DNA-Assembled Plasmonic Biosensor for Exosomal miRNA Detection

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Solution Overview

Problem

Current methods for diagnosing Alzheimer's disease, particularly through blood-based biomarkers, face challenges such as invasive procedures, high costs, and limited sensitivity and reproducibility in detecting exosomal miRNAs due to interference from other substances and low concentrations.

Innovation Solution

A label-free plasmonic biosensor based on DNA-assembled advanced plasmonic architecture (DAPA) using metal nanospheres conjugated with single-stranded DNA, capable of detecting exosome-derived miRNAs at very low concentrations by measuring localized surface plasmon resonance shifts, with a nanogap structure and specific capture probes for enhanced sensitivity and selectivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional diagnostic methods (brain imaging, cognitive function testing, cerebrospinal fluid tests) are used, then diagnostic capability is achieved, but invasiveness and cost increase

Engineering Contradiction:

Improvediagnostic capabilityVSAvoidinvasiveness and cost

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts and detects specific exosomal miRNA biomarkers from blood samples, separating the diagnostic function from invasive procedures. By focusing on circulating exosomes in blood rather than requiring cerebrospinal fluid analysis or brain imaging, the method achieves reliable diagnosis through non-invasive blood sampling

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The invention uses exosomes as intermediary carriers that transport biomarkers from the brain to blood circulation. These exosomes serve as mediators that allow indirect detection of brain pathology through blood-based assays, eliminating the need for direct brain access while maintaining diagnostic reliability

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If blood-based biomarker detection is performed, then non-invasiveness and cost-effectiveness are improved, but detection sensitivity and reproducibility deteriorate due to low concentrations and interfering substances

Engineering Contradiction:

Improvenon-invasiveness and cost-effectivenessVSAvoiddetection sensitivity and reproducibility

Core Design Contradiction:

Object-affected harmful factorsVSMeasurement precision

Solution Approach 1:

The invention segments the complex blood sample into specific exosomal compartments, isolating the target miRNA biomarkers from interfering substances. By focusing detection efforts on exosomes rather than total blood content, the method achieves high sensitivity despite low absolute concentrations

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention changes the detection parameter from total biomarker concentration in blood to specific exosomal miRNA levels. This parameter transformation allows differentiation of signal from noise, achieving reproducible detection by measuring biomarkers within the protected exosomal compartment rather than in the complex blood matrix

Inventive Principle:

Principle #35Parameter changes

3Quantity of substance

If exosomal miRNA detection is performed using conventional methods, then biomarker detection is achieved, but detection limit and accuracy deteriorate due to low concentrations and interference

Engineering Contradiction:

Improvebiomarker detectionVSAvoiddetection limit and accuracy

Core Design Contradiction:

Quantity of substanceVSMeasurement precision

Solution Approach 1:

The invention performs preliminary enrichment and isolation of exosomes from blood samples before detection. By pre-concentrating the target biomarkers within exosomes and removing interfering substances, the method achieves accurate detection at very low concentrations that would be undetectable in crude blood samples

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The invention uses complementary DNA (cDNA) as a copy of the target miRNA biomarker for detection purposes. This copying approach enables amplification and detection of the original low-concentration miRNA signal, achieving detection limits far below the original biomarker concentration

Inventive Principle:

Principle #26Copying

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

The DAPA-based biosensor achieves accurate and simultaneous detection of Alzheimer's disease biomarkers at attomolar levels, demonstrating high sensitivity and selectivity, and effectively differentiates between Alzheimer's patients and healthy controls, offering a non-invasive and cost-effective diagnostic tool.

Implementation Method 1

capable of detecting exosome-derived miRNAs at very low concentrations by measuring localized surface plasmon resonance shifts

Methodology Applied

Scientific EffectLocalized surface plasmon resonance: Resonance

Data Source

PatentUS20230193365A1Metal nanostructure based on biomolecules and nanoplasmonic biosensor using the same

Publication Date: 2023.06.22 KOREA UNIV RES & BUSINESS FOUND

AI summary

Disclosed are a metal nanostructure based on biomolecules and a nanoplasmonic biosensor using the same.