Mass spectrometry of intact neutral macromolecules using intense non‐resonant femtosecond laser vaporization with electrospray post‐ionization

Intact, nonvolatile, biological macromolecules can be transferred directly from the solid state into the gas phase, in ambient air, for subsequent mass spectral analysis using non‐resonant femtosecond (fs) laser desorption combined with electrospray ionization (ESI). Mass spectral measurements for neat samples, including a dipeptide, protoporphyrin IX and vitamin B12 adsorbed on a glass insulating surface, were obtained using an 800 nm, 70 fs laser with an intensity of 10¹³ W cm^?2. No appreciable signal was detected when atmospheric matrix‐assisted or neat (matrix‐free) fs laser desorption was performed without ESI, indicating neutral desorption. Copyright © 2009 John Wiley & Sons, Ltd.