TDE-Based Nucleic Acid Purification for Small RNA Isolation

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Solution Overview

Problem

Current methods for nucleic acid purification, particularly for small RNA molecules, face challenges such as the need for high alcohol concentrations which increase sample volume and processing time, and the use of toxic and hazardous reagents that complicate automation and environmental safety.

Innovation Solution

The use of tetraethylene glycol dimethyl ether (TDE) in combination with an aqueous buffer and chaotropic agents to effectively adsorb nucleic acids onto a solid phase, reducing the need for high alcohol concentrations and enhancing purification efficiency while minimizing the use of hazardous substances.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If high concentrations of alcohol are used to bind small RNA molecules to solid support, then binding efficiency is improved, but sample volume increases and processing time increases

Engineering Contradiction:
Improvebinding efficiencyVSAvoidprocessing time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The invention changes the chemical parameter of the binding buffer by using TDE instead of high concentration alcohol, maintaining effective binding while reducing sample volume and processing time requirements

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

TDE acts as an intermediary substance that facilitates nucleic acid binding to solid support without requiring high alcohol concentrations, thereby improving efficiency while reducing processing time

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If phenol extraction and salt precipitation methods are used for nucleic acid isolation, then high yield and purity are achieved, but the workflow becomes time-consuming and labor-intensive

Engineering Contradiction:
Improvenucleic acid purityVSAvoidworkflow time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The invention extracts and eliminates the time-consuming steps of phenol extraction and salt precipitation by using a simplified solid-phase binding method with TDE, achieving comparable purity faster

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention replaces the mechanical workflow of multiple manual steps (phenol extraction, precipitation, centrifugation) with a simpler chemical binding approach using TDE and solid support

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If toxic reagents such as phenol and high concentrations of chaotropic agents are used, then nucleic acid purification effectiveness is improved, but automation becomes difficult and environmental safety is compromised

Engineering Contradiction:
Improvepurification effectivenessVSAvoidautomation capability
Core Design Contradiction:
ReliabilityVSExtent of automation

Solution Approach 1:

The invention changes the chemical composition parameter by using TDE as a safer alternative to toxic reagents like phenol, enabling automation while maintaining purification effectiveness

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention converts the potentially harmful use of toxic reagents into a beneficial safe chemical system using TDE, which achieves the same purification goals without the hazards that prevent automation

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

4Reliability

If small RNA molecules are purified using conventional methods, then purification is achieved, but extensive sample dilution with high amounts of alcohol is required

Engineering Contradiction:
Improvepurification qualityVSAvoidsample volume
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The invention changes the binding chemistry parameter by using TDE, which enables effective binding of small RNA molecules without requiring extensive sample dilution with alcohol

Inventive Principle:
Principle #35Parameter changes

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

TDE facilitates efficient and high-yield nucleic acid purification with improved safety and reduced environmental impact, enabling more convenient and cost-effective nucleic acid isolation processes, including the purification of small RNA molecules without the need for extensive sample dilution or hazardous reagents.

Implementation Method 1

adsorption of a nucleic acid present in an aqueous adsorption solution to a solid substrate

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

a strong denaturing effect on proteins high concentrations of chaotropic agents also mediate cell lysis

Methodology Applied
Scientific EffectDenaturation:

Implementation Method 3

nucleic acid molecules are bound to the surface of the solid phase

Methodology Applied
Scientific EffectSurface interaction: Adsorption

Implementation Method 4

the solid material is washed with solutions containing decreasing chaotropic salt concentrations and increasing alcohol concentrations

Methodology Applied
Scientific EffectWashing:

Implementation Method 5

the solid material is brought into contact with a low salt solution or water under alkaline pH in order to remove the bound nucleic acid from the solid phase

Methodology Applied
Scientific EffectDesorption: Desorption

Data Source

PatentEP2094846B8Use of TDE for the isolation of nucleic acids
Publication Date: 2013.10.16 F HOFFMANN LA ROCHE & CO AG

AI summary

The invention provides the use of tetraethylene glycol dimethyl ether for adsorbing nucleic acids to solid phases such as those with silica surfaces. To this end, the invention also provides compositions comprising TDE. Methods are disclosed and claimed to purify nucleic acids from samples, as well as kits useful for performing these methods. Particularly, the invention encompasses methods for the purification of nucleic acids with low molecular weight. The nucleic acids purified by a method of the invention are suited for assays aiming at the detection of a target nucleic acid.