Creatinine Electrochemical Sensor Using Enzyme-Generated Complex

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing methods for quantifying creatinine in test samples, such as serum or urine, face challenges due to interference from endogenous ammonia levels and require complex and costly biosensors, which are insensitive to lower creatinine concentrations and prone to errors from albumin interference.

Innovation Solution

The use of a sensing composition comprising creatinine deaminase and a transition metal salt to enzymatically convert creatinine into N-methyl hydantoin, which forms an electroactive hydantoin-transition metal complex, allowing for accurate electrochemical quantification of creatinine through screen-printed electrodes with filtration membranes to minimize albumin interference.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If biosensors involving pH sensitive or ammonium ion selective electrode are used to measure ammonia for indirect creatinine estimation, then creatinine concentration can be estimated, but the measurement is interfered by endogenous ammonia level in the test sample

Engineering Contradiction:
Improvecreatinine concentration measurementVSAvoidendogenous ammonia interference
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and measures only the ammonia produced by creatinine deamination reaction, separating it from endogenous ammonia. This is achieved by using an enzyme electrode that specifically catalyzes creatinine deamination, allowing selective measurement of reaction-produced ammonia while ignoring pre-existing endogenous ammonia in the sample.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces creatinine deaminase enzyme as an intermediary that selectively converts creatinine to ammonia. This enzyme mediator creates a specific reaction pathway where ammonia is produced only from creatinine, not from other sources, thereby eliminating endogenous ammonia interference in the measurement.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If traditional biosensors are used for creatinine measurement, then creatinine can be quantified, but the device complexity and cost increase

Engineering Contradiction:
Improvecreatinine quantificationVSAvoidbiosensor structure
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges the enzyme catalytic function with the electrode detection function into a single integrated enzyme electrode. The creatinine deaminase is immobilized directly on the electrode surface, combining the biochemical reaction and electrical detection into one component, thereby simplifying the overall device structure while maintaining measurement accuracy.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The enzyme electrode is designed to be self-contained, with the creatinine deaminase enzyme embedded in the electrode matrix itself. This self-service design eliminates the need for separate reaction chambers, reagent additions, or complex sample preparation steps, making the device simpler and more cost-effective.

Inventive Principle:
Principle #25Self-service

3Measurement precision

If traditional biosensors are used for creatinine measurement, then creatinine can be detected, but sensitivity to lower creatinine concentrations is insufficient

Engineering Contradiction:
Improvelower creatinine concentration detectionVSAvoiddetection sensitivity
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent optimizes the electrochemical measurement parameters, including applying specific potential ranges (-0.2V to +0.8V vs Ag/AgCl) and using differential pulse voltammetry techniques. These parameter optimizations enhance the sensitivity of the electrode to detect low concentrations of ammonia produced from creatinine, thereby improving detection capability for lower creatinine levels.

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

This approach provides a simple, cost-effective, and accurate method for quantifying creatinine across a wide range of concentrations, overcoming interference issues and improving sensitivity and reliability compared to traditional methods.

Implementation Method 1

The test sample is contacted with a sensing composition comprising creatinine deaminase and a transition metal salt. The creatinine deaminase enzymatically reacts with creatinine to provide N-methyl hydantoin and ammonia.

Methodology Applied
Scientific EffectEnzymatic conversion: Enzyme

Implementation Method 2

N-methyl hydantoin reacts with transition metal salt to form a hydantoin-transition metal complex, which is electroactive and provides a current signal on application of a potential difference.

Methodology Applied
Scientific EffectComplex formation: Chemical Bonding

Implementation Method 3

The hydantoin-transition metal complex is electroactive and provides a current signal on application of a potential difference. The current signal provided by the hydantoin-transition metal complex can be measured.

Methodology Applied
Scientific EffectElectrochemical reaction: Redox Reactions

Data Source

PatentUS11592437B2Electrochemical measurement of creatinine in serum
Publication Date: 2023.02.28 INDIAN INSTITUTE OF SCIENCE
  • US11592437B2 patent drawing
  • US11592437B2 patent drawing
  • US11592437B2 patent drawing

AI summary

Methods and devices for quantifying creatinine in a test sample are provided. The test sample is contacted with a sensing composition to obtain a product comprising a hydantoin-transition metal complex and ammonia. The sensing composition comprises creatinine deaminase and a transition metal salt. The creatinine deaminase enzymatically reacts with creatinine to provide the N-methyl hydantoin and ammonia. The N-methyl hydantoin forms the hydantoin-transition metal complex with the transition salt. A potential difference is applied to the product to measure a current signal provided by the hydantoin-transition metal complex. Concentration of N-methyl hydantoin is obtained based on the measured current signal using a calibration equation. The concentration of N-methyl hydantoin is correlated with concentration of creatinine to quantify the creatinine in the test sample.