Hemoglobin Measurement Correction for Cellular Particle Interference

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Solution Overview

Problem

Automated hematology analyzers face challenges in accurately measuring hemoglobin concentration due to interference from cellular particles like white blood cells and platelets, leading to overestimation and reduced accuracy, especially in pathological samples with high particle concentrations.

Innovation Solution

A method that involves mixing a blood sample with a lytic reagent to lyse red blood cells, measuring the absorbance of the sample mixture at a predetermined wavelength, and correcting the hemoglobin concentration by accounting for the concentration and size of remaining cellular particles using a function that removes their contributory effect, thereby providing a corrected hemoglobin concentration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If cellular particles are not removed or diluted before measurement, then the measurement process is faster and simpler, but the hemoglobin concentration measurement accuracy deteriorates due to light absorption and scattering by particles

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

Solution Approach 1:

The patent extracts the harmful effect of cellular particles by measuring their contribution separately at 800 nm and subtracting it from the total absorbance measurement at 540 nm. This allows the measurement to proceed without physical removal or dilution of particles, maintaining speed while improving accuracy through mathematical extraction of the interference component.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces an intermediary measurement at 800 nm that specifically detects the cellular particle interference. This intermediary measurement acts as a mediator to quantify and subsequently remove the harmful effect of particles from the main hemoglobin measurement, resolving the contradiction between speed and accuracy.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If pre-dilution is performed to reduce particle concentration, then measurement accuracy improves, but the process becomes more complex and time-consuming

Engineering Contradiction:
Improvehemoglobin concentration accuracyVSAvoidprocess complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical approach of physical dilution with an optical/mathematical approach. Instead of mechanically reducing particle concentration through dilution, the system uses optical measurements at two wavelengths and mathematical correction to eliminate particle interference, simplifying the process while maintaining accuracy.

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

3Productivity

If absorbance measurement is performed at a single wavelength, then the measurement process is simpler and faster, but accuracy deteriorates due to inability to distinguish hemoglobin chromogen from cellular particles

Engineering Contradiction:
Improvemeasurement efficiencyVSAvoidhemoglobin concentration accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent segments the absorbance measurement into two distinct wavelength components: 540 nm for total absorbance (hemoglobin + particles) and 800 nm for particle-specific absorbance. This segmentation allows separate quantification and subtraction of the particle contribution, improving accuracy while maintaining measurement efficiency through automated dual-wavelength detection.

Inventive Principle:
Principle #1Segmentation

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 effectively corrects for particle interference, improving the accuracy of hemoglobin measurement by accounting for the concentration and size of cellular particles, reducing errors associated with high white blood cell and platelet counts, and eliminating the need for pre-dilution steps, which are time-consuming and error-prone.

Implementation Method 1

mixing a blood sample with a lytic reagent to lyse red blood cells

Methodology Applied
Scientific EffectLysis: Decomposition (biological)

Implementation Method 2

measuring spectrophotometric absorbance of the sample mixture at a predetermined wavelength

Methodology Applied
Scientific EffectAbsorption spectroscopy: Absorption Spectroscopy

Implementation Method 3

the cellular particles absorb and scatter the incident light used in the measurement

Methodology Applied
Scientific EffectLight absorption: Absorption (EM radiation)

Implementation Method 4

the cellular particles absorb and scatter the incident light used in the measurement

Methodology Applied
Scientific EffectLight scattering: Scattering

Data Source

PatentEP2356465B1Method of correction of particle interference to hemoglobin measurement
Publication Date: 2014.10.01 BECKMAN COULTER INC
  • EP2356465B1 patent drawingFigure 1
  • EP2356465B1 patent drawingFigure 2
  • EP2356465B1 patent drawingFigure 3A~3D

AI summary

A method of correction of particle interference to hemoglobin measurement of a blood sample on a hematology analyzer is provided. The method includes mixing an aliquot of a blood sample with a lytic reagent to lyse red blood cells and forming a sample mixture; measuring absorbance of the sample mixture at a predetermined wavelength of a hemoglobin chromogen formed in the sample mixture, and obtaining an apparent hemoglobin concentration of the blood sample using obtained absorbance; measuring concentration and size of cellular particles remaining in the sample mixture; removing contribution of the cellular particles to the apparent hemoglobin concentration using the concentration and the size of the cellular particles to obtain a corrected hemoglobin concentration of the blood sample; and reporting the corrected hemoglobin concentration of the blood sample.