Multi-spot Metal-capped Nanostructure Array Nucleic Acid Chip for Corneal Dystrophy Diagnosis
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Solution Overview
Problem
Current nucleic acid chips for diagnosing corneal dystrophy, particularly Avellino corneal dystrophy, face challenges such as complex labeling operations, long measurement times, and large-sized systems, making rapid and accurate diagnosis difficult, especially before sight-correction surgeries.
Innovation Solution
A multi-spot metal-capped nanostructure array nucleic acid chip utilizing LSPR optical properties, which involves forming a metal thin film layer on a substrate, arraying nanostructures at constant intervals, and immobilizing probe nucleic acids to enable simultaneous detection of multiple analyte DNAs, including BIGH3 gene mutations, using a label-free biosensor approach.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional nucleic acid chips with labeling operations are used for diagnosis, then detection capability is achieved, but the labeling operation becomes complicated and measurement time increases
Solution Approach 1:
The invention extracts and eliminates the labeling operation from the detection system. By using label-free localized surface plasmon resonance (LSPR) technology, the complex labeling steps required by conventional nucleic acid chips are completely removed, simplifying the overall detection process while maintaining detection capability through direct optical measurement of refractive index changes near the metal nanoparticle surface
Solution Approach 2:
The invention replaces the mechanical/chemical labeling operation with an optical detection system based on LSPR. Instead of using physical labels or fluorescent markers that require complex attachment procedures, the system uses the optical properties of metal nanoparticles to directly detect nucleic acid binding through refractive index changes, substituting a simplified optical measurement for complex mechanical labeling operations
2Measurement precision
If conventional nucleic acid chips with labeling operations are used, then detection is possible, but measurement time becomes long
Solution Approach 1:
The invention performs preliminary action by pre-functionalizing the metal nanoparticle surface with capture probes during chip fabrication. This eliminates the need for time-consuming labeling operations at the time of measurement, as the detection system is already prepared and ready for immediate use, reducing measurement time while maintaining detection capability
Solution Approach 2:
By extracting and removing the labeling operation entirely from the measurement process, the invention eliminates the time required for label attachment, washing, and optimization steps, thereby significantly reducing total measurement time while maintaining accurate detection through direct LSPR signal measurement
3Measurement precision
If conventional nucleic acid chips are used, then detection function is provided, but the system size becomes large
Solution Approach 1:
The invention uses ultra-thin metal film layers (few nanometers thick) deposited on transparent substrates to create the LSPR sensing surface. These thin film structures provide the necessary optical functionality for detection while occupying minimal space, enabling a compact system design that maintains full detection capability without requiring large instrument volumes
4Productivity
If multiple analytes are detected simultaneously, then diagnostic efficiency is improved, but device complexity increases
Solution Approach 1:
The invention segments the chip surface into multiple distinct sensing regions, each functionalized with different capture probes for specific analytes. This spatial segmentation allows simultaneous detection of multiple nucleic acid targets in parallel across different regions of the same chip, improving diagnostic efficiency while keeping each individual sensing region relatively simple in structure
Solution Approach 2:
The invention creates a universal LSPR chip platform that can detect multiple different analytes by simply changing the probe molecules immobilized on the metal nanoparticle surface. The underlying metal nanoparticle array structure and LSPR detection mechanism remain the same, providing multi-functionality without requiring complex device modifications, thereby enabling simultaneous multi-analyte detection with moderate complexity
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 chip allows for rapid, accurate, and simultaneous detection of multiple nucleic acids, including BIGH3 gene mutations, enhancing diagnostic efficiency and reducing the risk of misdiagnosis during sight-correction surgeries by providing a compact, easy-to-use system with high sensitivity.
Implementation Method 1
a new type of label-free biochip based on localized surface plasmon resonance (LSPR), a new optical property that is expressed only in nanostructures, was fabricated. When materials having a local surface, such as metal nanoparticles, are radiated with light having various wavelengths, the surface of the metal nanoparticles is polarized, unlike a bulk metal, and the strength of the electric field is increased. Electrons formed by the polarization form a Plasmon and oscillate locally on the surface of the metal nanoparticles. This phenomenon is referred to as LSPR. The LSPR optical properties sensitively respond to a change in permittivity, that is, a change in refractive index, which occurs near nanoparticles
Data Source
AI summary
A multi-spot metal-capped nanostructure array nucleic acid chip for diagnosing corneal dystrophy, and more particularly to a multi-spot metal-capped nanostructure array nucleic acid chip capable of employing LSPR (localized surface plasmon resonance) optical properties, a preparation method thereof, and a multi-spot metal-capped nanostructure array nucleic acid chip for diagnosing BIGH3 gene mutations, which can diagnose various corneal dystrophies. The metal-capped nanostructure array nucleic acid chip can be combined with analysis devices, including a light source, a detector, a spectrophotometer and a computer, to provide an LSPR optical property-based optical biosensor, and the use of the multi-spot metal-capped nanostructure array nucleic acid chip for diagnosing BIGH3 gene mutations allows the simultaneous diagnosis of various corneal dystrophies that are genetic ocular diseases.