Histone H1 Nucleosome Detection for Cancer Diagnosis

Solution Overview

Problem

Current methods for detecting cancer using circulating nucleosomes are inconsistent and not reliable due to variations in nucleosome levels in serum and plasma, and existing ELISA methods are not suitable for direct measurement in complex biological media like blood or serum, limiting their clinical application.

Innovation Solution

The use of histone H1 protein or its modifications/isoforms associated with cell-free nucleosomes as biomarkers in biological fluids for cancer detection, involving immunoassays to measure these markers in body fluids, allowing for non-invasive and high-throughput diagnosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current ELISA methods are used to detect circulating nucleosomes, then nucleosome levels can be measured, but the results are inconsistent and not reliable due to variations in nucleosome levels in serum and plasma

Engineering Contradiction:
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent extracts and isolates histone H1 protein or its modifications/isoforms from circulating nucleosomes in biological fluids. By specifically detecting these extracted biomarkers rather than measuring total nucleosome levels, the method achieves more reliable and consistent cancer detection results, resolving the inconsistency problem of current ELISA methods.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

Instead of measuring all nucleosomes uniformly, the patent focuses on detecting specific local characteristics - namely histone H1 modifications and isoforms. This selective detection of specific biomarker qualities within the nucleosome structure enables more reliable differentiation between healthy and cancerous conditions.

Inventive Principle:
Principle #3Local quality

2Ease of operation

If existing ELISA methods are used, then nucleosome detection is possible, but they are not suitable for direct measurement in complex biological media like blood or serum

Engineering Contradiction:
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent uses specific antibodies as intermediaries that selectively bind to histone H1 protein or its modifications/isoforms in complex biological media. These antibody intermediaries enable reliable detection by specifically targeting the biomarkers of interest while ignoring other components in the complex serum or plasma environment.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If histone H1 modifications or isoforms are used as biomarkers, then diagnostic accuracy is improved, but the detection method becomes more complex

Engineering Contradiction:
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the detection process into specific steps: using capture antibodies to isolate nucleosomes, then using detection antibodies specific to histone H1 modifications or isoforms. This segmentation of the detection methodology into targeted steps improves diagnostic accuracy while managing complexity through systematic procedure design.

Inventive Principle:
Principle #1Segmentation

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 provides a reliable and minimally invasive method for cancer diagnosis, capable of distinguishing between healthy and cancerous conditions by detecting specific histone H1 modifications or isoforms in nucleosomes, improving diagnostic accuracy and clinical utility.

Implementation Method 1

The use of histone H1 protein or its modifications/isoforms associated with cell-free nucleosomes as biomarkers in biological fluids for cancer detection, involving immunoassays to measure these markers in body fluids

Methodology Applied
Scientific EffectAntigen-antibody recognition:

Data Source

PatentEP3365681B1Method for detecting nucleosomes containing histone modifications and variants
Publication Date: 2023.06.07

AI summary

The present invention relates to a method for detecting and measuring the presence of cell free mono-nucleosomes and oligo-nucleosomes that contain histone H1or a histone H1 modification, variant or isoform,and the use of such measurements for the detection and diagnosis of disease.