LSPR Biosensor Direct miRNA Detection Without Labeling

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Solution Overview

Problem

Current methods for detecting and quantifying microRNAs (miRs) in biological fluids are hindered by issues of sensitivity, specificity, and the need for labeling and amplification steps, making them unsuitable for clinical point-of-care diagnosis and multiplex sensing.

Innovation Solution

A biosensor system utilizing localized surface plasmon resonance (LSPR) antennae affixed to a substrate, functionalized with single-stranded DNA, allows for direct hybridization and detection of miRs without labeling or amplification, enabling sensitive and specific quantification in physiological media.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If microarrays and qRT-PCR assays are used to detect miRs, then detection capability is achieved, but the methods require sequence-based amplification and radioactive labeling steps which reduce ease of operation and increase device complexity

Engineering Contradiction:
Improvedetection capabilityVSAvoidease of operation
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent extracts and eliminates the complex amplification and labeling steps from the detection process by using LSPR biosensors that directly detect miR binding events through surface plasmon resonance signal changes, achieving detection without sequence-based amplification or radioactive labeling

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the mechanical and chemical complexity of amplification reactions and labeling procedures with an optical detection system based on localized surface plasmon resonance, where miR binding is detected through changes in resonance conditions without requiring additional reagents or steps

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

2Measurement precision

If fluorescence- and electrochemical-based techniques are used for miR analysis, then detection is possible, but these techniques require fluorescent or protein labeling which increases device complexity and reduces ease of operation

Engineering Contradiction:
Improvedetection capabilityVSAvoiddevice complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent removes the requirement for fluorescent or protein labeling by using LSPR biosensors that detect miR through direct binding-induced changes in surface plasmon resonance properties, eliminating the need for additional labeling reagents and complex detection systems

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent substitutes fluorescence and electrochemical detection mechanisms with optical detection based on localized surface plasmon resonance, where the binding event itself modulates the optical signal without requiring fluorescent tags or electrochemical transducers

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

3Adaptability or versatility

If microring resonator- and surface enhanced Raman spectroscopy-based assays are used, then multiplexing capability is achieved, but these assays fail to work directly in biological fluids reducing reliability

Engineering Contradiction:
Improvemultiplex sensing capabilityVSAvoidreliability in biological fluids
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent employs localized surface plasmon resonance at the sensor surface to create a highly sensitive detection zone that can selectively detect miR binding events even in the presence of complex biological fluids, allowing direct measurement without extensive sample preparation

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent uses LSPR as an intermediary detection mechanism that translates miR binding events into measurable optical signals, enabling reliable detection in biological fluids by detecting changes in resonance conditions rather than relying on fluorescent or Raman labels that interfere with biological samples

Inventive Principle:
Principle #24Intermediary (Mediator)

4Measurement precision

If reverse transcription, labeling, and amplification steps are used in real-time PCR-based quantification, then quantification accuracy is improved, but the complexity and multiple time consuming steps reduce productivity and ease of operation

Engineering Contradiction:
Improvequantification accuracyVSAvoidproductivity
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent extracts and eliminates the time-consuming reverse transcription, labeling, and amplification steps from the quantification process by using LSPR biosensors that provide direct, real-time detection of miR binding events through optical signal changes

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent enables continuous detection of miR binding events in real-time through LSPR signal monitoring, eliminating the discrete, time-consuming steps of reverse transcription and amplification, allowing for rapid and continuous quantification without interruption

Inventive Principle:
Principle #20Continuity of useful action

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 high sensitivity and selectivity for miR detection, with a low limit of detection and the ability to quantify miRs in clinical samples, potentially serving as a diagnostic tool for diseases like pancreatic ductal adenocarcinoma.

Implementation Method 1

A plurality of localized surface plasmon resonance (LSPR) antennae having single-stranded DNA (ssDNA) affixed to a surface thereof have an absorption peak wavelength shift or a full width at half maximum (FWHM) shift when contacted by a microRNA (miR) of interest that is complementary to the ssDNA

Methodology Applied
Scientific EffectLocalized surface plasmon resonance: Resonance

Data Source

PatentUS12163183B2Systems and methods for localized surface plasmon resonance biosensing
Publication Date: 2024.12.10 INDIANA UNIVERSITY RESEARCH & TECHNOLOGY CORP
  • US12163183B2 patent drawing
  • US12163183B2 patent drawing
  • US12163183B2 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.