Surface-FIDA Method for Misfolded Protein Aggregate Detection
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Solution Overview
Problem
Current diagnostic methods for neurodegenerative diseases and amyloidoses lack reliable, objective, and quantifiable tests for detecting misfolded protein aggregates, hindering accurate diagnosis and monitoring of disease progression and treatment efficacy.
Innovation Solution
A method for qualitative and quantitative determination of disease indicators using a standard for selective quantification and characterization of misfolded protein aggregates, involving capture molecules immobilized on a substrate, labeled probes, and internal or external standards to detect specific aggregates in body fluids without extensive processing, enabling simultaneous analysis of multiple aggregate types.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional diagnostic methods are used for neurodegenerative diseases, then the diagnostic process is simple, but the detection precision and reliability of misfolded protein aggregates are insufficient
Solution Approach 1:
The diagnostic method is segmented into distinct functional modules: capture molecules immobilized on substrate for specific aggregate capture, fluorescently labeled probes for detection, and standardized reference materials for quantification. This segmentation allows each component to be optimized independently while maintaining overall system precision.
Solution Approach 2:
The invention employs standardized reference materials with known concentrations of misfolded protein aggregates to establish quantitative relationships between fluorescence signal intensity and aggregate concentration. This parameter standardization enables precise measurement across different experimental conditions and laboratories.
2Reliability
If extensive sample processing is performed to detect protein aggregates, then the detection reliability improves, but the analysis time and loss of time increase
Solution Approach 1:
Capture molecules are pre-immobilized on the substrate in specific patterns and orientations before sample application. This preliminary arrangement ensures that when the sample is applied, aggregates are immediately captured with high efficiency, eliminating the need for extensive processing steps while maintaining diagnostic reliability.
Solution Approach 2:
The invention introduces capture molecules as intermediary elements between the sample and detection system. These capture molecules specifically bind to misfolded protein aggregates, concentrating them on the substrate surface and enabling reliable detection without extensive sample preparation or concentration steps.
3Productivity
If multiple aggregate types are analyzed separately, then the measurement precision for each type is maintained, but the productivity and throughput decrease
Solution Approach 1:
The invention employs a universal substrate design with capture molecules arranged in distinct regions or patterns that can simultaneously capture different types of protein aggregates. Multiple fluorescently labeled probes with different emission wavelengths can be applied to detect different aggregate types in a single experiment, maintaining quantification accuracy while dramatically increasing throughput.
Solution Approach 2:
The invention transitions from sequential one-dimensional analysis to parallel two-dimensional analysis by spatially separating capture molecules for different aggregate types on the substrate surface. This spatial dimensionality allows simultaneous detection of multiple aggregate types while maintaining the ability to independently quantify each type through region-specific signal analysis.
4Measurement precision
If standardized reference materials are used for quantification, then the measurement precision and comparability improve, but the device complexity and manufacturing complexity increase
Solution Approach 1:
The invention creates simplified copies or models of misfolded protein aggregates with defined structures and concentrations that serve as reference standards. These standardized reference materials are manufactured using controlled protocols that reproduce specific aggregate types, enabling precise quantification without requiring complex natural sample preparation.
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 provides a rapid, sensitive, and specific method for detecting and quantifying misfolded protein aggregates, facilitating early diagnosis, monitoring disease progression, and assessing treatment effectiveness in neurodegenerative diseases and amyloidoses.
Implementation Method 1
The marked aggregates are detected by scanning or other types of surface imaging... Detection is preferably carried out using confocal fluorescence microscopy, fluorescence correlation spectroscopy (FCS)...
Implementation Method 2
capture molecules immobilized on a substrate... Capture molecules for AA-containing particles (e.g. anti-AA antibodies) are bound to this (preferably covalently)
Data Source
Figure 1A~1B
Figure 1C~1D
Figure 1E~1F
AI summary
The invention relates to a method for detecting indicators for detecting diseases (disease indicators), misfolded proteins in the aggregates thereof playing a roll. The invention also relates to a method for selectivity quantifying and/or characterizing said disease indicators.