Dependence of gas phase equilibrium on temperature: For all the above ionization situations, a common feature is that the plume strongly favors neutral species, which is achieved by proton transfer or by ion pair formation. However, because all the neutralization processes are exothermic, if temperature increases, the neutralization processes become less favored. For example, the equilibrium constant of ion pair formation (e.g. the one in equation 1) may drop from 10 7 , the value of 1,000 K, to 10 4 when the temperature is 1,800 K. The equilibrium constant of equation ( ) may drop from 10 15 , the value of 1,000 K, to 10 9 when the temperature is 1,800 K (see supporting information). If the partial pressures of the two species on either side of equation ( ) were assumed identical, the ratio of Pep-NH + over Pep-N would be 10 -5 , which is close to the experimentally determined ion yields of peptides in MALDI MS. Therefore, the reduced tendency of neutralization under higher temperature is beneficial for ion extraction and ion detection.