TEM Image Shift Calibration Using Non-Linear Target Correction

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Solution Overview

Problem

Current image shift calibration processes in single particle analysis (SPA) for cryogenic electron microscopes suffer from targeting errors due to non-linear components, sample height variations, and the inability to adjust predefined locations on-the-fly, limiting image shifts to less than 12 micrometers and increasing the number of mechanical stage moves.

Innovation Solution

A method that accounts for non-flatness and tilt of the sample by fitting non-linear models to targeting errors, allowing on-the-fly adjustments and recalibrating during data acquisition to improve targeting accuracy, using techniques such as Zernike polynomials and Gaussian process regression for image registration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If image shift calibration uses linear models, then the calibration process is simple, but targeting errors occur due to non-linear components and sample height variations

Engineering Contradiction:
Improvecalibration process complexityVSAvoidtargeting accuracy
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The patent changes the mathematical model from linear to non-linear (using Zernike polynomials and Gaussian process regression) to accurately represent the physical reality of image shift calibration, thereby improving targeting accuracy while accounting for sample height variations and optical aberrations

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements an iterative feedback mechanism where the non-linear model is trained on measured targeting errors and then used to predict and correct errors for subsequent images, continuously improving accuracy through recalibration during data acquisition

Inventive Principle:
Principle #23Feedback

2Measurement precision

If image shifts are limited to less than 12 micrometers, then targeting errors are minimized, but the number of mechanical stage moves increases

Engineering Contradiction:
Improvetargeting accuracyVSAvoiddata acquisition speed
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent replaces mechanical stage moves with electronic image shift calibration, allowing the electron beam to be deflected to target locations without physically moving the sample stage, thereby eliminating mechanical drift and increasing acquisition speed

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent performs preliminary non-linear calibration to establish accurate targeting models before data acquisition, enabling larger image shifts to be executed accurately without subsequent mechanical stage moves during the actual data collection process

Inventive Principle:
Principle #10Preliminary action

3Ease of manufacture

If predefined target locations are fixed, then the calibration process is straightforward, but on-the-fly adjustments cannot be made during data acquisition

Engineering Contradiction:
Improvecalibration process simplicityVSAvoidon-the-fly adjustment capability
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The patent transforms the static calibration process into a dynamic one by enabling the non-linear model to be recalibrated during data acquisition using newly acquired images, allowing the system to adapt to drifts and variations in real-time

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The system performs self-calibration by automatically training the non-linear model on measured targeting errors from acquired images and using the updated model to correct subsequent target locations, eliminating the need for manual intervention

Inventive Principle:
Principle #25Self-service

Data Source

PatentEP4345447B1A method of automated data acquisition for a transmission electron microscope
Publication Date: 2026.03.25 FEI CO
  • EP4345447B1 patent drawingFigure 1A
  • EP4345447B1 patent drawingFigure 1B
  • EP4345447B1 patent drawingFigure 2A

AI summary

A method of automated data acquisition for a transmission electron microscope, the method comprising: obtaining a reference image of a sample at a first magnification; for each of a first plurality of target locations identified in the reference image: steering an electron beam of the transmission electron microscope to the target location, obtaining a calibration image of the sample at a second magnification greater than the first magnification, and using image processing techniques to identify an apparent shift between an expected position of the target location in the calibration image and an observed position of the target location in the calibration image, training a non-linear model using the first plurality of target locations and the corresponding apparent shifts; based on the non-linear model, calculating a calibrated target location for a next target location; steering the electron beam to the calibrated target location and obtaining an image at a third magnification greater than the first magnification.