Chromatography Flow Path Surface Treatment for Hemoglobin Resolution

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Solution Overview

Problem

In hemoglobin analysis by liquid chromatography, the wide peaks of hemoglobin fractions often coalesce, leading to poor resolution due to adsorption of hemoglobin to metal surfaces within the chromatographic device, particularly iron-containing components, which hinders accurate separation of adjacent peaks like HbA2 and HbS.

Innovation Solution

A surface treating liquid with a surface treating agent having a molecular weight of 200 or less, featuring two or more chemical structures with directly bonded hydroxy (-OH) and oxo (=O) groups to phosphor atoms, is used to treat the flow path, forming a chelate with iron atoms and preventing hemoglobin adsorption, thereby narrowing peak widths and improving resolution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stress or pressure

If metal members (stainless steel) are used for the flow path and structural parts, then high pressure resistance is achieved, but hemoglobin adsorption occurs causing peak width increase and poor resolution

Engineering Contradiction:
Improvepressure resistanceVSAvoidpeak resolution
Core Design Contradiction:
Stress or pressureVSManufacturing precision

Solution Approach 1:

A surface treating agent (phosphoric acid, pyrophosphoric acid, or medronic acid) is introduced as an intermediary substance that coats the metal flow path surfaces. This intermediary layer prevents direct contact between hemoglobin and metal surfaces, eliminating adsorption while preserving the structural integrity and pressure resistance of the metal components.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The chemical properties of the flow path surface are changed by treating it with phosphoric acid, pyrophosphoric acid, or medronic acid. This treatment modifies the surface chemistry to reduce hemoglobin adsorption affinity, thereby improving peak resolution without changing the fundamental metal structure or pressure resistance characteristics.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If hemoglobin is strongly adsorbed to the column due to hydrophobic interaction or charge interaction, then retention is improved, but peak width increases and adjacent peaks cannot be separated

Engineering Contradiction:
Improvehemoglobin retentionVSAvoidpeak separation
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The surface chemistry parameters of the flow path are modified by applying phosphoric acid, pyrophosphoric acid, or medronic acid treatment. This changes the surface properties to reduce hydrophobic and electrostatic interactions between hemoglobin and the column, thereby narrowing peak widths and enabling separation of adjacent peaks while maintaining retention through optimized mobile phase conditions.

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

The use of this surface treating agent effectively reduces peak widths and enhances the resolution between hemoglobin peaks, allowing for clearer separation and analysis in liquid chromatography.

Implementation Method 1

A surface treating liquid with a surface treating agent having a molecular weight of 200 or less, featuring two or more chemical structures with directly bonded hydroxy (-OH) and oxo (=O) groups to phosphor atoms, is used to treat the flow path, forming a chelate with iron atoms and preventing hemoglobin adsorption

Methodology Applied
Scientific EffectChelation:

Implementation Method 2

the widths of hemoglobin peaks in a chromatogram obtained by liquid chromatography can be narrowed, and the resolution between the peaks improves

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentEP3842380B1A method of analyzing hemoglobin by liquid chromatography, use of a chromatographic device for analyzing hemoglobin in blood and use of a surface treatment liquid for treating the flow path of the chromatographic device.
Publication Date: 2024.05.15 ARKRAY INC
  • EP3842380B1 patent drawingFigure 1
  • EP3842380B1 patent drawingFigure 2
  • EP3842380B1 patent drawingFigure 3

AI summary

A flow path (40, 50) for liquid chromatography, which analyzes hemoglobin within a blood sample, is subjected to a surface treatment with a liquid in which is dissolved a surface treating agent having a molecular weight of 200 or less and having two or more chemical structures in each of which a hydroxy group (-OH) and an oxo group (=O) are respectively bonded directly to one phosphor (P) atom.