Blood Sample Analysis Using Axial Light Loss

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Solution Overview

Problem

Current methods for analyzing blood samples using particle analyzers face challenges in accurately differentiating and enumerating hard-to-ghost cells, which retain a significant amount of hemoglobin content, leading to difficulties in distinguishing reticulocytes from mature red blood cells, especially in patients with blood pathologies.

Innovation Solution

The method involves mixing a blood cell sample with a nucleic acid stain and a ghosting reagent to remove hemoglobin, followed by analysis using light scatter and axial light loss measurements to differentiate and enumerate hard-to-ghost cells, improving the accuracy of reticulocyte detection and population analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a ghosting reagent is used to remove hemoglobin from red blood cells, then the ability to detect reticulocytes is improved, but hard-to-ghost cells that retain significant hemoglobin content cannot be adequately differentiated from mature red blood cells

Engineering Contradiction:
Improvereticulocyte detection accuracyVSAvoidcell differentiation reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent introduces a new measurement dimension (axial light loss) to the traditional light scatter measurement to differentiate cell populations. By measuring light loss along the axial direction (the direction of light propagation) in addition to traditional perpendicular light scatter, the system creates a two-dimensional measurement space that enables separation of hard-to-ghost cells from both reticulocytes and mature red blood cells, resolving the differentiation reliability issue while maintaining reticulocyte detection accuracy

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The patent changes the measurement parameters by incorporating axial light loss measurement alongside traditional light scatter. This parameter expansion allows the system to capture additional cellular properties - specifically, the hemoglobin content characteristics that differ between hard-to-ghost cells and other cell types. The dual-parameter approach (light scatter + axial light loss) provides sufficient discrimination power to reliably identify all three cell populations simultaneously

Inventive Principle:
Principle #35Parameter changes

2Device complexity

If traditional light scatter measurement is used alone, then the analysis is simple, but it is insufficient to differentiate hard-to-ghost cells from reticulocytes and mature red blood cells

Engineering Contradiction:
Improvemeasurement system complexityVSAvoidcell population differentiation precision
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The patent adds axial light loss measurement as a second dimension to the traditional light scatter measurement. This dimensional expansion transforms the measurement space from one-dimensional to two-dimensional, enabling the system to resolve overlapping cell populations that cannot be distinguished using light scatter alone. The additional measurement dimension provides the necessary discriminatory power without requiring complex sample preparation or staining modifications

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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 enhances the accuracy of reticulocyte detection and enumeration, allowing for clearer differentiation between mature red blood cells and reticulocytes, and provides a valuable indicator for diagnosing blood pathologies by identifying an increased population of hard-to-ghost cells in diseased samples.

Implementation Method 1

mixing a blood cell sample with a nucleic acid stain and a ghosting reagent to remove hemoglobin from red blood cells

Methodology Applied
Scientific EffectGhosting:

Implementation Method 2

analyzing the ghosted blood cell sample in the cytometric flow cell by using light scatter and axial light loss measurements

Methodology Applied
Scientific EffectLight scatter: Scattering

Implementation Method 3

analyzing the ghosted blood cell sample in the cytometric flow cell by using light scatter and axial light loss measurements

Methodology Applied
Scientific EffectAxial light loss: Absorption (EM radiation)

Data Source

PatentEP2561350B1Method and system for analyzing a blood sample
Publication Date: 2017.06.28 BECKMAN COULTER INC
  • EP2561350B1 patent drawingFigure 1
  • EP2561350B1 patent drawingFigure 2
  • EP2561350B1 patent drawingFigure 3

AI summary

Methods, systems, and computer program products for the analysis of a blood sample are disclosed. One embodiment is a method of detecting and enumerating hard-to-ghost cells in a blood sample. Another embodiments is a method of analyzing reticulocytes in a blood sample. Methods of using blood count parameters are also provided.