The composition of liquid atmospheric pressure matrix-assisted laser desorption/ionization matrices and its effect on ionization in mass spectrometry

Abstract

New liquid atmospheric pressure (AP) matrix-assisted laser desorption/ionization (MALDI) matrices that produce predominantly multiply charged ions have been developed and evaluated with respect to their performance for peptide and protein analysis by mass spectrometry (MS). Both the chromophore and the viscous support liquid in these matrices were optimized for highest MS signal intensity, S/N values and maximum charge state. The best performance in both protein and peptide analysis was achieved employing light diols as matrix support liquids (e.g. ethylene glycol and propylene glycol). Investigating the influence of the chromophore, it was found that 2,5-dihydroxybenzoic acid resulted in a higher analyte ion signal intensity for the analysis of small peptides; however, larger molecules (>17 kDa) were undetectable. For larger molecules, a sample preparation based on α-cyano-4-hydroxycinnammic acid as the chromophore was developed and multiply protonated analytes with charge states of more than 50 were detected. Thus, for the first time it was possible to detect with MALDI MS proteins as large as ∼80 kDa with a high number of charge states, i.e. m/z values below 2000. Systematic investigations of various matrix support liquids have revealed a linear dependency between laser threshold energy and surface tension of the liquid MALDI sample.

Production and analysis of multiply charged negative ions by liquid atmospheric pressure matrix‐assisted laser desorption/ionization mass spectrometry

“…Interestingly, DHB has always been preferred to CHCA for the analysis of proteins in solid MALDI, arguably due to its greater ‘softness'. In liquid MALDI MS, other aspects such as proton affinity might have greater influence as this and previously published data suggest 12 …”

“…The same four liquid matrices used for peptide analysis were also investigated for protein analysis. In addition, a fifth liquid matrix that was prepared with CHCA as the only chromophore was also tested, since this was previously found to be superior to the DHB‐based liquid matrix for the detection of larger proteins 12 . For ubiquitin, both the CHCA‐ and DHB‐based liquid MALDI samples performed best with respect to positive ion signal intensities.…”

“…The mechanisms behind the production of multiply charged ions using laser‐based desorption techniques and the link to ESI have been discussed in previous publications 5,12,13 . Although many future application areas have been explored for liquid AP‐MALDI MS in the positive ion mode, no studies have explored its potential by switching to the negative ion mode.…”

Rapid Liquid AP-MALDI MS Profiling of Lipids and Proteins from Goat and Sheep Milk for Speciation and Colostrum Analysis

“…The combined lipid and protein MS analyses were performed by liquid AP-MALDI MS [ 21 , 22 , 23 ] on a Synapt G2-Si High Definition Mass Spectrometry (HDMS) mass spectrometer (Waters Corporation) equipped with an in-house developed AP-MALDI source, using a Waters research enabled software (WREnS)-controlled XY stage (Zaber Technologies Inc., Vancouver, Canada). A detailed source description has been reported previously [ 24 ].…”

Liquid Atmospheric Pressure Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Adds Enhanced Functionalities to MALDI MS Profiling for Disease Diagnostics

“…This modification to our usual glycerol-based LSM stemmed from recent work optimizing ion signal through substitution of glycerol with other diols. 33…”