Electrochemical Hemolysis Sensor for Whole Blood Analysis

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Solution Overview

Problem

Current methods for detecting hemolysis in blood samples are inadequate as they require centrifugation and cannot accurately assess the contribution of hemolysis to analyte levels in whole blood, leading to potential misdiagnosis due to artificial elevation of potassium and other analytes.

Innovation Solution

An electrochemical hemolysis sensor system with a permeable outer membrane and oxidoreductase enzymes that generate hydrogen peroxide, allowing for detection of hemolysis in whole blood without centrifugation, by measuring the decrease in electrical current indicative of hemoglobin presence.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If centrifugation is used to separate blood cells before detection, then measurement accuracy is improved, but device complexity and processing time increase

Engineering Contradiction:
Improvehemolysis detection accuracyVSAvoidcentrifugation equipment
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts and detects the specific marker (hemoglobin) that indicates hemolysis directly from whole blood, eliminating the need for centrifugation to separate blood components. The amperometric sensor directly measures hemoglobin concentration in the sample, providing accurate hemolysis detection without complex separation equipment.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The mechanical centrifugation system is replaced with an electrochemical amperometric detection system. Instead of using mechanical force to separate blood components and then optically detecting hemoglobin, the invention uses electrochemical reactions to directly measure hemoglobin concentration in whole blood, simplifying the overall system.

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

2Difficulty of detecting and measuring

If optical methods are used to detect hemoglobin in plasma, then detection capability is achieved, but the method cannot operate on whole blood and requires centrifugation

Engineering Contradiction:
Improvehemoglobin detectionVSAvoidsample preparation
Core Design Contradiction:
Difficulty of detecting and measuringVSEase of operation

Solution Approach 1:

Optical detection methods are replaced with electrochemical amperometric detection. The amperometric sensor uses electrochemical reactions between hemoglobin and hydrogen peroxide to generate measurable current signals, enabling direct detection in whole blood without the optical interference and sample preparation requirements of traditional colorimetric methods.

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

Solution Approach 2:

Hydrogen peroxide is introduced as an intermediary substance that reacts with hemoglobin in an electrochemical reaction. This mediator enables the amperometric detection of hemoglobin by converting the chemical information into electrical signals that can be measured directly, bypassing the need for optical methods and sample separation.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If hemolysis is not detected, then blood sample analysis proceeds, but artificial elevation of potassium leads to misdiagnosis

Engineering Contradiction:
Improveblood analysis throughputVSAvoiddiagnosis accuracy
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The invention performs preliminary detection of hemolysis by measuring hemoglobin concentration before proceeding with blood sample analysis. By detecting the presence of free hemoglobin in whole blood, the system can identify hemolyzed samples and flag them for separate handling, preventing misdiagnosis while maintaining efficient processing of valid samples.

Inventive Principle:
Principle #10Preliminary 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

The system effectively differentiates between hemolysis-induced analyte elevation and physiological abnormalities, providing accurate assessment of potassium and other analytes, thereby preventing misdiagnosis and ensuring appropriate treatment.

Implementation Method 1

another membrane comprising a hydrogen peroxide generating oxidoreductase enzyme

Methodology Applied
Scientific EffectEnzymatic oxidation: Enzyme

Implementation Method 2

oxidoreductase enzyme capable of generating hydrogen peroxide

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 3

outer membrane comprising a thickness in the range of about 0.1 to about 50 μm for enhancing efflux of hydrogen peroxide

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 4

detecting an electrochemical signal generated by hydrogen peroxide in the presence of Hb

Methodology Applied
Scientific EffectElectrochemical detection:

Data Source

PatentEP2972275B1Whole blood hemolysis sensor
Publication Date: 2019.07.10 INSTRUMENTATION LABORATORY COMPANY
  • EP2972275B1 patent drawingFigure 1
  • EP2972275B1 patent drawingFigure 2
  • EP2972275B1 patent drawingFigure 3

AI summary

The present invention pertains to a hemolysis sensor, a hemolysis sensor system and methods of utilizing the hemolysis sensor or hemolysis sensor system to monitor or detect hemolysis in a sample, such as a whole blood sample, a plasma sample, a serum sample or hemolyzed blood. The hemolysis sensor responds to extracellular hemoglobin levels, for example, extracellular hemoglobin in a whole blood sample as a method for detecting hemolysis in whole blood.