High performance charge detection mass spectrometry without ultra-high vacuum

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Physical Chemistry

Background:

• Charge detection mass spectrometry (CDMS) traditionally requires ultra-high vacuum (UHV) (<10^-9 Torr).
• UHV conditions are expensive and cumbersome, limiting broader application of CDMS.
• Collisions with background gas can interfere with accurate ion measurements in CDMS.

Purpose of the Study:

• To develop and validate a CDMS method capable of accurate measurements at significantly higher pressures than previously possible.
• To investigate the impact of elevated pressures on ion behavior and mass measurement accuracy in an electrostatic trap.
• To determine the feasibility of CDMS for analyzing large biomolecules and nanoparticles under non-UHV conditions.

Main Methods:

• Utilized an electrostatic trap designed to accommodate a wide range of ion energies.
• Implemented a dynamic ion signal analysis method for data processing.
• Performed CDMS measurements on antibody complexes, viruses, and polystyrene nanoparticles at pressures up to 1 × 10^-6 Torr.

Main Results:

• Achieved accurate CDMS mass measurements at pressures up to 1 × 10^-6 Torr, several orders of magnitude higher than prior limits.
• Successfully measured masses of large ions, including antibody complexes (~800 kDa), adeno-associated viruses (~4.8 MDa), and nanoparticles (35–330 MDa).
• Demonstrated that larger ions exhibit greater robustness to higher pressures, with sufficient smaller ions surviving for accurate mass determination.

Conclusions:

• CDMS measurements can be accurately performed at pressures up to 1 × 10^-6 Torr using an electrostatic trap and dynamic analysis.
• This advancement significantly reduces the need for expensive and complex ultra-high vacuum systems.
• The findings pave the way for more accessible and routine mass analysis of large molecules and nanoparticles.