Magnetic Nanoparticle Biosensor for Diluted DNA Detection

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Solution Overview

Problem

Current biosensors face limitations in sensitivity and detection limit due to the need for target DNA or RNA molecules, which are often extremely diluted in natural samples, making it difficult to achieve high specificity and sensitivity in hybridization assays, especially when using immobilized PNA probes on surfaces.

Innovation Solution

The development of nanoparticle biosensors with a magnetic core, silica layer, and an outer metal layer, allowing for the immobilization of PNA probes, which can be used to detect hybridization through changes in magnetic, optical, or electric signals, and enabling the concentration of target molecules using an external magnetic field.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If target DNA or RNA molecules are used in natural samples, then the detection can be performed, but the sensitivity and detection limit are insufficient due to extreme dilution of target molecules

Engineering Contradiction:
Improvedetection sensitivityVSAvoidconcentration of target molecules
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The system segments the detection function across multiple components: magnetic nanoparticles serve as concentrated binding sites, PNA probes provide specific recognition, and the external magnetic field enables spatial separation. This segmentation allows the system to overcome the dilution problem by distributing the detection function rather than relying on a single homogeneous solution.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The PNA probes are pre-immobilized on magnetic nanoparticles before contact with the sample, creating ready-to-detect concentrated binding sites. This preliminary action ensures that when the diluted sample is introduced, the target molecules immediately encounter high local concentrations of probes on the particle surfaces, enabling detection despite overall dilution.

Inventive Principle:
Principle #10Preliminary action

2Measurement precision

If immobilized PNA probes are used on surfaces, then hybridization detection can be performed, but the specificity is insufficient to discriminate single mutations

Engineering Contradiction:
Improvedetection specificityVSAvoidprobe immobilization uniformity
Core Design Contradiction:
Measurement precisionVSManufacturing precision

Solution Approach 1:

The system implements local quality by ensuring each magnetic nanoparticle is uniformly coated with PNA probes, creating consistent local binding environments. The spherical geometry of particles combined with controlled coating processes ensures uniform probe distribution across particle surfaces, providing reliable and reproducible hybridization conditions that enhance mutation discrimination capability.

Inventive Principle:
Principle #3Local quality

3Quantity of substance

If conventional biosensors are used, then the device structure is simple, but the detection limit is insufficient for diluted samples

Engineering Contradiction:
Improvedetection limitVSAvoidnanoparticle structure
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The system employs composite materials by combining magnetic nanoparticles with PNA probes to create a hybrid structure that integrates magnetic properties for separation with biochemical properties for specific recognition. This composite approach enables the system to achieve enhanced detection capabilities for diluted samples while managing the increased structural complexity through functional integration.

Inventive Principle:
Principle #40Composite materials

4Measurement precision

If magnetic nanoparticles are used for concentration, then the sensitivity is enhanced, but the device complexity increases due to multiple layers

Engineering Contradiction:
Improvedetection sensitivityVSAvoidnanoparticle layer structure
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The system applies the nesting principle by creating a hierarchical structure where PNA probes are attached to the surface of magnetic nanoparticles, forming a core-shell configuration. The magnetic core provides concentration capability while the outer probe layer provides detection function, with each layer nested within or on the other to create a compact, multi-functional particle structure.

Inventive Principle:
Principle #7Nested doll (Nesting)

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 enhances the sensitivity and specificity of nucleic acid detection, allowing for the discrimination of DNA sequences differing by a single mutation, and enables the detection of specific DNA strands in diluted samples, with potential applications in biomedicine and environmental monitoring.

Implementation Method 1

The nanoparticles are particularly formed by a magnetic core and an outer metal layer... enabling the concentration of target molecules using an external magnetic field

Methodology Applied
Scientific EffectMagnetic field: Magnetic Field

Implementation Method 2

The magnetic, electric and optical properties of the nanoparticles are used to improve the method, being focused on the magnetic, optical or electric signal difference obtained from said nanoparticles

Methodology Applied
Scientific EffectSurface plasmon resonance:

Implementation Method 3

detecting the hybridization of natural nucleic acids (DNA or RNA) of specific sequences... with PNA probes immobilized on nanoparticles... given the binding specificity between nucleotides through their nucleotide bases, what is known as the Watson-Crick parity rule

Methodology Applied
Scientific EffectHybridization:

Data Source

PatentEP1936378B1Nanoparticle biosensor, method of preparing same and uses thereof
Publication Date: 2014.11.05 CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS (CSIC)
  • EP1936378B1 patent drawingFigure 1~2
  • EP1936378B1 patent drawingFigure 3~4
  • EP1936378B1 patent drawingFigure 5

AI summary

The invention relates to the field of biosensors and, more specifically, to nanoparticle biosensors comprising: a magnetic core, a silica layer, one or more outer metal layers which can be of different types and deposited in an alternating manner and immobilized on the outer surface, and a layer of synthetic or natural organic or inorganic biosensor molecules that can bind to biomolecules. The invention also relates to a method of obtaining the nanoparticle biosensors as well as to the different uses thereof.