LSPR Biosensor for Label-Free microRNA Detection

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Solution Overview

Problem

Current methods for detecting and quantifying microRNAs, particularly in the context of pancreatic ductal adenocarcinoma, face challenges such as low sensitivity, specificity, and the need for labeling or amplification steps, which are not suitable for physiological media, limiting their effectiveness as diagnostic and prognostic biomarkers.

Innovation Solution

A biosensor system utilizing localized surface plasmon resonance (LSPR) antennae affixed to a substrate with functionalized single-stranded DNA, allowing for direct hybridization and detection of microRNAs without labeling or amplification, capable of measuring microRNA concentrations in physiological media with high sensitivity and specificity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If microarrays and qRT-PCR assays are used to detect microRNAs, then detection capability is achieved, but the methods require sequence-based amplification and radioactive labeling steps which reduce sensitivity and specificity

Engineering Contradiction:
Improvedetection precisionVSAvoiddetection process complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts and eliminates the complex amplification and labeling steps from the detection process by using localized surface plasmon resonance (LSPR) technology that directly detects microRNA binding events without requiring these intermediate steps, thereby simplifying the detection process while maintaining or improving precision

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces LSPR antennae as an intermediary detection mechanism that transduces the binding event between microRNA and probe into a measurable optical signal, replacing the need for radioactive labeling and amplification steps while achieving higher sensitivity and specificity

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If electrochemical and fluorescence-based assays are used to quantify microRNAs, then quantification is achieved, but these techniques require additional amplification or labeling and cannot be performed in physiological media

Engineering Contradiction:
Improvequantification precisionVSAvoidmedia compatibility
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent replaces electrochemical and fluorescence-based detection mechanisms with LSPR-based optical detection that does not require amplification or labeling, enabling direct quantification in physiological media through label-free detection of microRNA binding events

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The LSPR antennae perform self-detection by inherently transducing the binding event into an optical signal without requiring external amplification or labeling reagents, allowing the system to function directly in physiological media without additional preparation steps

Inventive Principle:
Principle #25Self-service

3Ease of operation

If microring resonators are used for detection, then label-free detection is achieved, but sensitivity is low and they do not work in physiological media

Engineering Contradiction:
Improvelabel-free operationVSAvoiddetection sensitivity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent employs localized surface plasmon resonance antennae that concentrate electromagnetic energy at specific nanoscale locations, creating highly localized sensing zones with enhanced sensitivity that can detect microRNA binding events in physiological media, overcoming the low sensitivity and media incompatibility issues of microring resonators

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent changes the detection parameter from the bulk optical properties measured by microring resonators to localized surface plasmon resonance properties that are highly sensitive to refractive index changes at the antenna surface, enabling both label-free operation and high sensitivity in physiological media

Inventive Principle:
Principle #35Parameter changes

4Adaptability or versatility

If nanopore-based sensors are used to detect microRNAs, then detection in circulation is achieved, but the technique requires complicated fabrication procedure, high probe concentration, and specific probe signature

Engineering Contradiction:
Improvecirculation detection capabilityVSAvoidfabrication simplicity
Core Design Contradiction:
Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The LSPR antenna platform provides a universal detection mechanism that can detect various microRNA targets in circulation without requiring complicated fabrication procedures, high probe concentrations, or specific probe signatures, as the LSPR signal transduction is independent of the specific microRNA sequence being detected

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 system achieves a low limit of detection for microRNAs, enabling precise quantification in clinical samples, overcoming previous limitations and providing a potential diagnostic and prognostic tool for PDAC and other cancers.

Implementation Method 1

localized surface plasmon resonance (LSPR) properties, which can be further controlled by modulating their local dielectric environment. Utilizing these properties, several molecular and biological sensors have been developed where analyte binding to nanostructure surface-bound receptors results in an increase in refractive index and consequently a LSPR peak shift.

Methodology Applied
Scientific EffectLocalized surface plasmon resonance: Resonance

Data Source

PatentUS10858693B2Systems and methods for localized surface plasmon resonance biosensing
Publication Date: 2020.12.08 INDIANA UNIVERSITY RESEARCH & TECHNOLOGY CORP
  • US10858693B2 patent drawing
  • US10858693B2 patent drawing
  • US10858693B2 patent drawing

AI summary

Biosensors and methods for localized surface plasmon resonance biosensing are disclosed. The biosensor can include a substrate having a substrate surface to which a plurality of localized surface plasmon resonance (LSPR) antennae are affixed. The LSPR antennae can be affixed via an affixation surface of the LSPR antenna. The LSPR antennae can have a functional surface opposite the affixation surface. Each functional surface can be functionalized by a plurality of single-stranded DNA.