Hemoglobin Measurement Correction for Carbamylation Errors
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Solution Overview
Problem
Conventional methods for measuring stable hemoglobin Alc (HbAlc) in blood samples, particularly in patients with renal failure or high aldehyde concentrations, face inaccuracies due to chemical modifications like carbamylation and aldehydation, which affect the separation and measurement of stable Alc, leading to fluctuations and overestimation of its values.
Innovation Solution
A method that involves obtaining a correction factor based on peak areas from capillary electrophoresis to distinguish and correct for chemically modified HbA0, allowing for the accurate measurement of both chemically modified and unmodified stable Alc, by considering the time distribution of optical measured values and molecular surface charges of hemoglobin.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional separation analysis is used to separate stable Alc from chemically modified hemoglobin, then the separation of stable Alc from unmodified hemoglobin is achieved, but the measurement accuracy of stable Alc is deteriorated due to co-elution of chemically modified hemoglobin fractions
Solution Approach 1:
The patent segments the hemoglobin analysis into multiple distinct fractions based on their electrophoretic mobility. By dividing the total hemoglobin into unmodified HbA0, carbamylated HbA0, aldehydated HbA0, and stable Alc fractions, the method enables separate quantification of each component, preventing the measurement errors caused by co-elution in conventional single-peak analysis
Solution Approach 2:
The patent introduces a new dimension of analysis by using capillary electrophoresis with detection of time distribution of optical measured values, which separates hemoglobin components based on their electrophoretic mobility through an electric field. This adds a temporal and spatial dimension to the analysis, allowing resolution of components that co-elute in conventional HPLC methods
2Measurement precision
If capillary electrophoresis is used to separate stable Alc from chemically modified hemoglobin by changing coating or migration conditions, then the separation resolution is improved, but the measurement accuracy of stable Alc is still deteriorated due to exclusion of chemically modified stable Alc from measurement
Solution Approach 1:
The patent employs feedback by using the detected peak areas of chemically modified HbA0 fractions (carbamylated and aldehydated) to calculate a correction factor. This correction factor is then applied to the measured stable Alc peak area to compensate for the chemically modified stable Alc that would otherwise be excluded, creating a closed-loop correction system that improves measurement accuracy
Solution Approach 2:
The patent introduces chemically modified HbA0 fractions as intermediary components in the analysis. By measuring these intermediate fractions and using them to calculate correction factors, the method indirectly accounts for the chemically modified stable Alc, serving as a mediator to recover information that would otherwise be lost
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
This approach enables more precise measurement of stable Alc, reflecting the average blood sugar level over one to two months, even in samples with chemical modifications, thereby improving diabetes management accuracy.
Implementation Method 1
A method of analyzing hemoglobin by capillary electrophoresis is disclosed in Japanese Patent Application Reissue No. 2008-139866
Implementation Method 2
the hemoglobin is subjected to chemical modification by carbamylation in which cyanate generated from urea binds with hemoglobin
Implementation Method 3
a time distribution of an optical measured value of hemoglobin at a flow path which separates hemoglobin in the blood sample
Data Source
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AI summary
A method of measuring stable Alc in a blood sample based on a time distribution of an optical measured value of hemoglobin at a flow path which separates hemoglobin in the blood sample on a basis of amounts of the charges of hemoglobin, the method comprising: a step of obtaining a correction factor, based on a peak area (A) of a fraction including HbA0 and either a peak area (G) of a first fraction including chemically-modified HbA0, or a peak area (D) of a second fraction including a component having a smaller amount of positive charge than HbAO adjacent to a fraction identified as HbAO, in the time distribution; and a step of correcting, based on the correction factor a peak area of a fraction including stable Alc in the time distribution.