Biological Sample Imaging Through X-Ray and Light Microscope Matching

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Solution Overview

Problem

Current methods lack a practical way to observe pathological changes in biological samples in three dimensions at cellular-level spatial resolution, as light microscopes face sample deformation and insufficient depth resolution, while X-ray microscopes provide low-contrast images due to electron density-based shading, making tissue identification difficult.

Innovation Solution

A method is developed to collate and precisely match images from X-ray and light microscopes by using cell nuclei as location markers, adjusting the orientation of X-ray microscope images through rotation operations, and selecting observation target regions in both images to align them accurately.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a light microscope is used to observe biological samples, then two-dimensional resolution of about 0.2 μm and accurate tissue identification capability are achieved, but sample deformation occurs and depth resolution is insufficient

Engineering Contradiction:
Improvetwo-dimensional resolutionVSAvoidsample deformation
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent combines X-ray microscope observation (which provides three-dimensional imaging without sample deformation) and light microscope observation (which provides high two-dimensional resolution and tissue identification) into a single integrated system. The image collation unit merges images from both microscopes, allowing the benefits of both techniques to be utilized simultaneously - achieving high-resolution three-dimensional observation without the drawbacks of either method alone.

Inventive Principle:
Principle #5Merging (Combining)

2Reliability

If an X-ray microscope is used to observe biological samples, then isotropic submicron three-dimensional resolution and non-destructiveness are achieved, but low-contrast gray-scale images are produced making tissue identification difficult

Engineering Contradiction:
Improvenon-destructivenessVSAvoidtissue identification capability
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent combines X-ray microscope observation (which provides three-dimensional imaging without sample deformation) and light microscope observation (which provides high two-dimensional resolution and tissue identification) into a single integrated system. The image collation unit merges images from both microscopes, allowing the benefits of both techniques to be utilized simultaneously - achieving high-resolution three-dimensional observation without the drawbacks of either method alone.

Inventive Principle:
Principle #5Merging (Combining)

3Measurement precision

If images from X-ray and light microscopes are to be matched, then precise orientation alignment is required, but orientation errors of 100 or more occur between the two image types

Engineering Contradiction:
Improveimage matching precisionVSAvoidimage collation complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces a fiducial marker as an intermediary reference object that is visible in both X-ray and light microscope images. These markers serve as common reference points that facilitate the collation process by providing identifiable landmarks for orientation alignment, thereby reducing the complexity of matching images from the two different microscopy systems.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces manual image alignment methods with automated image collation using fiducial markers. The system automatically calculates orientation corrections based on marker positions in both image types, substituting complex manual mechanical adjustment with computational image processing and registration algorithms.

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

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 precise matching of images from both microscopes, allowing for three-dimensional observation of biological samples at cellular-level spatial resolution, overcoming the limitations of each individual microscope type.

Implementation Method 1

acquiring an image of the biological sample embedded in a wax block captured by the X-ray microscope using X-rays having an energy of 4-12 keV

Methodology Applied
Scientific EffectX-ray absorption: Absorption (EM radiation)

Implementation Method 2

acquiring an image, captured by the light microscope, of a part of the biological sample included in the image captured by the X-ray microscope

Methodology Applied
Scientific EffectLight refraction: Refraction

Data Source

PatentUS20250218203A1Method for observing biological sample
Publication Date: 2025.07.03 RIGAKU CORP
  • US20250218203A1 patent drawing
  • US20250218203A1 patent drawing
  • US20250218203A1 patent drawing

AI summary

A method for collating and matching images of a same measurement point of a same biological sample captured by an X-ray microscope and a light microscope, the method comprising the steps of: acquiring an image of the biological sample embedded in a wax block captured by the X-ray microscope using X-rays having an energy of 4-12 keV; acquiring an image, captured by the light microscope, of a part of the biological sample included in the image captured by the X-ray microscope; and selecting, from the acquired X-ray and light microscope images, arbitrary observation target regions of the biological sample in the images as location markers to collate and match the X-ray microscope image with the light microscope image using the location markers.