Nucleic Acid Protective Agent for Maternal Plasma Preservation

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Solution Overview

Problem

Current methods for isolating and preserving fetal nucleic acids from maternal blood are inefficient, prone to contamination, and require immediate processing to prevent maternal cell lysis and nuclease activity, which limits the reliability and duration of fetal nucleic acid analysis.

Innovation Solution

A method involving a nucleic acid protective agent containing diazolidinyl urea or imidazolidinyl urea in a buffered salt solution, along with EDTA, that stabilizes blood cells and inhibits nuclease activity, allowing for extended storage and analysis of fetal nucleic acids without immediate plasma separation or freezing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If immediate plasma separation and freezing is performed to prevent maternal cell lysis and nuclease activity, then fetal nucleic acid integrity is maintained, but processing time and operational complexity increase

Engineering Contradiction:

Improvefetal nucleic acid integrityVSAvoidprocessing time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent applies preliminary action by adding the nucleic acid protective agent to the blood sample at the time of collection, before any processing steps. This pre-protection prevents maternal cell lysis and nuclease activity during storage, eliminating the need for immediate plasma separation and freezing. The agent is incorporated into the collection tube, ensuring protection is established before any harmful processes can occur.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The nucleic acid protective agent serves as an intermediary substance that mediates between the blood sample and environmental factors that cause degradation. The agent, comprising preservative, solvent, EDTA, and 2-amino acetic acid, acts as a protective barrier that prevents maternal cell lysis and inhibits nuclease activity, allowing the sample to be stored without immediate processing while maintaining fetal nucleic acid integrity.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If plasma separation is delayed to allow for extended storage, then maternal cell lysis releases genomic nucleic acids that contaminate fetal nucleic acid samples, but the protective agent prevents this contamination

Engineering Contradiction:

Improvestorage durationVSAvoidsample purity

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent extracts and isolates the fetal nucleic acids from the protected blood sample after storage. The protective agent remains in the sample, but the fetal nucleic acids can be separated and purified for analysis. This extraction step removes the valuable fetal genetic material while leaving the protective agent and maternal components behind, enabling extended storage without compromising sample purity.

Inventive Principle:

Principle #2Taking out (Extraction)

3Reliability

If formaldehyde is used to stabilize cell membranes and inhibit nuclease activity, then fetal nucleic acid preservation is improved, but formaldehyde toxicity and cross-linking of nucleic acids and proteins occurs

Engineering Contradiction:

Improvefetal nucleic acid preservationVSAvoidformaldehyde toxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical parameters of the preservation system by replacing formaldehyde with a different chemical composition. The nucleic acid protective agent uses a preservative in a buffered salt solution with solvent, EDTA, and 2-amino acetic acid, which achieves the same protective effect (preventing cell lysis and inhibiting nucleases) without the toxic cross-linking effects of formaldehyde. This parameter change maintains preservation efficacy while eliminating harmful effects.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs a disposable nucleic acid protective agent that provides short-term protection during storage and processing. The agent is designed to be effective for the duration needed (up to 72 hours) and then can be discarded or removed, avoiding the need for formaldehyde which requires careful handling, disposal, and decontamination procedures due to its toxicity and carcinogenicity.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

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 significantly increases the recoverable amount of fetal nucleic acids, maintains their integrity, and allows for storage at room temperature for up to 14 days, enhancing diagnostic reliability and reducing contamination from maternal nucleic acids.

Implementation Method 1

a preservative agent selected from diazolidinyl urea and/or imidazolidinyl urea in a buffered salt solution

Methodology Applied

Scientific EffectFormaldehyde release:

Implementation Method 2

contacting a drawn maternal blood sample that includes a plurality of blood cells with a nucleic acid protective agent... in an amount and time sufficient so that the blood cells are substantially prevented from (i) releasing genomic nucleic acids into the blood sample

Methodology Applied

Scientific EffectCell membrane stabilization:

Implementation Method 3

a nucleic acid protective agent comprising a preservative agent selected from diazolidinyl urea and/or imidazolidinyl urea... EDTA, and 2-amino acetic acid (glycine)... in an amount and time sufficient so that the blood cells are substantially prevented from... experiencing nuclease activity that degrades fetal nucleic acid

Methodology Applied

Scientific EffectNuclease inhibition:

Implementation Method 4

allows for extended storage and analysis of fetal nucleic acids without immediate plasma separation or freezing... maintains their integrity... allows for storage at room temperature for up to 14 days

Methodology Applied

Scientific EffectNucleic acid stabilization:

Data Source

PatentEP3708676B1Preservation of fetal nucleic acids in maternal plasma

Publication Date: 2024.10.30 STRECK LLC

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AI summary

A product for preserving and processing fetal nucleic acids located within maternal plasma is disclosed, whereby a sample of maternal blood containing fetal nucleic acids is treated to reduce both cell lysis of the maternal blood cells and deoxyribonuclease (DNase) and ribonuclease (RNase) activity within the fetal nucleic acids. Use of the product increases the amount of fetal nucleic acids that can be identified and tested while maintaining the structure and integrity of the fetal nucleic acids.