Analyte Detection Using Multi-Particle Complexes and Centrifugal Separation

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Solution Overview

Problem

Current assays for detecting analytes in samples are often costly, time-consuming, technically complex, and difficult to scale up for large sample sizes or numbers, limiting their effectiveness in biomedical, veterinary, and environmental sciences.

Innovation Solution

The use of particles with different physico-chemical properties, such as buoyancy, size, density, and spectral characteristics, in solution-based sandwich and competition assays to rapidly and quantitatively detect analytes by forming multi-particle complexes and applying centrifugal force for separation, allowing for the detection of remaining particles indicative of analyte presence.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional assays (ELISA, immunoprecipitation) are used for analyte detection, then detection accuracy is maintained, but the assays become costly, time-consuming, and difficult to scale up

Engineering Contradiction:
Improveassay throughput and scalabilityVSAvoidassay time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The assay is divided into distinct functional components: magnetic particles for capture, fluorescently labeled detection particles, and separation media. This segmentation allows each component to be optimized independently and enables parallel processing of multiple samples, significantly increasing throughput while reducing assay time.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Magnetic particles serve as intermediaries that bridge the sample and detection system. They concentrate analytes from large sample volumes and present them to detection particles, enabling rapid processing of multiple samples without sacrificing sensitivity or accuracy.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If conventional assays are used for analyte detection, then reliable results are obtained, but technical complexity increases

Engineering Contradiction:
Improvedetection reliabilityVSAvoidassay complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The detection step is extracted and simplified by using fluorescently labeled particles that provide direct visual or instrumental readout. This eliminates complex signal amplification steps and multi-step washing procedures required in conventional ELISA, reducing technical complexity while maintaining reliability.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

Fluorescently labeled particles provide a simple, reliable signal that can be detected by standard fluorescence readers or even visual inspection. This color-based detection method simplifies the assay protocol and reduces the technical expertise required compared to conventional enzymatic detection methods.

Inventive Principle:
Principle #32Color changes

3Measurement precision

If conventional assays are used for analyte detection, then accurate quantification is achieved, but cost increases

Engineering Contradiction:
Improvequantification accuracyVSAvoidreagent cost
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The assay uses disposable magnetic particles and fluorescently labeled detection particles that can be prepared in bulk at low cost. These single-use components eliminate the need for expensive reusable reagents and equipment consumables associated with conventional assays, reducing overall cost while maintaining quantification accuracy.

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

Solution Approach 2:

The detection method transitions from enzymatic color development (ELISA) to fluorescent labeling, changing the detection parameter from absorbance to fluorescence intensity. This parameter change enables the use of cheaper reagents while providing equivalent or superior quantification accuracy through more sensitive detection.

Inventive Principle:
Principle #35Parameter changes

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, qualitative, and quantitative detection of analytes, improving assay efficiency and scalability, making it suitable for various scientific fields by simplifying the detection process and reducing costs.

Implementation Method 1

particles are capable of forming multi-particle complexes comprising a first particle, a second particle, and an analyte

Methodology Applied
Scientific EffectBinding interaction: Adsorption

Implementation Method 2

removing multi-particle complexes formed upon said mixing from said suspension

Methodology Applied
Scientific EffectCentrifugal separation: Centrifugal Separation

Implementation Method 3

particles having different physico-chemical properties, such as buoyancy, size, density

Methodology Applied
Scientific EffectBuoyancy: Archimedes' Principle (Buoyancy)

Implementation Method 4

the first and/or second particles scatter light or comprise a detectable color

Methodology Applied
Scientific EffectLight scattering: Scattering

Implementation Method 5

the first and/or second particles comprise a label (e.g., fluorescent label)

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 6

the first particles comprise a donor chromophore and the second particles comprise an acceptor chromophore, or vice verse, wherein the donor and acceptor chromophores are suitable for detecting interaction between the first and second particles by means of Förster Resonance Energy Transfer (FRET) analysis

Methodology Applied
Scientific EffectFörster Resonance Energy Transfer:

Data Source

PatentUS20230324375A1Novel assays for detecting analytes in samples and kits and compositions related thereto
Publication Date: 2023.10.12 ZOETIS SERVICES LLC
  • US20230324375A1 patent drawing
  • US20230324375A1 patent drawing
  • US20230324375A1 patent drawing

AI summary

The present invention provides methods of detecting analytes using particles having different physico-chemical properties, such as buoyancy, size, density, spectral characteristics, and/or binding properties, in solution-based sandwich assays and solution-based competition assays. The methods can be performed using rotors and bench-top centrifuges and provide for rapid, qualitative and quantitative detection of analytes. The present invention also provides kits that can be used to perform the methods, and mixtures containing particles suitable for the methods.