Nitrogenous Aldehyde-Releasing Tissue Fixation via Pressure and Temperature Control

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Solution Overview

Problem

Current methods for fixing tissue samples using aldehyde-releasing compounds are slow due to equilibrium reactions, leading to potential underfixation and health risks associated with formaldehyde and other fixatives.

Innovation Solution

A method involving a tissue processor that uses a nitrogen-containing compound capable of releasing aldehydes under controlled pressure and temperature conditions, allowing for accelerated fixation by shifting the chemical equilibrium to increase aldehyde release, thereby mimicking conventional formalin fixation while reducing health risks.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If aldehyde-releasing compounds are used for tissue fixation, then health risks are reduced, but fixation speed decreases due to equilibrium reactions

Engineering Contradiction:
Improvehealth risksVSAvoidfixation speed
Core Design Contradiction:
Object-affected harmful factorsVSProductivity

Solution Approach 1:

The patent applies parameter changes by modifying temperature and pressure conditions during fixation. By increasing temperature to 37°C or higher and adjusting pressure, the equilibrium of aldehyde-releasing compounds is shifted to favor aldehyde release, thereby accelerating fixation speed while maintaining the safety benefits of using non-formalin fixatives

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements periodic action through cyclic pressure changes during the fixation process. By alternating between pressure phases, the system enhances aldehyde release from the fixing compound in a controlled manner, improving fixation efficiency without compromising operator safety

Inventive Principle:
Principle #19Periodic action

2Object-affected harmful factors

If aldehyde-releasing compounds are used for tissue fixation, then health risks are reduced, but underfixation risk increases due to slow reaction rate

Engineering Contradiction:
Improvehealth risksVSAvoidfixation completeness
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent ensures reliable and complete fixation by changing temperature parameters to 37°C or higher and adjusting pressure conditions. These parameter modifications accelerate the aldehyde release kinetics, ensuring that the fixation reaction reaches completion before the tissue is removed from the fixative, thereby preventing underfixation while maintaining safety

Inventive Principle:
Principle #35Parameter changes

3Productivity

If conventional formalin is used for fixation, then fixation speed is high, but health hazards increase due to formaldehyde exposure

Engineering Contradiction:
Improvefixation speedVSAvoidhealth hazards
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent uses an intermediary substance - an aldehyde-releasing compound - that serves as a safe alternative to direct formaldehyde use. These compounds (such as formalin-free fixatives) release aldehydes in a controlled manner under specific temperature and pressure conditions, providing both safety and effective fixation without direct formaldehyde exposure

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent overcomes the slow fixation speed of aldehyde-releasing compounds by changing temperature to 37°C or higher and adjusting pressure. These parameter modifications accelerate the decomposition of the aldehyde-releasing compound, enabling fixation speeds comparable to conventional formalin while maintaining the safety advantages of formalin-free fixatives

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

This method achieves faster and more controlled tissue fixation, reducing the risk of underfixation and health hazards, while allowing for multiple uses of the fixation reagent and enabling precise monitoring of aldehyde concentration to prevent over- or under-fixing.

Implementation Method 1

In an equilibrium reaction they normally only release the amount of aldehyde that is consumed by the reaction with the tissue sample

Methodology Applied
Scientific EffectEquilibrium reaction:

Implementation Method 2

fixation is accelerated by applying pressure and/or temperature so that the compound releases the aldehyde in an increased amount

Methodology Applied
Scientific EffectPressure-induced phase change: Pressure Increase

Implementation Method 3

fixation is accelerated by applying pressure and/or temperature so that the compound releases the aldehyde in an increased amount

Methodology Applied
Scientific EffectTemperature-induced phase change: Heating

Implementation Method 4

a concentration measuring device is set up to determine a content of the at least one compound in the fixing reagent

Methodology Applied
Scientific EffectOptical absorption spectroscopy: Absorption Spectroscopy

Data Source

PatentEP2873962B1Fixing of tissue samples using aldehyde-releasing compounds containing nitrogen
Publication Date: 2020.09.02 LEICA BIOSYSTEMS NUSSLOCH GMBH
  • EP2873962B1 patent drawingFigure 1
  • EP2873962B1 patent drawingFigure 2
  • EP2873962B1 patent drawing

AI summary

A method (100) for fixing at least one tissue sample (1) is proposed, which is carried out using a tissue processor (10) and in which the at least one tissue sample (1) is introduced at a first temperature level and at a first pressure level into a fixation reagent (2) which contains at least one nitrogenous compound capable of releasing at least one aldehyde in a pressure- and/or temperature-dependent manner, wherein the at least one tissue sample (1) is left in the fixation reagent (2) for at least one fixation period. During the fixation period, the fixation reagent (2) with the at least one tissue sample (1) introduced therein is brought to a second temperature level above the first temperature level and/or a second pressure level above the first pressure level.Furthermore, the concentration of at least one nitrogen-containing compound capable of pressure- and/or temperature-dependent release of at least one aldehyde in the fixation reagent (2) is determined using at least one concentration measuring device (14) of the tissue processor (10), and a signal is output based on a measured value from the at least one concentration measuring device (14). A corresponding tissue processor is also part of the invention.