Automated Nucleic Acid Purification via Ring Magnet Separation

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Solution Overview

Problem

Current methods for nucleic acid purification, particularly from samples like FFPE tissue and stool, face challenges due to interfering insoluble components such as cellular debris and paraffin, which complicate automated processes and lead to inefficiencies and contamination issues.

Innovation Solution

An automated system utilizing a sample vessel holder with a ring magnet to suspend magnetic particles, allowing for the separation of nucleic acids from debris under non-chaotropic conditions, minimizing contamination and enabling efficient automated purification.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If automated purification systems are implemented, then productivity and efficiency are improved, but device complexity increases

Engineering Contradiction:
Improvepurification efficiencyVSAvoidsystem complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The automated purification system integrates multiple functions into a single platform: magnetic particle suspension, automated vessel handling, debris separation, and nucleic acid purification. The system can process various sample types (FFPE tissue, stool, blood) using the same core mechanism, reducing the need for multiple specialized devices while maintaining high productivity

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

Magnetic particles serve as an intermediary medium that enables automated manipulation of biological samples. These particles bind to cellular debris and allow for easy separation and purification through magnetic field application, facilitating automation without requiring direct mechanical manipulation of complex biological materials

Inventive Principle:
Principle #24Intermediary (Mediator)

2Manufacturing precision

If magnetic particles are used under non-chaotropic conditions, then purity of nucleic acid isolation is improved, but loss of substance increases due to debris interference

Engineering Contradiction:
Improvepurification qualityVSAvoidnucleic acid yield
Core Design Contradiction:
Manufacturing precisionVSLoss of substance

Solution Approach 1:

The system performs preliminary separation of cellular debris using magnetic particles under non-chaotropic conditions before proceeding to nucleic acid extraction. This preliminary action removes interfering substances that would otherwise compromise purification quality, while the automated system ensures minimal nucleic acid loss through controlled transfer and recovery processes

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system optimizes parameters such as magnetic particle size, concentration, and magnetic field strength to maximize debris binding while minimizing nucleic acid adsorption. By carefully controlling these parameters, the system achieves high purity isolation without significant yield loss

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If multiple purification steps are performed manually, then manufacturing precision is improved, but loss of time increases

Engineering Contradiction:
Improvepurification reliabilityVSAvoidprocessing time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The automated system merges multiple purification steps into a single integrated workflow: sample preparation, magnetic particle addition, incubation, magnetic separation, and nucleic acid recovery all occur in sequence without manual intervention. This consolidation maintains purification reliability while dramatically reducing total processing time compared to manual execution of each step

Inventive Principle:
Principle #5Merging (Combining)

4Ease of operation

If automated systems are used, then ease of operation is improved, but device complexity increases

Engineering Contradiction:
Improveautomation levelVSAvoidsystem structure
Core Design Contradiction:
Ease of operationVSDevice complexity

Solution Approach 1:

The automated purification system performs operations autonomously without requiring skilled manual intervention. The system self-regulates timing, mixing, separation, and recovery parameters, making complex purification procedures accessible to users with minimal training while the underlying complexity is managed by integrated control systems

Inventive Principle:
Principle #25Self-service

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 approach effectively removes debris, enhances purification efficiency, reduces contamination risks, and improves the reproducibility and robustness of nucleic acid isolation, particularly from challenging samples like FFPE and stool, facilitating more reliable and cost-effective diagnostics.

Implementation Method 1

The sample vessel holder has at least one ring-shaped magnet, in the ring interior of which the sample vessel can be received

Methodology Applied
Scientific EffectMagnetic field: Magnetic Field

Implementation Method 2

suspending first magnetic particles in the solution; introducing the first sample vessel into a sample vessel holder, the sample vessel being introduced into the ring interior of a ring magnet associated with the sample vessel holder

Methodology Applied
Scientific EffectMagnetism: Magnetism

Data Source

PatentEP2998398B1Automated system for purifying nucleic acids, particularly from fixed tissue
Publication Date: 2018.01.03 SIEMENS HEALTHCARE DIAGNOSTICS INC
  • EP2998398B1 patent drawingFigure 1~5
  • EP2998398B1 patent drawingFigure 6~7

AI summary

The invention relates to an automated system for the purification of nucleic acids. It serves to carry out a process comprising the steps of: a) receiving the sample in a first sample vessel in an aqueous solution and lyseing the sample under non-chaotropic conditions; suspending first magnetic particles in the solution and placing the first sample vessel in a sample vessel holder, wherein the sample vessel is placed in the annular interior of a ring magnet associated with the sample vessel holder; separating the solution from the magnetic particles; and isolating the nucleic acids from the solution.The system comprises a storage unit for at least one sample vessel; a temperature-controlled device with at least one receptacle for the sample vessel; a sample vessel holder for receiving at least one sample vessel; a device for transporting the sample vessel holder from the storage unit to the temperature-controlled device; a device for transferring liquid from and/or into a sample vessel; and a control unit for controlling the transport device, the liquid transfer device, and the temperature of the temperature-controlled device. The sample vessel holder for receiving the at least one sample vessel has at least one ring-shaped magnet in the annular space of which the sample vessel can be received.