Core-Shell Microparticles for Multiplex Toxin Detection

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Solution Overview

Problem

Current multiplex assays for detecting anthropogenic markers and toxins in environmental and agricultural samples are labor-intensive, time-consuming, and costly, with issues like non-specific binding and the need for multiple washing steps, and lack a robust method for parallel detection of various analytes.

Innovation Solution

The development of core/shell microparticles with a polymer core and silicate shell, functionalized with different groups and coupled with specific analytes, allowing for simultaneous detection of multiple analytes without washing steps through a suspension array technology (SAT) test.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If traditional multiplex assays are used for detecting multiple analytes, then detection capability is improved, but labor intensity and time consumption increase significantly

Engineering Contradiction:
Improvedetection capabilityVSAvoidlabor efficiency
Core Design Contradiction:
Adaptability or versatilityVSProductivity

Solution Approach 1:

The invention divides the detection system into distinct functional components: coded microparticles serve as separate detection units for different analytes, each with unique optical codes and specific binding sites. This segmentation allows parallel detection of multiple analytes without requiring sequential processing, thereby improving productivity while maintaining versatility

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention creates a universal detection platform where coded microparticles can detect multiple types of analytes (anthropogenic markers, pesticides, toxins) using the same basic assay protocol and readout system. The microparticles themselves are multi-functional, combining optical coding, analyte binding, and signal generation capabilities in a single component

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

2Reliability

If amino group functionalized particles are used for binding, then binding capability is improved, but non-specific binding increases

Engineering Contradiction:
Improvebinding capabilityVSAvoidnon-specific binding
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention applies different functional groups to different regions or aspects of the microparticle system. The coding region uses amino groups for optical identification, while the binding region incorporates PEG chains to prevent non-specific binding. This local differentiation allows specific binding capability while eliminating harmful non-specific interactions

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The invention introduces PEG (polyethylene glycol) as an intermediary substance that mediates between the microparticle surface and the sample matrix. The PEG chains form a protective barrier that prevents non-specific binding of proteins and other molecules to the microparticle surface, while allowing specific analyte-microparticle interactions to proceed

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If multiple washing steps are implemented, then non-specific binding is reduced, but time consumption and complexity increase

Engineering Contradiction:
Improvebinding specificityVSAvoidassay time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The invention performs preliminary action by pre-functionalizing the microparticles with PEG chains during manufacturing, creating a non-fouling surface before the assay begins. This preliminary modification eliminates the need for multiple washing steps during the assay, as non-specific binding is prevented from the outset rather than requiring subsequent removal

Inventive Principle:
Principle #10Preliminary action

4Reliability

If hapten-carrier protein conjugates are prepared, then antigen presentation is improved, but preparation complexity and cost increase

Engineering Contradiction:
Improveantigen presentationVSAvoidpreparation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention extracts the carrier protein component from the traditional hapten-carrier conjugate system, retaining only the essential hapten portion coupled directly to the microparticle surface. This extraction eliminates the complex conjugation chemistry and purification steps required for hapten-carrier protein preparation, while maintaining effective antigen presentation through direct hapten-microparticle coupling

Inventive Principle:
Principle #2Taking out (Extraction)

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

Enables efficient, sensitive, and cost-effective simultaneous detection of multiple anthropogenic markers and toxins in environmental and agricultural samples, reducing the complexity and time required for analysis while minimizing non-specific binding.

Implementation Method 1

a polymer core having a luminophore

Methodology Applied
Scientific EffectLuminescence: Luminescence

Implementation Method 2

Coupling at least two different functional groups to the silicate shell of the core/shell microparticles

Methodology Applied
Scientific EffectChemical bonding: Chemical Bonding

Data Source

PatentEP3771487A1Method for the simultaneous determination of various analytes in an environmental sample and / or an agricultural raw material based on core-shell microparticles
Publication Date: 2021.02.03 BUNDESREPUBLIK DEUTSCHLAND VERTRETEN DURCH DEN BUNDESMINISTER FUR WIRTSCHAFT UND ENERGIE DIESER VERTRETEN DURCH DEN PRASIDENTEN DER BUNDESANSTALT FUR MATERIALFORSCHUNG UND PRUFUNG (BAM)
  • EP3771487A1 patent drawingFigure 1
  • EP3771487A1 patent drawingFigure 2A~2G
  • EP3771487A1 patent drawingFigure 3A~3D

AI summary

Method for producing a mixture of core/shell microparticles (1) for the simultaneous determination of various analytes in an environmental sample or in an agricultural commodity sample, comprising: - providing two cohorts (1.1, 1.2) of core/shell microparticles (1), comprising a polymer core (2) having a luminophore (6) and a silicate shell (3) enclosing the polymer core (2); - coupling at least two different functional groups (4, 5) to the silicate shell (3) of the core/shell microparticles (1), wherein a first of the at least two different functional groups (4, 5) is selected from a -NH2, -COOH, -CH(O), -NC, -C-SH, -CS-OH, -SO2-OH, -SCN, -NCS or -NCO group (4);and a second of at least two different functional groups (4, 5) is selected from a polyethylene glycol (5), a sulfobetaine (5) and a peptide (5) comprising an amino acid sequence that includes at least one sequence of five amino acids from the amino acid sequences CYSYSYS or CRERERE; - coupling of a first anthropogenic marker or toxin or a first hapten representing the first anthropogenic marker or the first toxin to the first functional group (1) of core/shell microparticles (1) of a first cohort (1.1); - coupling of a second anthropogenic marker or second toxin or a second hapten representing the second anthropogenic marker or the second toxin to the first functional group (1) of core/shell microparticles (1) of a second cohort (1.2);wherein the first and second cohorts differ with respect to a type and/or concentration of the luminophore (6) and/or with respect to a mean diameter and/or with respect to a mean density of the core/shell microparticles (1); and - combining and mixing at least subsets of the first (1.1) and second (1.2) cohorts of core/shell microparticles (1).;