Magnetic Particle Pathogen Isolation from Blood

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Solution Overview

Problem

Current methods for detecting bacterial infections in blood samples are time-consuming, often requiring enrichment steps that can compromise test sensitivity and delay diagnosis, leading to potential sepsis and septic shock.

Innovation Solution

The use of magnetic particles with target-specific binding moieties to isolate pathogens directly from blood samples, allowing for rapid detection by binding to targets and capturing them with a magnetic field, followed by washing to reduce particle aggregation, enabling early and accurate identification of pathogens at low concentrations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional blood culture methods are used to detect bacterial infections, then detection accuracy can be achieved, but the detection time is excessively long (up to 72 hours or more)

Engineering Contradiction:
Improvedetection accuracyVSAvoiddetection time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The detection process is divided into separate functional modules: magnetic particle binding module, magnetic separation module, and detection module. This segmentation allows each module to be optimized independently and enables parallel processing, reducing overall detection time while maintaining accuracy

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Magnetic particles with binding moieties are pre-prepared and can be stored ready for use. When a blood sample is received, the pre-prepared magnetic particles immediately begin binding to target bacteria, eliminating the need for time-consuming culture enrichment steps and enabling direct detection

Inventive Principle:
Principle #10Preliminary action

2Measurement precision

If enrichment steps are performed to increase bacterial cell numbers for detection, then detection sensitivity is improved, but the test time is significantly extended (days to a week)

Engineering Contradiction:
Improvedetection sensitivityVSAvoidenrichment time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

Magnetic particles serve as an intermediary between the blood sample and the detection system. These particles are functionalized with binding moieties that directly capture target bacteria at their natural concentrations in blood, eliminating the need for enrichment while maintaining high detection sensitivity through the magnetic separation and concentration capability

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The biological enrichment process (bacterial growth and multiplication) is replaced with a physical-chemical binding process using magnetic particles. This substitution allows for direct capture and concentration of bacteria at their native concentrations without requiring time-dependent biological replication

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

3Measurement precision

If multiple incubation steps are performed to isolate target bacteria, then isolation purity is improved, but the overall process time and complexity increase significantly

Engineering Contradiction:
Improveisolation purityVSAvoidprocess complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The magnetic particles are designed with multi-functionality: they provide binding capability through surface moieties, enable magnetic separation for isolation, and can be used for subsequent detection. This multi-functionality consolidates multiple steps (binding, separation, concentration) into a single reagent system, reducing process complexity while maintaining isolation purity

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

Solution Approach 2:

The binding affinity parameters of the magnetic particles are optimized to achieve high-specificity binding under physiological conditions. By adjusting parameters such as particle size, surface charge, and binding moiety density, the system achieves high isolation purity in a single binding step without requiring multiple sequential incubations

Inventive Principle:
Principle #35Parameter changes

4Productivity

If magnetic particles are used to capture target bacteria directly from blood, then detection speed is improved, but particle aggregation may occur reducing capture efficiency

Engineering Contradiction:
Improvedetection speedVSAvoidcapture efficiency
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The magnetic particles exhibit local quality differentiation: the core provides magnetic responsiveness for separation, while the surface is functionalized with binding moieties for specific bacterial capture. This spatial differentiation of functions allows rapid magnetic separation without aggregation, as the binding sites are distributed on the particle surface rather than requiring particle-particle contact

Inventive Principle:
Principle #3Local quality

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 enables the rapid detection of pathogens at very low levels, facilitating early and accurate diagnosis, reducing the risk of sepsis and septic shock by providing clinically relevant data in a timely manner.

Implementation Method 1

introducing magnetic particles including a target-specific binding moiety to a body fluid sample in order to create a mixture, incubating the mixture to allow the particles to bind to a target

Methodology Applied
Scientific EffectSpecific binding: Adsorption

Implementation Method 2

applying a magnetic field to capture target/magnetic particle complexes on a surface

Methodology Applied
Scientific EffectMagnetic field: Magnetic Field

Implementation Method 3

washing with a wash solution that reduces particle aggregation, thereby isolating target/magnetic particle complexes

Methodology Applied
Scientific EffectParticle aggregation reduction: Dispersion (of waves)

Data Source

PatentUS11448646B2Isolating a target analyte from a body fluid
Publication Date: 2022.09.20 DNAE GROUP HOLDINGS LIMITED

AI summary

The invention generally relates to using magnetic particles and magnets to isolate a target analyte from a body fluid sample. In certain embodiments, methods of the invention involve introducing magnetic particles including a target-specific binding moiety to a body fluid sample in order to create a mixture, incubating the mixture to allow the particles to bind to a target, applying a magnetic field to capture target/magnetic particle complexes on a surface, and washing with a wash solution that reduces particle aggregation, thereby isolating target/magnetic particle complexes.