High-Resolution Differential Ion Mobility Separations/Orbitrap Mass Spectrometry without Buffer Gas Limitations

Area of Science:

• Analytical Chemistry
• Physical Chemistry

Background:

• Differential ion mobility spectrometry (FAIMS) and mass spectrometry (MS) offer powerful isomer and isobar separation.
• High resolution in both FAIMS and MS dimensions is crucial for maximizing analytical performance.
• Orbitrap mass analyzers provide high mass resolution and accuracy.
• FAIMS resolution is often enhanced using helium (He) or hydrogen (H2) as carrier gases, which can elevate ion mobility.

Purpose of the Study:

• To address the challenge of maintaining ultrahigh vacuum (UHV) in Orbitrap MS when using He or H2 in FAIMS.
• To enable independent optimization of FAIMS carrier gas composition without compromising MS performance.
• To enhance the overall utility and flexibility of hybrid FAIMS/MS platforms.

Main Methods:

• Implementation of a differential pumping stage between the FAIMS and MS interfaces.
• Reconfiguration of vacuum lines to isolate the high vacuum (HV) pumping region.
• Evaluation of vacuum stability and MS performance under different FAIMS carrier gas conditions.

Main Results:

• Hardware modifications significantly reduced pressure increases caused by He or H2 aspiration from the FAIMS stage.
• The differential pumping step and isolated vacuum line reconfiguration effectively ameliorated vacuum complications.
• Free optimization of FAIMS carrier gas composition became feasible without negatively impacting Orbitrap MS performance.

Conclusions:

• The developed hardware modifications overcome the limitations of using light carrier gases in FAIMS/MS systems.
• This advancement allows for maximizing FAIMS resolution through carrier gas choice, leading to improved isomer and isobar separation.
• The enhanced FAIMS/MS platforms offer greater utility and flexibility for complex mixture analysis.