Red Blood Cell Surface AFM for Early Amyloid Aggregate Detection
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Solution Overview
Problem
Current methods for detecting amyloid aggregates in blood, such as PET and immunoassays, are inadequate for early-stage detection and cannot unambiguously identify all forms of amyloid aggregates, including monomers to fibrillar aggregates.
Innovation Solution
A method using atomic force microscopy (AFM) to analyze the surface layer of red blood cells in a blood sample, employing a passivation layer and imaging techniques to detect and quantify amyloid aggregates, including spherical oligomers, protofibrils, and fibrils, with nanometer-scale resolution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If PET or immunoassay methods are used to detect amyloid aggregates, then detection can be performed, but early-stage detection sensitivity is insufficient and all forms of aggregates cannot be unambiguously identified
Solution Approach 1:
The patent uses red blood cells as an intermediary substrate to capture and concentrate amyloid aggregates from blood samples. The aggregates bind to the red blood cell surface, enabling enhanced detection sensitivity and the ability to visualize different aggregate forms (monomers, oligomers, fibrils) simultaneously through AFM imaging.
2Productivity
If conventional detection methods are used, then detection is possible, but the detection time is prolonged and early diagnosis is delayed
Solution Approach 1:
The method performs preliminary concentration and immobilization of amyloid aggregates on red blood cell surfaces before detection. This preliminary action enables rapid AFM scanning and imaging, reducing total detection time to 30-45 minutes and facilitating early diagnosis.
3Measurement precision
If AFM surface layer analysis is used to detect amyloid aggregates, then early-stage detection sensitivity is improved and all aggregate forms can be identified, but the device complexity increases
Solution Approach 1:
The patent extracts and isolates amyloid aggregates from the complex blood matrix by concentrating them on red blood cell surfaces. This extraction simplifies the sample for AFM analysis, allowing detection of all aggregate forms with high sensitivity while reducing the complexity of sample preparation and analysis.
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 efficient and reliable detection of amyloid aggregates in blood, facilitating early diagnosis of neurodegenerative diseases like Alzheimer's and Parkinson's, with results obtainable within 30-45 minutes, and providing geometric parameters for disease indicators.
Implementation Method 1
performing an analysis of a surface layer of the blood sample by an atomic force microscope (AFM) to detect amyloid aggregates on a surface of the one or more red blood cells
Data Source
AI summary
An aspect of the invention relates to a method for detecting amyloid aggregates (40) in blood. The method comprises providing a blood sample (20) comprising one or more red blood cells and performing an analysis of a surface layer (22) of the blood sample (20) by an atomic force microscope (10) to detect amyloid aggregates on the surface of the red blood cells and to image detected amyloid aggregates. Further aspects relate to a corresponding atomic force microscope and a corresponding computer program product.