Cryo-EM Sample Preparation Device with Dual Jetting and Plunging Modes

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Solution Overview

Problem

Existing cryo-electron microscope sample preparation devices are limited in their ability to handle a wide range of samples effectively, particularly in achieving consistent vitrification without damage.

Innovation Solution

A device with a holder for sample carriers, incorporating a jetting and plunging mechanism, allows for both jetting and plunging modes of cryogenic fluid application, enabling flexible sample preparation through a single transfer mechanism, including a control unit for operation control and user input for mode selection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If a single device structure is used for sample preparation, then device complexity is reduced, but adaptability to different sample types deteriorates

Engineering Contradiction:
Improvedevice structureVSAvoidsample preparation flexibility
Core Design Contradiction:
Device complexityVSAdaptability or versatility

Solution Approach 1:

The device integrates both jetting and plunging functions into a single holder assembly. The holder can selectively position the sample carrier to receive either a jet of cryogenic fluid from a nozzle or be plunged into a reservoir of cryogenic fluid, enabling one device to perform multiple sample preparation modes for different sample types and requirements

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

2Adaptability or versatility

If multiple separate devices are used for jetting and plunging, then adaptability improves, but device complexity increases

Engineering Contradiction:
Improvesample preparation flexibilityVSAvoiddevice structure
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The jetting nozzle and plunging reservoir are integrated into a single holder assembly. The holder simultaneously accommodates both the nozzle for jetting mode and the reservoir for plunging mode, allowing the device to provide both sample preparation methods through one unified structure rather than requiring separate devices

Inventive Principle:
Principle #5Merging (Combining)

3Object-affected harmful factors

If the holder is positioned far from the cryogenic fluid source, then sample damage from premature cooling is reduced, but vitrification efficiency deteriorates

Engineering Contradiction:
Improvesample damageVSAvoidvitrification efficiency
Core Design Contradiction:
Object-affected harmful factorsVSProductivity

Solution Approach 1:

The holder is designed to be movable, allowing dynamic positioning of the sample carrier. The holder can be positioned at a distance from the cryogenic fluid source during transport to prevent premature cooling, then rapidly moved close to the source during the jetting or plunging operation to achieve efficient vitrification, thus adapting the position according to the operational phase

Inventive Principle:
Principle #15Dynamics

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

The device provides enhanced flexibility and reliability in preparing samples by allowing both jetting and plunging modes, improving vitrification success rates and reducing sample damage.

Implementation Method 1

at least one jetting device (J) that is arranged for providing a jet of cryogenic fluid to said sample carrier (S)... The jetting device allows a jet or stream of cryogenic fluid to be brought into contact with the specimen provided onto the sample carrier so that the specimen may be vitrified

Methodology Applied
Scientific EffectCryogenic cooling: Cooling

Implementation Method 2

the transfer mechanism may be arranged to function as the plunging device, by moving the sample carrier to the plunging position at an appropriate speed so that plunge freezing of the sample occurs

Methodology Applied
Scientific EffectPlunge freezing: Freezing

Implementation Method 3

a transfer mechanism that is operably coupled to the holder. The transfer mechanism is arranged for bringing the holder to a jetting position... The transfer mechanism is arranged for bringing the holder to a plunging position

Methodology Applied
Scientific EffectMechanical translation:

Data Source

PatentUS20250385071A1Device for preparing samples for use in a cryo-electron microscope
Publication Date: 2025.12.18 FEI CO
  • US20250385071A1 patent drawing
  • US20250385071A1 patent drawing
  • US20250385071A1 patent drawing

AI summary

A device for preparing samples for use in a cryo-electron microscope. The device comprises a holder for holding a sample carrier, at least one jetting device that is arranged for providing a jet of cryogenic fluid to said sample carrier, and a transfer mechanism that is operably coupled to the holder for bringing the holder to a jetting position. In the jetting position the holder is located near the at least one jetting device for receiving said jet of cryogenic fluid. The device further comprises a plunging reservoir for receiving a volume of cryogenic fluid, wherein the transfer mechanism is additionally arranged for bringing the holder to a plunging position. In the plunging position the holder is positioned at least partly inside an internal volume of said plunging reservoir for bringing the sample carrier in contact with cryogenic fluid.