Vitrified Sample Optical Screening for Cryo-EM Quality Assessment
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Solution Overview
Problem
The preparation process of vitrified samples for charged particle microscopy is trial-and-error, with quality assessment of the sample holder, ice thickness, and particle distribution being difficult and not easily accessible.
Innovation Solution
A method involving submersion of a sample embedded in a matrix into a coolant for vitrification, followed by directing a beam of light towards the sample to detect reflected, transmitted, and emitted light, and using a controller to determine properties such as matrix thickness and contamination.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If trial-and-error preparation process is used for vitrified samples, then sample quality may be achieved, but time consumption and difficulty of quality assessment increase
Solution Approach 1:
The patent applies preliminary action by performing light-based quality assessment of the sample holder, ice layer, and particle distribution immediately after sample preparation but before electron microscopy imaging. This preliminary optical screening allows researchers to identify suitable areas for further investigation without time-consuming electron microscopy screening, thus resolving the contradiction between achieving quality assessment and reducing preparation time.
2Measurement precision
If electron microscopy screening is used to assess sample quality, then accurate quality determination is achieved, but accessibility and ease of operation decrease
Solution Approach 1:
The patent introduces an intermediary optical assessment method that uses light transmission, reflection, or emission properties to evaluate sample quality. This intermediary method bridges the gap between simple visual inspection and complex electron microscopy screening, providing accessible quality assessment that can be performed with常规 optical equipment rather than requiring specialized electron microscopy facilities, thus improving ease of operation while maintaining reasonable measurement precision.
3Loss of information
If detailed electron microscopy screening is performed, then comprehensive quality information is obtained, but time and resource consumption increase
Solution Approach 1:
The patent applies partial action by using optical methods to screen and identify regions of interest that meet basic quality criteria, rather than performing detailed electron microscopy screening on the entire sample holder. This partial screening approach efficiently identifies suitable areas for further investigation, reducing time and resource consumption while retaining sufficient quality information to guide subsequent focused analysis.
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
Enables rapid and efficient assessment of sample quality, allowing identification of suitable areas for further investigation and reducing the need for time-consuming electron microscopy screening.
Implementation Method 1
freezing this layer fast enough to prevent the aqueous liquid from crystallising
Implementation Method 2
submerging the sample into a coolant to provide a vitrified sample
Implementation Method 3
the light reflected, transmitted and/or emitted from the sample is detected
Implementation Method 4
the light reflected, transmitted and/or emitted from the sample is detected
Data Source
AI summary
The invention relates to methods for determining a property of a sample before imaging in a charged particle microscope and samples prepared by such methods.