Metastatic Focus Size Determination via mRNA Quantitation

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Solution Overview

Problem

Current methods for determining cancer metastasis in lymph nodes are subjective and lack objectivity, failing to accurately assess the extent of cancer spread due to reliance on expert skill and inability to quantify metastasis effectively.

Innovation Solution

A method and apparatus that quantify cytokeratin 19 mRNA in lymph node samples to determine the size of metastatic foci by comparing results with set thresholds, enabling objective classification of cancer metastasis as negative, weakly positive, or strongly positive.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If tissue diagnosis with microscopy is used to determine cancer metastasis extent, then expert skill can identify metastatic cells, but the determination is subjective and lacks objectivity

Engineering Contradiction:
Improvemetastasis extent determination accuracyVSAvoidobjectivity of determination
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent replaces the mechanical/optical microscopy system with a molecular biology-based quantification system. Instead of visually examining tissue sections under a microscope, the invention uses mRNA extraction and quantification techniques to objectively measure metastatic cell presence through molecular markers, eliminating subjective visual assessment

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

Solution Approach 2:

The patent introduces mRNA molecules as intermediaries between the metastatic cells and the detection system. By quantifying specific mRNA transcripts from metastatic cells in the lymph node tissue, the system creates an objective molecular proxy that correlates with metastasis extent, replacing direct visual observation

Inventive Principle:
Principle #24Intermediary (Mediator)

2Difficulty of detecting and measuring

If microscopy-based tissue diagnosis is used, then visual inspection of stained sections can be performed, but it is difficult to obtain objective determination results

Engineering Contradiction:
Improveease of metastasis detectionVSAvoidobjectivity of result
Core Design Contradiction:
Difficulty of detecting and measuringVSReliability

Solution Approach 1:

The patent changes the measurement parameter from visual characteristics (cell morphology, staining intensity) to molecular quantity (mRNA copy number or expression level). This parameter transformation enables objective quantification through numerical measurement rather than subjective visual assessment, while maintaining ease of detection through standardized molecular assays

Inventive Principle:
Principle #35Parameter changes

3Reliability

If known metastasis diagnosis markers are used to diagnose presence of metastasis, then metastasis can be diagnosed, but the extent of metastasis cannot be determined

Engineering Contradiction:
Improvemetastasis diagnosis accuracyVSAvoidquantification of metastasis extent
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent implements a quantitative feedback mechanism where the amount of detected mRNA is measured and correlated with metastatic focus size. By establishing a relationship between mRNA quantity and physical metastasis extent, the system provides numerical feedback that enables precise quantification rather than merely qualitative presence/absence determination

Inventive Principle:
Principle #23Feedback

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 accurate and objective determination of cancer metastasis extent by correlating mRNA quantitation results with metastatic focus size, providing a reliable method for classifying micro and macro metastasis.

Implementation Method 1

Methods and apparatuses for the amplification of nucleic acids, including e.g. the amplification of CK19 mRNA are known e.g. from EP 1 813 682

Methodology Applied
Scientific EffectNucleic acid amplification:

Data Source

PatentEP1876245B1Method and apparatus for determining the size of a metastatic focus
Publication Date: 2012.06.13 SYSMEX CORP
  • EP1876245B1 patent drawingFigure 1
  • EP1876245B1 patent drawingFigure 2
  • EP1876245B1 patent drawingFigure 3

AI summary

A method which can objectively determine to what extent a cancer cell has metastasized to a lymph node, the method being a method for determining a size of a metastatic focus, including a step of quantitating a tumor marker mRNA in an assay sample prepared from a lymph node suspected of metastasis of a cancer cell, and a step of obtaining a size of a metastatic focus in the lymph node based on the quantitation result of the mRNA.