Blood Collection Device Stabilizing cfDNA Integrity
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Solution Overview
Problem
Current methods for stabilizing and preserving cell-free DNA (cfDNA) during collection, storage, and shipment are inadequate, leading to DNA integrity issues and contamination with genomic DNA, which affects accurate analysis and detection of cfDNA biomarkers.
Innovation Solution
A protocol using a unique protective agent composition that stabilizes DNA integrity for prolonged periods by inhibiting deoxyribonuclease activity and minimizing genomic DNA background, allowing for room temperature storage and transportation without significant degradation, using diazolidinyl urea and imidazolidinyl urea as preservatives and a quenching agent to neutralize aldehydes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If aldehyde-based fixation (formaldehyde) is used to preserve cfDNA, then sample stability is improved, but DNA integrity deteriorates due to cross-linking and degradation
Solution Approach 1:
The patent introduces an intermediary substance (protective agent composition containing preservative and quenching agent) that mediates between the need for sample stability and DNA integrity. The preservative stabilizes the sample without causing aldehyde cross-linking, while the quenching agent neutralizes any free aldehydes, thus protecting DNA from degradation while maintaining sample stability.
Solution Approach 2:
The patent extracts the harmful aldehyde component from the fixation process by using a preservative that does not rely on aldehyde-based mechanisms. This removes the source of DNA cross-linking and degradation while retaining the beneficial sample stabilization effect through alternative chemical mechanisms.
2Ease of operation
If blood samples are stored at room temperature for extended periods, then ease of operation is improved, but DNA degradation increases
Solution Approach 1:
The patent applies preliminary action by incorporating the protective agent composition into the blood collection device before sample collection. This preservative composition is already in place to immediately stabilize the sample upon collection, preventing DNA degradation during subsequent room temperature storage and transport without requiring later intervention.
Solution Approach 2:
The protective agent composition acts as an intermediary that enables room temperature storage by chemically protecting the DNA from degradation mechanisms that would otherwise occur at elevated temperatures, thus mediating between temperature conditions and DNA stability.
3Measurement precision
If genomic DNA background is minimized to improve cfDNA detection accuracy, then measurement precision is improved, but sample processing complexity increases
Solution Approach 1:
The patent minimizes genomic DNA background through preliminary action by stabilizing blood cells immediately upon collection with the protective agent composition. This prevents post-collection cell lysis that would release genomic DNA into the plasma, thereby maintaining low gDNA background levels without requiring complex processing steps to remove or manage cellular contamination.
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 effectively preserves cfDNA integrity, reducing background genomic DNA contamination and enabling accurate and precise analysis of cfDNA, even after extended periods, without the detrimental effects of aldehyde fixation, thus enhancing clinical analysis and diagnostic capabilities.
Implementation Method 1
a quenching agent for substantially abating any free aldehyde (e.g., formaldehyde) from reacting with DNA within a sample
Implementation Method 2
The protective agent composition may include a preservative composition, an aldehyde quenching agent, and an anticoagulant
Data Source
AI summary
Methods and devices for stabilizing a biological sample for analysis, comprising the steps of obtaining in a sample collection device a biological sample from a subject, the biological sample including at least one circulating cell-free first nucleic acid from the subject. The methods may include a step of contacting the biological sample while within the sample collection device with a protective agent composition that includes a preservative agent, an optional anticoagulant, and a quenching agent to form a mixture that includes the protective agent composition and the sample.