Integrated MicroED Pre-Screening for Simpler Diffraction Imaging

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Solution Overview

Problem

Standard transmission electron microscopy (TEM) systems used for microcrystal electron diffraction (MicroED) are large, expensive, and complex, requiring significant operator time and expertise to configure and operate effectively.

Innovation Solution

A custom, automated MicroED system with reduced size and cost, featuring a pre-screening technique and preset magnification configurations, which includes an electron source, sample assembly, camera assembly, and control system to generate and output microcrystal electron diffraction data, including atomic structure, specimen identity, contamination information, and three-dimensional diffraction data.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a standard transmission electron microscopy (TEM) system is used for MicroED, then high-resolution electron diffraction data can be collected, but the system becomes large, expensive, and complicated to configure and operate

Engineering Contradiction:
Improvediffraction data resolutionVSAvoidsystem configuration complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts and integrates only the essential components needed for MicroED into a dedicated system, removing unnecessary features of general-purpose TEM systems. This includes integrating the electron source, sample assembly, camera assembly, and control system into a compact configuration that performs specifically for microcrystal electron diffraction, thereby reducing overall system complexity while maintaining measurement precision

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The control system is designed to perform multiple functions automatically: pre-screening samples, determining optimal imaging positions, controlling sample assembly positioning, generating electron beams, rotating samples, capturing diffraction images, and processing data. This multi-functionality consolidates what would otherwise require separate specialized equipment and manual operations into a single integrated system

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

2Measurement precision

If a standard transmission electron microscopy (TEM) system is used for MicroED, then diffraction data can be collected, but significant operator time and expertise are required to configure and operate

Engineering Contradiction:
Improvediffraction data qualityVSAvoidoperator expertise required
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The system performs pre-screening of samples before actual MicroED data collection. The control system automatically captures pre-screen diffraction images, evaluates sample quality and orientation, and determines optimal imaging positions in advance. This preliminary action ensures that when full data collection begins, the system is already optimized, reducing the need for operator intervention and expertise during the main experiment

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The control system automatically performs multiple tasks that would otherwise require operator intervention: pre-screening samples, determining imaging positions, positioning the sample assembly, controlling rotation during data collection, and processing diffraction data. The system serves itself by making autonomous decisions throughout the MicroED process, significantly reducing the operator expertise and time required

Inventive Principle:
Principle #25Self-service

3Device complexity

If a custom automated MicroED system is designed, then system size and cost are reduced, but the system must integrate multiple functions into a compact configuration

Engineering Contradiction:
Improvesystem sizeVSAvoidintegrated functionality
Core Design Contradiction:
Device complexityVSAdaptability or versatility

Solution Approach 1:

The patent merges the electron source, sample assembly, camera assembly, and control system into a single integrated MicroED system. These components are physically and functionally combined in a compact configuration where the electron source generates beams that pass through the sample assembly to the camera assembly, all coordinated by the control system. This merging reduces system size and cost while maintaining the versatility needed for complete MicroED operations through automated multi-functionality

Inventive Principle:
Principle #5Merging (Combining)

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 system enables efficient and accurate MicroED operations with reduced operator expertise, accelerating drug discovery and providing rapid generation of structural data for artificial intelligence and machine learning systems, using minimal sample materials.

Implementation Method 1

generating, by the electron source, an electron beam towards the sample at the position

Methodology Applied
Scientific EffectElectron beam generation: Electron Beam

Implementation Method 2

capturing, by the camera assembly, scatterings of the electron beam by the sample as diffraction images

Methodology Applied
Scientific EffectElectron diffraction: Diffraction

Data Source

PatentUS20240387141A1System and Method for Fully Integrated Microcrystal Electron Diffraction (MICROED)
Publication Date: 2024.11.21 RGT UNIV OF CALIFORNIA
  • US20240387141A1 patent drawing
  • US20240387141A1 patent drawing
  • US20240387141A1 patent drawing

AI summary

An integrated microcrystal electron diffraction system and method are provided that include an electron source, a sample assembly configured to retain a sample, a camera assembly, and a control system. The control system pre-screens the sample on the sample assembly, collects image data of the sample via the camera assembly, and outputs microcrystal electron diffraction data based on the image data. Pre-screening includes capturing at least one pre-screen diffraction image of the sample; determining a position for the sample for imaging based on the at least one pre-screen diffraction image; and controlling the sample assembly to position the sample at the position. Collecting the image data includes generating an electron beam towards the sample at the position; rotating the sample assembly; and capturing, by the camera assembly, scatterings of the electron beam by the sample as diffraction images while the sample assembly is rotated.