MALDI 2 enhances sensitivity by two orders of magnitude

MALDI 2 is a further development of MALDI, in which laser energy is applied to a solid analye-matrix sample. The analyte-matrix cluster absorbs the laser energy and gets ionized, ablated and protonated within the gas phase.

Two theories have been proposed for these processes. The lucky survivor theory in which the analyte is already charged before it is released into the gas phase. Here counter ion reactions with the oppositely charged matrix ion can take place and form a neutral cluster which can not be detected anymore. Only the analyte ions which do not react with the matrix will make it to the detector.

The 2nd theory - assumes that the analyte is evapourated into the gas phase as neutral and gets gas phase protonated by the matrix.

The two theories have in common that there are a certain number of neutral matrix or matrix-analyte cluster present in the gas phase. These neutrals are lost within the MS but still have the potential to be ionized and therefore limit the ion yield.
MALDI 2 tries to target exactly these neutrals, which require more energy to ionize or to re-ionize, by inducing a second MALDI ionization.

To minimize spatial expansion of the ion plume source parameter, such as pressure, laser wavelength, beam focus and the timing are really important to make this technique work. Since spatial expansion is still present and therefore different starting conditions for the MALDI ions orthogonal TOF is highly benefical for mass analysis.

MALDI 2 increases sensitivity for lipids by two orders of magnitude.
http://science.sciencemag.org/content/early/2015/03/04/science.aaa1051.full