Automated Cell Clonality Analysis Using Neural Networks

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Solution Overview

Problem

Current methods for monoclonalization of human induced pluripotent stem cells (iPSCs) are inefficient and prone to human error, leading to technical variability and bottlenecks in high-throughput derivation, as they rely on manual inspection and are susceptible to biases and noise in grayscale imaging, making it difficult to automate the validation of clonality.

Innovation Solution

A system and method utilizing trained neural networks, specifically convolutional neural networks (CNNs), to analyze chronological images of cell cultures, identifying and classifying cells based on morphology and clonality, enabling automated verification of monoclonality and polyclonality, and integrating a sorting unit for isolating identified cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If manual inspection methods are used for validating monoclonality, then human judgment and flexibility are available, but time consumption increases and technical variability is introduced

Engineering Contradiction:
Improvevalidation reliabilityVSAvoidtime consumption
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent replaces manual mechanical inspection with an automated imaging system that uses cameras to capture cell culture images and computer processors to analyze clonality. This substitution eliminates human time investment while maintaining validation reliability through standardized digital analysis protocols.

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

Solution Approach 2:

The system creates digital copies of cell culture images through automated imaging, allowing repeated analysis without physical manipulation of the actual cell cultures. This copying enables rapid validation through multiple image analysis cycles, reducing time consumption while maintaining consistency.

Inventive Principle:
Principle #26Copying

2Ease of operation

If manual inspection methods are used for validating monoclonality, then flexibility in judgment is available, but technical variability and bias increase

Engineering Contradiction:
Improveoperational flexibilityVSAvoidvalidation precision
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The system transforms subjective visual judgment parameters into objective digital image parameters such as pixel intensity, color values, and spatial coordinates. This parameter transformation enables precise, repeatable clonality validation that is independent of operator variability while maintaining operational simplicity through automated processing.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The automated system provides consistent feedback through standardized image analysis algorithms that objectively determine clonality status. This feedback mechanism eliminates human bias and variability while maintaining operational flexibility through programmable analysis criteria that can be adjusted as needed.

Inventive Principle:
Principle #23Feedback

3Device complexity

If grayscale imaging is used for cell culture analysis, then imaging simplicity is maintained, but noise and difficulty in detection increase

Engineering Contradiction:
Improveimaging system complexityVSAvoidcell detection difficulty
Core Design Contradiction:
Device complexityVSDifficulty of detecting and measuring

Solution Approach 1:

The patent enhances grayscale images by detecting and highlighting cells with distinctive color properties or patterns. This color-based differentiation enables easier cell detection and clonality validation while maintaining the simplicity of the imaging hardware, as the enhancement is achieved through image processing algorithms rather than complex optical systems.

Inventive Principle:
Principle #32Color changes

Data Source

PatentUS20240054761A1Imaging system and method of use thereof
Publication Date: 2024.02.15 NEW YORK STEM CELL FOUNDATION INC
  • US20240054761A1 patent drawing
  • US20240054761A1 patent drawing
  • US20240054761A1 patent drawing

AI summary

The present disclosure provides a system and method for image analysis which utilize trained neural networks. The system and method are useful for generation and/or analysis of a variety of objects, such as biological cells to determine clonality.