Plasmonic Biosensing of Protein Secondary Structures in Neurodegeneration
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Solution Overview
Problem
Current methods for detecting neurodegenerative disorder biomarkers are insensitive to structural changes and lack the capability to differentiate between different structural forms of proteins, leading to misdiagnosis and ineffective monitoring of disease progression.
Innovation Solution
A neurodegenerative disorder biosensing system utilizing plasmonic nanostructures with capturing agents to bind to specific protein secondary structures, combined with optical detectors and data processing to distinguish between different protein secondary structure types, and a method involving plasmonic excitation for enhanced infrared absorption.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If mass spectrometry or ELISA methods are used to quantify target proteins, then the level of target proteins can be measured, but the methods are insensitive to changes in structural states and cannot discriminate between different structural forms
Solution Approach 1:
The patent replaces conventional mass spectrometry and ELISA methods with surface-enhanced infrared absorption (SEIRA) spectroscopy. This substitution enables direct detection of protein structural states through vibrational spectral signatures, allowing discrimination between different structural forms (monomers, oligomers, fibrils) based on their characteristic infrared absorption patterns rather than relying on indirect quantification methods.
Solution Approach 2:
The patent utilizes infrared absorption spectral signatures as a form of 'spectral fingerprinting' to identify and distinguish different protein structural states. Each structural form has a unique infrared absorption spectrum, similar to how different substances have different color properties, enabling visual and quantitative differentiation of structural states through spectral analysis.
2Loss of information
If conventional quantification methods are used, then target protein levels can be measured, but structural information and disease stage differentiation are lost
Solution Approach 1:
The patent introduces infrared absorption spectra as an intermediary that bridges the gap between protein structural states and disease diagnosis. The spectral signatures serve as a mediator that encodes structural information, allowing indirect but accurate detection of disease stage and protein aggregation state without requiring direct structural analysis techniques.
3Reliability
If antibody-based detection methods are developed to target specific structural forms, then structural specificity might be achieved, but validation results show antibodies are not specific to only one form of aggregate or monomers
Solution Approach 1:
The patent replaces antibody-based detection with infrared spectroscopy, which detects structural forms through their vibrational spectral signatures rather than through antibody-antigen binding. This substitution eliminates the limitation of antibody cross-reactivity while maintaining the ability to distinguish between different structural forms based on their unique spectral fingerprints.
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
Enables accurate detection and differentiation of neurodegenerative disorder biomarkers from small sample volumes, allowing for early diagnosis, monitoring, and evaluation of therapies.
Implementation Method 1
at least one plasmonic device including a plurality of plasmonic nanostructures configured to provide plasmonic excitation surface-enhanced infra-red absorption by molecular vibrational excitations of neurodegenerative disorder proteins
Implementation Method 2
at least one optical detector configured to detect reflected optical infra-red spectra reflected from the plurality of plasmonic nanostructures
Data Source
AI summary
A neurodegenerative disorder biosensing system including at least one plasmonic device including a plurality of plasmonic nanostructures; at least one optical detector; and at least one data processing device including at least one processor configured to process a plurality of absorption spectra determined from the reflected optical infra-red spectra, the plurality of absorption spectra representing time-resolved infra-red absorption by at least one of: (i) first protein secondary structure types formed from neurodegenerative disorder aggregated proteins and (ii) second protein secondary structure types formed from neurodegenerative disorder aggregated proteins. The at least one processor configured to process the plurality of absorption spectrum signals to identify the first protein secondary structure type and the second protein secondary structure type, and to distinguish the identified first protein secondary structure type from the second protein secondary structure type, and to distinguish the identified second protein secondary structure type from the first protein secondary structure type.