Modified LDL Immune Complex Detection for Coronary Artery Disease

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Solution Overview

Problem

Current methods for measuring modified LDL immune complexes are complex, time-consuming, and unreliable, particularly in studying large patient cohorts, due to interference from pre-formed immune complexes and the need for specific isolation and dissociation of antigens and antibodies, which limits the understanding of their role in chronic inflammatory processes like atherosclerosis.

Innovation Solution

A method involving the measurement of oxidized-LDL (ox-LDL) and advanced glycation endproduct-LDL (AGE-LDL) immune complexes in serum or plasma samples, using techniques such as PEG precipitation, affinity chromatography, and immunoassays to isolate and quantify these complexes, allowing for the prediction of coronary artery disease and type 1 diabetes complications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional methods are used to measure modified LDL immune complexes, then measurement can be performed, but the process becomes complex and time-consuming requiring specific isolation and dissociation procedures

Engineering Contradiction:
Improvemeasurement accuracyVSAvoidisolation and dissociation procedures
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts and measures only the modified LDL immune complexes from the complex serum matrix using specific antibodies that bind to modified LDL, eliminating the need for complex isolation and dissociation procedures while maintaining measurement accuracy

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses specific antibodies as intermediaries to directly detect modified LDL immune complexes in serum, serving as a mediator that simplifies the measurement process by eliminating the need for complex sample preparation steps

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If traditional methods are used to measure modified LDL immune complexes, then measurement can be performed, but reliability is reduced due to interference from pre-formed immune complexes

Engineering Contradiction:
Improvemeasurement reliabilityVSAvoidinterference from pre-formed immune complexes
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

Instead of trying to eliminate interference from pre-formed immune complexes, the patent inverts the approach by using antibodies that specifically recognize and bind to modified LDL within the immune complexes, turning the interference into a target for measurement

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The patent changes the measurement parameter from total immune complex levels to specific modified LDL immune complex levels using antigen-specific antibodies, thereby distinguishing target analytes from interfering substances and improving measurement reliability

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If complex isolation and dissociation procedures are used, then modified LDL can be measured, but productivity decreases when studying large patient cohorts

Engineering Contradiction:
Improvemodified LDL measurementVSAvoidthroughput for large patient cohorts
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent enables the measurement system to directly process serum samples without requiring complex manual isolation and dissociation procedures, allowing high-throughput automation and significantly improving productivity for large patient cohorts

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent replaces complex mechanical isolation and dissociation procedures with an immunological detection system using specific antibodies, enabling direct measurement in serum and facilitating automated high-throughput processing

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

4Ease of operation

If cholesterol is used as a surrogate marker for modified LDL, then measurement is simplified, but measurement precision and predictive power are reduced

Engineering Contradiction:
Improvemeasurement simplicityVSAvoidpredictive power for CAD
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent changes the measurement parameter from total cholesterol levels to specific modified LDL immune complex levels using antigen-specific antibodies, providing more precise and predictive measurements while maintaining operational simplicity through direct immunoassay methods

Inventive Principle:
Principle #35Parameter changes

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 method provides a reliable and efficient way to predict the risk of coronary artery disease and type 1 diabetes complications by accurately measuring ox-LDL and AGE-LDL immune complexes, exceeding the predictive power of classical risk factors and identifying high-risk individuals even at a young age.

Implementation Method 1

PEG precipitation

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Implementation Method 2

affinity chromatography

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentUS8911958B2Methods for assessing modified LDL immune complexes in subjects having or at risk of coronary artery disease
Publication Date: 2014.12.16 MUSC FOUNDATION FOR RESEARCH DEVELOPMENT(US)
  • US8911958B2 patent drawing
  • US8911958B2 patent drawing
  • US8911958B2 patent drawing

AI summary

The present invention relates to the analysis of modified LDL in the context of immune complexes. In particular, ox-LDL and AGE-LDL are shown to predict the development of coronary artery disease and other micro- and macrovascular disorders, particularly in the context of diabetes.