Potentiometric detection method

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Solution Overview

Problem

Existing urea concentration testing methods, including colorimetric and potentiometric methods, are cumbersome, require expensive instruments, and are prone to interference, with complicated calculations and high costs due to the use of NH4+ selective ionophores and complex electrode structures.

Innovation Solution

A potentiometric biosensor with a simplified structure that uses a first reaction reagent containing an electron mediator and a second reaction reagent containing urease, eliminating the need for NH4+ selective ionophores, and measures the potential difference without external voltage, providing a direct linear relationship between the potential difference and urea concentration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If colorimetric methods or conventional potentiometric methods are used for urea determination, then detection can be achieved, but the test procedures become cumbersome and require expensive instruments

Engineering Contradiction:
Improveurea concentration detectionVSAvoidtest procedure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention divides the detection system into distinct functional components: a test strip with separate reaction zones for different reagents (urease-containing and electron mediator-containing), and a handheld device for reading. This segmentation allows the complex detection process to be distributed across simple, modular components rather than requiring a single complex instrument.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention introduces an electron mediator as an intermediary substance that facilitates the detection process. The mediator undergoes redox reactions that produce measurable electrical signals, serving as an intermediate step between the urea-urease reaction and the final detection reading, thereby simplifying the overall measurement process.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If NH4+ selective ionophores and complex electrode structures are used, then urea concentration can be measured, but test costs increase and manufacturing becomes complex

Engineering Contradiction:
Improveurea concentration measurementVSAvoidbiosensor manufacturing
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The invention employs a disposable test strip design where the biosensor elements (electrodes, reagent layers) are integrated into a single-use strip. This eliminates the need for expensive, complex reusable sensors and ionophores, significantly reducing manufacturing complexity and test costs while maintaining measurement precision.

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

Solution Approach 2:

The test strip utilizes composite material structures combining conductive materials for electrodes, polymer matrices for reagent immobilization, and layered configurations for reagent delivery. These composite structures integrate multiple functions into unified components, simplifying manufacturing compared to assembling separate complex elements.

Inventive Principle:
Principle #40Composite materials

3Measurement precision

If conventional potentiometric biosensors with multiple reagents on both electrodes are used, then detection is possible, but interference from hematocrit and other ions increases

Engineering Contradiction:
Improvedetection capabilityVSAvoidion interference
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The invention applies local quality by placing specific reagents only in specific zones: the urease-containing reagent is localized to one reaction zone while the electron mediator-containing reagent is localized to another. This spatial differentiation ensures that each electrode region performs a specific function, reducing cross-interference from hematocrit and other ions that would affect both regions equally in conventional designs.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The invention extracts the electron mediator from the urease reagent formulation, placing them in separate reaction zones. This separation removes the source of potential interference that would occur if both reagents were mixed, as the mediator only becomes active when urease catalyzes the urea reaction, thereby eliminating background interference from free mediators.

Inventive Principle:
Principle #2Taking out (Extraction)

4Measurement precision

If complex calculation methods based on ion activity logarithms are used, then urea nitrogen content can be calculated, but the calculation process becomes complicated

Engineering Contradiction:
Improveurea nitrogen content determinationVSAvoidcalculation simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The invention replaces the mechanical/mathematical calculation system (logarithmic transformations of ion activities) with an electrical measurement system. The potential difference measured directly correlates with urea concentration through the Nernst equation, allowing the device to compute results electronically rather than requiring complex manual or computational mathematical transformations.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 reduces test costs, simplifies manufacturing, minimizes interference from hematocrit, and eliminates complex calculations, offering accurate and quick urea concentration measurements.

Implementation Method 1

the first reaction reagent contains an electron mediator but does not contain urease, and the second reaction reagent contains urease but does not contain an electron mediator... allowing the sample to chemically react with the first reaction reagent and the second reaction reagent

Methodology Applied
Scientific EffectRedox reactions: Redox Reactions

Implementation Method 2

the second reaction reagent contains urease but does not contain an electron mediator... allowing the sample to chemically react with the first reaction reagent and the second reaction reagent

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 3

testing the potential difference between the first electrode and the second electrode by means of the test instrument and an open-circuit potentiometric method

Methodology Applied
Scientific EffectPotentiometric detection: Electric Field

Data Source

PatentEP3879261B1Potentiometric detection method
Publication Date: 2026.01.14 LEADWAY HK
  • EP3879261B1 patent drawingFigure 1~2
  • EP3879261B1 patent drawingFigure 3~6(d)
  • EP3879261B1 patent drawingFigure 7~10

AI summary

Provided are a potentiometric biosensor (100) and a method for detecting urea concentration in a sample. The potentiometric biosensor (100) comprises an indication electrode (23) and a reference electrode (24). A second reaction reagent on the indication electrode (23) comprises a urease but does not comprise an electron transporter. A first reaction reagent on the reference electrode (24) comprises an electron transporter but does not comprise a urease. In the case where no external voltage is applied, after a blood sample has been added, the urease catalyzes the reaction of urea in the sample, thereby causing a potential difference between the indication electrode (23) and the reference electrode (24). Furthermore, the potential difference between the indication electrode (23) and the reference electrode (24) is in a linear relationship with the urea concentration in the sample, and the urea concentration in the sample can be calculated according to such linear relationship.