Short-Chain Nucleic Acid Isolation with Isopropanol Binding

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Solution Overview

Problem

Existing methods for purifying nucleic acids, particularly short-chain nucleic acids, are inefficient, leading to poor recovery and enrichment of these nucleic acids, especially in samples like maternal blood where fetal DNA is present in low concentrations.

Innovation Solution

A method involving the use of a nucleic acid-binding support material in the presence of a chaotropic compound and an alcohol, specifically isopropanol, to effectively bind and isolate short-chain nucleic acids. The method optimizes alcohol concentration and chaotropic compound strength to enhance the binding of short-chain nucleic acids.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If classical one-step extraction with phenol and chloroform is used, then nucleic acids can be isolated from starting material, but toxic substances remain as contaminants and water-soluble substances are not removed

Engineering Contradiction:

Improvepurity of isolated nucleic acidsVSAvoidtoxic contaminants in aqueous phase

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes toxic substances (phenol, chloroform) and water-soluble contaminants from the nucleic acid isolation process by using alternative reagents and multiple purification steps, thereby eliminating harmful factors while maintaining isolation effectiveness

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces intermediate purification steps including binding to solid support materials and selective elution as mediators between the starting material and final purified nucleic acids, allowing removal of contaminants without direct contact with toxic substances

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If selective adsorption to solid support materials is used, then toxic substances are avoided, but short-chain nucleic acids are not efficiently bound or enriched over long-chain nucleic acids

Engineering Contradiction:

Improveabsence of toxic contaminantsVSAvoidselectivity for short-chain nucleic acids

Core Design Contradiction:

Object-affected harmful factorsVSManufacturing precision

Solution Approach 1:

The patent changes critical parameters including alcohol concentration (10-40% v/v), chaotropic compound concentration (1-3 M), and pH (5-8) to optimize the binding conditions on solid support materials, enabling selective enrichment of short-chain nucleic acids while maintaining safety

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates locally optimized binding conditions at the solid support material interface by controlling the composition of binding buffers and local concentration of reagents, allowing differential binding behavior between short-chain and long-chain nucleic acids

Inventive Principle:

Principle #3Local quality

3Productivity

If standard solid phase binding with chaotropic buffers is used, then nucleic acids bind to solid phase, but short-chain nucleic acids bind less effectively than long-chain nucleic acids

Engineering Contradiction:

Improvebinding efficiency of nucleic acidsVSAvoidrecovery of short-chain nucleic acids

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

The patent optimizes binding parameters including increasing alcohol concentration to 10-40% v/v and adjusting chaotropic compound concentration to 1-3 M, which enhances the binding efficiency of short-chain nucleic acids to solid support materials and improves their recovery quantity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs dynamic optimization of binding conditions by adjusting reagent concentrations and incubation conditions based on the specific characteristics of the starting material and desired nucleic acid length, maximizing binding efficiency for short-chain nucleic acids

Inventive Principle:

Principle #15Dynamics

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 achieves efficient isolation and enrichment of short-chain nucleic acids, such as fetal DNA, over long-chain nucleic acids, significantly improving the sensitivity and reliability of prenatal diagnostics by increasing the concentration of fetal DNA in purified samples.

Implementation Method 1

binding nucleic acids to a nucleic acid-binding support material by contacting the starting material with said nucleic acid-binding support material in the presence of a chaotropic compound and an alcohol

Methodology Applied

Scientific EffectChaotropic effect:

Implementation Method 2

an alcohol, preferably isopropanol, said alcohol being present at a concentration of ≥5% (v/v) and preferably ≤40% (v/v)

Methodology Applied

Scientific EffectAlcohol precipitation: Precipitation

Data Source

PatentUS20250289841A1Method for isolating nucleic acids

Publication Date: 2025.09.18 QIAGEN GMBH

AI summary

The invention relates to a method and kits for isolating and/or purifying nucleic acids, in particular, short-chain nucleic acids, from a nucleic acid containing starting material, characterised by the following method steps: (a) bonding the nucleic acids to a nucleic acid bonding support material, wherein the starting material is brought into contact with the nucleic acid bonding support material in the presence of at least one chaotropic compound and preferably isopropanol, wherein the isopropanol is present in a concentration of ≥15% (v/v) and ≤35% (v/v), (b) optional elution of the bonded nucleic acids from the nucleic acid bonding support material. Said method is particularly suitable for the purification of foetal DNA from maternal blood.