Creatinine Sensor Stabilization with Manganese Ions

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Solution Overview

Problem

Dual sensor systems for creatinine measurement in physiological fluids experience a gradual decrease in sensitivity over time due to instability of the creatininase enzyme, leading to a short sensor life and interference issues with high manganese concentrations.

Innovation Solution

Exposing creatininase to a divalent manganese ion solution in concentrations ranging from 0.01 to 150 μM to stabilize or reactivate the sensor, with a composition that releases manganese ions for sustained periods, ensuring continuous enzyme activity and avoiding precipitation and interference.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If high concentrations of manganese ions are used to stabilize creatininase, then enzyme activity is improved, but precipitation and interference with other sensors occur

Engineering Contradiction:

Improveenzyme activityVSAvoidprecipitation and interference

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by reducing the manganese ion concentration from high levels (which cause precipitation and interference) to a specific low range of 0.01-150 μM. This parameter optimization maintains enzyme stabilization effectiveness while eliminating harmful side effects of precipitation and sensor interference.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If the sensor is used continuously for measurements, then productivity is improved, but sensitivity decreases due to enzyme instability

Engineering Contradiction:

Improvemeasurement throughputVSAvoidsensitivity

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent applies preliminary action by pre-stabilizing the creatininase enzyme with manganese ions before the sensor is put into continuous use. This preliminary stabilization ensures the enzyme maintains its activity throughout continuous measurements, preventing sensitivity loss while enabling high productivity.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent applies continuity of useful action by ensuring the enzyme remains continuously active and stable during prolonged measurement periods. The manganese ion stabilization prevents enzyme deactivation, allowing the sensor to maintain sensitivity throughout continuous operation without periodic reactivation.

Inventive Principle:

Principle #20Continuity of useful action

3Productivity

If the sensor operates for extended periods, then productivity is improved, but sensor lifetime is limited due to enzyme deactivation

Engineering Contradiction:

Improveoperational durationVSAvoidsensor lifetime

Core Design Contradiction:

ProductivityVSDuration of action of stationary object

Solution Approach 1:

The patent applies continuity of useful action by maintaining enzyme activity throughout extended operational periods. The manganese ion stabilization ensures the enzyme remains active continuously, extending the sensor's usable lifetime to match the desired operational duration for high productivity.

Inventive Principle:

Principle #20Continuity of useful action

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

Extends the sensor's lifetime from one week to several months, maintains sensitivity, and reduces calibration needs, providing more precise and accurate measurements while minimizing contamination risks.

Implementation Method 1

exposing the creatininase to an amount of a solution of a divalent manganese ion sufficient to increase the stability or to increase the activity of the sensor

Methodology Applied

Scientific EffectMetal ion binding to enzyme: Chemical Bonding

Data Source

PatentUS7888061B2Method of stabilising or reactivating a creatinine sensor with a divalent manganese ion

Publication Date: 2011.02.15 RADIOMETER AS

AI summary

A method is provided for stabilizing a creatinine sensor comprising creatininase as a bioactive molecule. The creatininase is stabilised by exposing it to a sufficient amount of a divalent manganese ion. This result may be obtained by exposing the sensor to a solution comprising the divalent manganese ion or by introducing a composition within the sensor providing sustained release of the divalent manganese ion.