Oligonucleotide Conjugates for Multiplex Biomarker Detection

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Solution Overview

Problem

Current diagnostic tools are limited in their ability to simultaneously detect multiple protein biomarkers, leading to inadequate understanding of cellular processes and disease states, and bioconjugate preparation methods are inefficient, costly, and lack flexibility, hindering their widespread use in biomedical research and diagnostics.

Innovation Solution

The development of methods for forming biomolecule-oligonucleotide conjugates with high efficiency and purity, using techniques such as conjugating modified biomolecules with oligonucleotides and isolating them using immobilized binders or alternative chromatography methods, enabling the creation of high-yielding, robust bioconjugates for multiplex assays and diagnostics.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional bioconjugate preparation methods are used, then diagnostic assays can detect protein biomarkers, but the number of simultaneous detections is limited to 1-10 markers and the preparation is inefficient and costly

Engineering Contradiction:

Improvenumber of biomarkers detected simultaneouslyVSAvoidpreparation efficiency

Core Design Contradiction:

Quantity of substanceVSProductivity

Solution Approach 1:

The diagnostic assay is segmented into multiple independent detection channels, each targeting a specific biomarker. Instead of using a single multiplexed assay that limits detection to 1-10 markers, the invention employs multiple separate antibody-oligonucleotide conjugates that can be simultaneously applied, effectively segmenting the detection process into parallel independent pathways that increase the total number of detectable biomarkers

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Oligonucleotide intermediaries are introduced as bridging molecules between antibodies and detectable labels. The antibody-oligonucleotide conjugates serve as intermediaries that can be efficiently prepared through oligonucleotide conjugation chemistry, enabling high-yielding preparation methods while maintaining the ability to detect multiple biomarkers simultaneously

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If conventional bioconjugate preparation methods are used, then diagnostic assays can be performed, but the preparation is costly and lacks flexibility

Engineering Contradiction:

Improveflexibility in assay designVSAvoidpreparation cost and complexity

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The invention employs universal oligonucleotide sequences that can be conjugated to multiple different antibodies through standardized chemistry. These universal oligonucleotide intermediaries serve multiple functions: they facilitate efficient conjugation, enable flexible pairing of antibodies with detectable labels, and allow for standardized preparation protocols. This universality increases adaptability in assay design while reducing preparation costs and complexity through reusable protocols and components

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention changes the chemical parameters of the conjugation process by using oligonucleotide-based chemistry instead of conventional protein crosslinking methods. This parameter change enables more efficient conjugation reactions with higher yields, reduces preparation costs, and provides greater flexibility in designing different antibody-label combinations without requiring complex optimization for each new assay

Inventive Principle:

Principle #35Parameter changes

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

These methods allow for the efficient preparation and purification of bioconjugates, enabling the simultaneous detection of multiple molecular targets, improving diagnostic assays and reducing costs, thereby enhancing research and clinical decision-making.

Implementation Method 1

the antibody is conjugated to an oligonucleotide sequence that is complementary to an oligonucleotide sequence on the bead

Methodology Applied

Scientific EffectHybridization:

Data Source

PatentUS9222936B2Methods and/or use of oligonucleotide conjugates for suppressing background due to cross-hybridization

Publication Date: 2015.12.29 EMD MILLIPORE CORP

AI summary

The present disclosure is directed to methods and/or uses of oligonucleotide conjugates for assays and detections and related systems and/or kits for suppressing background due to cross-hybridization. Certain methods are directed to a method for detecting one or more biological targets of a sample in a detection assay, comprising: providing a molecular probe, comprising a binding moiety and an oligonucleotide sequence, to a sample comprising one or more biological targets; binding the one or more biological targets with the binding moiety; providing a detectable component to the sample, wherein the detectable component comprises a signal generating moiety conjugated to an oligonucleotide sequence complementary to the oligonucleotide sequence of the molecular probe; hydridizing the oligonucleotide sequence of the target-bound molecular probe to the detectable component; and detecting a signal generated from the hydridized detectable component. Various other embodiments, applications etc. are disclosed herein.