Molecular Mouse Embryo Assay for IVF Product Quality Control

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Solution Overview

Problem

Current methods for assessing the impact of suboptimal environments on embryo development in IVF are limited, as they primarily rely on morphology and cannot detect growth-promoting or inhibiting factors early in development, and are not sensitive enough to identify subtle effects on embryo viability.

Innovation Solution

A molecular-based mouse embryo assay (mMEA) using transgenic murine embryos with reporter genes linked to embryonic viability markers such as Oct-4, Sox2, and Nanog, which allows for the evaluation of embryonic development and product acceptability by assessing the expression of these markers, providing a more sensitive and functional quality control for IVF products and culture conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If morphology-based assessment is used to evaluate embryo development, then the method is simple and easy to perform, but it cannot detect subtle effects on embryo viability or growth-promoting/inhibiting factors early in development

Engineering Contradiction:
Improvesimplicity of assessment methodVSAvoidsensitivity to detect subtle effects on embryo viability
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent introduces reporter genes (such as GFP) as intermediary elements that are operably linked to regulatory regions of embryonic viability markers (Oct-4, Sox2, Nanog). These reporter genes act as mediators that convert subtle molecular changes in gene expression into visually detectable signals, allowing early detection of embryo viability changes without requiring complex molecular analysis while maintaining sensitivity beyond traditional morphology-based assessment.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the assessment parameter from purely morphological characteristics to include reporter gene expression levels. By monitoring the expression levels of reporter genes linked to viability markers, the method detects subtle changes in embryonic development and viability that occur before morphological changes are visible, thereby increasing measurement precision while maintaining operational simplicity.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If traditional mouse embryo assay is used for quality control, then it provides basic developmental assessment, but it lacks sensitivity to detect embryo toxicity or suboptimal conditions early in development

Engineering Contradiction:
Improvebasic developmental assessment capabilityVSAvoidsensitivity to detect embryo toxicity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

Reporter genes serve as intermediary indicators that amplify subtle toxic effects or suboptimal conditions into detectable expression changes. When embryos are exposed to toxic substances or suboptimal culture conditions, the regulatory regions of viability markers respond by altering reporter gene expression, providing an early and sensitive warning signal that enhances the reliability of quality control assessments.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The assay enables preliminary detection of embryo toxicity and suboptimal conditions at very early developmental stages, before significant morphological damage occurs. By monitoring reporter gene expression early in development, the method can identify problematic conditions and allow for corrective actions before embryo viability is compromised, thereby improving overall assessment reliability.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If transgenic embryos with reporter genes are used, then sensitivity and detection capability are enhanced, but the complexity of the assay increases

Engineering Contradiction:
Improvedetection capability of viability markersVSAvoidcomplexity of transgenic embryo assay
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex molecular biology techniques (such as RT-PCR, Western blotting, or in situ hybridization) with a simplified optical detection system. Reporter genes like GFP produce fluorescent signals that can be detected using standard fluorescence microscopy, substituting complex biochemical analysis with a more straightforward visual assessment method that maintains high measurement precision while reducing assay complexity.

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

Solution Approach 2:

The assay utilizes color/fluorescence changes as a simple readout mechanism. Reporter genes encode proteins that produce visible fluorescent colors under appropriate illumination, allowing researchers to assess viability marker expression and detect developmental abnormalities through straightforward visual inspection or image analysis, thereby maintaining high detection capability while minimizing procedural complexity.

Inventive Principle:
Principle #32Color changes

Data Source

PatentEP2971059B1A method and quality control molecular based mouse embryo assay for use with in vitro fertilization technology
Publication Date: 2019.09.25 FUJIFILM IRVINE SCIENTIFIC INC
  • EP2971059B1 patent drawingFigure 1
  • EP2971059B1 patent drawingFigure 2A
  • EP2971059B1 patent drawingFigure 2B

AI summary

A method for qualitatively assessing products used in in vitro fertilization is provided. Also disclosed is an improved quality control assay for use in clinical Assisted Reproductive Technologies (ART).