Lipoprotein Particle Quantification via Phospholipid Intermediary

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Solution Overview

Problem

Current methods for accurately measuring the number and size of spherical lipoprotein particles, such as HDL, VLDL, IDL, and LDL, are unreliable due to limitations in NMR techniques and cholesterol measurement methods, which fail to provide clinically precise data for cardiovascular risk assessment.

Innovation Solution

A method involving the isolation and separation of free cholesterol and phospholipids from lipoprotein particles, using geometric relationships to calculate particle numbers and sizes based on measured FC and PL concentrations, eliminating the need for multiple measurements and technologies like NMR.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If NMR technique is used to size and count lipoprotein particles, then reproducibility is improved, but measurement precision deteriorates due to poor comparison with gel electrophoresis accuracy

Engineering Contradiction:
ImprovereproducibilityVSAvoidparticle sizing accuracy
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent uses phospholipid as an intermediary substance to indirectly measure lipoprotein particle numbers. Since phospholipids are structural components of the particle membrane and can be accurately quantified, this intermediary measurement provides a more precise pathway to determine particle numbers compared to direct NMR sizing, while maintaining the reproducibility advantage of NMR through standardized protocols.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If total cholesterol measurement is used to determine particle size or number, then ease of operation is improved, but measurement precision deteriorates due to loose correlation with particle sizes

Engineering Contradiction:
Improvemeasurement simplicityVSAvoidparticle number accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent extracts and measures only the phospholipid component from the lipoprotein particle, separating it from other components like cholesterol and triglycerides. This extraction of the specific phospholipid layer provides a more precise measurement of particle numbers compared to total cholesterol measurement, while maintaining operational simplicity through standardized phospholipid assay techniques.

Inventive Principle:
Principle #2Taking out (Extraction)

3Measurement precision

If multiple measurement technologies are used to accurately assess all lipoprotein particle types, then measurement precision is improved, but device complexity increases

Engineering Contradiction:
Improvecomprehensive particle assessment accuracyVSAvoidmeasurement system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies a universal phospholipid measurement approach that can assess all types of lipoprotein particles (HDL, LDL, VLDL, IDL, Lp(a)) through a single methodology. This multi-functional approach eliminates the need for multiple specialized techniques like NMR for some particles and gel electrophoresis for others, thereby reducing device complexity while maintaining comprehensive measurement precision across all particle types.

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

Data Source

PatentEP2972325B1System and method for assessing quantities or sizes of lipoprotein particles from lipoprotein particle compositions
Publication Date: 2020.09.23 HELENA LAB CORP
  • EP2972325B1 patent drawingFigure 1~2
  • EP2972325B1 patent drawingFigure 3
  • EP2972325B1 patent drawingFigure 3

AI summary

This invention relates to methods for assessing quantities of spherical or substantially spherical lipoprotein particles or portions thereof present in a biological sample based on the measurement of free cholesterol and/or phospholipid content in the lipoprotein particles. The invention also relates to the use of the assessed quantities of the lipoprotein particles or portions thereof to determine whether a subject is at increased risk for cardiovascular diseases and cardiodiabetes.