Multi-Particle Protein Corona Analysis for Low-Abundance Detection
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Solution Overview
Problem
Existing methods for analyzing biofluids struggle to effectively detect and quantify a wide range of proteins, particularly due to the overshadowing effect of high abundance proteins, and the interaction of diverse biofluids with particles is not well understood.
Innovation Solution
A method involving serial interrogation of a sample with multiple particle types to form biomolecule coronas, followed by separation and assaying to determine protein composition and concentration, which compresses the dynamic range of proteins and allows for detailed analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional protein analysis methods are used on biofluids, then high abundance proteins can be detected, but low abundance proteins are overshadowed and cannot be effectively detected
Solution Approach 1:
The method segments the protein analysis process by using multiple particle types with different surface properties. Each particle type selectively binds to different subsets of proteins, dividing the complex mixture into manageable groups that can be analyzed separately, thereby enabling detection of low abundance proteins that would otherwise be overshadowed
Solution Approach 2:
Particles serve as intermediary agents between the biofluid sample and the detection system. These particles with tailored surface properties mediate the binding process, allowing selective enrichment of specific proteins including low abundance ones, while preventing the overwhelming signal from high abundance proteins from dominating the entire analysis
2Adaptability or versatility
If fractionation methods are used to reduce high abundance protein signals, then protein profiles can be differentiated, but analysis of diverse proteomics remains limited
Solution Approach 1:
The particle-based platform provides universal functionality for protein analysis across diverse proteomics applications. By designing particles with different surface properties, the same basic platform can be adapted to analyze various protein types and concentrations without requiring entirely different methodologies, thereby enhancing versatility while managing complexity
3Measurement precision
If serial interrogation with multiple particle types is performed, then comprehensive protein profiling is achieved, but the process time and steps increase
Solution Approach 1:
Multiple particle types are prepared in advance with different surface properties tailored to bind specific protein subsets. This preliminary preparation allows the serial interrogation process to proceed more efficiently, as the particles are pre-configured for their specific binding functions, reducing the overall time required for comprehensive protein profiling
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 enables the detection of a diverse range of proteins, including low abundance ones, by compressing the dynamic range of protein signals and providing a comprehensive profile for diagnostic and therapeutic applications.
Implementation Method 1
contacting the sample to a first particle type and incubating the first particle type with the sample to form a first biomolecule corona
Data Source
AI summary
This disclosure provides methods and compositions for biomolecule corona analysis of biofluids. A biofluid may be contacted with a nanoparticle to form a biomolecule corona, and the composition of the resulting corona may be analyzed. Also provided are methods of preparing a biofluid for corona analysis by serial interrogation.