Serum Protein Positive Selection for Proteomic Analysis
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Solution Overview
Problem
Current proteomic analysis techniques face challenges in discerning small variations in low-abundance proteins and peptides due to the overwhelming presence of high-abundance species, leading to signal-to-noise ratio issues and inaccurate or incomplete analyses, especially in blood chemistry studies.
Innovation Solution
A method and kit for positive selection of proteins and peptides based on specific binding affinity, using collectors such as nucleic acid molecules, antibodies, or aptamers to bind specifically to high-abundance species, reducing their concentration and allowing for better detection of low-abundance species through mass spectrometry.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If direct mass spectrometry analysis is performed on serum samples, then high-abundance proteins can be detected, but low-abundance proteins and peptides cannot be discerned due to overwhelming signal from high-abundance species
Solution Approach 1:
The patent removes high-abundance proteins from the serum sample before mass spectrometry analysis through selective precipitation or affinity-based depletion methods. This extraction of the disturbing component (high-abundance proteins) allows the mass spectrometer to detect low-abundance proteins and peptides that would otherwise be obscured by the overwhelming signal from abundant species like albumin and immunoglobulins.
Solution Approach 2:
The patent applies different treatment conditions to different protein populations within the serum sample. By adjusting precipitation conditions (pH, temperature, salt concentration) or using affinity reagents with specific binding characteristics, the method selectively targets and removes high-abundance proteins while preserving low-abundance species, creating localized quality differences in protein detection capability.
2Adaptability or versatility
If traditional blood chemistry panels are used to analyze specific protein species, then concentration measurements can be obtained, but the scope is limited and multiple tests are required for comprehensive analysis
Solution Approach 1:
The patent employs a universal mass spectrometry-based approach that can simultaneously analyze hundreds to thousands of different proteins and peptides in a single experiment. After removing high-abundance interferents, the mass spectrometer serves as a multi-functional platform capable of detecting diverse protein species across different concentration ranges, replacing the need for multiple specialized antibody-based assays.
Solution Approach 2:
The patent performs preliminary depletion of high-abundance proteins before the comprehensive proteomic analysis. This preparatory step removes the dominant signal sources that would interfere with subsequent broad-spectrum detection, enabling the mass spectrometer to efficiently capture a comprehensive protein profile in one analysis rather than requiring sequential targeted tests.
3Measurement precision
If serum samples are analyzed without preprocessing, then the analysis is simple and quick, but the signal-to-noise ratio is poor due to high-abundance species masking low-abundance species
Solution Approach 1:
The patent extracts and removes high-abundance proteins from the serum sample through selective precipitation or affinity depletion. This extraction process eliminates the dominant signal sources that create noise in mass spectrometry detection, thereby improving the signal-to-noise ratio and enabling reliable detection of low-abundance proteins without requiring overly complex instrumentation.
Solution Approach 2:
The patent alters physical and chemical parameters of the serum sample (pH, temperature, salt concentration, organic solvent content) to selectively precipitate or bind high-abundance proteins. By changing these parameters, the method achieves selective removal of interferents while maintaining the stability and detectability of low-abundance proteins, improving measurement precision with relatively simple parameter adjustments.
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 extraction of a composition with reduced high-abundance species, improving the signal-to-noise ratio and facilitating the detection of low-abundance proteins and peptides, thereby enhancing the accuracy and completeness of proteomic analysis and blood chemistry signatures.
Implementation Method 1
positive selection of proteins and peptides based on specific binding affinity, using collectors such as nucleic acid molecules, antibodies, or aptamers to bind specifically to high-abundance species
Data Source
AI summary
This invention relates to methods and kits for positive selection of species of interest based on peptide/protein sequence from a biological sample. The species of interest may be proteins and/or peptides of interest which may be placed through a mass spectrometer to obtain a blood peptide/protein signature. The blood peptide/protein signature may be used in proteomic analysis. The techniques include but are not limited to the use of collectors comprising nucleic acid molecules to extract a composition that has a lower concentration of a high abundance species of interest from a sample. This limits the level of influence that any collectors species may have on the results of a mass spectra.