Cell-Free RNA Preservation via Protective Agents

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Solution Overview

Problem

The stability and isolation of cell-free RNA in blood samples are compromised due to ribonuclease activity and cell lysis, making it difficult to accurately measure and diagnose diseases such as cancer, as the RNA is susceptible to degradation post-blood draw.

Innovation Solution

A method involving a protective agent, which can include preservative agents, enzyme inhibitors, and metabolic inhibitors, is used to inhibit RNA synthesis, fix blood cells, and stabilize RNA against nucleases and proteases, allowing for the preservation and isolation of cell-free RNA, thereby maintaining its integrity and diagnostic value.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If cell-free RNA is isolated from blood samples without preservation, then the isolation process is simple and quick, but the RNA is degraded by ribonuclease activity and cell lysis, reducing its diagnostic accuracy

Engineering Contradiction:

Improvediagnostic accuracyVSAvoidpreservation system complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by adding preservation agents to the blood collection tube at the time of blood draw, before any cell lysis or RNA degradation can occur. This pre-emptive measure stabilizes the cell-free RNA immediately, preventing subsequent degradation by ribonucleases and maintaining diagnostic accuracy throughout storage and transport.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses preservation agents as intermediary substances that mediate between the blood sample and the diagnostic testing process. These agents create a protective environment that isolates the cell-free RNA from degrading factors, enabling accurate measurement without requiring immediate processing.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Duration of action of stationary object

If blood samples are processed immediately after drawing, then RNA degradation is minimized, but the ability to store and transport samples is limited

Engineering Contradiction:

Improvesample storage durationVSAvoidRNA stability

Core Design Contradiction:

Duration of action of stationary objectVSReliability

Solution Approach 1:

The preservation agents are introduced at the time of blood draw to immediately stabilize the cell-free RNA. This preliminary stabilization allows the sample to be stored and transported for extended periods without degradation, maintaining RNA integrity and diagnostic reliability throughout the storage duration.

Inventive Principle:

Principle #10Preliminary action

3Quantity of substance

If cell lysis is allowed to occur after blood draw, then cellular RNA is released for analysis, but cell-free RNA is mixed with cellular RNA, making isolation difficult

Engineering Contradiction:

Improvetotal RNA available for analysisVSAvoidRNA isolation difficulty

Core Design Contradiction:

Quantity of substanceVSEase of manufacture

Solution Approach 1:

The preservation agents prevent cell lysis from occurring after blood draw. By maintaining cell membrane integrity in advance, the patent ensures that cellular RNA remains trapped within cells while cell-free RNA remains in the plasma, enabling clear separation and isolation of cell-free RNA without contamination.

Inventive Principle:

Principle #10Preliminary action

4Measurement precision

If ribonuclease activity is present in the blood sample, then natural RNA turnover occurs, but cell-free RNA is subjected to nuclease-mediated degradation, reducing its diagnostic value

Engineering Contradiction:

Improvecell-free RNA detection accuracyVSAvoidribonuclease degradation

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful effect of ribonuclease activity into a beneficial preservation mechanism. Preservation agents bind to or inhibit ribonucleases, transforming these degrading enzymes into inactive forms that cannot threaten cell-free RNA integrity, thereby protecting rather than exposing the RNA to degradation.

Inventive Principle:

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

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 preserves and isolates cell-free RNA, maintaining its integrity and diagnostic value, allowing for accurate detection of disease presence and severity, even after extended periods, by inhibiting RNA synthesis and stabilizing it against degradation.

Implementation Method 1

inhibit RNA synthesis

Methodology Applied

Scientific EffectInhibition of RNA synthesis:

Implementation Method 2

stabilize RNA against nucleases and proteases

Methodology Applied

Scientific EffectStabilization against nucleases:

Implementation Method 3

fix blood cells

Methodology Applied

Scientific EffectCell fixation:

Data Source

PatentUS11761025B2Preservation of cell-free nucleic acids

Publication Date: 2023.09.19 STRECK LLC

AI summary

A method for preserving and processing cell-free nucleic acids located within a blood sample is disclosed, wherein a blood sample containing cell-free nucleic acids is treated to reduce both blood cell lysis and nuclease activity within the blood sample. The treatment of the sample aids in increasing the amount of cell-free nucleic acids that can be identified and tested while maintaining the structure and integrity of the nucleic acids.