Isobaric Mass Tags for Multiplex Analyte Quantification
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Solution Overview
Problem
Current methods for determining analytes in complex mixtures, such as proteins, peptides, and nucleotides, face challenges in accurately identifying and quantifying multiple samples simultaneously due to limitations in mass spectrometry analysis, particularly in distinguishing between isobaric and isomeric compounds.
Innovation Solution
The use of isobaric or isomeric labeling reagents with unique reporter groups and linkers that fragment differently under dissociative energy, allowing for the identification and quantification of analytes in multiplex analyses by correlating the presence of these reporters with the analytes' amounts in mass spectrometry.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If isobaric or isomeric labeling reagents are used for multiplex analysis, then the ability to simultaneously identify and quantify multiple analytes is improved, but the complexity of mass spectrometry analysis increases due to difficulty in distinguishing between isobaric and isomeric compounds
Solution Approach 1:
The labeling reagent is divided into three distinct functional segments: a reactive group that covalently binds to the analyte, a linker that connects the reporter to the analyte, and a reporter group that produces a detectable signal. This segmentation allows each component to be optimized independently and facilitates the differentiation of isobaric/isomeric compounds through unique fragmentation patterns of the linker-reporter junction.
Solution Approach 2:
The patent introduces unique local characteristics to the linker and reporter groups of each labeling reagent in the set. Each linker-reporter combination has distinct chemical properties and fragmentation behaviors, creating locally unique signatures that enable differentiation of isobaric and isomeric compounds during mass spectrometry analysis, while maintaining the same overall mass-to-charge ratio.
2Measurement precision
If multiple labeling reagents with unique reporters are used to differentiate analytes, then the precision of analyte identification is improved, but the difficulty of detecting and measuring increases due to isobaric and isomeric interference
Solution Approach 1:
The linker acts as an intermediary component between the analyte and the reporter group. It is specifically designed to facilitate clean fragmentation at the linker-reporter junction, serving as a mediator that separates the analyte signal from the reporter signal. This intermediary function enables precise detection of the reporter ion as a distinct fragment, eliminating interference from isobaric and isomeric compounds that would otherwise co-elute and confound detection.
3Productivity
If isobaric labeling reagents are used to maintain the same mass-to-charge ratio, then the efficiency of multiplex analysis is improved, but the reliability of quantification decreases due to inability to distinguish between different analytes
Solution Approach 1:
The patent changes the chemical parameters of the linker and reporter groups while maintaining the overall mass-to-charge ratio constant. By modifying the chemical composition, bond types, and structural arrangement of these components, each labeling reagent produces a unique fragmentation pattern and ion signature. This parameter change strategy allows isobaric compounds to be reliably distinguished through their distinct mass spectral fingerprints, ensuring quantification reliability while maintaining multiplexing efficiency.
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 the simultaneous analysis and quantification of multiple analytes in complex samples by fragmenting the labeling reagents to produce distinct signatures, improving the accuracy and efficiency of identifying and quantifying analytes in proteomic and genomic analyses.
Implementation Method 1
isobaric or isomeric labeling reagents with unique reporter groups and linkers that fragment differently under dissociative energy
Data Source
AI summary
This invention pertains to methods, mixtures, kits and/or compositions for the determination of analytes by mass analysis using unique labeling reagents or sets of unique labeling reagents. The labeling reagents can be isomeric or isobaric and can be used to produce mixtures suitable for multiplex analysis of the labeled analytes.