Layered Substrate for Label-Free Optical Detection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current microarray detection systems face limitations due to the need for fluorescent labeling of target molecules, which can alter their conformation and binding properties, and lack real-time kinetics information, especially for proteins and DNA, and existing label-free technologies like SPR and optical interferometry are not suitable for high-throughput applications.
Innovation Solution
A label-free optical detection system using a layered substrate with a high refractive index base layer and a low refractive index coating layer, combined with a tunable light source and photodetector array, allows for real-time measurement of target molecule binding without labeling, enabling high-throughput screening and real-time kinetics analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fluorescent labeling is used for target molecules, then detection sensitivity is improved, but the conformation and binding properties of the molecules are altered
Solution Approach 1:
The invention extracts and eliminates the fluorescent label from the detection system, using label-free optical detection methods instead. This removes the harmful element (fluorescent label) that alters molecule conformation and binding properties, while maintaining detection capability through alternative optical means.
Solution Approach 2:
The invention introduces an intermediary substrate structure (layered substrate with specific refractive indices) that mediates the detection process. This substrate acts as an intermediary between the target molecules and the detection system, enabling sensitive detection without direct interaction between the label and the target molecule.
2Ease of manufacture
If label-free detection technologies like SPR are used, then the need for labeling is eliminated, but high-throughput capability is not achieved
Solution Approach 1:
The invention segments the detection field into multiple independent detection regions on a single substrate, allowing simultaneous detection of multiple samples. This segmentation enables high-throughput capability while maintaining the label-free detection advantage of SPR technology.
Solution Approach 2:
The invention transitions from single-point detection to planar array detection, adding spatial dimensionality to the detection system. This allows multiple measurements to be performed simultaneously across the substrate surface, dramatically increasing throughput while preserving label-free operation.
3Productivity
If standard fluorescent microarrays are used, then high throughput is achieved, but real-time kinetics information is lost
Solution Approach 1:
The invention implements continuous real-time monitoring of binding events, maintaining the detection process continuously rather than taking discrete snapshots. This continuous action preserves kinetic information while maintaining high throughput through parallel detection across multiple sites on the substrate.
4Loss of information
If SPR technology is used, then real-time kinetics information is obtained, but compatibility with SiO2-based microarray chemistries is lost
Solution Approach 1:
The invention creates a universal substrate platform that can accommodate various microarray chemistries (DNA-DNA, protein-protein, protein-DNA, etc.) while simultaneously providing real-time optical detection. The layered substrate design with specific refractive indices provides a universal interface that works with different biological molecules and detection modalities.
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 provides sensitive, label-free detection of target molecules with high throughput and real-time binding information, suitable for biological and environmental samples, and can be adapted for SiO2-based microarray substrates, overcoming the limitations of existing technologies.
Implementation Method 1
The present invention provides methods and devices for the label-free detection of target molecules of interest... using a layered substrate with a high refractive index base layer and a low refractive index coating layer, combined with a tunable light source and photodetector array
Implementation Method 2
A layered substrate comprising a base layer, at least one coating layer having a refractive index different from that of the base layer
Data Source
AI summary
This disclosure provides methods and devices for the label-free detection of target molecules of interest. The principles of the disclosure are particularly applicable to the detection of biological molecules (e.g., DNA, RNA, and protein) using standard SiO2-based microarray technology.