Disposable Electrochemical Sensor for Hemoglobin Detection

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Solution Overview

Problem

Current methods for measuring hemoglobin and hematocrit in blood samples face challenges such as inaccuracies due to varying plasma protein and electrolyte concentrations, require larger sample volumes, and are not user-friendly, leading to potential life-threatening complications from wrongful treatment.

Innovation Solution

A disposable electrochemical sensor strip with a reagent composition including a hemoglobin-sensitive redox mediator, polymer binder, surfactant, and buffer, designed for simultaneous measurement of hemoglobin and hematocrit in small blood samples, using linear scan voltammetry and amperometry to provide accurate results.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If colorimetric methods with oxidants like ferricyanide are used to measure hemoglobin, then measurement capability is achieved, but measurement precision deteriorates due to interference from other oxidizable species in the sample

Engineering Contradiction:
Improvehemoglobin measurement accuracyVSAvoidinterference from oxidizable species
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent divides the measurement into two separate channels: a first channel measures total oxidizable species (including hemoglobin and interferents) using ferricyanide, while a second channel measures only interferents using a different redox mediator. By subtracting the second channel's signal from the first, the patent isolates the hemoglobin signal and eliminates interference from other oxidizable species.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses two different redox mediators with selective properties: ferricyanide that reacts with all oxidizable species, and a second mediator that reacts only with interferents but not hemoglobin. These mediators act as intermediaries that enable selective detection and mathematical separation of the hemoglobin signal from interfering substances.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If spectrometric measurement systems are used for hemoglobin detection, then measurement capability is achieved, but device complexity increases due to cuvette filling and background turbidity issues

Engineering Contradiction:
Improvehemoglobin detection accuracyVSAvoidcuvette filling and background control mechanisms
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical spectrometric measurement system (requiring cuvette filling, optical paths, and turbidity control) with an electrochemical system. The electrochemical sensor directly measures hemoglobin through electron transfer reactions at the electrode surface, eliminating the need for complex optical components and manual cuvette handling.

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

Solution Approach 2:

The patent employs a disposable electrochemical sensor strip that is pre-loaded with reagents and electrodes. This single-use design eliminates the need for cleaning, calibration, and maintenance of expensive spectrometric equipment, while ensuring consistent measurement quality without complex background control mechanisms.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Measurement precision

If conductivity-based methods are used to measure hematocrit, then measurement capability is achieved, but measurement precision deteriorates due to strong influence from plasma protein and electrolyte concentrations

Engineering Contradiction:
Improvehematocrit measurement accuracyVSAvoidinfluence from plasma protein and electrolyte concentration
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent replaces the conductivity-based measurement method with an electrochemical method that measures hemoglobin concentration directly through redox reactions. Since hemoglobin is the primary chromophore and electroactive species in blood, this substitution eliminates the confounding influence of plasma proteins and electrolytes that plague conductivity-based hematocrit measurement.

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

4Measurement precision

If conventional hemoglobin measurement methods are used, then measurement capability is achieved, but loss of time increases due to lengthy reaction and measurement procedures

Engineering Contradiction:
Improvehemoglobin concentration accuracyVSAvoidreaction and measurement time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces slow colorimetric reaction-based methods with rapid electrochemical detection. The electrochemical sensor enables real-time measurement of hemoglobin as blood contacts the sensor surface, reducing measurement time from minutes to seconds while maintaining or improving accuracy through direct electron transfer detection.

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

Solution Approach 2:

The patent enables continuous measurement capability where blood flow through the sensor continuously generates electrochemical signals proportional to hemoglobin concentration. This eliminates the need for discrete sampling and batch processing, allowing for real-time monitoring without interruption or delay.

Inventive Principle:
Principle #20Continuity of useful 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 sensor strip enables accurate measurement of hemoglobin concentration in small blood samples (1.6-10 µL) with extended linear range, minimizes interference from oxidizable species, and determines hematocrit using a correlation with hemoglobin content, offering a reliable and user-friendly solution for clinical applications.

Implementation Method 1

the ferrous iron of hemoglobin is oxidized by an oxidant, e.g. ferricyanide, to produce HbFe(III)

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 2

a first amount of a reagent composition that includes at least an effective amount of a hemoglobin sensitive redox mediator in contact with the first electrically conductive layer to define a working electrode

Methodology Applied
Scientific EffectRedox Reactions: Redox Reactions

Implementation Method 3

returns a measurable electrical signal indicative of the hemoglobin content of a blood sample

Methodology Applied
Scientific EffectElectrochemical detection:

Data Source

PatentEP2568281B1Disposable sensor for electrochemical detection of hemoglobin
Publication Date: 2018.11.07 NOVA BIOMEDICAL CORP
  • EP2568281B1 patent drawingFigure 1
  • EP2568281B1 patent drawingFigure 2
  • EP2568281B1 patent drawingFigure 3

AI summary

A disposable biosensor for determining the content of hemoglobin and hematocrit in a sample of whole blood that includes a laminated strip with a first and second end, at least a reference, a working electrode and a blank electrode embedded in the laminated strip, a capillary channel with an open path for receiving the blood sample beginning from the first end and connecting to a vent opening spaced from the first end, the open path being sufficiently long to expose the reference electrode, the working electrode and the blank electrode to the blood sample, and conductive contacts located at the second end of the laminated strip. The laminated strip has a base layer with a conductive coating, a reagent holding layer, a channel forming layer and a cover layer having an inlet notch at the first end and a vent opening at the end of the capillary channels . The working electrode contains a reagent sensitive to hemoglobin or hemotocrit. The blank electrode is used to measure oxidizable species in the fluid sample and to correct the current signal of the working electrode. The construction of the biosensor allows accurate measurement of the impedance of the fluid sample, which is used to further correct the current signal of the working electrode. The capillary channel is constructed to have a small volume.