Nucleosome Detection via Multi-Epitope Antibody Panel
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Solution Overview
Problem
Current methods for detecting and measuring mono-nucleosomes and oligo-nucleosomes in biological samples, such as ELISA assays, are inconsistent and not suitable for direct measurement in complex media like blood or plasma, leading to unreliable results and limited clinical application as biomarkers for diseases.
Innovation Solution
A method involving multiple binding agents that target different nucleosome epitopes, including histone variants and nucleotides, to detect and quantify nucleosomes in a sample, allowing for the detection of nucleosomes not detectable by existing methods, and enabling their use as biomarkers in blood samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If current ELISA methods using monoclonal anti-histone antibodies are used to detect nucleosomes, then the assay can be performed with standardized reagents, but the detection reliability is poor and results are inconsistent
Solution Approach 1:
The patent employs a panel of multiple monoclonal antibodies targeting different histone variants (H2A, H2B, H3, H4) and DNA components, allowing the assay to detect various forms of nucleosomes universally. This multi-target approach ensures that at least one antibody pair will reliably detect nucleosomes regardless of their specific composition or modification state, thereby improving detection reliability while maintaining reagent standardization.
2Adaptability or versatility
If ELISA assays are performed in complex biological media like blood or plasma, then the method can be applied clinically as a biomarker test, but the measurement precision deteriorates due to interference from complex media components
Solution Approach 1:
The patent introduces a capture antibody step as an intermediary mechanism. The capture antibody specifically binds to the target nucleosome-histone-DNA complex, separating it from interfering components in complex media. This is followed by detection antibodies that recognize different epitopes, creating a sandwich assay structure that enhances specificity and precision even in complex biological matrices like blood or plasma.
Solution Approach 2:
By using multiple antibody pairs targeting different components (histones, DNA, and their complexes), the assay achieves universal detection capability across various sample types. This multi-functional detection strategy ensures accurate measurement regardless of the specific composition of complex media, thereby maintaining measurement precision while enabling broad clinical applicability.
3Reliability
If multiple binding agents targeting different nucleosome epitopes are used, then the detection capability is improved and more nucleosomes are detected, but the device complexity increases
Solution Approach 1:
The patent segments the detection process into distinct functional steps: capture antibody binding, detection antibody binding, and signal generation. Each monoclonal antibody is engineered to recognize a specific epitope on different histone variants or DNA components. This segmentation allows the complex multi-antibody system to be organized into modular, standardized reagent components that can be manufactured and validated independently, reducing overall assay complexity while maintaining high detection capability.
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 enables the detection of nucleosomes in samples where existing methods fail, providing a more reliable and minimally invasive means for disease diagnosis and monitoring, with potential for wider clinical application.
Implementation Method 1
contacting the sample with a first binding agent which binds to nucleosomes; contacting the nucleosomes or sample with two or more second binding agents which bind to different or separate nucleosome epitopes
Data Source
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AI summary
The invention relates to a method for detecting and measuring the presence of mono-nucleosomes and oligo-nucleosomes and the use of such measurements for the detection and diagnosis of disease.