Toward plasma proteome profiling with ion mobility-mass spectrometry

Area of Science:

• Proteomics
• Analytical Chemistry
• Biochemistry

Background:

• Complex biological mixtures pose challenges for proteomic analysis due to limited component resolution.
• Existing mass spectrometry methods often struggle with dynamic range and sensitivity for low-abundance species.

Purpose of the Study:

• To apply ion mobility-mass spectrometry (IMS-MS) to enhance component resolution in proteomic analyses.
• To demonstrate the utility of IMS-MS for rapid and sensitive profiling of complex biological samples.

Main Methods:

• Utilized liquid chromatography coupled with ion mobility-mass spectrometry (LC-IMS-MS).
• Employed gas-phase ion mobility separation prior to mass spectrometry analysis.
• Performed collision-induced dissociation on all ions within a single experimental sequence.

Main Results:

• Achieved over an order of magnitude enhancement in component resolution without increasing data acquisition time.
• Increased measurement sensitivity and dynamic range by separating high-abundance from low-abundance species.
• Successfully analyzed a plasma digest in 3.3 hours, identifying 438 unique proteins.

Conclusions:

• IMS-MS significantly improves resolution and sensitivity in proteomic analyses of complex mixtures.
• The developed method allows for rapid, comprehensive, and sensitive plasma profiling.
• This approach provides a foundation for future comparative plasma profiling studies.