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 10(13) 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.