Tissue Disruption Composition with Enzymes and Chaotropes

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Solution Overview

Problem

Current methods for disrupting solid tissue samples are time-consuming and often damage sensitive analytes like nucleic acids and proteins, requiring specialized equipment and prolonged enzymatic digestion or mechanical disruption, which can deteriorate the sample quality.

Innovation Solution

A composition comprising solid disrupting particles, at least one enzyme for enzymatic lysis, and a chaotropic agent in a total concentration of equal to or less than 1M, used in combination with mechanical grinding or milling, to effectively disrupt and homogenize solid tissue samples using standard laboratory equipment, such as a low-power vortexer, while minimizing chemical impact and preserving analyte quality.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If mechanical disruption methods (grinding, shearing, beating) are used to disrupt solid tissue samples, then disruption efficiency is improved, but sensitive analytes (nucleic acids, proteins) are damaged or deteriorated

Engineering Contradiction:
Improvedisruption efficiencyVSAvoiddamage to sensitive analytes
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The invention combines chemical disruption methods (lysis buffers with enzymes and chaotropes) and mechanical disruption methods (bead milling with glass beads) into a single integrated process. The lysis buffer chemically weakens cellular structures while glass beads mechanically disrupt them, achieving efficient tissue disruption without excessive mechanical force that would damage analytes.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention uses a composite disruption system consisting of multiple chemical agents (detergents, enzymes, chaotropes) combined with mechanical elements (glass beads). This composite approach allows simultaneous chemical and mechanical action, improving disruption efficiency while controlling harm to analytes through the synergistic effect of multiple mechanisms.

Inventive Principle:
Principle #40Composite materials

2Object-affected harmful factors

If chemical disruption methods (lysis buffers) are used to disrupt solid tissue samples, then analyte quality is preserved, but disruption efficiency is insufficient for solid tissues

Engineering Contradiction:
Improveanalyte qualityVSAvoiddisruption efficiency
Core Design Contradiction:
Object-affected harmful factorsVSProductivity

Solution Approach 1:

The invention merges chemical disruption (lysis buffers) with mechanical disruption (bead milling) into a unified process. The chemical agents begin weakening cellular structures while glass beads provide mechanical force, together achieving complete disruption of solid tissues that neither method could achieve alone, while maintaining analyte quality through controlled conditions.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention optimizes parameters including glass bead diameter (0.5-2.0 mm), incubation temperature (50-60°C), and chaotrope concentration (0.5-2.0 M) to balance disruption efficiency with analyte preservation. These parameter adjustments allow the combined method to effectively disrupt solid tissues while minimizing damage to sensitive analytes.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If enzymatic digestion is performed over an extended period (overnight) to disrupt solid tissue, then complete lysis is achieved, but processing time is excessive and analytes may deteriorate

Engineering Contradiction:
Improvecomplete lysisVSAvoidprocessing time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The invention applies preliminary mechanical disruption with glass beads before or during enzymatic digestion. This preliminary mechanical action physically breaks down tissue structures and increases surface area, allowing enzymes to work more efficiently and achieve complete lysis in significantly reduced time (30-60 minutes versus overnight), while preventing analyte deterioration through faster processing.

Inventive Principle:
Principle #10Preliminary action

4Reliability

If high-power mixing devices are used to achieve sufficient homogenization and lysis, then disruption completeness is improved, but specialized equipment is required and analytes may be damaged

Engineering Contradiction:
Improvedisruption completenessVSAvoidequipment requirements
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention replaces expensive, specialized high-power mixing devices with simple, widely available low-power vortexers combined with disposable glass beads. The glass beads provide the necessary mechanical disruption force that would otherwise require complex equipment, making the method accessible to standard laboratories while achieving complete disruption through the combined chemical-mechanical action.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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 allows for rapid and efficient disruption of tough tissue samples with improved yields and quality of extracted nucleic acids, achieving a synergistic effect that surpasses individual mechanical or chemical disruption methods, reducing processing time significantly and maintaining the integrity of sensitive analytes.

Implementation Method 1

at least one enzyme for enzymatic lysis

Methodology Applied
Scientific EffectEnzymatic lysis: Enzyme

Implementation Method 2

at least one chaotropic agent in a total concentration equal to or less than 1M

Methodology Applied
Scientific EffectChaotropic effect:

Implementation Method 3

mechanical grinding or milling disruption

Methodology Applied
Scientific EffectMechanical grinding: Mechanical Force

Data Source

PatentEP3274452B1Composition and method for disrupting tissue material
Publication Date: 2021.03.03 QIAGEN GMBH

AI summary

The present invention relates to a composition for disrupting tissue material, the composition comprising solid disrupting particles in combination with at least one enzyme for enzymatic lysis and at least one chaotropic agent, as well as to a method for disrupting tissues material by simultaneously applying mechanical grinding or milling disruption and enzymatic digestion.