Single-Molecule Pycnometry and Shape Analysis of Ions in the Gas Phase

Area of Science:

• Analytical Chemistry
• Physical Chemistry
• Biophysics

Background:

• Mobility-classified mass spectrometry analyzes ions and clusters based on mobility and mass.
• Current methods often assume globular analyte shapes for density determination.
• Accurate characterization of molecular size and shape is crucial for understanding molecular behavior.

Purpose of the Study:

• To develop a shape-independent method for precise analyte density determination using mobility-classified mass spectrometry.
• To accurately characterize molecular size and shape parameters for various analytes.
• To establish a robust method applicable to diverse molecules and limited sample quantities.

Main Methods:

• Utilizing analyte-poly(ethylene glycol) (PEG) cluster ions for density analysis, inspired by classical pycnometry.
• Entrapping analytes within globular PEG-analyte droplets.
• Independently deriving mobility diameter and volume-equivalent diameter from mass-mobility data.

Main Results:

• Precise analyte density determination (<1% deviation from literature values) independent of analyte shape.
• Successful characterization of size and shape parameters for lysozyme, cyano-cobalamin, and glucose.
• Demonstrated applicability to a wide mass range (180–14,300 Da) and various molecular types.

Conclusions:

• The developed pycnometry-inspired method provides accurate, shape-independent density and shape information.
• This technique is versatile, applicable to diverse molecules, supramolecular assemblies, and biomolecules with minimal sample.
• The approach is robust, relying solely on mass-mobility data and independent of specific mobility theories or drift gases.