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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.