Modular Protein Connector for Rapid Marker Library Assembly

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Solution Overview

Problem

Existing methods for generating large libraries of biological structures, such as markers, are time-consuming and require excessive reagents due to the need for cyclical staining, imaging, and data processing, especially in spatial biology applications requiring numerous markers.

Innovation Solution

A connector comprising a protein backbone with reactive and affinity interactors that allow for efficient assembly and cleavage, enabling rapid production of markers and capture constructs using bioconjugate formation and enzyme-cleavable sites.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If cyclical staining, imaging, and blanking processes are used to generate large libraries of markers, then the number of markers can be increased, but the time required and reagent consumption increase significantly

Engineering Contradiction:
Improvenumber of markersVSAvoidtime required for staining and imaging
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The connector is divided into separate functional modules (reactive interactor, affinity interactor, cleavage site) that can be independently synthesized and then rapidly assembled. This segmentation allows parallel production of different marker variants, dramatically reducing the time required to generate large libraries compared to sequential cyclical methods.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The connector serves as an intermediary building block that pre-integrates the reactive interactor and affinity interactor. This intermediate structure can be rapidly produced and stored, then quickly combined with different targets to generate diverse markers without repeating the full staining and imaging cycle for each variant.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If cyclical staining, imaging, and blanking processes are used to generate large libraries of markers, then the number of markers can be increased, but reagent consumption increases significantly

Engineering Contradiction:
Improvenumber of markersVSAvoidreagent consumption
Core Design Contradiction:
Quantity of substanceVSLoss of substance

Solution Approach 1:

By segmenting the marker into reusable connector components and variable target-specific components, reagents can be synthesized independently and in parallel. The connector portion with its reactive and affinity interactors can be produced once and reused across multiple marker variants, reducing overall reagent consumption compared to generating complete markers through repeated cyclical processes.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The modular connector design allows for recovery and reuse of the core connector structure across different marker applications. While the target-specific portions may be discarded after use, the valuable connector component with integrated interactors can be recovered and repurposed for generating additional marker variants, reducing net reagent consumption.

Inventive Principle:
Principle #34Discarding and recovering

3Ease of manufacture

If traditional marker generation methods are used, then markers can be produced, but the process is time-consuming and inefficient

Engineering Contradiction:
Improveease of marker productionVSAvoidproduction speed of markers
Core Design Contradiction:
Ease of manufactureVSProductivity

Solution Approach 1:

The connector is designed with pre-integrated reactive and affinity interactors that are synthesized and validated in advance. This preliminary preparation of the core structure allows for rapid assembly with different target components when needed, dramatically increasing production speed compared to traditional methods where the complete marker must be generated and validated from scratch each time.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The connector's modular design with built-in reactive and affinity interactors allows it to self-assemble with target components through spontaneous biochemical reactions (covalent bonding and affinity binding). This self-service capability eliminates the need for complex, time-consuming assembly procedures and validation steps for each new marker variant, improving both ease of manufacture and productivity.

Inventive Principle:
Principle #25Self-service

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

Facilitates rapid, cost-effective generation of large libraries of markers with diverse properties and high specificity, allowing for efficient capture and analysis of biological samples.

Implementation Method 1

a first reactive interactor arranged towards a first end of the protein backbone and configured to covalently bind to a second reactive interactor

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Implementation Method 2

a first affinity interactor arranged towards a second end of the protein backbone and configured to bind to a second affinity interactor

Methodology Applied
Scientific EffectAffinity binding: Adsorption

Data Source

PatentUS20260104421A1Connector, marker, capture construct and data storage device
Publication Date: 2026.04.16 LEICA MICROSYSTEMS CMS GMBH
  • US20260104421A1 patent drawing
  • US20260104421A1 patent drawing
  • US20260104421A1 patent drawing

AI summary

A connector for generating a biological structure includes a protein backbone, a first reactive interactor arranged towards a first end of the protein backbone and configured to covalently bind to a second reactive interactor, and a first affinity interactor arranged towards a second end of the protein backbone and configured to bind to a second affinity interactor. The protein backbone includes a cleavage site between the first end and the second end of the protein backbone. One of the first reactive interactor and the first affinity interactor is configured to bind to a first affinity reagent including the second reactive interactor or the second affinity interactor. Another one of the first reactive interactor and the first affinity interactor is configured to bind to a label or a second affinity reagent comprising the second reactive interactor or the second affinity interactor.