Cryo-EM Sample Fixing Apparatus with Graphene Window Layer
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Solution Overview
Problem
Cryogenic-electron microscopy sample preparation procedures lack precise control over ice thickness, leading to inefficiencies in achieving high-quality image and structural resolution.
Innovation Solution
An apparatus comprising a substrate with a window hole, a first pattern with sample fixing holes, and a window layer, where the depth of the sample fixing holes is controlled by the thickness of the first pattern, and the window layer can be made of graphene oxide, graphene, or molybdenum disulfide.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional sample preparation procedures are used, then sample screening can be performed, but precise control over ice thickness cannot be achieved
Solution Approach 1:
The sample preparation system is segmented into distinct functional layers: a support film layer, a spacer layer with controlled thickness, and a cover film layer. The spacer layer is divided into multiple spacers that define the ice thickness, allowing precise control over the ice layer thickness while maintaining high-throughput sample preparation.
Solution Approach 2:
The spacer layer with predetermined thickness is prepared in advance before sample application. This preliminary structuring of the support film with built-in thickness control eliminates the need for extensive post-sample ice thickness adjustment and screening, enabling both precise control and high productivity.
2Reliability
If extensive sample screening is performed to identify good sample grids, then image quality can be improved, but the efficiency of high-throughput 3D structural analysis is hindered
Solution Approach 1:
The invention changes the critical parameter of ice thickness from an uncontrolled variable to a precisely controlled dimension through the spacer layer structure. By controlling the spacer thickness parameter, the system ensures that all samples prepared on the film have consistent, optimal ice thickness, eliminating the need for screening and enabling high-throughput analysis with reliable image quality.
3Manufacturing precision
If the depth of sample fixing holes is not controlled, then manufacturing is simpler, but uniform formation of vitreous ice cannot be achieved
Solution Approach 1:
The spacer layer acts as an intermediary element between the support film and the cover film, mediating the ice thickness control. The spacers within the spacer layer provide a physical template that ensures uniform vitreous ice formation without requiring complex control mechanisms, balancing manufacturing precision with apparatus simplicity.
Data Source
AI summary
An apparatus for fixing sample and a manufacturing method therefor are provided. The apparatus for fixing sample according to the embodiments of the present invention comprises a substrate having a window hole, a first pattern disposed on the substrate and having a sample fixing hole, and a window layer disposed below the first pattern in the window hole. The sample fixing hole is disposed on the window layer. The method for manufacturing an apparatus for fixing sample comprises preparing a substrate having a first surface and a second surface, forming a first layer on the first surface and a second layer on the second surface, patterning the second layer to form a second pattern, etching the substrate using the second pattern as an etching mask to form a window hole exposing the first layer, patterning the first layer to form a first pattern having a sample fixing hole, and forming a window layer contacting the first pattern in the window hole. The sample fixing hole is formed at a position corresponding to the window hole.