Creatinine Sensor Calibration Modulator Correction

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing methods for calibrating creatine and creatinine measuring devices are inaccurate due to the presence of enzyme modulators, which can vary unpredictably in samples and affect sensor sensitivity, leading to prolonged cycle times to account for residual modulators from previous samples.

Innovation Solution

A method that determines the degree of enzyme modulation in samples and calibration solutions, accounting for the concentration and time-dependent changes of modulators like Ca2+ and HCO3-, allowing for rapid and accurate measurements by estimating the remaining modulator levels in the enzyme layer after a short rinse.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If the sensor is calibrated without accounting for enzyme modulators, then the calibration process is simple and fast, but the measurement accuracy deteriorates due to unpredictable modulation effects from samples

Engineering Contradiction:
Improvemeasurement accuracyVSAvoidcalibration complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by measuring the concentration of enzyme modulators (such as calcium and bicarbonate ions) in calibration solutions and samples, then using these concentration values to calculate correction factors that adjust the sensor sensitivity. This transforms the calibration process from a simple sensitivity determination to a corrected sensitivity calculation that accounts for modulator concentrations, thereby improving measurement accuracy without excessive complexity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements feedback by using the measured modulator concentrations to dynamically adjust the calibration process. The system measures modulator levels, calculates their effect on enzyme activity, and applies correction factors to the sensitivity values accordingly. This feedback loop ensures that calibration accounts for actual modulator present in the solution, improving accuracy while maintaining a systematic approach

Inventive Principle:
Principle #23Feedback

2Measurement precision

If a long rinse period is used between samples, then the residual enzyme modulator is removed and measurement accuracy is maintained, but the cycle time increases and productivity decreases

Engineering Contradiction:
Improvemeasurement accuracyVSAvoidsample throughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent applies self-service by enabling the system to compensate for residual modulators through mathematical correction rather than requiring complete physical removal through extended rinsing. The system measures the modulator concentration in the sample, calculates the expected residual effect based on rinse time, and applies an appropriate correction factor to the measurement, allowing shorter rinse times while maintaining accuracy

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent changes the approach from physical removal of modulators (requiring long rinse times) to mathematical correction of their effects. By measuring modulator concentrations and using them to calculate correction factors, the system can tolerate shorter rinse times while maintaining measurement accuracy, thereby increasing sample throughput

Inventive Principle:
Principle #35Parameter changes

3Productivity

If the rinse time between samples is shortened to increase throughput, then productivity improves, but residual enzyme modulators affect the next measurement and accuracy deteriorates

Engineering Contradiction:
Improvesample throughputVSAvoidmeasurement accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The system performs self-correction by measuring modulator concentrations and automatically applying correction factors to compensate for residual modulators from previous samples. This allows the use of shorter rinse times to increase throughput while maintaining accuracy through mathematical compensation rather than requiring complete physical removal

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent uses feedback from modulator concentration measurements to adjust the calibration and measurement process. By measuring the modulator levels in each sample and using this information to calculate correction factors, the system can accurately compensate for residual modulators even when rinse times are shortened, thereby maintaining accuracy while improving productivity

Inventive Principle:
Principle #23Feedback

4Measurement precision

If calibration is performed with calibration solutions containing different amounts of enzyme modulator, then the sensor can be corrected for modulation effects, but the calibration process becomes more complex and time-consuming

Engineering Contradiction:
Improvesensor sensitivity accuracyVSAvoidcalibration time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies parameter changes by using calibration solutions with known, varying modulator concentrations to establish a relationship between modulator level and sensor response. By measuring modulator concentrations in these calibration solutions and calculating corresponding correction factors, the system creates a calibration model that can be applied to samples, improving sensitivity accuracy while keeping the calibration process systematic and manageable

Inventive Principle:
Principle #35Parameter changes

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

Enables accurate and efficient measurement of creatine and creatinine concentrations with cycle times reduced to less than two minutes, maintaining high accuracy despite short rinse times, thereby increasing the sample throughput.

Implementation Method 1

Sensors typically use enzymes to convert Crn and Cr into measurable products

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

sarcosine oxidase which converts sarcosine into glycine, formaldehyde and hydrogen peroxide

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 3

hydrogen peroxide which can be detected in an amperometric system

Methodology Applied
Scientific EffectAmperometric detection:

Implementation Method 4

the presence of enzyme modulators in a sample can modulate (i.e. increase or decrease) the activity of the enzymes in the sensor

Methodology Applied
Scientific EffectEnzyme modulation:

Data Source

PatentEP3320333B1Method for correcting crea sensor for calcium inhibition
Publication Date: 2023.08.09 RADIOMETER AS
  • EP3320333B1 patent drawingFigure 1
  • EP3320333B1 patent drawingFigure 2
  • EP3320333B1 patent drawingFigure 3

AI summary

A method of calibrating a device for measuring the concentration of creatinine in a sample including one or more enzyme modulators, the device comprising an enzyme layer, the method comprising: determining sensitivities of the device for each of one or more calibration solutions; determining a degree of modulation for the sample to be measured, determining a degree of modulation for each calibration solution; wherein said determining of each of the degrees of modulation comprises estimating the concentration of an enzyme modulator in the enzyme layer of the device; and calculating the sensitivity of the device for the sample, wherein the said calculating comprises adjusting the sensitivity of the device for each calibration solution by a factor comprising the determined degrees of modulation of the sample and the calibration solution.