Quantitative study of solvent and surface effects on analyte ionization in desorption ionization on silicon (DIOS) mass spectrometry

Abstract

Deuterated solvents and DIOS surfaces derivatized with different functional groups are used to investigate impacts of local chemical environment on analyte ionization. Both solvent molecules and surface functional groups are found to directly participate in analyte protonation in the condensed phase. The corresponding protonation effectiveness is quantitatively estimated based on the relative MS peak intensities of [M ϩ 2] ϩ /[M ϩ 1] ϩ . A direct correlation between ionization of triethylamine and the relative acidities of the surface and the solvent is evident. In addition, the proton donating effectiveness of a solvent is found to be related to its vapor pressure. Improved MS detection of small molecules via proper surface treatment and solvent selection is demonstrated. (J Am Soc Mass Spectrom 2008, 19, 8 -13) © 2008 American Society for Mass Spectrometry E xtensive research in metabolite profiling in recent years has revived interest in desorption ionization on porous silicon mass spectrometry (DIOS-MS). Elimination of matrix molecules in DIOS-MS reduces background noise in the low-mass range and enables direct detection of biologically significant small molecules [1][2][3][4]. It also overcomes matrix-induced analyte redistribution on a sample surface, which allows two-dimensional imaging of tissue samples with good spatial accuracy [5]. Recent studies have shown that the local chemical properties of a DIOS substrate, including the residual solvent on the surface and the surface functional groups, are critical in analyte ionization [6 -9]. Quantitative investigation of these factors, however, is lacking. In this report, we semiquantitatively assessed contributions of various proton sources in DIOS-MS and the feasibility of improving MS detection of lipids and peptides by proper sample treatment. Experimental DIOS Substrate PreparationDIOS substrates were prepared by dipping the wafer into a solution of 5% HF/EtOH for 1 min to remove the oxidized layer, followed by a 1.5-min anodic etching in 25% HF/EtOH at 5 mA/cm 2 [10,11]. Before MS experiments, the DIOS substrates were dipped in 5% HF/ EtOH to regenerate the H-terminated surface. For OHterminated surfaces, the DIOS substrates were dipped in a solution of 15% H 2 O 2 /MeOH (or 15% D 2 O 2 / MeOH-d 4 ) for 30 min. For RNH 2 -terminated surfaces, the same OH-terminated surfaces were refluxed in a solution of 10% APTMS/toluene under N 2 for 4 h. To remove residual solvent molecules, the DIOS or chemically modified DIOS substrates were dried under high vacuum overnight, unless specified otherwise.

Metabolite imaging using matrix-enhanced surface-assisted laser desorption/ionization mass spectrometry (ME-SALDI-MS)

“…These results suggest that unlike in MALDI where charge exchange occurs mostly in the gas phase, in ME-SALDI most analytes are probably ionized at the vacuum-substrate interface before and during desorption. Therefore, similar to SALDI, the condensed-phase acidity (pK a ) of an analyte seems to play a more important role, whereas gas-phase secondary ionization is limited because of the relatively low plume density [19,20]. The lack of proton donors that often leads to disappointing detection sensitivity in SALDI, however, is no longer an issue in ME-SALDI: acidic matrix molecules become the main source of protons in analyte ionization, as supported by the detection of significant enhanced matrix anions in the negative-mode detection (Supplemental Material F4).…”

“…ME-SALDI combines valuable attributes from both conventional MALDI and SALDI methods. In particular: (1) the introduction of the solid conventional MALDI matrix, such as CHCA, to SALDI takes advantage of its strong proton-donating capability and protects analytes from deconstructive overheating [19,20]; (2) the presence of porous surface absorbs incident photons more effectively than conventional MALDI matrices. The application of ME-SALDI in MS imaging is demonstrated for the first time in this report.…”

Halohydrination of epoxy resins using sodium halides as cationizing agents in MALDI‐MS and DIOS‐MS

“…The residual solvent on a DIOS surface was reported to have a large effect on signal enhancement. Very recently, Liu and He published a quantitative study of solvent and surface effects on analyte ionization in DIOS‐MS 27. Both solvent molecules and surface functional groups on the porous silicon were found to directly participate in analyte protonation in the condensed phase.…”

Fluorinated surfaces: smart substrates for matrix‐free laser desorption ionization

“…Since Desorption Ionization on porous Silicon (DIOS) was proposed, hundreds of papers have tried to shine light on the key parameters controlling the D/I process; interestingly, several papers highlight an increase in the efficiency of the porous silicon (PSi) samples functionalized with a specific fluorosilane [(3-pentafluorophenyl)propyldimethylchlorosilane (PFPPDCS)]. [8][9][10][11] Here, we report that fluorinated bulk surfaces of electrical conductors and UV absorbing materials are effective matrixfree substrates. Our approach has two main advantages compared to the so far proposed nanostructures-based matrix-free methods: (1) nanostructures are no longer required to achieve matrix-free D/I; (2) a number of materials, once fluorinated, can be used as substrates (e.g.…”