Booster-microchannel plate (BMCP) detector for signal amplification in MALDI-TOF mass spectrometry for ions beyond m/z 50 000

Abstract

Top-down proteomics deals with the characterization of intact biomolecules, which reduces the sample complexity and facilitates the detection of modifications at the protein level. The combination of the matrix-assisted laser desorption/ionization (MALDI) technique with time-of-flight (TOF) mass analysis allows for the generation of gaseous ions in low charge states from high-mass biomolecules, followed by their mass-to-charge ratio (m/z) separation, as high-mass ions drift down the flight tube more slowly than lighter ones. However, the detection efficiency of conventional microchannel plate (MCP) detectors is strongly reduced with decreasing ion velocity—corresponding to an increase in ion mass—which impedes the reliable detection of high-mass biomolecules. Herein, we present a simple modification of the MCP detector that allows for the amplification of the signal from ionized proteins of up to m/z 150 000. Two circular electrodes were assembled in front of the conventional detector and set to negative electrical voltages to affect the positively charged ions directly before they impinge on the MCP, possibly through a combination of a velocity boost and ion optical effects. In the present study, three booster electrode configurations were experimentally tested to maximize the signal intensification. Compared to the conventional MCP assembly, the signal intensity was amplified in a proof-of-concept experiment by a factor of 24.3 and of 10.7 for the singly charged BSA ion (m/z 66 400) and for the singly charged IgG ion (m/z 150 000), respectively, by applying the booster-MCP (BMCP) detector.