White Blood Cell Discrimination via Oblique Light Scattering

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Hematology analyzers and flow cytometers fail to accurately analyze white blood cells in the presence of significant red blood cell numbers, leading to inaccurate measurements due to red blood cells being mistaken for white blood cells or incomplete lysis, particularly in cases where red blood cells are hard to lyse.

Innovation Solution

The method involves obliquely illuminating blood samples with light from multiple angles to analyze light side scattered from cells, leveraging the difference in light scattering profiles between red and white blood cells, specifically using wide angle side scatter and directional anisotropy to distinguish between the two cell types without the need for lysis or additional dyes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If red blood cells are lysed to improve white blood cell analysis accuracy, then measurement precision improves, but reliability deteriorates due to incomplete lysis in certain patient populations

Engineering Contradiction:
Improvewhite blood cell analysis accuracyVSAvoidlysis completeness
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent extracts and analyzes only the side scatter signal from red blood cells at specific angles (75-105 degrees) to identify and exclude them from white blood cell analysis. By taking out the problematic red blood cell signal through angular separation, the system achieves accurate white blood cell counting without requiring lysis, thus maintaining reliability across all patient populations including those with hard-to-lyse red blood cells.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces a new dimension - the angular dimension of light scattering - to differentiate between red and white blood cells. By measuring side scatter at multiple rotational angles (75-105 degrees) and analyzing the angular distribution pattern, the system creates an additional discrimination parameter that enables accurate white blood cell identification without lysis, resolving the contradiction between precision and reliability.

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

2Measurement precision

If red blood cells are lysed to eliminate interference, then measurement precision improves, but device complexity increases due to additional reagents and processing steps

Engineering Contradiction:
Improvewhite blood cell analysis accuracyVSAvoidlysis reagent and processing requirements
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the chemical lysis system with an optical detection system. Instead of using lysis reagents and chemical processing, the system uses light scattering at multiple angles to physically distinguish and exclude red blood cells from analysis. This substitution eliminates the need for lysis reagents and associated processing steps, reducing device complexity while maintaining measurement precision.

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

Solution Approach 2:

The patent introduces light scattering angle analysis as an intermediary mechanism between the blood sample and the detection system. By using the angular distribution of side scatter as an intermediary parameter, the system can identify and exclude red blood cells without direct chemical interaction, simplifying the overall system by replacing complex chemical processing with optical measurement.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Device complexity

If standard illumination is used to simplify the system, then device complexity is reduced, but measurement precision deteriorates due to inability to distinguish cell types

Engineering Contradiction:
Improveillumination system simplicityVSAvoidcell type discrimination accuracy
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The patent adds the angular dimension to illumination by rotating the light source around the sample and measuring side scatter at multiple angles (75-105 degrees). This dimensional addition creates distinctive angular scattering patterns for different cell types, enabling accurate discrimination while maintaining relatively simple illumination hardware that can be rotated to different positions.

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

Solution Approach 2:

The patent employs dynamic illumination by rotating the light source to different angular positions around the sample during measurement. This dynamic approach allows the system to collect angular scattering data from multiple orientations, improving cell type discrimination accuracy while using a single movable illumination source rather than multiple fixed sources, thus balancing complexity and precision.

Inventive Principle:
Principle #15Dynamics

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 discrimination and analysis of white blood cells in the presence of red blood cells, reducing measurement errors and increasing accuracy in clinical devices, even in samples with hard-to-lyse red blood cells, without requiring lysis or additional labels, thereby improving the reliability of white blood cell assessment.

Implementation Method 1

Light side scattered from cells in the sample is analyzed to provide accurate discrimination of white blood cell types for white blood cell analysis and counting based on a difference in light scattering profile of red blood cell side scatter as compared to white blood cell side scatter

Methodology Applied
Scientific EffectLight scattering: Scattering

Data Source

PatentUS10788413B2Method to distinguish and analyze white blood cells in the presence of red blood cells
Publication Date: 2020.09.29 MASSACHUSETTS INST OF TECH
  • US10788413B2 patent drawing
  • US10788413B2 patent drawing

AI summary

Method for distinguishing between red blood cells and white blood cells. The method includes obliquely illuminating the blood sample with light from at least two rotational angles and analyzing light side scattered from cells in the sample to provide accurate discrimination of white blood cell types based on the anisotropy of red blood cell side scatter as compared to more isotropic white blood cell side scatter.