Multimodal Optical Sectioning Microscope for Tissue Imaging

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Solution Overview

Problem

Full-Field Optical Coherence Tomography (FF-OCT) systems face limitations in providing sufficient contrast for diagnostic purposes, particularly in distinguishing metabolic structures like tumorous areas, as they primarily offer morphological information and lack the contrast needed for accurate diagnostics compared to histology slides.

Innovation Solution

A multimodal optical sectioning microscope is developed, combining FF-OCT with a supplementary full-field optical sectioning imaging system, sharing a common optical channel to provide additional contrasts while maintaining a compact apparatus, enabling simultaneous acquisition of FF-OCT and fluorescence images with the same transverse resolution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If FF-OCT system uses standard imaging configuration, then lateral resolution is improved, but optical sectioning capability deteriorates

Engineering Contradiction:
Improvelateral resolutionVSAvoidout-of-focus light
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent segments the imaging process into two distinct functional paths: a wide-field path for collecting out-of-focus light and a confocal path for capturing in-focus signals. By spatially separating these functions and processing them differently, the system achieves both high lateral resolution and effective optical sectioning without compromising either capability.

Inventive Principle:
Principle #1Segmentation

2Measurement precision

If FF-OCT system adds optical sectioning capability, then sectioning ability is improved, but device complexity increases

Engineering Contradiction:
Improveoptical sectioning abilityVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent merges FF-OCT and confocal microscopy into a single integrated system that shares common components (light source, beamsplitter, detectors) while maintaining distinct functional paths. This combination achieves superior optical sectioning capability without proportionally increasing device complexity, as the systems complement each other's strengths.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The imaging system is designed with multi-functionality, allowing it to operate in different modes (wide-field FF-OCT, confocal FF-OCT, and hybrid mode) depending on the imaging requirements. This universal design enables the system to adapt to various diagnostic needs without requiring separate dedicated systems.

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

3Productivity

If FF-OCT system provides only morphological information, then image acquisition speed is improved, but diagnostic accuracy deteriorates

Engineering Contradiction:
Improveimage acquisition speedVSAvoidmetabolic information
Core Design Contradiction:
ProductivityVSLoss of information

Solution Approach 1:

The patent combines FF-OCT's rapid morphological imaging capability with confocal microscopy's ability to provide metabolic and molecular information through fluorescence detection. This merger enables simultaneous acquisition of both structural and functional data, eliminating the need for separate imaging sessions and preserving diagnostic accuracy while maintaining speed.

Inventive Principle:
Principle #5Merging (Combining)

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 enhances contrast in FF-OCT images, providing both morphological and metabolic information, similar to histology slides, by integrating fluorescence imaging capabilities, thus improving diagnostic accuracy without the need for histology slide preparation.

Implementation Method 1

The signal is extracted from the background of incoherent backscattered light using a phase-shifting method. Due to the randomness of the tissues structures, it is possible to record only two interferometric images

Methodology Applied
Scientific EffectOptical interference: Interference

Implementation Method 2

The principle of fluorescence microscopy relies on the addition of a fluorescent agent to the sample - sometimes with specificity to a cellular structure - followed by the illumination of the sample using light with a spectrum corresponding to the absorption spectrum of said fluorescent agent. The subsequent fluorescence emission is characterized by a shifted spectrum compared to the absorption spectrum

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 3

FF-OCT allows for ultra high resolution (typically ∼1μm in 3D) images of scattering samples such as biological tissues, in depth, using a non-invasive process

Methodology Applied
Scientific EffectOptical focusing: Focusing

Data Source

PatentEP2615967B1Optical tissue sectioning using full field optical coherence tomography
Publication Date: 2017.08.16 LLTECH MANAGEMENT
  • EP2615967B1 patent drawingFigure 1
  • EP2615967B1 patent drawingFigure 2
  • EP2615967B1 patent drawingFigure 3A~3C

AI summary

According to a first aspect, the invention relates to a multimodal optical sectioning microscope (200, 400, 600) for full-field imaging of a volumic and scattering sample comprising: - a full-field OCT system for providing an image of a first section in depth of the sample comprising an illumination sub-system (201, 401, 601) and a full-field imaging interferometer with a detection sub system (208, 408, 608) and an optical conjugation device for optically conjugating the sample and said detection sub system, wherein said optical conjugation device comprises a microscope objective (203, 403, 603), - a supplementary full-field optical sectioning imaging system for providing a fluorescent image of a second section in depth of said sample comprising a structured illumination microscope with an illumination sub system (623), means (421, 422) for generating at the focal plane of said microscope objective of said full-field imaging interferometer a variable spatial pattern illumination and a detection sub system (624), optically conjugated with said focal plane of the microscope objective.