Burst Nucleation of Matrix on Doped Graphene for Quantitative MALDI-TOF Mass Spectrometry with Tunable Ion Yield

Abstract

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an effective and widely used mass spectrometric approach that provides multiple information of biomolecules such as structural characterization and label-free identification. The quantitation using MALDI MS, however, has been limited mainly due to uncontrollable ion yield in MALDI MS from heterogeneous cocrystallization of analyte and matrix. In this work, we observed the highly uniform formation of matrix crystals on graphene surface. The uniformly distributed analyte-matrix cocrystal films formed on graphene substrate allows the highly reproducible mass spectra with improved mass resolution and mass accuracy. Based on the area of MALDI MS laser irradiation, amount of analyzed peptide at defined area can be estimated and allows the direct measurement of ion yield of MALDI MS. In addition, we demonstrate that ion yield of MALDI MS can be tuned by controlling the electron and hole doping of the graphene substrates, enabling selective suppression of spectral interference by matrix. Finally, with a constant ion yield, we demonstrate that the total ion count of analyte ion is linearly corresponding to amount of analyte, thus enables absolute quantitation of analyte in MALDI MS.