Method of preparing a cryogenic sample with improved cooling characteristic

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Solution Overview

Problem

Existing methods for preparing cryogenic samples by vitrification often result in inconsistent sample quality, as they fail to evenly cool the sample carrier, leading to uneven vitrification and potential sample damage.

Innovation Solution

The method involves using a pair of conduits with mouthpieces that have at least two nozzle openings each, allowing for simultaneous flushing of cryogenic fluid from both sides of the sample carrier, ensuring even cooling and vitrification across the entire surface.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If a single conduit with one mouthpiece is used for cryogenic flushing, then the device complexity is reduced, but the cooling uniformity and sample quality consistency deteriorate

Engineering Contradiction:
Improveconduit configurationVSAvoidcooling uniformity
Core Design Contradiction:
Device complexityVSManufacturing precision

Solution Approach 1:

The single mouthpiece is segmented into multiple nozzle openings (at least two nozzles) arranged to face different regions of the sample carrier. This segmentation allows cryogenic fluid to be delivered to multiple locations simultaneously, achieving uniform cooling across the entire sample carrier surface while maintaining a relatively simple single-conduit structure.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The cooling approach transitions from a single-point delivery (one mouthpiece) to a multi-point distributed delivery system (multiple nozzles across the sample carrier surface). This dimensional expansion in the spatial distribution of cooling points enables comprehensive and uniform cooling coverage without proportionally increasing device complexity.

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

2Speed

If rapid cooling is applied to vitrify the sample, then the vitrification speed is improved, but the cooling uniformity deteriorates leading to uneven vitrification

Engineering Contradiction:
Improvevitrification speedVSAvoidvitrification uniformity
Core Design Contradiction:
SpeedVSManufacturing precision

Solution Approach 1:

The rapid cooling process is segmented into multiple simultaneous cooling zones through the use of multiple nozzles positioned across the sample carrier. Each nozzle delivers cryogenic fluid to a specific region, ensuring that all areas of the sample carrier undergo vitrification at comparable rates, thus achieving both speed and uniformity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different regions of the sample carrier receive tailored cooling through locally positioned nozzles. The nozzle arrangement ensures that central and peripheral regions are both adequately cooled, with each location receiving appropriate cryogenic fluid delivery to achieve uniform vitrification quality across the entire sample.

Inventive Principle:
Principle #3Local quality

3Device complexity

If conventional single-sided flushing is used, then the device structure is simplified, but the sample carrier cooling effectiveness deteriorates

Engineering Contradiction:
Improveflushing structureVSAvoidsample preparation reliability
Core Design Contradiction:
Device complexityVSReliability

Solution Approach 1:

The flushing system transitions from single-sided cooling to multi-directional cooling by positioning nozzles on opposite sides of the sample carrier. This dimensional approach allows cryogenic fluid to simultaneously cool both faces of the sample carrier, significantly improving cooling effectiveness and sample preparation reliability while maintaining structural simplicity.

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

Solution Approach 2:

The cooling function is merged into a single integrated flushing operation that simultaneously delivers cryogenic fluid to multiple sides and regions of the sample carrier through coordinated nozzle operation. This combined approach achieves comprehensive cooling in one action, improving reliability without requiring multiple separate flushing systems.

Inventive Principle:
Principle #5Merging (Combining)

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 approach achieves more consistent and improved sample quality by ensuring that both the central and peripheral parts of the sample carrier are vitrified simultaneously, reducing the risk of sample damage and enhancing the reliability of cryogenic sample preparation.

Implementation Method 1

pumping cryogenic fluid through said conduits so as to concurrently flush from said mouthpieces, thereby suddenly immersing the sample in cryogenic fluid from two opposite sides

Methodology Applied
Scientific EffectHeat conduction: Conduction (thermal)

Implementation Method 2

subjected to rapid cooling using a cryogen

Methodology Applied
Scientific EffectPhase change: Phase Change

Data Source

PatentUS12270602B2Method of preparing a cryogenic sample with improved cooling characteristic
Publication Date: 2025.04.08 FEI CO
  • US12270602B2 patent drawing
  • US12270602B2 patent drawing
  • US12270602B2 patent drawing

AI summary

The invention relates to a method and an apparatus for preparing a cryogenic sample, whereby the sample is subjected to rapid cooling using a cryogen. A pair of conduits for transporting cryogenic fluid are provided, each of which conduits opens out into a mouthpiece, which mouthpieces are arranged to face each other across an intervening gap, wherein in the gap a sample that is provided on a substantially planar sample carrier can be received. Cryogenic fluid can be pumped through the conduits so as to concurrently flush from the mouthpieces and suddenly immerse the sample in cryogenic fluid from two opposite sides. As defined herein, at least one of the mouthpieces comprises at least two nozzle openings for evenly cooling the substantially planar sample carrier during the flushing.