Biological Sample Screening for Cryo-EM Resource Optimization

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Solution Overview

Problem

Preparing biological samples for charged particle devices, such as electron microscopes, is time-consuming and labor-intensive, with uncertainties in sample preparation leading to resource wastage, as the success of sample preparation is only confirmed after the process is completed, and many steps are challenging and unpredictable.

Innovation Solution

A method involving the use of a sample holder configured for charged particle devices, where a biological material is transferred onto the holder, and a specimen is screened using ambient ionization mass spectrometry to evaluate the sample's quality before analysis, allowing for conditional analysis and optimizing resource use.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional sample preparation methods are used for charged particle microscopy, then sample preparation can be completed, but the process is time-consuming and labor-intensive with unpredictable results

Engineering Contradiction:
Improvepredictability of sample preparation successVSAvoidsample preparation time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent applies preliminary action by performing sample screening and quality assessment before the main charged particle microscopy analysis. The method prepares samples using a simplified protocol and screens them using accessible imaging techniques to evaluate quality metrics (integrity, homogeneity, concentration) before committing resources to time-consuming microscopy preparation and analysis. This advance evaluation prevents wasting time on samples that will fail during or after expensive microscopy sessions.

Inventive Principle:
Principle #10Preliminary action

2Loss of energy

If traditional sample preparation methods are used, then samples can be prepared, but resources are wasted because success is only confirmed after preparation is complete

Engineering Contradiction:
Improvewaste of expensive microscopy resourcesVSAvoidlack of pre-analysis quality information
Core Design Contradiction:
Loss of energyVSLoss of information

Solution Approach 1:

The patent implements feedback by creating a closed-loop sample selection process. Samples are prepared, screened using accessible imaging, evaluated against quality criteria, and only those meeting thresholds are selected for charged particle microscopy. The screening results provide feedback that guides sample selection decisions, enabling researchers to identify and discard unsuitable samples before expensive microscopy analysis, thereby reducing resource waste while providing quality information in advance.

Inventive Principle:
Principle #23Feedback

3Productivity

If simplified sample preparation is used, then preparation time is reduced, but sample quality and integrity may be compromised

Engineering Contradiction:
Improvesample preparation throughputVSAvoidsample layer thickness uniformity
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent applies parameter changes by establishing specific quality thresholds and criteria for sample selection based on screening results. Instead of requiring perfect sample preparation, the method adjusts acceptance parameters to identify samples that meet minimum quality standards (integrity, homogeneity, concentration thresholds) suitable for charged particle microscopy. This allows simplified preparation protocols to produce acceptable samples by selecting from a pool that meets defined parameter criteria rather than requiring all samples to achieve ideal preparation.

Inventive Principle:
Principle #35Parameter changes

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 ensures that resources are used effectively by evaluating sample quality before analysis, reducing waste and improving the reliability of sample preparation, particularly for costly and time-consuming charged particle microscopy.

Implementation Method 1

performing ambient ionization mass spectrometry on the specimen

Methodology Applied
Scientific EffectAmbient ionization: Ionisation

Data Source

PatentUS11668720B2Method of preparing a biological sample for study in a charged particle device
Publication Date: 2023.06.06 FEI CO
  • US11668720B2 patent drawing
  • US11668720B2 patent drawing
  • US11668720B2 patent drawing

AI summary

The invention relates to a method of preparing a biological sample for study in an analysis device, said method comprising the steps of: providing a biological material to be studied; providing a sample holder that is configured to be placed in said analysis device; and transferring said biological material onto said sample holder for preparing said biological sample. According to the invention, the method comprises the steps of: acquiring a specimen of said biological material provided on said sample holder; transferring said specimen to a screening device for screening said specimen; and evaluating said biological sample based on results obtained by said screening device. With the method, time and resources may be more effectively used in studying biological samples, for example using charged particle microscopy in the form of cryo-EM.