Vaporization of Intact Neutral Biomolecules Using Laser-Based Thermal Desorption

J Am Soc Mass Spectrom. 2023 Jul 5;34(7):1538-1542. doi: 10.1021/jasms.3c00194. Epub 2023 Jun 15.


The production of a clean neutral molecular sample is a crucial step in many gas-phase spectroscopy and reaction dynamics experiments investigating neutral species. Unfortunately, conventional methods based on heating cannot be used with most nonvolatile biomolecules due to their thermal instability. In this paper, we demonstrate the application of laser-based thermal desorption (LBTD) to produce neutral molecular plumes of biomolecules such as dipeptides and lipids. Specifically, we report mass spectra of glycylglycine, glycyl-l-alanine, and cholesterol obtained using LBTD vaporization, followed by soft femtosecond multiphoton ionization (fs-MPI) at 400 nm. For all molecules, the signal from the intact precursor ion was observed, highlighting the softness and applicability of the LBTD and fs-MPI approach. In more detail, cholesterol underwent hardly any fragmentation. Both dipeptides fragmented significantly, although mostly through only a single channel, which we attribute to the fs-MPI process.

MeSH terms

  • Dipeptides
  • Laser Therapy*
  • Lasers*
  • Mass Spectrometry / methods
  • Volatilization


  • Dipeptides