Molecular Structure Determination via Diffraction and Electron Microscopy
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Solution Overview
Problem
The determination of molecular structure from diffraction patterns is hindered by the loss of phase information, which is crucial for resolving the 3D structure of molecules, as existing methods only capture amplitudes and not phases of structure factors.
Innovation Solution
A method and system that combine diffraction patterns and electron microscopy images to extract phase information, utilizing a diffraction tilt series and electron microscopy tilt series to determine the amplitudes and phases of structure factors, respectively, and integrate these to reconstruct the molecular structure.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If diffraction patterns are used to determine molecular structure, then amplitudes of structure factors can be obtained, but phase information is lost
Solution Approach 1:
The patent combines diffraction patterns and electron microscopy images into a unified analysis framework. By merging the amplitude information from diffraction patterns with the phase information from electron microscopy images, the method recovers complete structure factor information (both amplitude and phase) necessary for molecular structure determination.
Solution Approach 2:
The patent introduces an intermediary computational framework that processes both diffraction patterns and electron microscopy images. This intermediary system performs joint optimization to extract both amplitude and phase information, acting as a mediator that transforms two separate data sources into complete structural information.
2Device complexity
If existing methods only capture amplitudes from diffraction patterns, then the process is simple, but molecular structure cannot be resolved due to missing phase information
Solution Approach 1:
The patent creates a multi-functional method that simultaneously extracts both amplitude and phase information from combined diffraction and electron microscopy data. This universal approach replaces the limited single-function methods that only captured amplitudes, enabling complete molecular structure determination while maintaining practical feasibility.
3Reliability
If Friedel pairs have unequal intensities due to dynamical scattering, then traditional phase extraction methods fail, but the patent accounts for this by integrating diffraction tilt series and electron microscopy tilt series
Solution Approach 1:
The patent transitions from analyzing single diffraction patterns to analyzing diffraction tilt series (adding the tilt angle dimension). This dimensional expansion allows the method to capture dynamical scattering effects and recover accurate phases by examining how intensities vary with tilt angle, thereby resolving the Friedel pair intensity inequality problem.
Solution Approach 2:
The patent implements a feedback mechanism where the diffraction tilt series and electron microscopy tilt series are iteratively processed together. The method uses feedback from the joint optimization process to refine both amplitude and phase estimates, accounting for dynamical scattering effects and improving phase extraction accuracy through repeated refinement.
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 allows for the accurate determination of molecular structure by capturing the amplitudes from diffraction patterns and phases from electron microscopy images, effectively addressing the limitations of previous methods by accounting for unequal intensities of Friedel pairs and dynamical scattering.
Implementation Method 1
The scattered waves from the crystal interfere with each other and may form a two-dimension diffraction pattern. High intensities in the diffraction pattern are constructively formed when the scattering angles satisfy the Bragg condition.
Implementation Method 2
In particular, the phase information may be read out from Fourier transform of the electron microscopy image.
Data Source
Figure 1
Figure 2A~2B
Figure 3
AI summary
Molecular structure may be determined based on structure factors solved from the diffraction pattern and the electron microscopy image of a sample, such as 3D protein crystals. In particular, the amplitudes of the structure factors may be determined based on intensities of diffraction peaks in the multiple diffraction patterns. The phases of the structure factors may be determined based on electron microscopy images and the intensities of the diffraction peaks. The sample is tilted in order to obtain 3D structure data.