Cryo-EM Sample Management Cassettes With Funnel-Guided Grid Transfer
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Solution Overview
Problem
Current cryo-electron microscopy (cryo-EM) sample preparation and handling procedures are complex, prone to damage, and require expensive robotics, making them difficult and costly.
Innovation Solution
The use of simplified structures and methods for automated cryo-EM sample storage and handling, including forceps, funnels, and pucks, that facilitate the transfer of cryo-cooled samples into grid boxes or clip rings using liquid nitrogen as a coolant, without compromising performance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Extent of automation
If complex robotics are used for automated sample handling, then automation extent is improved, but device complexity and cost increase
Solution Approach 1:
The system uses self-aligning funnels and gravity-assisted sample transfer mechanisms that automatically position samples without requiring complex robotic positioning systems. The funnels are designed to naturally guide samples into correct receptacles through their geometric configuration, eliminating the need for active control systems.
Solution Approach 2:
The invention employs simple, inexpensive components such as disposable funnels, basic forceps, and straightforward rack designs rather than expensive, complex robotic manipulators. These simple components perform the handling function adequately without requiring sophisticated engineering.
2Device complexity
If manual handling procedures are used, then device complexity is reduced, but reliability decreases due to sample damage
Solution Approach 1:
The system introduces intermediary components such as funnels and transfer racks that mediate between the sample and the final storage location. These intermediaries protect samples by providing guided transfer paths that prevent direct manual manipulation and reduce handling errors.
Solution Approach 2:
The funnels are pre-positioned and pre-aligned in their receptacles before sample transfer begins. This preliminary arrangement ensures that samples will be correctly positioned during transfer without requiring complex real-time adjustment mechanisms, thereby improving reliability while maintaining simplicity.
3Temperature
If ethane cooling systems are used, then cooling performance is improved, but device complexity and safety hazards increase
Solution Approach 1:
The invention extracts and eliminates the ethane cooling component from the system, using only liquid nitrogen for cooling. This removal simplifies the cooling system by eliminating the need for ethane storage, handling, and temperature control infrastructure, while maintaining adequate cooling performance for cryo-EM sample preparation.
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
These innovations provide a cost-effective and efficient method for cryo-EM sample storage and handling, compatible with existing cryocrystallography tools, reducing complexity and cost while maintaining high-quality imaging.
Implementation Method 1
The sample is transferred from ethane to liquid nitrogen (LN2), loaded into grid boxes, transferred to additional containers, and then into a storage Dewar.
Implementation Method 2
To vitrify the buffer for the best imaging, the sample-containing foil+grid is plunged, e.g., at about 1-2 meters per second (m/s) into liquid ethane at a temperature (T) of about 90 Kelvin (K)
Data Source
AI summary
Presented are systems, methods, and devices for provisioning controlled sample support, precision sample immersion, and/or post-cooling sample storage of cryo-electron microscopy (cryo-EM) samples and grids. A puck is presented for manual or automated storage of cryo-EM sample grids after the grids and samples have been cryocooled. The puck carries one or more cryo-EM sample grids and includes a puck top portion and a puck bottom portion, each formed with a cryogenic-temperature compatible material. The bottom portion includes multiple receptacles that each accepts and holds a sample grid. The top portion includes an array of funnels. The puck top and bottom portions are assembled together by inserting the top portion into the bottom portion. When the puck may be immersed in a liquid cryogen, each funnel guides a sample grid released into an upper portion of the funnel downward and into a grid receptacle within a bottom portion of the funnel.