3D Embryo Reconstruction via OCT and Light Sheet Microscopy

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Solution Overview

Problem

Current embryo selection methods in Assisted Reproductive Technology (ART) rely on subjective morphological evaluations using optical microscopy, which are inaccurate and lead to high implantation failures, as they cannot effectively assess the morphology of spherical embryos in 3D, especially with high fragmentation rates or at the blastocyst stage.

Innovation Solution

The use of 3D reconstruction and printing technologies, such as Optical Coherence Tomography (OCT), Light Sheet Microscopy (including SPIM), and Micro Magnetic Resonance Imaging, to create non-invasive, high-resolution 3D images of human oocytes and embryos, allowing for detailed morphological assessments and improved embryo selection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If optical microscopy is used for embryo selection, then the process is simple and fast, but the accuracy and reliability of embryo quality assessment is low

Engineering Contradiction:
Improveembryo morphology assessment accuracyVSAvoidimaging system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent transitions from 2D optical microscopy to 3D imaging by acquiring multiple focal planes and reconstructing volumetric data. This dimensional change enables comprehensive assessment of spherical embryo structures, fragmentation distribution, and cellular organization that cannot be captured in single 2D planes, directly resolving the limitation of morphological assessment accuracy.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The patent replaces conventional optical microscopy with advanced imaging modalities including Optical Coherence Tomography (OCT) and light sheet microscopy. These systems substitute traditional optical mechanisms with interferometric and selective plane illumination approaches, achieving superior resolution and 3D capability while reducing phototoxicity through non-invasive imaging.

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

2Speed

If time-lapse imaging is used to acquire embryo morphokinetic data, then temporal resolution is improved, but spatial resolution and 3D morphology assessment capability deteriorates

Engineering Contradiction:
Improvetemporal resolution of morphokinetic dataVSAvoidspatial resolution and 3D morphology assessment
Core Design Contradiction:
SpeedVSMeasurement precision

Solution Approach 1:

The patent merges the temporal resolution advantage of time-lapse imaging with the spatial resolution and 3D capability of OCT and light sheet microscopy. By combining multiple focal planes into volumetric reconstructions and integrating temporal sequences, the system achieves both high temporal and spatial resolution simultaneously, overcoming the limitation where time-lapse systems only captured 7 focal planes without rotation capability.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent adds the third spatial dimension to time-lapse imaging by acquiring and reconstructing multiple focal planes into 3D volumetric data. This enables assessment of spherical embryo structures, fragmentation distribution, and cellular organization at each time point, transforming 2D temporal sequences into 3D temporal datasets for comprehensive morphokinetic analysis.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Ease of operation

If conventional optical microscopy is used for embryo observation, then the system is simple to operate, but the ability to assess spherical embryo structures and fragmentation is limited

Engineering Contradiction:
Improveoperation simplicityVSAvoidembryo structure assessment capability
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent creates 3D digital copies of embryos through volumetric reconstruction from multiple focal planes. These digital models can be rotated, sectioned, and analyzed without manipulating the actual embryo, preserving the simple operation of non-invasive imaging while enabling comprehensive 3D assessment of spherical structures, fragmentation patterns, and cellular organization.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent replaces conventional optical microscopy with OCT and light sheet microscopy systems that provide 3D imaging capability. These systems substitute traditional 2D optical sectioning with interferometric and selective plane illumination methods, achieving superior spatial resolution and comprehensive embryo structure assessment while maintaining operational simplicity through automated acquisition and reconstruction.

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

4Duration of action of moving object

If repeated optical imaging is performed to study embryo development, then temporal monitoring is enabled, but phototoxic effects and sample damage increase

Engineering Contradiction:
Improvetemporal monitoring capabilityVSAvoidphototoxic effects and sample damage
Core Design Contradiction:
Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent replaces conventional optical microscopy with OCT and light sheet microscopy that use non-invasive or minimally invasive imaging mechanisms. OCT uses low-coherence interferometry with near-infrared light that penetrates tissue without significant phototoxicity, while light sheet microscopy uses thin sheets of light that illuminate only the focal plane, dramatically reducing overall light exposure and photodamage during temporal monitoring.

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

Solution Approach 2:

The patent applies local quality by using light sheet microscopy that illuminates only the specific focal plane being imaged rather than the entire sample. This localized illumination approach minimizes phototoxic effects to the immediate region of interest while enabling continuous temporal monitoring, as unilluminated regions receive no photodamaging exposure.

Inventive Principle:
Principle #3Local quality

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

This approach enhances the accuracy of embryo selection, increases ART success rates, and provides a pedagogic and informative tool for training and patient education, while minimizing phototoxic effects and sample damage.

Implementation Method 1

A new and original approach of OCT called full-field OCT has been proposed recently by a research team and is based on white-light interference microscopy. Full-field OCT allows to obtain tomographic pictures by combination of interferometric images recorded by a detector array such as CCD camera.

Methodology Applied
Scientific EffectInterference: Interference

Implementation Method 2

Light sheet microscopy including Selective Plane Illumination Microscopy (SPIM) is also a new technique in which the illuminated plane in a sample is the only being imaged, associated with a virtual elimination of background signal and a drastic reduction of the amount of light required to explore the sample.

Methodology Applied
Scientific EffectLight sheet illumination: Light

Data Source

PatentUS10628944B2Methods for three dimensional reconstruction and determining the quality of an embryo
Publication Date: 2020.04.21 INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
  • US10628944B2 patent drawing
  • US10628944B2 patent drawing
  • US10628944B2 patent drawing

AI summary

The present invention relates generally to the fields of reproductive medicine. More specifically, the present invention relates to methods and devices for determining the quality of an embryo. More specifically, the present invention relates to the use of three dimensional reconstructions for determining the quality of an embryo.