Rapid Confocal Microscopy for Real-Time Tumor Identification

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Solution Overview

Problem

Current surgical procedures for removing tumors, such as basal cell carcinoma, are time-consuming and labor-intensive due to the need for tedious histology section preparation, which prolongs surgery duration and increases patient risk.

Innovation Solution

The development of rapid confocal microscopy techniques, including improved tissue fixation, image merging, illumination correction, and multimodal image presentation, allows for the creation of high-resolution images of excised tissue, enabling faster diagnosis and guiding surgical excisions without the need for extensive histology section preparation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional histology section preparation is used, then accurate tumor identification is achieved, but surgical procedure time is excessively long

Engineering Contradiction:
Improvetumor identification accuracyVSAvoidsurgical procedure time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces the mechanical histology preparation system (sectioning, staining, mounting) with a confocal microscopy system that uses optical sectioning and fluorescence imaging to achieve real-time tumor visualization, eliminating the time-consuming mechanical preparation steps while maintaining diagnostic accuracy

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

Solution Approach 2:

The patent changes the detection parameters from conventional light microscopy to confocal microscopy with specific wavelength excitation (e.g., 488nm) and fluorescence emission detection, enabling rapid real-time imaging that provides tumor identification within minutes rather than hours

Inventive Principle:
Principle #35Parameter changes

2Reliability

If multiple incremental excisions are performed, then complete tumor removal is achieved, but patient exposure to infection risk increases

Engineering Contradiction:
Improvecomplete tumor removalVSAvoidinfection risk
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent enables preliminary real-time visualization and mapping of tumor boundaries before excision begins, allowing surgeons to plan the optimal excision strategy in advance and reduce the number of incremental steps needed, thereby minimizing patient exposure to infection risk

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent implements real-time feedback during surgery through confocal imaging, allowing immediate assessment of excision margins and guiding subsequent removal steps, ensuring complete tumor removal with fewer iterations and reduced infection exposure

Inventive Principle:
Principle #23Feedback

3Productivity

If confocal microscopy is used for real-time imaging, then surgical procedure time is reduced, but device complexity increases

Engineering Contradiction:
Improvesurgical efficiencyVSAvoidmicroscopy system complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent describes a confocal microscopy system that performs multiple functions including optical sectioning, fluorescence imaging, and real-time tumor visualization within a single integrated platform, reducing the need for multiple separate devices and simplifying the overall surgical workflow

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

Solution Approach 2:

The patent uses fluorescent dyes as intermediaries that selectively bind to tumor tissues, enabling specific and simplified detection of tumor boundaries without requiring complex tissue preparation or multiple staining steps, thereby reducing device complexity while maintaining high surgical efficiency

Inventive Principle:
Principle #24Intermediary (Mediator)

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

These techniques significantly reduce the time required for surgical procedures, potentially replacing traditional histology sections, thereby decreasing surgical risks and costs while providing rapid and accurate tumor identification.

Implementation Method 1

Confocal microscopy is capable of directly observing, in real time, very small structures in a very small field of view and can directly observe tumors in excised tissue

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

Dual mode reflectance and fluorescence confocal laser scanning microscopy for in vivo imaging melanoma progression in murine skin

Methodology Applied
Scientific EffectReflectance: Reflection

Data Source

PatentEP2318875B1Rapid confocal microscopy to support surgical procedures
Publication Date: 2019.11.06 SLOAN KETTERING INST FOR CANCER RES
  • EP2318875B1 patent drawingFigure 1
  • EP2318875B1 patent drawingFigure 2A
  • EP2318875B1 patent drawingFigure 2B

AI summary

One embodiment of techniques for confocal microscopy includes illuminating a spot on a surface of a biological sample. A first emission intensity from the spot is detected in a first range of optical properties; and a second emission intensity in a second range. A pixel that corresponds to the spot is colored using a linear combination of the first and second emission intensities. Sometimes, the pixel is colored to approximate a color produced by histology. In some embodiments, a surface of a sample is contacted with a solution of acridine orange. Then, a spot is illuminated with a laser beam of wavelength about 488 nanometers (nm). Fluorescence emission intensity is detected above about 500 nm. Sometimes, a certain illumination correction is applied. In some embodiments, a sample holder that compresses a sample is removable from a stage that is fixed with respect to a focal plane of the microscope.