Nucleic Acid Extraction from Heterogeneous Biological Samples

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Solution Overview

Problem

Current methods for nucleic acid extraction from biological samples, particularly bodily fluids, face challenges in achieving high quality and yield due to sample heterogeneity and adverse factors, limiting their effectiveness for diagnostic and monitoring applications in cancer research and medicine.

Innovation Solution

A method involving sample pre-processing and extraction enhancement operations, combined with affinity exclusion or enrichment techniques, to isolate high-quality nucleic acids from heterogeneous collections of nucleic acid-containing materials, such as cells and microvesicles, using agents like RNase inhibitors and specific surface molecules to enhance yield and purity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If traditional nucleic acid extraction methods are used on bodily fluids, then the extraction process is simple, but the quality and yield of nucleic acid are low due to sample heterogeneity and adverse factors

Engineering Contradiction:
Improvenucleic acid qualityVSAvoidextraction process complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The extraction process is divided into distinct segments: pre-processing step to concentrate nucleic acid-containing materials, followed by separate enhancement operations (extraction enhancement agents, affinity exclusion/enrichment). This segmentation allows each step to optimize for its specific function, improving overall nucleic acid quality while managing complexity through structured progression.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A pre-processing step is performed before the main extraction to concentrate nucleic acid-containing materials from the bodily fluid sample. This preliminary action removes heterogeneity and adverse factors early in the process, ensuring that subsequent extraction steps work with pre-concentrated, cleaner material, thereby improving final nucleic acid quality and yield.

Inventive Principle:
Principle #10Preliminary action

2Quantity of substance

If extraction enhancement operations and affinity exclusion techniques are applied, then nucleic acid yield and purity are improved, but the extraction process becomes more complex

Engineering Contradiction:
Improvenucleic acid yieldVSAvoidextraction process complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

Extraction enhancement agents and affinity exclusion reagents act as intermediaries between the sample and the nucleic acid. These agents selectively bind to or enhance the recovery of nucleic acid-containing materials while excluding other sample components. This intermediary approach increases nucleic acid yield and purity by facilitating selective separation without requiring complex mechanical or manual procedures.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Quantity of substance

If heterogeneous collections of nucleic acid-containing materials are processed, then comprehensive nucleic acid recovery is achieved, but the heterogeneity reduces extraction efficiency

Engineering Contradiction:
Improvenucleic acid recoveryVSAvoidextraction efficiency
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The method employs parameter changes including pH adjustment, temperature control, and chemical concentration variations during pre-processing and enhancement steps. These parameter changes optimize the extraction conditions at each stage, enabling efficient processing of heterogeneous materials by adjusting the chemical and physical environment to favor nucleic acid recovery while managing sample complexity.

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

The method achieves high-quality nucleic acid extractions with improved yield and integrity, enabling effective analysis for diagnostics, prognostics, and monitoring, particularly in cancer research, by reducing heterogeneity and mitigating adverse factors in biological samples.

Implementation Method 1

using agents like RNase inhibitors and specific surface molecules to enhance yield and purity

Methodology Applied
Scientific EffectEnzyme inhibition: Enzyme

Implementation Method 2

affinity exclusion or enrichment techniques, to isolate high-quality nucleic acids from heterogeneous collections of nucleic acid-containing materials

Methodology Applied
Scientific EffectAffinity binding: Adsorption

Data Source

PatentUS11407991B2Nucleic acid extraction from heterogeneous biological materials
Publication Date: 2022.08.09 EXACT SCIENCES CORP
  • US11407991B2 patent drawing
  • US11407991B2 patent drawing
  • US11407991B2 patent drawing

AI summary

Methods for extracting high quality nucleic acids from a heterogenous collection of nucleic acid-containing materials from a biological sample are disclosed. The heterogenous collection of nucleic-acid containing materials may contain cells or microvesicles, or both. The extractions obtained by the methods described herein are characterized by high yield and high integrity, making the extracted nucleic acids useful for various applications in which high quality nucleic acid extractions are preferred, e.g., a diagnosis, prognosis, or therapy evaluation for a medical condition.