Amyloid Aggregate Detection via Fluorescence Correlation Spectroscopy
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Solution Overview
Problem
Current methods for diagnosing amyloid-associated diseases, such as Alzheimer's and Parkinson's, are inadequate due to the lack of early biomarkers, leading to delayed diagnosis and ineffective treatment, as they often rely on post-mortem analysis and cannot detect individual amyloid aggregates in living patients.
Innovation Solution
A method involving the use of fluorescence correlation spectroscopy (FCS) and fluorescence intensity fluctuation analysis (FIFA) to detect and quantify individual amyloid aggregates in bodily fluids like blood and cerebrospinal fluid, allowing for early diagnosis and prognosis without amplification of aggregates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If post-mortem analysis methods are used to detect amyloid deposits, then detection sensitivity is improved, but diagnostic timing is delayed until after death
Solution Approach 1:
The patent uses fluorescent detection agents as intermediaries that bind to individual amyloid aggregates in bodily fluids. These agents enable indirect detection of amyloid aggregates through fluorescence signals, allowing early diagnosis in living patients without requiring post-mortem tissue analysis. The detection agent acts as a mediator between the amyloid aggregates and the detection system.
Solution Approach 2:
The patent replaces mechanical/surgical tissue extraction and histological processing with optical detection methods. Instead of physically examining brain tissue under microscopes after death, the system uses fluorescence correlation spectroscopy to detect amyloid aggregates in blood or cerebrospinal fluid, substituting mechanical tissue analysis with optical field-based detection.
2Measurement precision
If amplification methods are used to detect amyloid aggregates, then detection sensitivity is improved, but detection time and process complexity increase
Solution Approach 1:
The detection agents self-bind to amyloid aggregates through specific molecular recognition without requiring external amplification steps. The fluorescent probes automatically associate with their target amyloid aggregates in the sample, and the fluorescence signal directly reports aggregate presence and concentration, eliminating the need for time-consuming amplification procedures.
Solution Approach 2:
The patent changes the detection parameter from measuring amyloid aggregate mass or concentration directly to measuring fluorescence intensity and correlation properties. This parameter transformation allows detection of individual aggregates without amplification, as the fluorescence signal provides sufficient sensitivity to detect single aggregate events through temporal correlation analysis.
3Ease of operation
If conventional detection methods are used, then procedural simplicity is maintained, but detection of individual aggregates is not achieved
Solution Approach 1:
The patent replaces conventional bulk detection methods with fluorescence correlation spectroscopy, an optical technique that measures temporal fluctuations in fluorescence intensity to resolve individual aggregate events. This substitution maintains procedural simplicity while achieving single-aggregate resolution through statistical analysis of fluorescence signal dynamics.
Solution Approach 2:
The patent adds a temporal dimension to the detection by measuring fluorescence intensity fluctuations over time rather than static signal levels. This time-resolved measurement approach enables resolution of individual aggregates within bulk samples by analyzing the temporal correlation of fluorescence events, transforming a spatial detection problem into a temporal one.
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 non-invasive, early detection of amyloid aggregates in living patients, facilitating timely treatment and monitoring of disease progression, and identifying effective therapeutic agents by assessing changes in aggregate levels.
Implementation Method 1
determining the presence and/or amount and/or concentration and/or size of individual amyloid aggregates in the sample comprises an analysis based on time-resolved detection comprising fluorescence correlation spectroscopy (FCS)
Implementation Method 2
adding a detection agent to a sample of bodily fluid from the subject, the detection agent binding to and/or associating with and/or reacting with individual amyloid aggregates
Data Source
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AI summary
The invention relates generally to methods for the diagnosis and/or prognosis of an amyloid-associated disease, methods of treating an amyloid-associated disease, and methods of identifying an agent for the treatment of an amyloid-associated disease, as well as related uses and kits of parts