Electrochemical Creatinine and Albumin Biosensor

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Solution Overview

Problem

Current methods for detecting and measuring creatinine and albumin to creatinine ratio (ACR) in biological samples rely on immunological techniques or complex electrode modifications, which are not stable against ambient variations and require cumbersome sample collection processes, prone to contamination and variability.

Innovation Solution

A non-enzymatic and non-antibody-based electrochemically active device that uses iron-creatinine complex chemistry for creatinine detection and methylene blue with metal ions for albumin detection, allowing for quantitative measurement of creatinine and albumin in reduced sample volumes through redox current analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If immunological techniques or complex electrode modifications are used for detection, then measurement precision is improved, but device complexity increases and stability against ambient variations deteriorates

Engineering Contradiction:
Improvedetection accuracyVSAvoidelectrode modification complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex immunological techniques and modified electrode systems with a simple electrochemical sensing system using iron-creatinine complex chemistry. The detection is achieved through straightforward redox current measurements without requiring enzyme immobilization, antibody coatings, or complex electrode surface modifications, thereby reducing device complexity while maintaining measurement precision.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the detection parameter from complex immunological reactions to simple electrochemical redox reactions. By measuring redox currents at standard potentials, the system achieves accurate detection of creatinine and albumin without requiring complex device modifications, thus resolving the contradiction between measurement precision and device complexity.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If 24-hour urine collection is used for microalbuminuria testing, then measurement precision is improved, but ease of operation deteriorates and loss of time increases

Engineering Contradiction:
Improvemicroalbuminuria detection accuracyVSAvoidsample collection convenience
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent replaces the cumbersome 24-hour urine collection process with a simple random spot urine sample analysis. The electrochemical sensor directly measures creatinine and albumin concentrations in the random sample, and the ACR calculation automatically corrects for dilution variations, achieving accurate microalbuminuria detection without requiring prolonged sample collection procedures.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent introduces the albumin-to-creatinine ratio (ACR) as an intermediary parameter that corrects for urine concentration variations. By measuring both albumin and creatinine in the same random sample and calculating their ratio, the system eliminates the need for 24-hour collection while maintaining measurement precision for microalbuminuria detection.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of operation

If random urine samples are used for albumin measurement, then ease of operation is improved, but measurement precision deteriorates due to variable urine concentrations

Engineering Contradiction:
Improvesample collection convenienceVSAvoidalbumin measurement accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent uses creatinine as an intermediary reference substance to correct for urine concentration variations. Since creatinine is excreted at a constant rate and its level tracks urine dilution, the albumin-to-creatinine ratio provides an accurate measure of albumin excretion regardless of the random sample's concentration, thereby maintaining measurement precision while improving ease of operation.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes from measuring absolute albumin concentration to measuring the albumin-to-creatinine ratio. This parameter transformation inherently corrects for dilution effects, allowing accurate microalbuminuria assessment from random urine samples without requiring standardized collection procedures.

Inventive Principle:
Principle #35Parameter changes

4Reliability

If non-enzymatic and non-antibody-based receptors are used, then stability against ambient variations is improved, but manufacturing precision requirements increase

Engineering Contradiction:
Improvestability against ambient variationsVSAvoidreceptor fabrication accuracy
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent replaces enzymatic and antibody-based receptors with simple iron-based electrochemical sensors. The iron-creatinine complex chemistry and methylene blue-albumin interactions provide stable, reproducible signals without requiring precise enzyme immobilization or antibody coating procedures, thereby reducing manufacturing precision requirements while improving stability against ambient variations.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes from using biological receptors (enzymes and antibodies) to using inorganic and organic chemical receptors (iron ions and methylene blue). This parameter change in receptor chemistry provides inherent stability against ambient temperature and pH variations while requiring only simple fabrication procedures, thus resolving the contradiction between reliability and manufacturing precision.

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 stable detection of creatinine and albumin in urine and blood samples, correcting for sample dilution and providing a point-of-care solution for ACR measurement with minimal invasive sample collection and no special storage requirements.

Implementation Method 1

uses iron-creatinine complex chemistry for creatinine detection and methylene blue with metal ions for albumin detection, allowing for quantitative measurement of creatinine and albumin in reduced sample volumes through redox current analysis

Methodology Applied
Scientific EffectRedox reactions: Redox Reactions

Implementation Method 2

uses iron-creatinine complex chemistry for creatinine detection and methylene blue with metal ions for albumin detection, allowing for quantitative measurement of creatinine and albumin in reduced sample volumes through redox current analysis

Methodology Applied
Scientific EffectRedox reactions: Redox Reactions

Data Source

PatentUS11867654B2Device and method for detecting creatinine and albumin to creatinine ratio
Publication Date: 2024.01.09 INDIAN INSTITUTE OF SCIENCE
  • US11867654B2 patent drawing
  • US11867654B2 patent drawing
  • US11867654B2 patent drawing

AI summary

An electrochemically active, creatinine-binding device is provided to detect and measure quantitatively, creatinine in biological samples. The device of the present invention is also provided with a device to detect and measure quantitatively creatinine and albumin bioanalytes, simultaneously and to determine albumin to creatinine ratio (ACR). The present invention also provides an electrochemically active, creatinine-binding and albumin-binding device, for collection and retention of biological samples, having creatinine and albumin bioanalytes. In the present invention, a device holder is provided to receive the electrochemically active, creatinine-binding and albumin-binding device. The device, point-of-care biosensor and the method of the present invention, facilitate quantitative measurement of creatinine and albumin bioanalytes in urine and blood samples, and albumin to creatinine ratio (ACR), in urine samples, electrochemically, by determining redox current values.