Optical Coherence Tomography for Cell Sheet Stratification

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Solution Overview

Problem

Current methods for evaluating the stratification and differentiation of cell sheets, essential for assessing the quality of regenerative tissues, are invasive or have low Z-resolution, making it difficult to non-invasively assess the inner structure and quality of cell sheets for transplantation.

Innovation Solution

A method using an optical instrument with high resolution, such as Optical Coherence Tomography (OCT), to acquire and analyze cross-sectional images of cell sheets, measuring cell density and distribution, allowing for non-invasive evaluation of stratification and differentiation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If phase-contrast microscopy is used to observe cell sheets, then non-invasive observation is achieved, but only surface layer observation is possible and stratified structure cannot be evaluated

Engineering Contradiction:
ImproveinvasivenessVSAvoidZ-resolution
Core Design Contradiction:
Object-affected harmful factorsVSMeasurement precision

Solution Approach 1:

The optical system segments the light path into reference light and measurement light components. The reference light reflects from a reference mirror while measurement light penetrates the cell sheet, allowing separate detection of different depth information through interference patterns.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention transitions from two-dimensional surface observation to three-dimensional internal structure observation by utilizing the Z-axis (depth) information through optical coherence tomography, enabling cross-sectional imaging of stratified cell structures.

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

2Measurement precision

If tissue staining is used to evaluate cell sheet quality, then stratification and differentiation can be assessed, but the technique is invasive and cannot evaluate the transplantation sheet itself

Engineering Contradiction:
Improveevaluation accuracyVSAvoidinvasiveness
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The invention introduces an optical coherence tomography system as an intermediary non-invasive measurement tool that provides internal structural information without requiring tissue fixation or staining, thereby preserving the cell sheet for transplantation while enabling quality assessment.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Object-affected harmful factors

If optical microscope is used to image stratified tissue, then non-invasive observation is achieved, but Z-resolution is low and superposed images result

Engineering Contradiction:
ImproveinvasivenessVSAvoidimage resolution
Core Design Contradiction:
Object-affected harmful factorsVSManufacturing precision

Solution Approach 1:

The system uses partial coherence of light with controlled temporal and spatial coherence properties to achieve depth sectioning. By limiting the coherence length of the light source, only light from specific depth ranges interferes constructively, providing excessive depth discrimination capability.

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The invention changes the optical parameters by using broadband light sources with limited coherence length and varying the optical path length to achieve depth-resolved imaging, transforming the imaging capability from surface-only to depth-resolved three-dimensional visualization.

Inventive Principle:
Principle #35Parameter changes

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, non-invasive determination of cell sheet stratification and differentiation, improving the quality assessment of regenerative tissues by providing detailed, three-dimensional imaging and analysis of cell layers and density.

Implementation Method 1

a light source 301, a condensing optical system which irradiates cells on a culture surface with light from the light source

Methodology Applied
Scientific EffectLight: Light

Implementation Method 2

an optical microscope is based on the principle that all the light other than that coming from the focal position is reflected onto an image

Methodology Applied
Scientific EffectReflection: Reflection

Data Source

PatentUS10717962B2Cell culture device and image analysis device
Publication Date: 2020.07.21 HITACHI HIGH TECH CORP
  • US10717962B2 patent drawing
  • US10717962B2 patent drawing
  • US10717962B2 patent drawing

AI summary

Provided is a method for non-invasively and quantitatively determining multilayerization and differentiation when culturing a cell sheet. Provided is a method for determining a cell state by imaging a cell sheet by using an optical instrument characterized by having a high resolution, and then analyzing the inner structure thereof.