Surfactant-Based sdLDL-C Determination Method

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Solution Overview

Problem

Current methods for determining small dense low-density lipoprotein cholesterol (sdLDL-C) are either complex, require expensive equipment, or lack specificity and accuracy, making them unsuitable for wide clinical use.

Innovation Solution

A method and kit using surfactants to inhibit reactions between sdLDL-C and cholesterol ester hydrolase/oxidase, allowing for selective measurement of sdLDL-C by forming hydrogen peroxide or reduced coenzyme, which is then correlated with a standard sample to determine concentration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If the ultracentrifugation method is used to determine sdLDL-C, then measurement accuracy is improved, but device complexity and measurement time increase significantly

Engineering Contradiction:
ImprovesdLDL-C determination accuracyVSAvoidequipment complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical ultracentrifugation system with a chemical reaction system. Instead of using centrifugal force to separate lipoproteins by density, the invention uses selective enzymatic reactions in the presence of surfactants to specifically determine sdLDL-C. This substitution eliminates the need for expensive ultracentrifuge equipment while maintaining measurement accuracy through biochemical specificity.

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

Solution Approach 2:

The patent changes the measurement parameters from physical separation based on density (ultracentrifugation) to chemical reaction based on enzymatic specificity. By controlling reaction conditions including surfactant concentration, enzyme types and amounts, and reaction temperature, the method achieves selective determination of sdLDL-C without requiring complex mechanical separation equipment.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If the fractionation method is used to separate and determine sdLDL-C, then measurement accuracy is improved, but measurement time and operational complexity increase

Engineering Contradiction:
ImprovesdLDL-C determination accuracyVSAvoidmeasurement time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent extracts only the essential function of lipoprotein separation by using surfactants to selectively inhibit enzyme reactions with specific lipoprotein types. Instead of performing complete fractionation to separate all lipoprotein classes, the method directly targets sdLDL-C by exploiting differential surfactant-lipoprotein interactions, thereby reducing measurement time while maintaining accuracy for the specific analyte of interest.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent performs preliminary selective inhibition of enzyme reactions with non-sdLDL lipoproteins by pre-incubating the sample with surfactants before adding cholesterol-measuring enzymes. This preliminary action selectively masks or inhibits reactions with HDL, VLDL, and other lipoproteins, allowing direct subsequent measurement of sdLDL-C without requiring time-consuming sequential fractionation steps.

Inventive Principle:
Principle #10Preliminary action

3Loss of information

If the electrophoresis method is used to measure LDL particle size, then particle size information is obtained, but operational complexity increases and sdLDL determination capability is lost

Engineering Contradiction:
ImproveLDL particle size informationVSAvoidoperational simplicity
Core Design Contradiction:
Loss of informationVSEase of operation

Solution Approach 1:

The patent replaces the electrophoresis mechanical separation system with a biochemical reaction system. Instead of using electric fields to separate lipoproteins by charge and size, the invention uses selective enzymatic reactions modulated by surfactants to specifically determine sdLDL-C. This substitution simplifies operations to standard biochemical procedures while providing direct sdLDL-C quantification capability that electrophoresis cannot provide.

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

4Ease of operation

If the turbidity-based method is used to measure sdLDL amount, then measurement simplicity is improved, but specificity and accuracy deteriorate

Engineering Contradiction:
Improvemeasurement simplicityVSAvoidsdLDL-C determination accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent introduces surfactants as intermediary substances that mediate between the measurement simplicity of turbidity methods and the specificity of enzymatic methods. The surfactants selectively interact with different lipoprotein types to modulate enzyme accessibility, creating a system that maintains operational simplicity while achieving high specificity for sdLDL-C determination through controlled biochemical reactions.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

The method provides a simple and accurate determination of sdLDL-C, improving clinical utility and reducing operational complexity and costs compared to existing techniques.

Implementation Method 1

a surfactant (hereinafter referred to as surfactant A) which preferentially inhibits the reaction of sdLDL-C with cholesterol ester hydrolase and cholesterol oxidase

Methodology Applied
Scientific EffectSurfactant inhibition: Surfactant

Implementation Method 2

allowing cholesterol ester hydrolase and cholesterol oxidase to act on the sample to eliminate HDL-C, VLDL-C, CM-C and LgLDL-C

Methodology Applied
Scientific EffectEnzymatic hydrolysis and oxidation: Enzyme

Implementation Method 3

cholesterol oxidase, or cholesterol ester hydrolase, cholesterol dehydrogenase and oxidized coenzyme

Methodology Applied
Scientific EffectOxidation: Oxidation

Data Source

PatentUS8163512B2Method for determination of cholesterol in small dense low-density lipoprotein
Publication Date: 2012.04.24 KYOWA MEDEX CO LTD

AI summary

A method for determination of sdLDL-C in a reaction solution containing a surfactant that preferentially inhibits the reaction of sdLDL-C with enzymes for cholesterol measurement such as cholesterol ester hydrolase. In the method, the enzymes for cholesterol measurement act on a sample to eliminate HDL-C, VLDL-C, CM-C and LgLDL-C. A reagent that causes the reaction of sdLDL-C remaining in the reaction solution to form hydrogen peroxide or reduced coenzyme is then added, following which the formed hydrogen peroxide or reduced coenzyme is measured. The sdLDL-C concentration in the sample may be determined by comparing the measurement value with and a previously-prepared calibration curve.