Tissue Fixative Using Amphiphilic Infiltration to Prevent Dehydration

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Solution Overview

Problem

Existing fixatives using alcohol as a solvent dehydrate tissues, while those using water as a solvent for polyamines result in slow structural changes and formation of artifacts, and formalin-based fixatives cause irreversible protein denaturation and artifacts.

Innovation Solution

A fixative comprising a hydrophilic denaturant dissolved in a lipophobic solvent with an amphiphilic infiltration agent to accelerate penetration and avoid tissue alteration, using a mixture of short-chain alcohols and a polyamine like urotropine, with pH adjustment and bactericidal substances for effective preservation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If alcohol is used as a solvent in fixative, then the denaturing agent can dissolve effectively, but the tissue to be preserved is dehydrated and damaged

Engineering Contradiction:
Improvesolubility of denaturing agentVSAvoidtissue dehydration
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent uses water as an intermediary solvent that does not dehydrate tissue, and adds amphiphilic infiltration agents (like ethanol or acetone) as mediators to facilitate the penetration of the hydrophilic denaturing agent through lipid membranes without using alcohol as the primary solvent. This resolves the contradiction by achieving solubility through the denaturing agent's hydrophilic nature while avoiding tissue dehydration.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the parameter of solvent hydrophilicity from hydrophobic (alcohol) to hydrophilic (water), and adjusts the penetration capability by adding amphiphilic substances. This parameter change allows the denaturing agent to dissolve in water while the amphiphilic infiltration agent compensates for reduced lipid solubility, maintaining effective tissue penetration without dehydration.

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If water is used as a solvent for polyamines, then tissue dehydration is avoided, but the structural change in tissue proceeds too slowly and artifacts form

Engineering Contradiction:
Improvetissue preservation qualityVSAvoidfixation speed
Core Design Contradiction:
Object-affected harmful factorsVSProductivity

Solution Approach 1:

The patent introduces amphiphilic infiltration agents (such as short-chain alcohols or ketones) as intermediaries that accelerate the penetration of the hydrophilic denaturing agent into tissue by temporarily interacting with lipid structures. This mediator approach speeds up fixation while water remains the primary solvent to prevent dehydration and artifacts.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The amphiphilic infiltration agent performs preliminary action by first penetrating the lipid-rich cell membranes and preparing the tissue structure for rapid subsequent penetration by the hydrophilic denaturing agent. This preliminary lipid-soluble phase acceleration enables the water-based denaturing agent to work more quickly without direct alcohol-tissue contact.

Inventive Principle:
Principle #10Preliminary action

3Productivity

If fat on cell walls is not dissolved, then the denaturant penetration is slow, but dissolving fat too quickly may cause osmotic damage to tissue

Engineering Contradiction:
Improvedenaturant penetration speedVSAvoidosmotic damage to tissue
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The amphiphilic infiltration agent acts as a controlled intermediary that gradually facilitates lipid dissolution and denaturant penetration. By being present in controlled concentrations (0.1-10%), it mediates the interaction between the hydrophilic denaturing agent and lipid membranes, enabling progressive penetration without sudden osmotic shocks to the tissue.

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

The fixative achieves rapid tissue penetration, reduces artifacts, and preserves cellular structures effectively, suitable for serological-immunological and molecular biological examinations without causing DNA/RNA/protein cross-linking, enhancing diagnostic accuracy.

Implementation Method 1

an amphiphilic infiltration agent dissolved in the solvent for dissolving fats on the surface of the biological tissue to accelerate penetration of the denaturant into the biological tissue

Methodology Applied
Scientific EffectLipid dissolution: Solvation

Implementation Method 2

a hydrophilic denaturant for structurally altering the molecules of the organic tissue

Methodology Applied
Scientific EffectDenaturation:

Implementation Method 3

amphiphilic infiltration agent dissolved in the solvent for dissolving fats on the surface of the biological tissue to accelerate penetration of the denaturant into the biological tissue

Methodology Applied
Scientific EffectPenetration enhancement: Permeation

Data Source

PatentEP3414547B1Fixativ
Publication Date: 2025.07.02 BIOSEPAR FUR MEDIZIN UND LABORTECHN MBH
  • EP3414547B1 patent drawingFigure 1

AI summary

The invention relates to a fixative for the preservation of organic tissue and cell aggregates, comprising a hydrophilic denaturant for structural change of the molecules of the organic tissue, a lipophobic solvent, in which said denaturant is dissolved, and an amphiphilic infiltration agent which is dissolved in the solvent for dissolving fats on the surface of the biological tissue in order to accelerate a penetration of the denaturant into the biological tissue.