Butanamide Stabilization of Extracellular Nucleic Acids

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Solution Overview

Problem

Current methods for stabilizing extracellular nucleic acids in cell-containing samples, such as blood, face challenges including contamination with intracellular nucleic acids, degradation, and the need for immediate centrifugation or freezing, which complicates sample handling and storage, especially in facilities lacking centrifuges or cold chain capabilities.

Innovation Solution

The use of butanamide as a stabilizer, which reduces contamination with genomic DNA and allows for the preservation of extracellular nucleic acids, enabling storage at room temperature for extended periods without compromising sample quality, and facilitates efficient nucleic acid isolation using standard methods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If centrifugation is performed to obtain cell-free fraction, then extracellular nucleic acids can be isolated, but cell breakage occurs causing contamination with intracellular nucleic acids

Engineering Contradiction:
Improvepurity of extracellular nucleic acid isolationVSAvoidcontamination with intracellular nucleic acids
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by adding a stabilizing agent to the blood sample immediately at the time of collection. This stabilizer prevents cell lysis and nucleic acid degradation before any processing steps occur, thereby preventing contamination with intracellular nucleic acids and preserving the integrity of extracellular nucleic acids for subsequent isolation

Inventive Principle:
Principle #10Preliminary action

2Reliability

If immediate centrifugation or freezing is required for sample processing, then nucleic acid degradation is prevented, but sample handling complexity increases and requires specialized equipment

Engineering Contradiction:
Improveprevention of nucleic acid degradationVSAvoidrequirement for centrifuges and cold chain capabilities
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies self-service by incorporating a stabilizing agent that automatically prevents nucleic acid degradation and cell lysis upon sample collection. The stabilizer functions autonomously without requiring external equipment such as centrifuges or freezers, enabling samples to be stored and transported under simple conditions while maintaining nucleic acid integrity

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent applies parameter changes by introducing a chemical stabilizer that alters the physical-chemical parameters of the sample environment. The stabilizer changes the conditions to prevent cell lysis and nucleic acid degradation, allowing samples to remain stable at room temperature without requiring temperature-controlled storage or processing equipment

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If cells are not completely removed from plasma/serum, then sample processing is simplified, but residual cells release intracellular nucleic acids causing contamination

Engineering Contradiction:
Improvesimplicity of sample processingVSAvoidpurity of extracellular nucleic acid population
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent applies preliminary action by adding a stabilizing agent to the blood sample immediately at the time of collection. This stabilizer prevents cell lysis and nucleic acid degradation before any processing steps occur, thereby preventing contamination with intracellular nucleic acids and preserving the integrity of extracellular nucleic acids for subsequent isolation

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentEP2976425B1Stabilization and isolation of extracellular nucleic acids
Publication Date: 2019.11.06 QIAGEN GMBH
  • EP2976425B1 patent drawingFigure 1
  • EP2976425B1 patent drawingFigure 2
  • EP2976425B1 patent drawingFigure 3

AI summary

The present invention provides methods, compositions and devices for stabilizing the extracellular nucleic acid population in a cell-containing biological sample using butanamide.