Microscopy Image Overlay Using Surface Replicas to Protect Specimens

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current microscopy methods, such as CLEM, face limitations in flexibility and specimen compatibility due to the need for sequential imaging and costly, risky specimen transfer between microscopes, and integrated systems compromise on performance.

Innovation Solution

A method and system that image a specimen's surface using one microscopy method and a replica of the surface using another, allowing simultaneous or subsequent examination with different microscopy methods, enabling flexible imaging without the need for a shared specimen chamber.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If sequential imaging with specimen transfer between microscopes is used, then high-resolution imaging is achieved, but specimen damage risk and time consumption increase

Engineering Contradiction:
Improveimaging resolutionVSAvoidspecimen integrity
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The invention creates a physical replica of the specimen surface through replica preparation techniques (such as shadow casting or lift-out methods). This replica can be imaged by electron microscopy while the original specimen remains intact for subsequent imaging by other microscopy methods, eliminating the need to transfer the actual specimen between microscopes and thus preventing specimen damage while maintaining high-resolution imaging capability

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The imaging process is segmented into two independent parts: imaging the original specimen and imaging its replica. This segmentation allows simultaneous or separate examination of both the original and replica using different microscopy methods without requiring specimen transfer, thereby maintaining specimen integrity while achieving high-resolution imaging

Inventive Principle:
Principle #1Segmentation

2Reliability

If integrated CLEM systems with shared specimen chamber are used, then specimen transfer is eliminated, but imaging performance is compromised

Engineering Contradiction:
Improvespecimen stabilityVSAvoidimaging performance
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

Instead of forcing both microscopy methods to share a common specimen chamber with compromised performance, the invention uses a replica that can be imaged by electron microscopy. The replica preparation process creates a structure suitable for electron microscopy imaging, allowing each microscope to operate at its optimal performance level independently

Inventive Principle:
Principle #26Copying

3Loss of information

If sequential imaging of the same specimen is used, then comprehensive analysis is achieved, but time consumption increases

Engineering Contradiction:
Improveinformation completenessVSAvoidimaging time
Core Design Contradiction:
Loss of informationVSLoss of time

Solution Approach 1:

The imaging task is segmented between the original specimen and its replica. The replica is prepared from the same specimen surface, allowing simultaneous or parallel imaging of both the original and replica by different microscopy methods. This parallel processing eliminates the sequential time consumption while maintaining complete information acquisition

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

By creating a replica that captures the same structural information as the original specimen surface, the system enables simultaneous imaging of both the original and replica. This copying approach allows comprehensive information analysis to occur in parallel rather than sequentially, significantly reducing total imaging time

Inventive Principle:
Principle #26Copying

Data Source

PatentUS11764031B2Method for microscopic image generation and system for same
Publication Date: 2023.09.19 LEICA MIKROSYSTEME GMBH
  • US11764031B2 patent drawing

AI summary

The present invention concerns a method and a system for imaging at least a part of a specimen by means of two microscopy imaging methods, where a surface (11) of the specimen (10) is imaged by means of a first microscopy imaging method, where a replica (25) of the surface (11) to be imaged by means of the first microscopy imaging method is produced and this replica (25) is simultaneously imaged by means of a second microscopy imaging method, where the images produced by means of the first and the second microscopy imaging methods are overlaid at the correct scale.