Nucleotide-Based Tissue Transparentization Preserving Cell Viability

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Solution Overview

Problem

Existing methods for transparentizing biological tissue are limited by the need to fix tissues with formaldehyde, causing cell death and preventing observation of living tissues at high depths.

Innovation Solution

Application of a solution containing nucleotides, nucleotide derivatives, macromolecules with nucleotides, or nucleotide polymers to biological tissue, allowing for transparentization in a living state.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Illumination intensity

If water is replaced with an organic molecule having a high refractive index to match the refractive index of a biomolecule, then light transparency is improved, but cells die

Engineering Contradiction:
Improvelight transparencyVSAvoidcell viability
Core Design Contradiction:
Illumination intensityVSReliability

Solution Approach 1:

The patent changes the chemical composition parameter of the transparentizing agent from organic molecules to nucleotide-based compounds (ATP, ADP, AMP). This parameter change allows achieving light transparency improvement while maintaining cell viability, as nucleotides are naturally present in cells and do not cause the same toxic effects as traditional organic transparentizing agents

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses nucleotides that are naturally metabolizable by cells, effectively treating them as temporary, non-toxic transparentizing agents that cells can process and eliminate, thus avoiding long-term toxicity and cell death

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Illumination intensity

If a lipid having a high refractive index is removed to lower the refractive index of tissue, then light transparency is improved, but cell structure collapses

Engineering Contradiction:
Improvelight transparencyVSAvoidcell structure integrity
Core Design Contradiction:
Illumination intensityVSShape

Solution Approach 1:

The patent changes the approach from removing lipids to using nucleotide-based transparentizing agents that do not disrupt cell membranes or structural components. This parameter change in the transparentizing mechanism preserves cell structure integrity while achieving light transparency

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces nucleotides as intermediary substances that mediate between light transmission requirements and cell structure preservation. These nucleotides act as a bridge, providing transparency without the need to remove or damage structural lipids

Inventive Principle:
Principle #24Intermediary (Mediator)

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 three-dimensional observation of deep tissue structures without cell death, allowing for the observation of blood vessels, gene expression, and substance localization over time.

Implementation Method 1

water is replaced with an organic molecule having a high refractive index to match the refractive index of a biomolecule, thereby increasing light transparency

Methodology Applied
Scientific EffectRefraction: Refraction

Data Source

PatentEP4036246B1A method for transparentizing biological tissue in a living state
Publication Date: 2025.04.09 OSAKA UNIVERSITY
  • EP4036246B1 patent drawingFigure 1~2
  • EP4036246B1 patent drawingFigure 3
  • EP4036246B1 patent drawingFigure 4

AI summary

A method for transparentizing biological tissue in a living state, which comprises applying a solution to the biological tissue, the solution containing one or more compounds selected from the group consisting of a nucleotide, a nucleotide derivative, a macromolecule containing a nucleotide or a nucleotide derivative, and a nucleotide polymer; a composition for transparentizing biological tissue in a living state, which comprises the aforementioned compound; and a kit for transparentizing biological tissue in a living state, which comprises the aforementioned compound.