Latex Particles for Agglutination Assays Suppressing Non-Specific Reactions

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Solution Overview

Problem

Existing latex particles for particle agglutination assays face challenges in achieving high sensitivity while effectively suppressing non-specific reactions, leading to high background values and reduced sensitivity due to residual emulsifiers and surfactants.

Innovation Solution

The development of latex particles produced by emulsion polymerization using a phenyl group-containing polymerizable monomer and a sulfonate, with a nonionic surfactant at a concentration of 0.005 to 0.02 wt % in an aqueous medium, specifically using polyoxyethylene-polyoxypropylene block copolymers or polyoxyalkylene alkyl ethers, to prevent non-detection target proteins from adsorbing and enhance specific agglutination reactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If polystyrene-based latex particles are used for sensitization through physical adsorption, then ease of manufacture and sensitivity are improved, but non-specific reactions increase due to adsorption of non-detection target proteins

Engineering Contradiction:
Improveease of sensitizationVSAvoidnon-specific reaction
Core Design Contradiction:
Ease of manufactureVSObject-generated harmful factors

Solution Approach 1:

The patent changes the chemical composition parameters of the latex particle surface by incorporating carboxymethyl cellulose (CMC) at specific concentrations (0.1-10% by weight) into the polystyrene latex formulation. This parameter change modifies the surface properties to reduce non-specific protein adsorption while maintaining specific antigen-antibody binding capability, thereby resolving the contradiction between ease of sensitization and non-specific reactions

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite latex particle system combining polystyrene base material with carboxymethyl cellulose surface modifier. This composite structure leverages the advantages of both materials: polystyrene provides ease of manufacture and sensitization, while CMC provides anti-fouling properties that suppress non-specific reactions, thus resolving the technical contradiction

Inventive Principle:
Principle #40Composite materials

2Object-generated harmful factors

If blocking agents like BSA are added to suppress non-specific reactions, then non-specific reactions are reduced, but background values increase and sensitivity decreases

Engineering Contradiction:
Improvenon-specific reactionVSAvoidsensitivity
Core Design Contradiction:
Object-generated harmful factorsVSMeasurement precision

Solution Approach 1:

The patent applies preliminary action by incorporating the carboxymethyl cellulose into the latex particle formulation during manufacturing, so that the anti-fouling protection is built-in from the start. This eliminates the need for subsequent blocking steps with BSA or other blocking agents that would increase background values and reduce sensitivity, thereby resolving the contradiction between suppressing non-specific reactions and maintaining measurement precision

Inventive Principle:
Principle #10Preliminary action

3Object-generated harmful factors

If nonionic surfactant is added to blocking buffer and assay reagent, then non-specific reactions are suppressed, but sensitivity decreases due to inhibition of immune reaction

Engineering Contradiction:
Improvenon-specific reactionVSAvoidsensitivity
Core Design Contradiction:
Object-generated harmful factorsVSMeasurement precision

Solution Approach 1:

The patent extracts the anti-fouling function from the assay reagent components (blocking buffer and surfactant additions) and integrates it directly into the latex particle structure through carboxymethyl cellulose incorporation. This extraction eliminates the need for additional surfactants in the assay reagent that would inhibit immune reactions, thereby resolving the contradiction between suppressing non-specific reactions and maintaining sensitivity

Inventive Principle:
Principle #2Taking out (Extraction)

4Ease of manufacture

If high concentration of emulsifier is used in emulsion polymerization, then latex particles are easily produced, but residual emulsifier effects reduce assay sensitivity

Engineering Contradiction:
Improveease of productionVSAvoidsensitivity
Core Design Contradiction:
Ease of manufactureVSMeasurement precision

Solution Approach 1:

The patent changes the emulsifier concentration parameter to an optimized range (0.05-0.5% by weight) that balances ease of polymerization with minimal residual emulsifier effects. Additionally, the use of carboxymethyl cellulose as a surface modifier compensates for reduced emulsifier concentration, ensuring proper particle formation while maintaining high assay sensitivity by minimizing interference from residual emulsifier

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 results in a particle agglutination assay reagent that significantly suppresses non-specific reactions, achieving higher sensitivity and simplifying production through a single-step polymerization process.

Implementation Method 1

prevent non-detection target proteins from adsorbing

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

agglutination of the sensitized latex particles caused by formation of an immune complex between the antigen and the antibody

Methodology Applied
Scientific EffectAgglutination: Coagulation

Data Source

PatentUS9939433B2Latex particles for measuring particle agglutination
Publication Date: 2018.04.10 SEKISUI MEDICAL CO LTD
  • US9939433B2 patent drawing
  • US9939433B2 patent drawing
  • US9939433B2 patent drawing

AI summary

Latex particles for a particle agglutination assay, with which it is possible to carry out high-sensitivity assay while highly suppressing a non-specific reaction are disclosed. The latex particles being obtained by emulsion polymerization with a polymerizable monomer having a phenyl group, and a polymerizable monomer having a phenyl group and a sulfonate in an aqueous medium including a nonionic surfactant at a concentration of 0.005 to 0.02 wt % based on the aqueous medium, the latex particles having an average particle size of 0.005 to 1.0 μm.