Modular Connector System for Multiplexed Biological Sample Analysis

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Solution Overview

Problem

Current methods for analyzing biological samples with multiple fluorescent markers are time-consuming and expensive, limiting the ability to identify and visualize multiple cell types simultaneously in imaging experiments.

Innovation Solution

A connector system comprising a first affinity reagent, a backbone with a cleavage site, and a first affinity interactor that binds specifically to a second affinity interactor with a label, allowing for efficient and cost-effective generation of markers with diverse fluorescent properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If multiple fluorescent dyes are distributed to all markers to identify cell types, functional markers, and morphological markers, then the identification capability is improved, but the cost and time expenditure for generating diverse markers increases significantly

Engineering Contradiction:
Improveidentification capabilityVSAvoidtime expenditure
Core Design Contradiction:
Adaptability or versatilityVSLoss of time

Solution Approach 1:

The marker system is segmented into modular components: a backbone structure, affinity reagents for specific target recognition, and fluorescent labels. This segmentation allows independent optimization and combination of components, enabling rapid generation of diverse markers without proportional increase in time and cost expenditure.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The backbone structure serves as a universal platform that can bind multiple different affinity reagents and fluorescent labels. This multi-functionality allows a single backbone design to support numerous marker variants, significantly reducing the overall time and cost required to generate diverse markers for multiple targets.

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

2Adaptability or versatility

If multiple fluorescent dyes are distributed to all markers to identify cell types, functional markers, and morphological markers, then the identification capability is improved, but the cost for generating diverse markers increases significantly

Engineering Contradiction:
Improveidentification capabilityVSAvoidcost
Core Design Contradiction:
Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The universal backbone design allows a single structural platform to support multiple affinity reagents and fluorescent labels. This reduces manufacturing costs by eliminating the need to separately optimize and produce entirely distinct marker molecules for each target, thereby improving ease of manufacture while maintaining high adaptability.

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

Solution Approach 2:

The system allows changing parameters such as the type of affinity reagent, fluorescent label, and their combinations on the same backbone without fundamental redesign. This parameter-based customization approach reduces manufacturing complexity and cost while maintaining the ability to identify multiple cell types and markers.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If a limited number of fluorescent dyes are used, then the cost and time expenditure are reduced, but the number of structures that can be marked and identified simultaneously is limited

Engineering Contradiction:
ImproveefficiencyVSAvoidnumber of structures identified
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

By segmenting the marker into backbone and interchangeable affinity reagent-label components, the system enables efficient reuse of the backbone structure across multiple markers. This segmentation allows a limited set of backbones combined with varied affinity reagents and labels to identify many more structures than would be possible with complete marker redesign for each target.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The backbone acts as an intermediary platform that mediates between the affinity reagent (specificity) and the fluorescent label (detection). This intermediary role allows decoupling of specificity and detection functions, enabling efficient combination of limited fluorescent dyes with multiple affinity reagents to mark and identify numerous structures simultaneously.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 rapid and cost-effective generation of markers for biological sample analysis, allowing for the simultaneous visualization of multiple target molecules with distinct fluorescent labels, thereby improving the efficiency and accuracy of imaging experiments.

Implementation Method 1

comprising at least one first affinity reagent configured to bind directly or indirectly to a target molecule

Methodology Applied
Scientific EffectAffinity binding: Adsorption

Implementation Method 2

wherein the first affinity interactor is configured to specifically bind to a second affinity interactor comprising a label in order to bind the label to the backbone

Methodology Applied
Scientific EffectAffinity binding: Adsorption

Data Source

PatentEP4092414B1Connector, marker and method for analysing biological samples
Publication Date: 2025.01.29 LEICA MICROSYSTEMS CMS GMBH
  • EP4092414B1 patent drawingFigure 1
  • EP4092414B1 patent drawingFigure 2
  • EP4092414B1 patent drawingFigure 3

AI summary

A connector (100) is provided for analysing biological samples comprising at least one first affinity reagent (102) configured to bind directly or indirectly to a target molecule (104); a backbone (106) connected to the first affinity reagent (102) and comprising at least one first affinity interactor (110); wherein the first affinity interactor (110) is configured to specifically bind to a second affinity interactor (112) comprising a label (114) in order to bind the label (114) to the backbone (106); wherein the backbone (106) comprises a cleavage site (108) for irreversibly separating the first affinity reagent (102) and the first affinity interactor (110) with the label (114). In a further aspect, a marker and a method for analysing biological samples are provided.