Creatininase Stabilization via Low-Concentration Manganese
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Solution Overview
Problem
Creatinine sensors with creatininase experience a gradual decrease in sensitivity over time, leading to a short sensor life due to instability issues, particularly when high concentrations of manganese are required for reactivation, which can cause precipitation and interference with other sensors.
Innovation Solution
Exposing creatininase to a solution of divalent manganese ions at concentrations between 2-10 µM for at least 80% of the sensor's operative lifetime to stabilize and reactivate the sensor, avoiding adverse effects on other enzymes and preventing precipitation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high concentrations of manganese are used to reactivate creatininase, then sensor activity is restored, but precipitation and interference with other sensors occur
Solution Approach 1:
The patent applies parameter changes by reducing the manganese concentration from high levels (which cause precipitation) to a specific low range of 2-10 µM. This parameter optimization restores creatininase activity while avoiding the harmful effects of precipitation and interference with other sensors, thus resolving the contradiction between reliability and harmful factors.
2Measurement precision
If creatinine sensors are used over time, then measurement capability is maintained initially, but sensitivity gradually decreases leading to short sensor life
Solution Approach 1:
The patent applies preliminary action by periodically reactivating the creatininase with low concentration manganese solution during the sensor's operational lifetime. This maintenance action prevents the gradual sensitivity loss and extends the sensor life, addressing the contradiction between maintaining measurement precision and extending duration of action.
3Reliability
If creatininase is stabilized with divalent metal ions, then enzyme activity is maintained, but other divalent ions cause similar inhibition issues
Solution Approach 1:
The patent applies local quality by specifically selecting manganese ions with a concentration of 2-10 µM for reactivating creatininase, while other divalent metal ions remain inhibited by EDTA in the buffer solution. This localized application of manganese at controlled concentration maintains enzyme activity without causing the inhibition problems associated with other divalent ions, resolving the contradiction between reliability and harmful factors.
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
This method extends the sensor's lifetime, maintains sensitivity, and prevents interference, allowing for more precise and accurate creatinine measurements without the need for frequent calibrations.
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
Data Source
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AI summary
A method is provided for stabilising 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 in a concentration of in the range of 0.01-150 μM. 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.