Template-Based Image Alignment for Slide Fiducial Mark Identification

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Solution Overview

Problem

High-content imaging systems face challenges in accurately aligning and identifying fiducial marks on slides due to lack of contrast, printing defects, and large distances between marks and sample arrays, making it difficult to determine the precise location and rotation of biological samples.

Innovation Solution

A computer-implemented system and method for template-based imaging that includes an image acquisition module, a template generation module, and an offset calculation module, which creates a template image from common features of multiple slides, sets pixel values accordingly, and calculates offsets to align the template with new images, allowing for accurate determination of sample coordinates.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fiducial marks are printed on the slide to serve as reference marks, then the position of biological samples can be located, but it becomes difficult to identify the reference marks due to lack of contrast, printing defects, and large distance from the sample array

Engineering Contradiction:
Improveposition location accuracyVSAvoidreference mark identification difficulty
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent segments the reference mark identification problem by creating multiple candidate reference marks in the template image, then selecting the best match through comparison. Instead of relying on a single difficult-to-identify mark, the system divides the task into generating multiple candidates and selecting the optimal one based on correlation analysis.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent performs preliminary actions by pre-generating a template image containing multiple candidate reference marks before actual sample analysis. This template is created in advance and stored for reuse, eliminating the need to identify reference marks from scratch for each new image, thus resolving the identification difficulty.

Inventive Principle:
Principle #10Preliminary action

2Area of stationary object

If the distance between reference marks and sample array is large to fit in the field of view, then the entire array can be captured, but it becomes difficult to identify the reference marks

Engineering Contradiction:
Improvefield of view coverageVSAvoidreference mark visibility
Core Design Contradiction:
Area of stationary objectVSDifficulty of detecting and measuring

Solution Approach 1:

The patent creates a copy of the reference mark pattern in the template image that can be overlaid on the actual image. This template copy contains multiple candidate reference marks at known positions, allowing the system to identify reference marks through pattern matching rather than direct visual detection, thus overcoming the visibility issue when marks are far from samples.

Inventive Principle:
Principle #26Copying

3Adaptability or versatility

If the location and rotation of the aggregate array varies from slide to slide, then flexibility in sample disposal is achieved, but precise alignment and coordinate determination becomes challenging

Engineering Contradiction:
Improveslide layout flexibilityVSAvoidalignment precision
Core Design Contradiction:
Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The patent changes the parameter of reference mark representation by using multiple candidate marks with different characteristics in the template. By varying the parameters of candidate reference marks (positions, intensities, patterns), the system can adapt to different slide layouts and rotations while maintaining precise alignment through optimal parameter matching.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements feedback through correlation analysis between the template image and actual images. The system calculates correlation values for multiple candidate reference marks and uses this feedback to select the best match, then uses this selection to determine precise alignment and coordinates, resolving the challenge of varying slide configurations.

Inventive Principle:
Principle #23Feedback

Data Source

PatentUS11960073B2System and method for template-based image analysis
Publication Date: 2024.04.16 MOLECULAR DEVICES LLC
  • US11960073B2 patent drawing
  • US11960073B2 patent drawing
  • US11960073B2 patent drawing

AI summary

A computer-implemented system and method for template-based imaging are disclosed. A first image of a first slide, a second image of a second slide, and a third image of a third slide are received, wherein the third image includes a representation of a sample disposed on the third slide. Values of pixels of a template image that are associated with a plurality of features common to the first and second slides and represented in the first and second images are set to a non-background value and values of pixels of the template image not associated with the plurality of features are set to a background value. An offset between the template image and the third image is developed and coordinates of pixels in the third image that are associated with the representation of the sample are determined in accordance with the offset.