Biological Sample Stabilization Using Dialkylacetamides

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Solution Overview

Problem

Current methods for stabilizing biological samples, particularly nucleic acids and proteins in compact tissue samples, face challenges in maintaining integrity and stability without destroying the sample, especially when dealing with diverse tissue types and requiring simple, rapid handling for molecular and histological analysis.

Innovation Solution

A method involving a composition with dialkylacetamides or dialkylformamides, such as N,N-dimethylacetamide, is used to stabilize biological samples by inhibiting degradation and modification of biomolecules, allowing for qualitative and quantitative analysis of nucleic acids and proteins, while maintaining morphological integrity, even at room temperature.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If conventional stabilization methods (freezing, chemical fixatives) are used to preserve nucleic acids and proteins, then sample stability is improved, but sample destruction or morphological damage occurs

Engineering Contradiction:
Improvenucleic acid and protein stabilityVSAvoidsample destruction
Core Design Contradiction:
Stability of the object's compositionVSObject-generated harmful factors

Solution Approach 1:

The patent changes the chemical parameters of the stabilization composition by using dialkylacetamides and dialkylformamides with specific molecular structures (where R1-R6 are hydrogen, alkyl, or aryl groups). These chemical parameter changes enable stabilization without the destructive effects of conventional methods, as the specific molecular structure of these compounds allows them to inhibit degradation while maintaining sample integrity.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs composite stabilization compositions containing multiple components including dialkylacetamides, dialkylformamides, and optionally other stabilizing agents. This composite approach combines the benefits of different compounds to achieve comprehensive stabilization of nucleic acids, proteins, and morphological structures without sample destruction.

Inventive Principle:
Principle #40Composite materials

2Stability of the object's composition

If deep freezing is used to stabilize biological samples, then nucleic acid degradation is prevented, but complex cooling equipment and handling procedures are required

Engineering Contradiction:
Improvenucleic acid integrityVSAvoidcooling equipment and handling procedures
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical cooling system (freezers, ice, cold chains) with a chemical stabilization system based on dialkylacetamides and dialkylformamides. This substitution eliminates the need for complex cooling equipment and temperature-controlled handling procedures, allowing stabilization at ambient temperatures while maintaining nucleic acid integrity.

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

3Shape

If formalin fixation is used to preserve tissue morphology, then morphological integrity is maintained, but nucleic acid quality for molecular analysis deteriorates

Engineering Contradiction:
Improvetissue morphologyVSAvoidnucleic acid quality
Core Design Contradiction:
ShapeVSReliability

Solution Approach 1:

The patent changes the chemical parameters of fixation by using dialkylacetamides and dialkylformamides instead of formalin. These compounds have different chemical properties that allow them to stabilize tissue morphology through different mechanisms that do not cross-link or degrade nucleic acids, thus maintaining both morphological integrity and nucleic acid quality.

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 enables stable storage and analysis of biological samples at moderate temperatures without significant degradation, facilitating simultaneous molecular and histological examination, and is applicable to both frozen and fresh samples, reducing the need for complex cooling and handling procedures.

Implementation Method 1

bringing the biological sample into contact with a composition comprising a substance of the following structural formula: where R1 is a hydrogen radical or a methyl radical, R2 and R3 are the same or different hydrocarbon radicals with a carbon chain length of 1 - 20, and R4 is an oxygen, a sulfur or a selenium radical

Methodology Applied
Scientific EffectChemical stabilization:

Data Source

PatentEP2164963B1Method for stabilising a biological sample
Publication Date: 2014.05.07 QIAGEN GMBH
  • EP2164963B1 patent drawingFigure 1
  • EP2164963B1 patent drawingFigure 2
  • EP2164963B1 patent drawingFigure 3

AI summary

The invention relates to a method for stabilising a biological sample and bringing into contact of the biological sample with a composition comprising a substance of the following structural formula (I), where R1 = H or methyl, R2 and R3 = the same or different hydrocarbon groups with a carbon chain length of 1 - 20 and R4 = an oxygen, sulphur or selenium group.