iPS Cell Colony Discrimination via Phase Contrast Imaging

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Solution Overview

Problem

Current methods for generating induced pluripotent stem cells (iPS cells) from humans for regenerative medicine rely on marker genes like fluorescent proteins, which are not suitable for human applications, necessitating an alternative approach to visualize and differentiate iPS cell colonies.

Innovation Solution

An image processing apparatus and method that uses phase contrast imaging to extract features from cell colonies based on brightness information, allowing for automatic discrimination of iPS cell colonies without the need for marker genes, integrated with an incubation observing apparatus for temperature-controlled environments.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If marker genes like fluorescent proteins are used to visualize iPS cell colonies, then the presence/absence of initialization can be verified, but the method is not suitable for human applications in regenerative medicine

Engineering Contradiction:
Improveverification accuracyVSAvoidapplicability to human cells
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The invention extracts and eliminates the marker gene component from the visualization system. Instead of using fluorescent protein genes to mark iPS cells, the system uses automatic image processing to extract and analyze morphological features directly from phase contrast images, thereby removing the harmful element (marker genes) while preserving the verification function

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces the biological/markers-based visualization mechanism with an optical/image processing mechanism. Phase contrast imaging combined with automatic image processing algorithms substitutes for the fluorescent marker gene approach, enabling marker-free visualization and discrimination of iPS cell colonies

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

2Adaptability or versatility

If automatic image processing is used to discriminate iPS cell colonies without marker genes, then human regenerative medicine applications become feasible, but the complexity of image processing increases

Engineering Contradiction:
Improveapplicability to human cellsVSAvoidimage processing system complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The image processing system performs self-service by automatically acquiring phase contrast images, processing them through algorithms that extract morphological features, and discriminating iPS cell colonies without requiring manual intervention or marker gene introduction. The system serves itself to complete the entire discrimination process autonomously

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The invention changes the parameters used for cell discrimination from genetic markers (fluorescent protein expression) to morphological parameters (shape, size, texture features extracted from images). This parameter transformation enables human cell applications while managing system complexity through software-based analysis

Inventive Principle:
Principle #35Parameter changes

3Ease of manufacture

If phase contrast imaging with automatic processing is implemented, then marker gene usage is eliminated, but the measurement precision of cell discrimination must be maintained

Engineering Contradiction:
Improvesimplicity of cell culture processVSAvoiddiscrimination accuracy
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The system implements feedback through automatic image processing that continuously analyzes phase contrast images, extracts morphological features, and adjusts discrimination criteria based on learned patterns from training data. This feedback mechanism maintains high discrimination accuracy without requiring marker genes, simplifying the cell culture process

Inventive Principle:
Principle #23Feedback

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

Enables accurate discrimination of iPS cell colonies without using fluorescent protein genes, facilitating their generation for human regenerative medicine applications by leveraging phase contrast imaging and automatic processing techniques.

Implementation Method 1

an imaging unit acquiring a phase contrast image of the incubation container housed in the temperature-controlled room

Methodology Applied
Scientific EffectPhase contrast imaging: Interference

Data Source

PatentUS9063343B2Image processing apparatus, incubation observing apparatus, and image processing method
Publication Date: 2015.06.23 NIKON CORP
  • US9063343B2 patent drawing
  • US9063343B2 patent drawing
  • US9063343B2 patent drawing

AI summary

An image processing apparatus includes an outline extracting processing unit inputting a phase contrast image of a cell colony acquired by an observing unit, and extracting an outline of the cell colony, an extracting unit extracting a feature quantity of an outline part of the cell colony based on brightness information at an outside and brightness information at an inside of the outline on the phase contrast image, and an automatic discriminating unit automatically discriminating whether or not the cell colony is an iPS cell colony based on a discriminant criterion determined in advance and the feature quantity extracted by the extracting unit.