Multiplex FISH and Sequencing for Accurate Breast Cancer Biomarker Diagnosis

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Solution Overview

Problem

Current diagnostic methods for breast cancer lack accuracy and precision, leading to high rates of misdiagnosis, overdiagnosis, and unnecessary chemotherapy, and are time-consuming, failing to provide comprehensive and personalized treatment recommendations due to limited biomarker analysis and reliance on multiple tests.

Innovation Solution

A method combining multiplex fluorescence in situ hybridization (FISH) and sequencing to detect and confirm the presence of multiple mRNA and miRNA biomarkers in formaldehyde-fixed tissue samples, using laser capture microdissection to isolate and validate positive results, thereby enhancing diagnostic accuracy and reducing analysis biases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If multiple diagnostic tests are performed to improve diagnostic accuracy, then diagnostic precision is improved, but loss of time increases

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidtime-consuming
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent combines multiple diagnostic tests into a single integrated assay that simultaneously performs FISH for biomarker detection and sequencing for validation. This merging of multiple separate tests into one unified diagnostic platform reduces the time required while maintaining high diagnostic accuracy through cross-validation of results.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent performs preliminary FISH screening to identify potential biomarkers before proceeding to sequencing validation. This preliminary action filters out false positives early, reducing the need for multiple sequential tests and thereby decreasing overall diagnostic time while maintaining precision.

Inventive Principle:
Principle #10Preliminary action

2Ease of operation

If conventional FISH methods are used to detect biomarkers, then ease of operation is improved, but measurement precision deteriorates

Engineering Contradiction:
Improveease of detectionVSAvoidtranscript abundance measurement accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent implements a feedback mechanism where FISH results are used to guide subsequent sequencing analyses. The FISH screening identifies candidate biomarkers, and sequencing then validates and quantifies these findings with higher precision, creating a feedback loop that maintains ease of operation while improving measurement accuracy.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent segments the diagnostic process into two distinct but complementary stages: FISH-based screening for ease of detection and sequencing-based validation for precise quantification. This segmentation allows each method to optimize for its strength while the combination achieves both ease of operation and high precision.

Inventive Principle:
Principle #1Segmentation

3Device complexity

If single biomarker analysis is performed to simplify the diagnostic process, then device complexity is reduced, but loss of information increases

Engineering Contradiction:
Improvediagnostic test complexityVSAvoidcomprehensive biomarker profile
Core Design Contradiction:
Device complexityVSLoss of information

Solution Approach 1:

The patent creates a universal diagnostic platform that can simultaneously detect multiple biomarkers through FISH and validate them through sequencing. This multi-functional approach allows a single integrated assay to provide comprehensive biomarker profiling without requiring multiple separate tests, thereby reducing overall complexity while preventing information loss.

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

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 precise, rapid, and personalized diagnosis of breast cancer by simultaneously assessing multiple biomarkers, reducing diagnostic errors and enabling tailored treatment plans, while minimizing false positives and negatives.

Implementation Method 1

determining by multiplex fluorescence in situ hybridization (FISH) whether or not mRNA species of disease-associated biomarkers are present

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

that part of said sample in which said mRNA species of disease-associated biomarkers was determined in step (a) to be present is subject to laser capturing and isolation

Methodology Applied
Scientific EffectLaser ablation: Laser Ablation

Data Source

PatentEP3775277B1Method for diagnosing diseases using multiplex fluorescence and sequencing
Publication Date: 2025.12.03 MULTIPLEXDX SRO
  • EP3775277B1 patent drawingFigure 1
  • EP3775277B1 patent drawingFigure 2
  • EP3775277B1 patent drawingFigure 3

AI summary

The present invention relates to methods for diagnosing a disease by determining via multiplex fluorescence in situ hybridization (FISH) whether or not mRNA species and/or at least one miRNA species of disease-associated biomarkers are present in a sample obtained from a subject, and by determining by multiplex sequencing whether or not said mRNA species of disease-associated biomarkers and/or said miRNA species of disease-associated biomarkers of step(a) are present in said sample. The present invention also relates to kits for performing the methods for diagnosis as described and provided herein as well as use of such kits for performing the methods for diagnosis as described and provided herein.