Apolipoprotein Detection via Polystyrene Adsorption

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Solution Overview

Problem

Current methods for detecting and quantifying apolipoproteins, particularly apoE isoforms, are complex, time-consuming, and not easily implementable in clinical settings, lacking reliable and accurate techniques for fast determination in samples.

Innovation Solution

A method involving direct electrostatic and hydrophobic interaction of apolipoproteins with polystyrene surfaces, followed by antibody binding and detection, allowing for the quantification of apoE isoforms like apoE4 without the need for capture antibodies or prior isolation, applicable to various apolipoproteins including apoAI, apoAIV, apoCI, apoCII, apoCIII, and apoJ.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If PCR-RFLP, capillary electrophoresis, or other genetic methods are used for APOE genotyping, then genotyping accuracy is improved, but the complexity of the procedure and time consumption increase significantly

Engineering Contradiction:
Improvegenotyping accuracyVSAvoidprocedure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention extracts only the necessary functional information (apolipoprotein isoform presence) from the complex genetic analysis process. Instead of performing complete genomic DNA analysis through PCR and sequencing, the method directly detects apolipoprotein isoforms in plasma using immunoassay techniques, extracting only the clinically relevant information needed for risk assessment.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention introduces apolipoprotein isoform detection as an intermediary between genetic genotype and disease risk phenotype. Rather than directly analyzing DNA sequences or using complex genetic markers, the method uses apolipoprotein isoform levels in plasma as an intermediate biomarker that reflects the functional outcome of APOE genotypes, simplifying the path to clinical decision-making.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Adaptability or versatility

If isoelectric focusing (IEF) with immunodetection is used for apoE isoform characterization, then detection capability for rare variants is improved, but the time required and technical expertise needed increase

Engineering Contradiction:
Improvedetection capability for rare variantsVSAvoidanalysis time
Core Design Contradiction:
Adaptability or versatilityVSLoss of time

Solution Approach 1:

The invention employs commercially available ELISA kits that are self-contained and require minimal technical preparation. The kits include pre-coated antibodies, buffer solutions, and detection reagents that work together in a standardized protocol, allowing laboratory personnel with basic immunoassay training to perform the analysis without requiring specialized expertise in electrophoresis or rare variant identification.

Inventive Principle:
Principle #25Self-service

3Measurement precision

If sandwich ELISA with isoform-specific antibodies is used for apoE detection, then specificity for particular isoforms is improved, but the availability of required antibodies and implementation difficulty worsen

Engineering Contradiction:
Improveisoform detection specificityVSAvoidimplementation ease
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The invention uses a universal detection approach where a single ELISA kit can detect multiple apolipoprotein isoforms (apoE2, apoE3, apoE4) through a common assay protocol. The kit employs a capture antibody that recognizes a conserved epitope across all isoforms, allowing simultaneous quantification of different isoforms without requiring separate antibody preparations or optimized protocols for each variant.

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

4Reliability

If complex genetic analysis methods are used for disease risk prediction, then predictive accuracy is improved, but the ease of clinical implementation deteriorates

Engineering Contradiction:
Improvedisease risk prediction accuracyVSAvoidclinical implementation ease
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The invention replaces the mechanical and procedural complexity of genetic analysis (DNA extraction, PCR amplification, gel electrophoresis, sequencing) with a simpler immunoassay-based detection system. The ELISA method uses antibody-antigen binding chemistry to directly detect apolipoprotein isoforms in plasma, eliminating multiple mechanical steps and reducing the need for specialized equipment while maintaining clinical utility for Alzheimer's disease risk prediction.

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

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 simple, reliable, and cost-effective means for apolipoprotein detection and quantification, enabling efficient patient stratification and risk assessment for neurodegenerative and cardiovascular diseases, suitable for clinical and research use.

Implementation Method 1

direct electrostatic and hydrophobic interaction of apolipoproteins with polystyrene surfaces

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

direct electrostatic and hydrophobic interaction of apolipoproteins with polystyrene surfaces

Methodology Applied
Scientific EffectHydrophobic interaction: Hydrophobe

Implementation Method 3

Contacting the surface to which the apolipoprotein is bound formed in step (i) with an antibody specific for said apolipoprotein under suitable conditions for the formation of a complex between the antibody and the apolipoprotein

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentEP3274725B1Methods for apolipoprotein detection
Publication Date: 2019.01.09 BIOCROSS
  • EP3274725B1 patent drawingFigure 1
  • EP3274725B1 patent drawingFigure 2
  • EP3274725B1 patent drawingFigure 3

AI summary

The present invention relates to methods for the detection and quantification of apolipoproteins and isoforms thereof in a sample, as well as to predictive methods of the probability of neurodegenerative or cardiovascular disease development based on apolipoprotein levels as determined by the detection methods of the invention.