AXL Detection in Circulating Tumor Cells via Fluorescent Optical Imaging

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Solution Overview

Problem

Current methods for detecting AXL in cancer patients with acquired resistance to EGFR inhibitors are invasive and burdensome, particularly for non-small cell lung cancer patients, as they require repetitive tissue biopsies.

Innovation Solution

A method involving the isolation of circulating tumor cells from blood using a high-density microporous biochip, followed by optical image analysis with fluorescent markers specific to AXL, allowing for the detection of AXL expression in circulating tumor cells across multiple wavelength ranges.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If tissue biopsy is used to detect AXL expression, then measurement precision is improved, but ease of operation deteriorates due to repetitive sampling difficulty and physical burden on patients

Engineering Contradiction:
ImproveAXL expression detection accuracyVSAvoidPatient burden and sampling difficulty
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent extracts the target of detection from tissue samples to circulating tumor cells in blood. By isolating CTCs from peripheral blood and detecting AXL expression on these cells, the method eliminates the need for repetitive tissue biopsies while maintaining detection capability. This extraction principle resolves the contradiction by shifting the detection target to a more accessible sample type that can be repeatedly obtained without significant patient burden.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces circulating tumor cells as an intermediary between the primary tumor tissue and the detection system. These CTCs serve as a surrogate marker that reflects the molecular characteristics of the primary tumor including AXL expression status. This intermediary approach allows indirect detection of AXL expression without requiring direct tissue sampling, thus resolving the contradiction between detection precision and operational ease.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If optical image analysis with fluorescent markers is used, then ease of operation is improved, but measurement precision may deteriorate compared to tissue biopsy

Engineering Contradiction:
ImproveNon-invasive screening capabilityVSAvoidAXL detection accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent replaces the mechanical tissue biopsy procedure with an optical detection system. By using fluorescent markers that bind specifically to AXL protein and detecting them through optical imaging, the method substitutes a minimally invasive optical approach for the invasive mechanical biopsy. This substitution maintains ease of operation while achieving sufficient measurement precision through specific fluorescent labeling and image analysis.

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

Solution Approach 2:

The patent utilizes color changes through fluorescent markers to detect AXL expression. Different fluorescent markers emit specific wavelengths of light when excited, allowing differentiation of AXL-positive cells from AXL-negative cells. This color-based detection method provides a clear, quantifiable signal that maintains measurement precision while enabling non-invasive optical analysis of circulating tumor cells.

Inventive Principle:
Principle #32Color changes

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 non-invasive screening of lung cancer patients for resistance to EGFR-TKI by accurately identifying AXL-positive circulating tumor cells, potentially predicting treatment outcomes and prognosis.

Implementation Method 1

reacting the isolated circulating tumor cells with a fluorescent marker binding specifically to the circulating tumor cells and a fluorescent marker binding specifically to AXL; receiving optical images of the circulating tumor cells reacted with the fluorescent marker specific to the circulating tumor cells and the AXL reacted with the fluorescent marker specific to the AXL under a plurality of wavelength ranges

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP3680659B1AXL-based cancer patient screening method
Publication Date: 2022.06.08 CYTOGEN CO LTD
  • EP3680659B1 patent drawingFigure 1
  • EP3680659B1 patent drawingFigure 2
  • EP3680659B1 patent drawingFigure 3(a)~3(b)

AI summary

According to one embodiment of the present invention, there is provided a method of screening a lung cancer patient having acquired resistance to an EGFR inhibitor by optical image analysis of circulating tumor cells and AXL.