LDL-C Measurement Kit Using Selective Surfactant Extraction

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Solution Overview

Problem

Current methods for measuring low-density lipoprotein cholesterol (LDL-C) are either complex, time-consuming, or lack precision, particularly in clinical settings, and are influenced by factors like triglyceride levels and the need for physical fractionation processes.

Innovation Solution

A method involving the reaction of cholesterol ester hydrolase and cholesterol oxidase, or their combinations with oxidized coenzymes, in the presence of specific surfactants and a polyanion, to selectively measure LDL-C without prior separation of lipoproteins, using substances like polyoxyethylene-polyoxyalkylene alkylaryl ethers and quaternary ammonium salts.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If ultracentrifugation method is used to separate LDL, then measurement precision is improved, but device complexity and operation time increase

Engineering Contradiction:
ImproveLDL-C measurement precisionVSAvoidultracentrifuge complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts and targets only LDL particles from the serum sample using specific surfactants that selectively bind to LDL, allowing direct measurement without complex separation operations. This eliminates the need for ultracentrifugation while maintaining measurement precision.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention introduces surfactants as intermediary substances that selectively interact with LDL particles, enabling specific detection and measurement of LDL-C without requiring physical separation by ultracentrifugation. The surfactants act as mediators between the measurement system and LDL particles.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If Friedewald formula calculation method is used, then productivity is improved, but measurement precision deteriorates due to triglyceride interference

Engineering Contradiction:
Improvecalculation speedVSAvoidLDL-C calculation accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The invention extracts and measures only LDL-C directly from serum using selective surfactant binding, eliminating the need for calculation based on total cholesterol, HDL-C, and triglycerides. This direct measurement approach maintains high productivity while improving precision by removing triglyceride-related calculation errors.

Inventive Principle:
Principle #2Taking out (Extraction)

3Measurement precision

If electrophoresis method is used to separate LDL, then measurement precision is improved, but device complexity and cost increase

Engineering Contradiction:
ImproveLDL separation precisionVSAvoidelectrophoresis system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts LDL particles selectively using specific surfactants that bind preferentially to LDL, enabling direct measurement without electrophoresis separation. This simplifies the system while maintaining the ability to specifically measure LDL-C.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces the mechanical electrophoresis separation system with a chemical binding approach using surfactants. This substitution eliminates complex electrophoresis equipment while achieving selective LDL measurement through biochemical interactions.

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

4Measurement precision

If physical fractionation operations are performed, then measurement precision is improved, but loss of time increases

Engineering Contradiction:
ImproveLDL-C measurement accuracyVSAvoidsample preparation time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The invention extracts LDL particles directly from undiluted or minimally processed serum using selective surfactant binding in a single-step reaction. This eliminates time-consuming physical fractionation operations while maintaining measurement precision through specific LDL-surfactant interactions.

Inventive Principle:
Principle #2Taking out (Extraction)

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 simple and precise measurement of LDL-C without physical fractionation, improving speed and accuracy while being less affected by triglyceride levels, thus enhancing clinical utility.

Implementation Method 1

cholesterol ester hydrolase

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Implementation Method 2

cholesterol oxidase

Methodology Applied
Scientific EffectOxidation: Oxidation

Data Source

PatentEP2363498B1Method for quantitatively determining cholesterol in low-density lipoproteins, reagent for quantitative determination, and quantitative determination kit
Publication Date: 2016.05.25 KYOWA MEDEX CO LTD
  • EP2363498B1 patent drawing
  • EP2363498B1 patent drawing

AI summary

A method for measuring cholesterol in low-density lipoprotein contained in a sample, which comprises reacting a sample with (i) a combination of cholesterol ester hydrolase and cholesterol oxidase or (ii) a combination of cholesterol ester hydrolase, an oxidized coenzyme and cholesterol dehydrogenase in the presence of: [a] a polyoxyethylene-polyoxyalkylene alkylaryl ether; [b] one or more surfactants selected from the group consisting of a polyoxyethylene-polyoxyalkylene copolymer, a polyoxyethylene alkenyl ether, a polyoxyethylene branched alkyl ether, and a polyoxyethylene-polyoxyalkylene branched alkyl ether; [c] one or more surfactants selected from the group consisting of a primary amine, a secondary amine, a tertiary amine, and a quaternary ammonium; and [d] a polyanion, and measuring a substance formed or consumed in the reaction.