Fibrinogen-Based Blood Sample Separation Device

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Solution Overview

Problem

Current sample preparation methods for detecting infectious agents in blood are complex, labor-intensive, and often inefficient, particularly in diagnosing sepsis, due to limitations in extracting and concentrating microorganisms and biomarkers from blood samples, which hinders early detection and antibiotic susceptibility testing.

Innovation Solution

A method and device that utilizes thrombin or thrombin-like enzymes to convert fibrinogen into fibrin, forming a fibrin network that traps target molecules or particles, allowing for their separation and concentration within a small volume, enabling efficient detection and analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If multi-centrifugation or filtration methodologies are used to enrich target microorganisms from blood samples, then separation of microorganisms is achieved, but the process becomes incompatible with routine automated laboratory assay workflows and requires lengthy manual or complex robotic pipetting steps

Engineering Contradiction:
Improveseparation efficiencyVSAvoidworkflow complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent introduces magnetic particles as an intermediary substance that mediates between the blood sample and the separation process. These particles are coated with affinity groups that specifically bind to target microorganisms, allowing them to act as carriers that facilitate separation through magnetic field application rather than complex centrifugation or filtration systems

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical separation systems (centrifugation equipment, filtration systems) with a magnetic field-based system. By using magnetic particles coated with affinity groups, the separation is achieved through magnetic attraction rather than mechanical force, enabling compatibility with automated laboratory workflows and eliminating the need for complex robotic pipetting

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Ease of operation

If affinity groups on magnetic beads are used to capture target microorganisms, then separation is simplified, but the spectrum of pathogenic microorganisms cannot be covered due to lack of generic affinity groups and encapsulation of microorganisms

Engineering Contradiction:
Improveseparation easeVSAvoidmicroorganism coverage
Core Design Contradiction:
Ease of operationVSAdaptability or versatility

Solution Approach 1:

The patent designs magnetic particles with universal affinity groups that can bind to multiple classes of microorganisms. By using non-specific affinity groups that recognize common structural features across different microorganism types (gram-negative, gram-positive bacteria, fungi), a single magnetic particle formulation can serve multiple detection purposes, covering a broad spectrum of pathogenic microorganisms

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

Solution Approach 2:

The patent modifies the surface properties of magnetic particles by coating them with specific affinity groups that can interact with encapsulated microorganisms. By changing the chemical parameters of the particle surface (coating with proteins, antibodies, or other binding molecules), the magnetic particles gain the ability to penetrate or bind to encapsulated microorganisms that would otherwise be inaccessible

Inventive Principle:
Principle #35Parameter changes

3Reliability

If lengthy manual or complex robotic pipetting steps are used for sample preparation, then target molecules can be extracted, but the process becomes slow, costly, and labor-consuming

Engineering Contradiction:
Improveextraction effectivenessVSAvoidprocessing speed
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent combines multiple separate steps (mixing, incubation, separation) into a single integrated process. By adding magnetic particles directly to the blood sample and using magnetic field application to simultaneously achieve binding and separation, the method eliminates the need for multiple pipetting steps, centrifugation rounds, and manual transfers, thereby dramatically increasing processing speed while maintaining extraction effectiveness

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent extracts only the essential function from complex procedures - the separation of target microorganisms from blood. By using magnetic particles that can be easily separated from the liquid phase through magnetic field application, the method removes the need for lengthy centrifugation and multiple pipetting steps, achieving rapid extraction without sacrificing effectiveness

Inventive Principle:
Principle #2Taking out (Extraction)

4Measurement precision

If large volumes of blood (5-10 ml) are processed to detect cell numbers as low as 1 CFU per milliliter, then detection sensitivity is improved, but the complexity of extracting and purifying specific infection biomarkers increases

Engineering Contradiction:
Improvedetection sensitivityVSAvoidextraction complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent uses magnetic particles as intermediaries that specifically bind to target microorganisms in large blood volumes. These particles act as concentrated collection points that gather rare microorganisms from extensive sample volumes, enabling detection of 1 CFU/ml sensitivity while simplifying the extraction process - the magnetic particles naturally concentrate the targets without requiring complex purification steps

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 approach enables rapid and sensitive detection of microorganisms from large blood volumes, concentrating targets to a small volume for further analysis, simplifying sample processing and reducing contamination risks, while being adaptable to various sample types and automated systems.

Implementation Method 1

the invention concerns a device that allows effective separation and concentration of target molecules or particles from samples containing fibrinogen proteins prior to their detection and analysis

Methodology Applied
Scientific EffectEnzyme catalysis: Enzyme

Implementation Method 2

A method and device that utilizes thrombin or thrombin-like enzymes to convert fibrinogen into fibrin, forming a fibrin network that traps target molecules or particles

Methodology Applied
Scientific EffectCoagulation: Coagulation

Implementation Method 3

forming a fibrin network that traps target molecules or particles, allowing for their separation and concentration within a small volume

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Data Source

PatentEP3067431B1Device including blood components for separating target molecules or particles from samples
Publication Date: 2019.07.24 DEBIOPHARM INTERNATIONAL SA
  • EP3067431B1 patent drawingFigure 1
  • EP3067431B1 patent drawingFigure 2
  • EP3067431B1 patent drawingFigure 3(a)~3(c)

AI summary

A sample collection device for separating target molecules or particles from a sample comprising: (i) an identification code; (ii) a container for containing the said sample; and (iii) a fibrinogen-containing sample in the container, the device being operable to form a fibrin clot that traps in a separable manner the said target molecules or particles upon the exposure of the said sample to thrombin or a thrombin-like enzyme within the said device, wherein the concentration of fibrinogen within the said sample is between 10 to 100 mg/ml.