Reflection-Type Confocal Microscopy for Unstained Tissue Imaging

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current pathological diagnosis techniques using bright field microscopes are time-consuming and require staining, making them unsuitable for quick intraoperative tissue diagnosis, while reflection-type microscopes with coherent interaction struggle with sufficient signal intensity and observing cell side walls without staining.

Innovation Solution

A reflection-type confocal optical system with a CW laser source and a blocking unit that adjusts optical path differences to selectively block coherent light, enhancing the detection of incoherent Rayleigh scattered light for high-resolution, unstained imaging, equivalent to confocal fluorescence microscopy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a bright field microscope is used for pathological diagnosis, then diagnostic accuracy can be achieved, but the observation time becomes too long due to sample preparation requirements

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidobservation time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies preliminary action by pre-processing the light signal through coherent interaction before detection. The coherent light source creates interference patterns that encode tissue structural information in advance, allowing direct observation without time-consuming staining and sectioning procedures. This enables rapid intraoperative diagnosis while maintaining diagnostic accuracy.

Inventive Principle:
Principle #10Preliminary action

2Speed

If a reflection-type microscope with coherent interaction is used, then observation speed is improved, but sufficient signal intensity cannot be obtained and cell side walls cannot be observed

Engineering Contradiction:
Improveobservation speedVSAvoidsignal intensity
Core Design Contradiction:
SpeedVSIllumination intensity

Solution Approach 1:

The patent applies parameter changes by optimizing the coherence length of the light source to match the depth of the tissue layer being observed. By adjusting the spectral bandwidth and coherence properties of the light, the system enhances signal intensity from cellular structures including side walls, while maintaining rapid observation speed through non-stained imaging.

Inventive Principle:
Principle #35Parameter changes

3Loss of time

If unstained imaging technique is used for rapid diagnosis, then sample preparation time is reduced, but imaging resolution and contrast are insufficient

Engineering Contradiction:
Improvesample preparation timeVSAvoidimaging resolution
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The patent introduces coherent light as an intermediary that mediates between the tissue sample and the detector. The coherent interaction creates optical path difference information that acts as an intermediary representation of tissue structure, enabling high-resolution unstained imaging by converting subtle refractive index variations into detectable interference patterns without requiring chemical stains.

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

Enables quick, high-resolution, unstained imaging of tissues without staining, providing sufficient signal intensity and sectioning capability suitable for rapid pathological diagnosis, equivalent to confocal fluorescence microscopy.

Implementation Method 1

the microscope utilizing the coherent interaction is known

Methodology Applied
Scientific EffectCoherent interaction: Coherent Light

Implementation Method 2

enhancing the detection of incoherent Rayleigh scattered light

Methodology Applied
Scientific EffectRayleigh scattering: Rayleigh Scattering

Implementation Method 3

a reflection-type confocal optical system with a CW laser source

Methodology Applied
Scientific EffectConfocal imaging: Focusing

Implementation Method 4

the sectioning capability capable of obtaining a cross-sectional image of any position in the Z-direction

Methodology Applied
Scientific EffectOptical sectioning: Depth of Field

Data Source

PatentEP3467480B1Observing device and observing method
Publication Date: 2023.08.23 NIKON CORP

AI summary

An observation apparatus in this embodiment includes a light source configured to irradiate an observation target with light, and a processing unit configured to generate an image based on light derived from χ(3) included in light obtained from the observation target.