Experimental results from equimolar PEG and protein standards samples are presented from a MALDI‐TOF mass spectrometer equipped with both ionizing detectors and the novel single molecule sensitive cryodetectors. The data are consistent with a model hypothesis suggesting that the observed decrease in signal strength in conventional ionizing detector MALDI‐TOF mass spectrometers can be explained by the exponentially decreasing quantum efficiency of ionizing detectors. Cryodetectors, in contrast, have a mass independent detection efficiency of 100% on impact and provide additional information on the molecule state owing to the calorimetric nature of the detection mechanism.