STEM Detector Integrated into Light Microscopy Lens

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Solution Overview

Problem

Current microscopy techniques face challenges in achieving high temporal correlation and resolution for observing biological samples in liquid environments, particularly with the combination of light microscopy and scanning transmission electron microscopy (STEM), as they often require different equipment setups and suffer from radiation damage and limited sample space.

Innovation Solution

Integration of a STEM detector into a light-optical lens, allowing for simultaneous high-resolution detection of high atomic number materials and time-correlated light microscopy, with a sample holder designed as a thin electron-permeable membrane and a conical electron drift space to maintain a vacuum and enable efficient electron beam penetration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If light microscopy is used to observe biological samples, then temporal correlation and overview information are improved, but resolution is limited to approximately 200 nm

Engineering Contradiction:
ImproveresolutionVSAvoidtemporal correlation
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent merges light microscopy and electron microscopy into a single correlative microscopy system, allowing simultaneous observation at different resolutions. The light-optical lens is integrated with a STEM detector, enabling both light microscopy (for temporal correlation and overview) and electron microscopy (for high resolution) to be performed on the same sample at the same time, eliminating the loss of temporal correlation that occurs when using separate instruments.

Inventive Principle:
Principle #5Merging (Combining)

2Measurement precision

If electron microscopy is used to achieve nanometer-scale resolution, then measurement precision is improved, but the electron beam damages biological material

Engineering Contradiction:
ImproveresolutionVSAvoidradiation damage
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The system uses periodic alternation between light microscopy and electron microscopy observation modes. Light microscopy is used for initial observation and localization without damage, and electron microscopy is applied periodically only to specific regions of interest at high resolution, minimizing cumulative radiation damage while still achieving the desired measurement precision.

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The light-optical lens acts as an intermediary that guides the electron beam to specific regions of interest identified by light microscopy. This intermediary function allows the system to use the gentle light microscopy for initial observation and only apply the damaging electron beam where absolutely necessary, reducing overall radiation exposure to the biological sample.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If separate instruments are used for light microscopy and electron microscopy, then each method can be optimized, but temporal correlation is lost and localization errors occur

Engineering Contradiction:
Improvelocalization accuracyVSAvoidsystem integration
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent combines light microscopy and electron microscopy into a single integrated instrument with a unified coordinate system. The light-optical lens and STEM detector share the same optical path and sample stage, ensuring that both methods observe the exact same location without localization errors. This merging eliminates the need for complex registration and coordinate transformation between separate instruments.

Inventive Principle:
Principle #5Merging (Combining)

4Productivity

If a STEM detector is integrated into a light-optical lens, then simultaneous detection of high atomic number materials and light microscopy is achieved, but the device complexity increases

Engineering Contradiction:
Improvedetection efficiencyVSAvoidlens integration
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The integrated lens system serves multiple functions simultaneously: it acts as both a light-optical lens for light microscopy and a mounting structure for the STEM detector. This multi-functional design allows the same physical component to enable both light microscopy and electron microscopy detection, improving productivity by allowing simultaneous observation while the modular integration keeps the added complexity manageable.

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

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 efficient detection of high atomic number materials with high resolution and full time-correlation of light microscopy, allowing for precise observation of cellular processes and structures without radiation damage, and supports applications in biomedical research, materials science, and diagnostics.

Implementation Method 1

a thin membrane (2), connected to a sample holder, is provided in the electron microscope. The membrane (2) is made of a material which is permeable to electrons

Methodology Applied
Scientific EffectElectron beam transmission: Electron Beam

Implementation Method 2

Scanning transmission electron microscopy (STEM) is particularly advantageous for achieving nanometer-scale resolution of high-atomic-number nanoparticles

Methodology Applied
Scientific EffectElectron scattering: Scattering

Implementation Method 3

light microscopy, for example via fluorescence contrast on fluorescent protein markers in cells

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP3117448B1Device for correlative scanning transmission electron microscopy (STEM) and light microscopy
Publication Date: 2020.12.02 LEIBNIZ INSTITUT FUR NEUE MATERIALIEN GMBH
  • EP3117448B1 patent drawingFigure 1
  • EP3117448B1 patent drawingFigure 2
  • EP3117448B1 patent drawingFigure 3

AI summary

The invention relates to a device for correlative scanning transmission electron microscopy (STEM) and light microscopy. In order to create a device for correlative microscopy which enables an improved combination of light microscopy and STEM methods, a STEM detector (7) according to the invention is combined with a photo-optical lens (8). This detection device combines the efficient detection by means of STEM microscopy of materials having a high atomic number, for example specific nanoparticle markers in a specimen in a liquid, such as a cell, with simultaneous light microscopy.