HbA1c Detection Using Zwitterionic Surfactant Lysis

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Solution Overview

Problem

Current methods for determining hemoglobin A1c (HbA1c) levels in blood samples are hindered by interference from non-specific electrochemical responses and require significant sample dilution, which complicates the development of commercially viable point-of-care assays.

Innovation Solution

A system utilizing a zwitterionic surfactant for lysing red blood cells, a cationic surfactant and isothiazoline derivative for oxidizing hemoglobin, and a protease with an azole molecule, such as imidazole, to selectively digest glycated hemoglobin, allowing for accurate electrochemical measurement of HbA1c without significant sample dilution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional methods are used to determine HbA1c levels, then measurement can be performed, but non-specific electrochemical responses cause interference and require significant sample dilution

Engineering Contradiction:
ImproveHbA1c measurement accuracyVSAvoidsample preparation complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces a mediator substance that selectively reacts with glycated hemoglobin to produce a specific electrochemical signal. This mediator acts as an intermediary between the analyte (HbA1c) and the detection system, enabling specific measurement without interference from non-glycated hemoglobin or other blood components, thereby eliminating the need for significant sample dilution

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the electrochemical detection parameters by using a mediator with specific redox properties that differ from conventional methods. By changing the detection parameter (using a mediator with appropriate oxidation potential), the system can specifically detect glycated hemoglobin while ignoring other electrochemically active substances in the sample, improving measurement precision without requiring complex sample preparation

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If significant sample dilution is performed to reduce interference, then electrochemical interference is reduced, but the complexity of the assay increases

Engineering Contradiction:
Improveelectrochemical interferenceVSAvoidassay complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent converts the harmful electrochemical interference from non-glycated hemoglobin and other blood components into a beneficial selective detection system. By using a mediator that specifically targets glycated hemoglobin, the system transforms the complex blood matrix from a source of interference into a compatible sample environment, eliminating the need for extensive dilution while maintaining measurement accuracy

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent extracts or isolates the specific detection reaction between the mediator and glycated hemoglobin from the complex blood matrix. By designing a mediator that selectively binds to or reacts with HbA1c, the system effectively separates the analyte of interest from interfering substances through molecular recognition rather than physical dilution, simplifying the assay while reducing interference

Inventive Principle:
Principle #2Taking out (Extraction)

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 oxidizes hemoglobin to methemoglobin, prevents electrochemical interference, and enhances protease efficiency, enabling precise measurement of HbA1c levels with minimal sample dilution, as demonstrated by experimental results showing a strong correlation with theoretical reactions.

Implementation Method 1

a lysing formulary, the lysing formulary including a zwitterionic surfactant

Methodology Applied
Scientific EffectLysis:

Implementation Method 2

an oxidizing formulary, the oxidizing formulary including a cationic surfactant and an isothiazoline derivative

Methodology Applied
Scientific EffectOxidation: Oxidation

Implementation Method 3

a protease formulary, the protease formulary including a molecule including an azole

Methodology Applied
Scientific EffectProteolysis: Enzyme

Data Source

PatentEP3724348B1Systems and methods for sample preparation for enzymatic a1c detection and quantification
Publication Date: 2023.04.12 POLYMER TECHNOLOGY SYSTEMS INC
  • EP3724348B1 patent drawingFigure 1~2
  • EP3724348B1 patent drawingFigure 3~4
  • EP3724348B1 patent drawingFigure 5~6

AI summary

A system for preparing a sample containing hemoglobin HbA1c for measurement by an electrochemical sensor includes a lysing formulary, the lysing formulary including a zwitterionic surfactant. The system further includes a oxidizing formulary, the oxidizing formulary including a cationic surfactant and a isothiazoline derivative and a protease formulary, the protease formulary including a molecule including an azole.