ODN Derivative Duplex Biosensors for Protein Isoform Discrimination

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Solution Overview

Problem

Current molecular biosensors face challenges in detecting low concentration protein biomarkers in biological mixtures due to high background signals and the need for multiple antibodies, which limits their application in complex biochemical environments like human serum and urine.

Innovation Solution

The development of oligodeoxyribose nucleotide (ODN) derivatives duplexes with selective and non-selective protein binders, where each duplex generates a unique optical signature upon protein binding, allowing for discrimination among closely related proteins like GSTs, MMPs, and FGFs, even in the presence of abundant serum proteins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescent molecular sensors are used to detect proteins, then sensitive detection down to single molecule level is achieved, but high background signal complicates use in complex biochemical mixtures

Engineering Contradiction:

Improvedetection sensitivityVSAvoidbackground signal

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The sensor system is segmented into multiple independent sensor elements, each with a specific binder tailored to recognize particular protein families. This segmentation allows the system to process complex mixtures by distributing detection tasks across specialized sensors, reducing cross-reactivity and background noise while maintaining high sensitivity for target analytes.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Each sensor element is equipped with a specific binder that provides localized recognition capability for particular protein families. This local quality approach ensures that each sensor region is optimized for its specific target, enabling precise detection in complex mixtures without interference from other protein types.

Inventive Principle:

Principle #3Local quality

2Reliability

If multiple antibodies are used for detecting different target proteins, then high affinity and selectivity are achieved, but high cost and need for stepwise protocols limit high-throughput analysis

Engineering Contradiction:

Improvebinding affinity and selectivityVSAvoidthroughput

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The sensor array platform provides universal functionality by integrating multiple binder types (antibodies, aptamers, synthetic receptors) into a single multiplexed system. This allows simultaneous detection of multiple protein targets in parallel using a single array, eliminating the need for separate stepwise protocols for each target while maintaining high affinity and selectivity through the diverse binder repertoire.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Adaptability or versatility

If non-selective synthetic receptors are used in cross-reactive sensor arrays, then protein differentiation is enabled through unique optical fingerprints, but difficulty operating within biological mixtures limits diagnostic application

Engineering Contradiction:

Improveprotein differentiation capabilityVSAvoidperformance in biological mixtures

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The sensor array is segmented into multiple sensor elements, each with a specific binder tailored to recognize particular protein families. This segmentation allows the system to process complex mixtures by distributing detection tasks across specialized sensors, reducing cross-reactivity and background noise while maintaining high sensitivity for target analytes.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Inventive Principle:

Principle #3Local quality

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

This approach enables high-throughput protein analysis and effective diagnosis of diseases by generating distinct optical signatures for specific protein biomarkers, improving diagnostic accuracy and overcoming the limitations of existing technologies.

Implementation Method 1

The development of oligodeoxyribose nucleotide (ODN) derivatives duplexes with selective and non-selective protein binders, where each duplex generates a unique optical signature upon protein binding

Methodology Applied

Scientific EffectFluorescence resonance energy transfer (FRET):

Data Source

PatentUS10281459B2Protein biosensors, cross reactive sensor arrays and methods of use thereof

Publication Date: 2019.05.07 YEDA RES & DEV CO LTD

AI summary

The present invention is directed to fluorescent protein biosensors based on oligonucleotide cross reactive sensor arrays including a selective and a non-selective protein surface binding domain for protein detection. Interaction of different protein isoforms with the sensors of this invention yields a unique optical signature for each protein. The unique optical signature allows differentiating between closely related protein isoforms and diagnosing diseases and disorders associated with the proteins also in biofluids.