Eukaryotic Nucleic Acid Isolation from Stool Samples

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Solution Overview

Problem

Current methods for diagnosing gastrointestinal disorders, such as gastrointestinal cancer and inflammatory bowel disease, are invasive, time-consuming, and costly, and face challenges in distinguishing eukaryotic nucleic acids from the high bacterial load in stool samples, leading to unfavorable signal-to-noise ratios and degradation of eukaryotic signals.

Innovation Solution

A method involving the separation of eukaryotic cells from bacterial cells in stool samples using a buffer, surfactant, and ribonuclease inhibitor, followed by chaotropic agent treatment, to isolate eukaryotic nucleic acids, which can be analyzed for biomarkers using techniques like microarray sequencing and PCR, enabling the detection of gastrointestinal disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If standard diagnostic methods like colonoscopy are used, then diagnostic accuracy is improved, but patient comfort and cost deteriorate due to invasiveness and high cost

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidpatient comfort
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent extracts eukaryotic nucleic acids from the complex stool sample matrix by separating them from bacterial cells through density gradient centrifugation. This extraction allows diagnostic analysis to be performed on isolated eukaryotic material rather than the entire stool sample, enabling non-invasive testing while maintaining diagnostic accuracy

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses eukaryotic nucleic acids as an intermediary biomarker that can be detected in stool samples to indirectly diagnose gastrointestinal disorders. This intermediary approach allows diagnosis without direct visualization or intervention in the gastrointestinal tract, improving patient comfort while maintaining diagnostic capability

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If standard diagnostic methods like colonoscopy are used, then diagnostic accuracy is improved, but time consumption and cost deteriorate

Engineering Contradiction:
Improvediagnostic accuracyVSAvoiddiagnostic time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary isolation of eukaryotic nucleic acids from stool samples using a standardized protocol involving buffer treatment, centrifugation, and purification. This preliminary preparation creates ready-to-analyze samples that can be processed through various detection methods more quickly than traditional diagnostic procedures

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent creates a copy or representation of the gastrointestinal disease state through detection of eukaryotic nucleic acid biomarkers in stool samples. This molecular copy allows diagnosis without requiring the time-consuming procedure of direct visualization through colonoscopy

Inventive Principle:
Principle #26Copying

3Ease of operation

If eukaryotic nucleic acids are isolated from stool samples, then non-invasive diagnosis is enabled, but signal-to-noise ratio deteriorates due to high bacterial load

Engineering Contradiction:
Improvenon-invasive capabilityVSAvoidsignal-to-noise ratio
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent segments the complex stool sample into distinct components based on density, separating eukaryotic cells from bacterial cells through density gradient centrifugation. This segmentation isolates the eukaryotic nucleic acid signal from the overwhelming bacterial background, improving signal-to-noise ratio while maintaining the non-invasive nature of the test

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent extracts eukaryotic nucleic acids specifically from the stool sample matrix by separating them from bacterial cells. This extraction process removes the bacterial noise while retaining the diagnostic eukaryotic signal, enabling non-invasive diagnosis with improved signal-to-noise ratio

Inventive Principle:
Principle #2Taking out (Extraction)

4Ease of operation

If eukaryotic nucleic acids are isolated from stool samples, then non-invasive diagnosis is enabled, but nucleic acid degradation worsens the reliability of detection

Engineering Contradiction:
Improvenon-invasive capabilityVSAvoidnucleic acid stability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent performs preliminary isolation of eukaryotic nucleic acids from stool samples using a standardized protocol that includes buffer treatment, centrifugation, and purification steps designed to protect nucleic acids from degradation. This preliminary preparation ensures nucleic acid stability while maintaining the non-invasive advantage of stool-based testing

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses eukaryotic nucleic acids as a stable intermediary biomarker that can be isolated and protected from degradation during the diagnostic process. By focusing on isolated nucleic acids rather than whole cells or tissues, the method maintains reliability while enabling non-invasive diagnosis

Inventive Principle:
Principle #24Intermediary (Mediator)

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

This method effectively isolates eukaryotic nucleic acids, allowing for the detection of biomarkers indicative of gastrointestinal disorders, providing a non-invasive and cost-effective diagnostic approach for both humans and animals.

Implementation Method 1

separating the suspension into a portion enriched for eukaryotic cells and a portion enriched for bacterial cells

Methodology Applied
Scientific EffectDensity gradient separation: Density Gradient

Implementation Method 2

adding a chaotropic agent and optionally a surfactant to the portion enriched for eukaryotic cells to form a lysate

Methodology Applied
Scientific EffectChaotropic lysis:

Implementation Method 3

fractioning the lysate into a cell debris layer, a layer comprising eukaryotic nucleic acids and a lipid layer

Methodology Applied
Scientific EffectCentrifugal separation: Centrifugal Separation

Data Source

PatentEP3532637B1Method for isolation of eukaryotic nucleic acids from stool samples
Publication Date: 2024.07.10 GENEOSCOPY INC
  • EP3532637B1 patent drawingFigure 1(a)~1(b)
  • EP3532637B1 patent drawingFigure 2
  • EP3532637B1 patent drawingFigure 3

AI summary

Provided herein are materials and methods for isolation of eukaryotic nucleic acid from a human or non-human animal stool sample. Also provided are methods of analysis of eukaryotic biomarkers present in a human or non-human animal stool sample.