Fiducial Marker Alignment in Electron Tomography

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Solution Overview

Problem

Current fiducial marker-based alignment methods in electron tomography face challenges such as mechanical instability, specimen transformation, and high computational costs, particularly in large-field datasets with lens distortions, leading to inaccuracies and inefficiencies in fiducial marker tracking.

Innovation Solution

The development of a system that aligns fiducial markers using a processor and memory to apply affine transformations constrained by an upper bound of transformation deviation, combined with a Gaussian mixture model and a divide-and-conquer strategy to improve fiducial marker tracking, ensuring accurate alignment even in datasets with massive numbers of markers and lens distortions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional fiducial marker alignment methods are used, then alignment can be performed, but alignment accuracy deteriorates due to mechanical instability and specimen transformation

Engineering Contradiction:
Improvealignment accuracyVSAvoidmechanical stability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent applies preliminary action by performing fiducial marker detection and alignment calculations before final 3D reconstruction. The system pre-processes the tilt series data to establish accurate projection parameters and marker positions, creating a reliable foundation for subsequent reconstruction steps. This includes detecting fiducial markers in multiple micrographs, calculating their 3D positions, and using these to determine accurate projection parameters before the actual tomographic reconstruction occurs.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If conventional alignment methods are used, then processing can be completed, but computational time increases for large-field datasets with lens distortions

Engineering Contradiction:
Improveprocessing speedVSAvoidcomputational complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the alignment process into distinct modular steps: fiducial marker detection, parameter calculation, distortion correction, and 3D position calculation. Each step processes specific aspects of the data independently, allowing for optimized computation at each stage. The system segments the large-field dataset into manageable portions corresponding to different micrographs and their associated fiducial markers, processing each segment with appropriate algorithms before integrating results.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent applies parameter changes by dynamically adjusting projection parameters based on detected fiducial marker positions. The system calculates optimal tilt angles, magnifications, and distortion parameters for each micrograph based on the actual observed marker positions rather than using fixed predetermined values. This adaptive parameter adjustment significantly improves alignment accuracy while reducing the need for complex iterative corrections later in the process.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If more fiducial markers are tracked, then alignment quality improves, but computational cost increases

Engineering Contradiction:
Improvealignment qualityVSAvoidcomputational cost
Core Design Contradiction:
Measurement precisionVSUse of energy by moving object

Solution Approach 1:

The patent applies partial action by selectively processing only the most informative fiducial markers for alignment calculations. Rather than equally processing all detected markers, the system identifies and prioritizes markers that provide the most constraining geometric information for determining projection parameters. This selective approach achieves high alignment quality using a subset of markers, reducing computational cost while maintaining or improving alignment accuracy compared to processing all markers uniformly.

Inventive Principle:
Principle #16Partial or excessive action

Data Source

PatentUS11308633B2Apparatus and method for fiducial marker alignment in electron tomography
Publication Date: 2022.04.19 KING ABDULLAH UNIV OF SCI & TECH
  • US11308633B2 patent drawing
  • US11308633B2 patent drawing
  • US11308633B2 patent drawing

AI summary

Provided is an apparatus and method for aligning fiducial markers. The apparatus may align positions of the fiducial markers on the two or more micrographs forming a two or more point sets corresponding to the two or more micrographs; create a first set of matched fiducial markers and unmatched fiducial markers; transform unmatched fiducial markers into transformed point sets and match the unmatched fiducial markers resulting in a second set of matched fiducial markers. The matching of the second set of matched fiducial markers results in improved alignment of a large number of fiducial markers. The aligned positions of fiducial markers may be constrained by an upper bound of transformation deviation of aligning positions of fiducial markers on two or more micrographs.