameter changes

3Ease of manufacture

If prior art methods are used to form 3-phenylimino-3H-phenothiazine derivatives, then the synthesis route is established, but the mediator does not achieve satisfactory low background current and stability

Engineering Contradiction:
Improvesynthesis routeVSAvoidmediator stability
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent optimizes the synthesis parameters and conditions to produce mediators with improved stability and low background current characteristics. By carefully controlling reaction conditions, reagent ratios, and purification methods, the patent achieves mediators that maintain both ease of manufacture and high reliability performance.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite mediator compounds combining phenothiazine core structures with specific phenylimino substituents that provide both synthetic accessibility and the desired electrochemical properties of low background current and stability.

Inventive Principle:
Principle #40Composite materials

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 method results in mediators with significantly reduced background current and improved stability, enhancing the accuracy of glucose concentration measurements in electrochemical test sensors, even at quicker test times and varying temperatures.

Implementation Method 1

adding sodium persulfate to the reactants solution to couple the first and second reactants resulting in a reaction solution including the 3-phenylimino-3H-phenothiazine mediator

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 2

The transfer of redox equivalents from the site of chemical reaction in the enzyme to the surface of the electrode is accomplished using electron transfer mediators

Methodology Applied
Scientific EffectElectron transfer:

Implementation Method 3

the relevant chemical reaction is the oxidation of glucose to gluconolactone or its corresponding acid. This oxidation is catalyzed by a variety of enzymes

Methodology Applied
Scientific EffectRedox reactions: Redox Reactions

Data Source

PatentEP2229590B1Process of making 3-phenylimino-3h-phenothiazine or 3-phenylimino-3h-phenoxazine mediator
Publication Date: 2018.11.21 ASCENSIA DIABETES CARE HLDG AG
  • EP2229590B1 patent drawingFigure 1A~1B
  • EP2229590B1 patent drawingFigure 2
  • EP2229590B1 patent drawingFigure 3A

AI summary

A method of forming a 3-phenylimino-3H-phenothiazine or a 3-phenylimino-3H-phenoxazine mediator includes providing a first reactant including phenothiazine or phenoxazine, providing a first solvent, providing a second reactant and providing a second solvent. The first reactant, first solvent, second reactant and second solvent are combined to form a reactants solution. Sodium persulfate is added to the reactants solution to couple the first and second reactants resulting in a reaction solution including the 3-phenylimino-3H-phenothiazine or the 3-phenylimino-3H-phenoxazine mediator.