Retinal Sheet Manufacturing with OCT-Based Graft Quality Screening

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Solution Overview

Problem

Current methods for producing retinal sheets from retinal organoids are inefficient and require expert skills, leading to non-uniform grafts and high costs due to labor-intensive purification processes and quality control issues, with potential damage during transplantation.

Innovation Solution

A method using optical coherence tomography (OCT) to identify suitable regions in retinal organoids for transplantation, combined with confocal image analysis and acoustic microscopy, to excise uniform retinal sheets of specific thickness and free of foreign structures, enabling efficient production without expert skill.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If retinal organoids of 1-2 mm size are used for quality evaluation, then expert visual assessment can identify suitable grafts, but the process is labor-intensive, costly, and requires advanced discriminatory skills

Engineering Contradiction:
Improvequality evaluation accuracyVSAvoidinspection efficiency
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent replaces expert visual assessment with optical coherence tomography (OCT) imaging technology. OCT provides objective, quantitative measurement of retinal organoid thickness and structure, eliminating the need for expert visual inspection while maintaining or improving measurement precision. This substitution of mechanical/optical measurement for human expertise resolves the contradiction between accurate quality evaluation and inspection efficiency.

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

Solution Approach 2:

The patent introduces OCT imaging as an intermediary tool between the retinal organoid and the evaluation process. The OCT system captures cross-sectional images that reveal internal structure and thickness, serving as a mediator that translates complex biological structures into quantifiable data. This intermediary enables automated, high-throughput quality assessment without requiring expert visual skills.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If multiple small grafts (major axis about 1 mm) are excised to cover degenerative areas, then transplantation can be performed, but an adequate quantity is extremely difficult to prepare due to current manufacturing processes

Engineering Contradiction:
Improvenumber of graftsVSAvoidgraft uniformity
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent performs preliminary identification of suitable excision regions using OCT imaging before actual graft preparation. By pre-mapping the retinal organoid structure and identifying regions with appropriate thickness and uniformity, the process ensures that multiple grafts can be excised with consistent quality. This preliminary assessment enables efficient production of adequate graft quantities while maintaining uniformity.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent divides the retinal organoid into multiple suitable graft regions based on OCT imaging data. By identifying and segmenting the organoid into multiple excisable portions that each meet quality criteria, the process can produce an adequate quantity of grafts from a single organoid while maintaining manufacturing precision through objective imaging guidance.

Inventive Principle:
Principle #1Segmentation

3Productivity

If a large retinal sheet is prepared for transplantation, then fewer insertions are needed, but transplantation through a large incision may cause damage during transplantation

Engineering Contradiction:
Improvetransplantation efficiencyVSAvoidtransplantation damage
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent segments the retinal organoid into multiple appropriately-sized grafts rather than preparing one large sheet. This segmentation allows each graft to be small enough for safe transplantation through minimal incisions, reducing mechanical damage risk, while the overall process remains efficient by producing multiple grafts from a single organoid through standardized excision protocols.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent optimizes graft size parameters based on OCT imaging data, selecting dimensions that balance transplantation safety with coverage efficiency. By controlling graft size within specific ranges (e.g., 0.5-2.0 mm in minor axis, 1.0-10.0 mm in major axis), the process minimizes transplantation damage while maintaining sufficient coverage capability, resolving the contradiction between transplantation efficiency and safety.

Inventive Principle:
Principle #35Parameter changes

4Ease of manufacture

If retinal sheets are excised without objective evaluation, then the process is simpler, but the grafts are non-uniform and quality control is poor

Engineering Contradiction:
Improveexcision simplicityVSAvoidsheet uniformity
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent replaces subjective expert assessment with objective OCT imaging measurement to evaluate retinal organoid thickness and structure. This substitution maintains manufacturing simplicity by using automated imaging and analysis while dramatically improving manufacturing precision through quantitative, reproducible measurements that ensure uniform graft quality.

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

Solution Approach 2:

The patent implements feedback through OCT imaging that provides real-time information about retinal organoid structure and thickness. This feedback mechanism guides the excision process, allowing operators to identify and excise only those regions that meet quality criteria, thereby maintaining ease of manufacture while ensuring manufacturing precision through data-driven decision-making.

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 the production of uniform retinal sheets suitable for transplantation, reducing labor and costs, and minimizing damage during transplantation by using objective evaluation methods.

Implementation Method 1

a step of performing one or more selected from optical coherence tomography (OCT), confocal image analysis, and acoustic microscopy analysis (preferably OCT) on the retinal organoid derived from pluripotent stem cells to identify, as a region suitable for transplantation, a region with a thickness of 70 μm or more

Methodology Applied
Scientific EffectOptical coherence tomography: Tomography

Implementation Method 2

a step of performing one or more selected from optical coherence tomography (OCT), confocal image analysis, and acoustic microscopy analysis (preferably OCT) on the retinal organoid derived from pluripotent stem cells

Methodology Applied
Scientific EffectAcoustic microscopy: Acoustic Microscopy

Data Source

PatentEP4643894A1Method for manufacturing retinal sheet
Publication Date: 2025.11.05 VCCT INC
  • EP4643894A1 patent drawingFigure 1
  • EP4643894A1 patent drawingFigure 2A~2B
  • EP4643894A1 patent drawingFigure 3A~3C

AI summary

The present invention relates to a method for producing a sheet for transplantation from a retinal organoid derived from pluripotent stem cells, and the like. Specifically, the present invention relates to a method for producing a retinal sheet for transplantation from a retinal organoid derived from pluripotent stem cells, the method including a step of performing optical coherence tomography (OCT) on the retinal organoid derived from pluripotent stem cells to identify, as a region suitable for transplantation, a region with a thickness of 70 µm or more and free of foreign structures characterized by differences in brightness, and a step of excising a fragment from the region suitable for transplantation to obtain the retinal sheet for transplantation.