Urine cfDNA Preservation Composition for Nuclease and Formaldehyde Control

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Solution Overview

Problem

The inherent instability of cell-free DNA (cfDNA) in urine hinders its clinical utility for non-invasive diagnostic applications due to high nuclease activity, cellular DNA contamination, and rapid degradation, necessitating a preservative method that stabilizes nucleated blood cells and quenches formaldehyde while blocking enzymatic activity.

Innovation Solution

A urine preservative composition comprising a stabilizing agent, formaldehyde quenching agent, and nuclease inhibitor is used to stabilize nucleated blood cells, quench free formaldehyde, and inhibit DNase activity, allowing for extended preservation of cfDNA at various temperatures without refrigeration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If urine is collected for cfDNA analysis, then non-invasive sampling is achieved, but cfDNA degrades rapidly due to high nuclease activity and cellular DNA contamination

Engineering Contradiction:

Improvenon-invasive samplingVSAvoidcfDNA stability

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The preservative composition is added to the urine collection container before sample collection, so that stabilization occurs immediately upon excretion. This preliminary action prevents nuclease-mediated degradation and cellular DNA release before they can compromise the cfDNA integrity, thereby maintaining reliability while preserving the non-invasive sampling advantage

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The preservative composition acts as an intermediary substance that mediates between the unstable cfDNA and the harmful urinary environment (nucleases, formaldehyde). It provides a protective chemical environment that allows cfDNA to remain stable in urine without requiring invasive alternative sampling methods

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If stabilizing agents are added to urine, then nucleated blood cells are stabilized, but free formaldehyde is released which can damage cfDNA structure

Engineering Contradiction:

Improvenucleated cell stabilizationVSAvoidformaldehyde damage to cfDNA

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The harmful free formaldehyde generated by stabilizing agents is extracted from the system through the inclusion of formaldehyde quenching agents (glycine, Tris, urea, allantoin, sulfites). These agents specifically bind and neutralize formaldehyde, removing its damaging effect on cfDNA while allowing the stabilizing agents to continue their function of preventing cellular DNA release

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The formaldehyde quenching agents convert the harmful effect of free formaldehyde into a beneficial outcome by demonstrating that controlled formaldehyde generation followed by immediate quenching creates optimal conditions for both cell stabilization and cfDNA preservation. The formaldehyde intermediate is transformed from a damaging agent into a useful stabilizing mechanism

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Ease of operation

If urine samples are stored without preservative, then sample handling is simple, but cfDNA concentration decreases due to enzymatic hydrolysis

Engineering Contradiction:

Improvesample handlingVSAvoidcfDNA concentration

Core Design Contradiction:

Ease of operationVSQuantity of substance

Solution Approach 1:

The preservative composition enables the urine sample to self-stabilize without requiring external intervention such as refrigeration or frequent processing. The nucleases are inhibited and cfDNA is protected automatically, allowing simple sample handling at room temperature while maintaining cfDNA concentration, thus achieving both ease of operation and substance preservation

Inventive Principle:

Principle #25Self-service

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

The method effectively stabilizes cfDNA in urine for up to 7 days, maintaining its integrity and concentration, enabling flexible sample handling and processing for diagnostic analysis.

Implementation Method 1

blocking of the high nuclease activity in urine

Methodology Applied

Scientific EffectEnzyme inhibition: Enzyme

Implementation Method 2

quenching substantially all available free formaldehyde that may be present from stabilizing/preserving agents

Methodology Applied

Scientific EffectChemical reaction: Chemical Bonding

Data Source

PatentUS12584161B2Stabilization of nucleic acids in urine

Publication Date: 2026.03.24 STRECK LLC

AI summary

A composition and method for preserving a urine sample and a preservative delivery vessel are disclosed wherein treatment of the urine sample aids in preserving circulating cell-free nucleic acids in urine over a wide range of dilution ratios within temperature fluctuations that can occur during urine sample handling, storage and transportation. The urine sample preservation composition and method and preservative delivery vessel provide a method for obtaining high quality stabilized urinary cell-free nucleic acids for clinical diagnostics development and application.