Integrated DEP and Plasmonic Platform for Biomarker Detection

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Solution Overview

Problem

Current methods for detecting biomarkers, particularly miRNAs, in biological samples face challenges such as high cost, slow turnaround time, inability to quantify low copy numbers, inter-sample variability, and molecular crowding, which limits their effectiveness in early disease detection.

Innovation Solution

An integrated dielectrophoretic (DEP) and surface plasmonic platform using an interdigitated array of microelectrodes with nano-scale plasmonic structures, which applies a DEP force to concentrate fluorescently labeled biomarkers on hotspots, enhancing fluorescence intensity and allowing for the detection of approximately 1 fM of fluorescent molecules in low conductivity buffers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If E-beam lithography is used to fabricate metallic nano-structures, then fluorescence enhancement is improved, but device complexity and manufacturing cost increase significantly

Engineering Contradiction:

Improvefluorescence detection sensitivityVSAvoidfabrication process complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent changes the fabrication parameters from E-beam lithography to conventional photolithography, achieving the same fluorescence enhancement effect through simpler processes. The metallic nano-structures are still formed with precise control over their dimensions and arrangement, but using widely available, cost-effective manufacturing techniques rather than specialized nanofabrication methods.

Inventive Principle:

Principle #35Parameter changes

2Ease of manufacture

If conventional photolithography is used to fabricate metallic nano-structures, then manufacturing cost and complexity are reduced, but the ability to handle large sample volumes is improved

Engineering Contradiction:

Improvefabrication cost and complexityVSAvoidsample volume handling capacity

Core Design Contradiction:

Ease of manufactureVSQuantity of substance

Solution Approach 1:

The patent divides the detection platform into multiple independent metallic nano-structure arrays, each capable of handling samples. This segmentation allows the system to process large sample volumes by distributing the analysis across multiple zones or channels, while each individual zone maintains the precision achieved through conventional photolithography fabrication.

Inventive Principle:

Principle #1Segmentation

3Measurement precision

If fluorophore molecules are placed within 100 nm from metallic nano-structures, then fluorescence enhancement is maximized, but chemical reactions between fluorophore and metal occur

Engineering Contradiction:

Improvefluorescence intensityVSAvoidchemical reactions between fluorophore and metal

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent introduces an intermediary layer or surface modification on the metallic nano-structures that prevents direct contact between the fluorophore molecules and the metal surface. This intermediary maintains the close proximity needed for plasmonic enhancement while blocking harmful chemical reactions such as quenching or catalytic degradation of the fluorophores.

Inventive Principle:

Principle #24Intermediary (Mediator)

4Measurement precision

If qRT-PCR is used for miRNA detection, then detection sensitivity is sufficient, but turnaround time is slow and cost is high

Engineering Contradiction:

Improvebiomarker detection sensitivityVSAvoidassay turnaround time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces the complex mechanical and chemical amplification steps of qRT-PCR with a direct optical detection system based on plasmonic enhancement. By using metallic nano-structures to amplify the fluorescence signal of labeled miRNAs, the system achieves comparable or superior sensitivity without requiring reverse transcription, amplification cycles, or sophisticated thermal cycling equipment, thereby dramatically reducing assay time and cost.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 significantly improves the detection limit and sensitivity of biomarkers, enabling rapid, cost-effective, and high-throughput analysis of miRNAs in biological samples, surpassing traditional methods like qRT-PCR in sensitivity and speed.

Implementation Method 1

applies a DEP force to concentrate fluorescently labeled biomarkers on hotspots

Methodology Applied

Scientific EffectDielectrophoresis: Dielectric

Implementation Method 2

interactions of metal surfaces, particles and colloids with fluorophore molecules have been utilized in assays. These metallic components increase the electric field (felt by the fluorophore) and subsequently decrease the radiative decay rate of the fluorophore

Methodology Applied

Scientific EffectSurface plasmon: Surface Acoustic Wave

Implementation Method 3

fluorescence-based optical sensing techniques involve fluorescently labeling and measuring the fluorescence intensity of the target biomarkers in the sample

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS10794894B2Integrated dielectrophoretic and surface plasmonic apparatus and methods for improvement in the detection of biological molecules

Publication Date: 2020.10.06 NORTH DAKOTA STATE UNIV RES FOUND

AI summary

The present invention relates to an apparatus and methods for an integrated dielectrophoretic (DEP) and surface plasmonic platform to quantify as little as 1 femptomolar to 1 picomolar of fluorescent molecules in low conductivity buffers.