Potentiometric Creatinine Biosensor Using Ammonium Ion Extraction

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Standard multi-enzyme amperometric creatinine biosensors face manufacturing complexity, accuracy issues due to enzyme failures, and short shelf life, primarily because they require immobilization of multiple enzymes and are sensitive to contamination and interfering species.

Innovation Solution

A potentiometric creatinine biosensor design featuring an active electrode with a membrane containing an enzyme that directly produces ammonium ions upon contact with a liquid sample, and an inactive electrode without such enzymes, using an internal fill solution with a low free ammonia ion concentration to improve stability and simplify manufacturing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If multiple enzymes are immobilized onto electrode surfaces to enable creatinine detection through cascade reactions, then the biosensor can achieve creatinine measurement capability, but the manufacturing complexity increases significantly

Engineering Contradiction:
Improvebiosensor functionalityVSAvoidmanufacturing complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts the enzyme immobilization step entirely from the manufacturing process. Instead of immobilizing multiple enzymes onto electrode surfaces, the invention uses free-floating enzymes in solution that naturally associate with the electrode during operation, eliminating the complex immobilization procedure while maintaining biosensor functionality

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces an intermediary substance (ammonium ion-selective membrane) that mediates between the enzymatic reaction and the electrode measurement. The membrane selectively transports ammonium ions generated by the enzyme-creatinine reaction to the ion-selective electrode, enabling detection without direct enzyme-electrode contact

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If multiple enzymes are used in the biosensor system, then creatinine detection is enabled, but the accuracy is compromised by enzyme failures due to manufacturing defects, material defects, contamination, or interfering species

Engineering Contradiction:
Improvedetection capabilityVSAvoidmeasurement accuracy
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent removes enzymes from the system entirely, replacing them with a chemical reagent (creatininease) that operates in solution without immobilization. This eliminates enzyme-related failure modes including manufacturing defects, material defects, contamination sensitivity, and interfering species susceptibility, thereby improving measurement accuracy

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the operational parameters of the detection system by using a different reaction mechanism (direct chemical reaction with creatininease) that is less sensitive to environmental variations and contamination, reducing the impact of interfering species on measurement accuracy

Inventive Principle:
Principle #35Parameter changes

3Reliability

If multiple enzymes are immobilized onto electrode surfaces, then the biosensor can function, but the shelf life becomes short (e.g., a matter of weeks)

Engineering Contradiction:
Improvebiosensor functionalityVSAvoidshelf life
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent extracts enzymes from the immobilized state and uses them in solution instead. This eliminates the degradation issues associated with immobilized enzymes, significantly extending the shelf life of the biosensor from weeks to potentially years, as the system no longer relies on stable enzyme attachment to electrode surfaces

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs a disposable test strip design where the reagents are contained in a single-use format. This eliminates the need for long-term stability of immobilized enzymes, as each strip is used immediately and discarded, allowing the use of less stable but more effective reagents that would otherwise have short shelf lives

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

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 biosensor achieves a lower limit of detection and easier fabrication compared to standard amperometric sensors, with improved accuracy and extended shelf life by simplifying enzyme immobilization and reducing sensitivity to contaminants.

Implementation Method 1

the enzyme Creatinine Amidohydrolase reacts with Creatinine and H2O in the sample to produce Creatine

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

the enzyme Creatinine Amidohydrolase reacts with Creatinine and H2O in the sample to produce Creatine

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Implementation Method 3

the Sarcosine Oxidase enzyme reacts with the Sarcosine as well as O2 and H2O in the sample to produce Glycine, Formaldehyde and H2O2

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 4

H2O2 →O2 +2H+ +2e-

Methodology Applied
Scientific EffectElectrochemical oxidation:

Implementation Method 5

an active electrode comprising an internal fill solution and a first membrane, the first membrane separating the internal fill solution from a liquid sample

Methodology Applied
Scientific EffectIon-selective electrode potential:

Data Source

PatentEP3191825B1Creatinine biosensor
Publication Date: 2019.02.27 SIEMENS HEALTHCARE DIAGNOSTICS INC
  • EP3191825B1 patent drawingFigure 1
  • EP3191825B1 patent drawing
  • EP3191825B1 patent drawing

AI summary

This disclosure relates to creatinine biosensors and the uses thereof. More specifically, this disclosure describes potentiometric creatinine sensors which utilizes one or both of a type of enzyme capable of directly producing ammonium ions (NH4+) as a consequence of coming into contact with a liquid sample and an internal fill solution with a low free ammonium ion concentration.