Fiducial Marker Identification in Single-Color Fluorescence Microscopy

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Solution Overview

Problem

Conventional fluorescence microscope image registration systems require multiple images with different fluorescence colors, leading to resource inefficiency and potential registration errors due to chromatic aberration, and struggle with sample movement over time.

Innovation Solution

A fiducial identification system processes a single fluorescence microscope image depicting both the sample and fiducial markers with a common fluorescence color, using a 2D normal distribution function to identify marker positions and determine registration transformations, thereby reducing resource usage and minimizing registration errors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If multiple images with different fluorescence colors are used for registration, then fiducial markers can be distinguished from sample, but resource efficiency decreases and chromatic aberration errors increase

Engineering Contradiction:
Improveregistration accuracyVSAvoidresource efficiency
Core Design Contradiction:
Measurement precisionVSLoss of energy

Solution Approach 1:

The patent merges the identification of fiducial markers and sample into a single fluorescence image by using a common fluorescence color for both. This eliminates the need for multiple images with different fluorescence colors, thereby improving resource efficiency while maintaining registration accuracy through computational distinction of markers based on spatial distribution patterns

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent introduces a reference distribution function as an intermediary to distinguish fiducial markers from sample. This mathematical model serves as a mediator that enables accurate marker identification in a single-color image by comparing observed intensity distributions against expected marker patterns, eliminating chromatic aberration errors while maintaining precision

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If multiple images with different fluorescence colors are used for registration, then fiducial markers can be distinguished from sample, but device complexity increases

Engineering Contradiction:
Improveregistration accuracyVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent combines multiple imaging operations into a single fluorescence image acquisition, reducing the complexity of coordinating multiple images with different fluorescence colors. The system maintains registration accuracy by using computational methods to distinguish markers from sample within the unified image

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent extracts fiducial marker information from a single fluorescence image by applying reference distribution function comparison. This extraction method isolates marker positions without requiring separate imaging channels, thereby simplifying the overall system while maintaining precise registration capability

Inventive Principle:
Principle #2Taking out (Extraction)

3Productivity

If conventional registration methods are used with sample movement, then registration can be performed, but registration errors increase over time

Engineering Contradiction:
Improveregistration speedVSAvoidregistration accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent performs preliminary identification of fiducial markers using reference distribution function comparison before registration is performed. This preliminary action establishes accurate marker positions that serve as stable reference points for subsequent registration, maintaining precision even when sample movement occurs between imaging sessions

Inventive Principle:
Principle #10Preliminary action

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 accurately registers images captured at different time points with reduced resource usage and improved accuracy by using a common fluorescence color for the sample and fiducial markers, compensating for sample movement and minimizing chromatic aberration effects.

Implementation Method 1

A fluorescent dye refers to a substance that emits light of a particular wavelength (e.g., having a particular color) in response to being exposed to light of a wavelength that 'excites' the fluorescent dye

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS11255785B2Identifying fiducial markers in fluorescence microscope images
Publication Date: 2022.02.22 APPLIED MATERIALS INC
  • US11255785B2 patent drawing
  • US11255785B2 patent drawing
  • US11255785B2 patent drawing

AI summary

Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, for obtaining a fluorescence microscope image that depicts a sample and a plurality of fiducial markers, identifying the plurality of fiducial markers in the image, and using the plurality of fiducial markers to register the image. The sample and the plurality of fiducial markers have a common fluorescence color, and identifying the plurality of fiducial markers in the image includes comparing a spatial intensity distribution of a plurality of fluorescent regions of the image to a reference distribution function.