Liquid Cell Rotation for High-Angle Electron Tomography

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Solution Overview

Problem

Current transmission electron beam tomography methods struggle to acquire reliable high-angle tilting tomographic data from samples in liquid media due to limited sample tilt ranges, which restricts the resolution and accuracy of three-dimensional reconstructions, especially for biological samples that require complex and time-consuming preparation processes.

Innovation Solution

A liquid cell device with electron-transparent membranes that allows for rotation over an angular range of at least 120 degrees, maintaining a projected viewable area of at least 10 square micrometers, enabling high angular range tomographic data acquisition by preventing liquid medium movement and ensuring sample immobility during data collection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If conventional transmission electron beam tomography is used with liquid cell devices, then samples in liquid medium can be investigated, but the total sample tilt range is limited to less than 120 degrees, reducing tomographic reconstruction reliability

Engineering Contradiction:
Improveability to investigate samples in liquid mediumVSAvoidtomographic reconstruction reliability
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The liquid cell device is designed with a rotational stage that enables dynamic tilting over a total angular range of at least 120 degrees. The device includes a main body with an aperture allowing the electron beam to pass through while the entire assembly can be rotated dynamically during data acquisition to achieve the required tilt range for reliable tomography

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The liquid cell device is segmented into distinct functional components: a main body containing the liquid sample, electron-transparent membranes for beam transmission, and a rotational mounting interface. This segmentation allows independent optimization of each component, enabling the device to maintain liquid containment while achieving high-angle tilting capability

Inventive Principle:
Principle #1Segmentation

2Measurement precision

If the sample tilt interval is increased to improve resolution perpendicular to the tilt axis, then the total sample tilt range must be increased, but conventional liquid cell devices cannot accommodate tilt ranges of at least 120 degrees

Engineering Contradiction:
Improveresolution perpendicular to tilt axisVSAvoidsample tilt range capability
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The device incorporates a rotational stage that enables dynamic tilting over a total angular range of at least 120 degrees. The main body with aperture and electron-transparent membranes is designed to rotate dynamically during data acquisition, allowing the sample to be positioned at various tilt angles while maintaining liquid containment and beam transmission

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The invention adds a rotational dimension to the conventional liquid cell device. By mounting the device on a rotational stage and enabling tilting in addition to the standard x-y-z positioning, the system transforms from a three-degree-of-freedom stage to a four-degree-of-freedom system, achieving the required tilt range for high-resolution tomography

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Ease of manufacture

If complex sample preparation processes such as dehydration, fixing and staining are used, then samples can be investigated in conventional instruments, but sample preparation artefacts are introduced and the process is time-consuming

Engineering Contradiction:
Improvesample preparation simplicityVSAvoidsample integrity
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The liquid cell device creates an inert liquid environment that protects the sample from vacuum damage. By sealing the sample in liquid between electron-transparent membranes, the device maintains a physiologically relevant environment during imaging, eliminating the need for dehydration, fixing, and staining processes that would otherwise be required for vacuum-compatible preparation

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

Solution Approach 2:

The liquid medium acts as an intermediary between the sample and the vacuum environment of the electron microscope. The electron-transparent membranes serve as intermediaries that allow electron beam transmission while maintaining the liquid seal, enabling direct imaging of hydrated samples without complex preparation

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

This solution enhances the reliability and accuracy of three-dimensional structural determination by overcoming projection artifacts and improving the resolution of internal sample structures, particularly for low-symmetry crystalline phases, and allows for more comprehensive sampling of reciprocal space.

Implementation Method 1

a liquid cell device for acquiring high angular range tomographic data from a sample in a liquid medium in a transmission electron beam instrument

Methodology Applied
Scientific EffectElectron beam transmission: Electron Beam

Implementation Method 2

during rotation of the liquid cell device around the rotational axis through an angular range of at least 120 degrees

Methodology Applied
Scientific EffectRotational motion:

Data Source

PatentUS12099022B2Devices and methods for high angle liquid electron tomography
Publication Date: 2024.09.24 NANOMEGAS SPRL
  • US12099022B2 patent drawing
  • US12099022B2 patent drawing
  • US12099022B2 patent drawing

AI summary

Devices and methods are described for performing high angle tilting tomography on samples in a liquid medium using transmission electron beam instruments.