PNNL

Abstract

A variety of mass spectrometry imaging (MSI) modalities now exist, each with their own strengths and limitations. Herein, the analyses of model mammalian tissue with matrix-assisted laser desorption/ionization (MALDI) and nanospray desorption electrospray ionization (nano-DESI) MSI are compared. In both cases, 21T Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) with absorption mode FT processing (aFT) was used, allowing for unmatched mass resolution per unit time. Measured mass resolving powers of MALDI and nano-DESI base peaks were 637k (m/z 798.54108) and 613k (m/z 760.58508) using 1.536 s transients, respectively, illustrating nearly the full theoretical benefits of aFT processing. The molecular coverage and dynamic range capabilities were greater in MALDI analysis, whereas nano-DESI provided superior mass error. The mass splits (i.e., the mass difference between neighboring peaks) within single pixels were collated across all pixels from each respective MSI experiment, which was powerful in informing whether the observed mass splits were biological or artificial (e.g., matrix related). Mass splits down to 2.4 mDa were observed (i.e., sodium adduct ambiguity) in each experiment, and both modalities highlighted comparable degrees of molecular complexity overall for mass splits =15 mDa. Case study evaluations highlighted the resolution of low mDa differences for m/z >1000 (e.g., 4.6 mDa), which is particularly notable given the contextually short detection period. Overall, MALDI and nano-DESI were found to be complementary and coupling to 21T FTICR-MS with aFT processing permitted the detection and identification of features that are otherwise routinely unobserved in MSI applications using more conventional instrumentation.