Split Affinity Marker for Multiplex Proximity Detection

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Solution Overview

Problem

Existing markers for biological samples lack flexibility and reliability, particularly in detecting multiple target analytes with high specificity and reducing false-positive rates, especially in multiplex assays and diagnostic tests.

Innovation Solution

A marker comprising two parts with specific affinity reagents and polymeric backbones, where labelling moieties form upon proximity, allowing optical detection of target analytes, and can be controlled through catalytic conditions to enhance specificity and reduce false positives.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If traditional markers with single affinity reagents and labels are used, then the marker structure is simple, but the flexibility and reliability in detecting multiple target analytes is insufficient

Engineering Contradiction:
Improveflexibility in detecting multiple target analytesVSAvoidmarker structure complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The marker is divided into two separate marker parts: a first marker part with a first affinity reagent and first labelling moiety parts, and a second marker part with a second affinity reagent and second labelling moiety parts. This segmentation allows each part to independently bind to different target analytes or different epitopes, enabling flexible multiplex detection while maintaining manageable complexity through modular design

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The marker system is designed to perform multiple functions: it can detect different target analytes simultaneously, determine proximity between targets, and provide high-specificity detection through dual-affinity reagent binding. The universal design allows the same marker structure to be applied across various diagnostic and research applications

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

2Productivity

If traditional markers are used for multiplex assays, then the assay throughput is high, but the false-positive rate increases due to cross-reactivity

Engineering Contradiction:
Improvemultiplex assay throughputVSAvoidassay specificity and false-positive rate
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The first and second affinity reagents are pre-bound to their respective target analytes or epitopes before the labelling moiety reaction occurs. This preliminary specific binding ensures that only markers with both affinity reagents correctly bound to their targets will form the complete labelling structure, eliminating false positives from cross-reactivity while maintaining high multiplex throughput

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The polymeric backbone with labelling moiety parts acts as an intermediary that bridges the first and second affinity reagents. The labelling moieties only form when both affinity reagents are correctly bound, serving as a mediator that verifies dual-specificity and prevents false-positive signals from single-affinity reagent binding events

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If markers with bright labels are used to detect small quantities of analytes, then the detection sensitivity is high, but the reliability and specificity are reduced

Engineering Contradiction:
Improvedetection sensitivity for low abundance analytesVSAvoiddetection reliability and specificity
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The affinity reagents perform preliminary specific binding to the target analytes before the labelling reaction occurs. This ensures that even low-abundance analytes are specifically captured with high reliability, and only then are the bright labelling moieties activated, maintaining both sensitivity and reliability simultaneously

Inventive Principle:
Principle #10Preliminary action

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 precise determination of target analyte proximity and location with reduced false positives, suitable for multiplex assays and diagnostic tests, improving assay specificity and reliability.

Implementation Method 1

The first labelling moiety parts and the second labelling moiety parts are configured to bind to the respective other one to form labelling moieties

Methodology Applied
Scientific EffectChemical Bonding: Chemical Bonding

Implementation Method 2

The first affinity reagent and the second affinity reagent are each configured to bind specifically to one of the target analytes of the biological sample

Methodology Applied
Scientific EffectAffinity binding: Adsorption

Data Source

PatentEP4589298A1Marker and method for analysing a biological sample
Publication Date: 2025.07.23 LEICA MICROSYSTEMS CMS GMBH
  • EP4589298A1 patent drawingFigure 1
  • EP4589298A1 patent drawingFigure 2
  • EP4589298A1 patent drawingFigure 3

AI summary

In a first aspect a marker (100, 404, 500) for analysing a biological sample with a plurality of target analytes (107, 113, 406, 506) is provided. The marker (100, 404, 500) comprises a first marker part (102) comprising a first affinity reagent (106, 400, 502) and a first label, the first label comprising a first polymeric backbone (108) attached to the first affinity reagent (106, 400, 502) and a plurality of first labelling moiety parts (110) attached to the first polymeric backbone (108), and a second marker part (104) comprising a second affinity reagent (112, 402, 504) and a second label, the second label comprising a second polymeric backbone (114) attached to the second affinity reagent (112, 402, 504) and a plurality of second labelling moiety parts (116) attached to the second polymeric backbone (114). The first labelling moiety parts (110) and the second labelling moiety parts (116) are configured to bind to the respective other one (110, 116) to form labelling moieties (118). The first affinity reagent and the second affinity reagent are each configured to bind specifically to one of the target analytes of the biological sample. In a further aspect, a method for analysing a biological sample is provided.