Oligonucleotide Polymer Conjugates for Multiplex Tissue Detection

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Solution Overview

Problem

Existing methods for multiplex immunohistochemistry (MIHC) lack efficient and reproducible techniques for simultaneously and quantitatively detecting multiple protein targets in formalin-fixed, paraffin-embedded tissues, often suffering from interference and reduced antibody activity due to high labeling densities.

Innovation Solution

Development of polymers comprising oligonucleotide sequences with specific spacers and linkers, coupled with labels, which allow for controlled labeling and spacing to minimize interference, enabling simultaneous detection of multiple targets while maintaining antibody activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If high labeling density is used to detect multiple protein targets, then detection sensitivity is improved, but antibody activity is reduced due to interference

Engineering Contradiction:

Improvedetection sensitivityVSAvoidantibody activity

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The polymer is divided into multiple repeating units, each carrying a label. This segmentation allows the labels to be distributed along the polymer chain rather than concentrated at a single point, reducing steric interference while maintaining detection sensitivity through multiple labeling sites.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The labels are arranged in a linear sequence along the polymer chain, transitioning from a single-point labeling approach to a distributed linear arrangement. This dimensional extension along the polymer backbone reduces spatial congestion and maintains antibody binding activity while preserving detection sensitivity.

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

2Adaptability or versatility

If multiple labels are attached to detect multiple targets, then multiplexing capability is improved, but background noise increases due to interference

Engineering Contradiction:

Improvemultiplexing capabilityVSAvoidbackground noise

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The polymer chain serves as an intermediary structure that organizes multiple labels in a controlled manner. It acts as a mediator between the detection system and the targets, arranging labels to minimize steric hindrance and reduce background noise while enabling simultaneous detection of multiple protein targets.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Volume of moving object

If labels are spaced closer together to reduce polymer size, then conjugate compactness is improved, but detection sensitivity decreases due to steric interference

Engineering Contradiction:

Improveconjugate sizeVSAvoiddetection sensitivity

Core Design Contradiction:

Volume of moving objectVSMeasurement precision

Solution Approach 1:

The patent optimizes parameters including the number of repeating units, the sequence of labels, and their spacing along the polymer chain. By carefully adjusting these parameters, the conjugate achieves an optimal balance between compactness and detection sensitivity, preventing steric interference while maintaining reasonable size.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20260056191A1Polymers and conjugates comprising the same

Publication Date: 2026.02.26 VENTANA MEDICAL SYSTEMS INC

AI summary

Polymers and conjugates comprising polymers are disclosed herein. In some embodiments, the conjugates disclosed are suitable for use as detection probes in immunohistochemical and in situ hybridization assays.