HbA1c Measurement Correction for Chyle Interference

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Solution Overview

Problem

The enzymatic method for measuring HbA1c using whole blood as a sample is prone to errors due to the influence of coexisting substances, such as chyle, which affects the accuracy of hemoglobin concentration measurements in automated analyzers.

Innovation Solution

A method that optically measures hemoglobin concentration at a first wavelength (450-610 nm) and HbA1c concentration at a second wavelength (550-750 nm), with the hemoglobin concentration being corrected using information from a third wavelength (690-900 nm to account for lipid particle and hemoglobin concentrations, thereby eliminating measurement errors caused by coexisting substances.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If hemoglobin concentration is measured optically at a first wavelength (450-610 nm) in whole blood samples, then the measurement process is simple and fast, but the measurement accuracy deteriorates due to interference from coexisting substances like chyle and lipid particles

Engineering Contradiction:
Improvemeasurement speedVSAvoidhemoglobin concentration measurement accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent applies parameter changes by measuring absorbance at multiple wavelengths (first wavelength 450-610 nm, second wavelength 690-900 nm) and using these spectral parameters to calculate corrected hemoglobin concentration. The correction formula uses the ratio of absorbance at different wavelengths to compensate for interference from chyle and lipid particles, thereby maintaining measurement speed while improving accuracy.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces an intermediary calculation step where the absorbance at the second wavelength (690-900 nm) serves as a mediator to detect and quantify the interference from coexisting substances. This intermediary measurement enables the system to calculate a correction factor that is then applied to the primary hemoglobin concentration measurement, effectively separating the signal from the interference.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If the measurement method uses whole blood as sample, then the sampling process is simplified, but the reliability of HbA1c% calculation deteriorates due to errors from coexisting substances affecting the denominator (hemoglobin concentration)

Engineering Contradiction:
Improvesampling easeVSAvoidHbA1c% calculation accuracy
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent uses parameter changes by measuring at two different wavelength ranges and applying a correction formula that accounts for the spectral characteristics of both hemoglobin and interfering substances. This allows the system to maintain the ease of whole blood sampling while improving the reliability of the final HbA1c% calculation through mathematical correction of the hemoglobin concentration denominator.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If correction for coexisting substances is implemented using additional wavelength measurements, then the measurement accuracy improves, but the device complexity increases

Engineering Contradiction:
Improvehemoglobin concentration measurement accuracyVSAvoidmeasurement system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies universality by designing the measurement system to perform multiple functions using the same optical path and detectors. The system measures both the primary hemoglobin concentration (at 450-610 nm) and the interference signal (at 690-900 nm) sequentially or simultaneously using the same cuvette and spectrophotometer, thereby improving accuracy without requiring separate measurement chambers or additional complex hardware.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 allows for accurate measurement of HbA1c% in whole blood samples by correcting for the influence of coexisting substances without altering the reagent composition, ensuring precise results even with special specimens like chyle.

Implementation Method 1

the hemoglobin concentration being optically measured in a first step

Methodology Applied
Scientific EffectOptical absorption: Absorption (EM radiation)

Implementation Method 2

the hemoglobin A1c concentration being optically measured in a second step at a wavelength selected from 550 nm to 750 nm

Methodology Applied
Scientific EffectOptical absorption: Absorption (EM radiation)

Implementation Method 3

concentration information on lipid particles and concentration information on hemoglobin that are measured at a second wavelength selected from 690 nm to 900 nm

Methodology Applied
Scientific EffectOptical absorption: Absorption (EM radiation)

Data Source

PatentEP3498860B1Method for measuring hba1c
Publication Date: 2022.08.03 SEKISUI MEDICAL CO LTD
  • EP3498860B1 patent drawingFigure 1
  • EP3498860B1 patent drawingFigure 2
  • EP3498860B1 patent drawingFigure 3

AI summary

Provided is a method of avoiding the influence of a coexisting substance in the measurement of HbA1c% for a whole blood sample by an enzymatic method. Specifically, provided is a method of measuring a ratio of a hemoglobin A1c concentration to a hemoglobin concentration in a sample by an enzymatic method, the method including: a first step of optically measuring the hemoglobin concentration; and a second step of optically measuring the hemoglobin A1c concentration, wherein, when HbA1c% is calculated by dividing the hemoglobin A1c concentration measured in the second step by the hemoglobin concentration measured in the first step, the hemoglobin concentration serving as a denominator, which is measured at a first wavelength, is corrected using a result measured at a second wavelength.