Waveguide-Based Multiplex Pathogen Biomarker Detection
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Solution Overview
Problem
Current biomarker detection strategies face challenges such as low sensitivity, high non-specific binding, and inaccurate quantitation in complex biological samples, limiting their use for early disease detection due to the need for ultra-sensitive detection of multiple pathogen biomarkers.
Innovation Solution
A method using a sandwich assay with a patterned waveguide and inorganic fluorescent reporter molecules, including a substrate with a film or lipid bilayer, recognition ligands, and additional recognition ligands for capturing and quantifying multiple pathogen biomolecules, minimizing non-specific interactions and enhancing sensitivity through spatial filtering and photostable quantum dots.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional plate-based immunoassays are used for multiplex detection, then the assay can detect multiple biomarkers, but the sensitivity is poor and non-specific binding is high
Solution Approach 1:
The patent introduces a waveguide as an intermediary between the traditional plate-based assay and the detection system. The waveguide enables evanescent field excitation that is confined to a thin region near the sensor surface, acting as a spatial filter that excludes fluorescence from bulk solution and reduces non-specific binding signals while maintaining sensitivity for surface-bound analytes
Solution Approach 2:
The patent applies local quality by using evanescent field excitation that is localized to a specific region near the waveguide surface (typically within 200-500 nm). This localized excitation ensures that only fluorophores in close proximity to the sensor surface are excited, creating a spatially differentiated detection zone that enhances signal-to-noise ratio by excluding background fluorescence from the bulk solution
2Duration of action of stationary object
If quantum dots are used as fluorescence reporters, then photostability and multiplexing capability are improved, but quantum efficiency is reduced and stability at neutral pH is poor
Solution Approach 1:
The patent uses composite materials by combining quantum dots with shellac, a natural polymer matrix. This composite structure provides multiple benefits: the shellac matrix protects the quantum dots from aggregation and degradation at neutral pH, improves colloidal stability in physiological buffers, while maintaining the photostability and fluorescence properties of the quantum dots. The composite approach allows the system to achieve both photostability and biochemical compatibility
3Productivity
If multiple biomarkers are detected simultaneously, then early disease detection capability is improved, but accurate quantitation of each biomarker becomes difficult
Solution Approach 1:
The patent employs color changes by using quantum dots with distinct emission wavelengths (e.g., 505 nm, 565 nm, 605 nm, 655 nm) that can be simultaneously excited by a single wavelength (488 nm). Each quantum dot emits at a characteristic wavelength, enabling spectral resolution and independent quantitation of multiple biomarkers in a single assay. The waveguide-based detection system captures and resolves these different wavelengths, allowing simultaneous multiplex detection with accurate quantitation of each biomarker based on its spectral signature
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 approach enables sensitive and accurate quantitation of multiple pathogen biomarkers, achieving a lower limit of detection of 1 pM in serum, surpassing traditional plate-based assays, with reduced variability and improved signal-to-noise ratios, facilitating early disease detection.
Implementation Method 1
interrogating the sandwich assay element with excitation light from the waveguide
Implementation Method 2
inorganic fluorescent reporter molecule
Implementation Method 3
enhancing sensitivity through spatial filtering
Data Source
AI summary
The present invention addresses the simultaneous detection and quantitative measurement of multiple biomolecules, e.g., pathogen biomarkers through either a sandwich assay approach or a lipid insertion approach. The invention can further employ a multichannel, structure with multi-sensor elements per channel.