Ion Mobility Tags for Quantitative Peptide Analysis
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Solution Overview
Problem
Conventional ion mobility spectrometry-mass spectrometry (IMS-MS) techniques face challenges in quantification and multiplexing of complex samples due to similarities in analyte collision cross-section profiles, limiting the resolution and quantitative characterization of multiple components.
Innovation Solution
The use of covalent tags and shifting agents, including compounds with a linker and normalizing group separated by a cleavable group and a crown ether, which form intra-molecular complexes with analytes, enhancing separation and allowing for quantitative and multiplexed analyses through IMS-MS by modifying collisional cross-sections and enabling identification of specific samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional IMS-MS techniques are used for separation and analysis, then the analysis speed is fast (millisecond timescale), but the resolution and quantification capability of complex samples are limited due to similarities in collision cross-section profiles
Solution Approach 1:
The patent introduces IMS mobility tags as intermediary compounds that bind to analytes and modify their collision cross-section profiles. These tags serve as mediators between the analyte and the IMS-MS detection system, creating enhanced separation based on tag-analyte complex properties rather than native analyte properties alone. The tags contain crown ether moieties that specifically complex with basic residues in peptides, creating distinctive mobility signatures that enable better resolution and quantification of complex samples.
Solution Approach 2:
The patent employs parameter changes by modifying the collision cross-section of analytes through covalent attachment of IMS tags with different structural parameters. The tags contain variable numbers of ethylene oxide units and different linker lengths, which systematically change the mobility parameters of the tagged analytes. This parameter variation enables differentiation of analytes with similar native cross-sections, improving measurement precision without increasing spectral complexity.
2Measurement precision
If conventional IMS techniques are used, then the separation is based on native collision cross-sections, but the ability to resolve complex components and perform quantitative characterization is challenging
Solution Approach 1:
The IMS tag is segmented into distinct functional modules: a crown ether moiety for complexation with basic residues, a linker region with variable length and composition, and terminal groups for covalent attachment to the analyte. This segmentation allows independent optimization of each functional element and enables systematic variation of tag parameters to create multiplexed tagging schemes for quantitative analysis of multiple analytes simultaneously.
Solution Approach 2:
The patent utilizes parameter changes in the tag structure, specifically varying the number of ethylene oxide units and linker length, to create a library of tags with distinct mobility characteristics. These parameter variations enable multiplexed quantitative analysis by providing unique mobility signatures for different analytes or sample conditions, facilitating detailed quantitative characterization without compromising ease of operation.
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 significantly improves the separation and quantitation of multiple components in complex samples, enabling higher-order multiplexing without increasing spectral complexity, thereby overcoming the limitations of conventional IMS-MS methods.
Implementation Method 1
the analyte is capable of intra-molecular complexing with Q wherein Q is a crown ether
Implementation Method 2
IMS exploits the differences of particles in diffusion through a gas at different speeds, depending on their collision cross sections with the gas molecules
Data Source
AI summary
Compound tags and shifting agents are provided that find use in ion mobility spectrometry (IMS), mass spectrometry (MS), or a combination of IMS and MS, and which can substantially increase separation of multiple components in complex samples and facilitate quantitative and multiplexed analyses. In some cases, the compounds include a linker and a normalizing group, each including a structural unit and separated by a cleaveable group, and a crown ether. Also provided are methods for analyzing peptides in a sample. In some cases, the method includes coupling the compound to peptides which include a terminal guanidinium moiety capable of forming an intra-molecular complex with the crown ether.