ME-SIMS

Compounds 225a-f showed interesting dynamic phenomena on the NMR time scale with broad lines at room temperature and appearance of two sets of sharp peaks at -50 °C corresponding to conformers 226 and 227 (Fig. 3). By contrast, 225 g-1 exist essentially as one conformer. These results show that the presence of a Me substituent adjacent to the 0 atom in ring B and syn to the ring junction hydrogen (see 225 g) prejudices the molecule in favor of conformer 226, thus placing the Me substituent pseudoequatorially (cf. 226, = Me). Sim-... 

The ionization methods reported for IMS included MALDI [41,76-80], Secondary Ion Mass Spectrometry (SIMS) [19, 81-86], Matrix-enhanced (ME)-SIMS [87, 88], Desorption Electrospray Ionization (DESI) [89-99], Nanostructure Initiator Mass Spectrometry (NIMS) [100-102], Atmospheric Pressure Infrared MALDI Mass Spectrometry (AP-IR-MALDI-MS) [103], Laser Ablation-inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) [104-106], Laser Desorption Postionization (LDPI) [107], Laser Ablation Electrospray Ionization Mass Spectrometry (LAESI) [108, 109], and Surface-assisted Laser Desorption/ioniza-tion Mass Spectrometry (SALDI) [110-112], Another method was called probe electrospray ionization (PESI) that was used for both liquid solution and the direct sampling on wet samples. 

Today, the quest for molecular nanoimaging with SIMS, permitted by the improvements in beam focusing, demands reliable signals from ever smaller volumes. In that context, the use of matrices for signal enhancement constitutes an opportunity. Hereafter we introduce the main sample preparation protocols devised in the last two decades for molecular signal enhancement, which are usually grouped under the generic term of ME-SIMS. The specific case of substrate effects, discussed separately in Sections 42.2.1 and 42.2.2, will not be considered anymore here. 

Fitzgerald, J.J.D., Kunnath, E, Walker, A. (2010) Matrix-enhanced secondary ion mass spectrometry (ME SIMS) using room temperature ionic liquid matrices. Anal. Chem., 82,4417, 419. 

Using ME-SIMS we have demonstrated the possibility of obtaining peptide signals, from a nervous tissue extract from the pond snail Lymnaea stagnalis, identical to those obtained with MALDI-MS, up to w/s2,590 (10). The analysis readily identified five known peptides with ME-SIMS using 2,5-dihydroxybenzoic... 

The described protocol for IMS allows the mapping of molecular distributions directly in tissue sections and on cell surfaces. The different approaches to SIMS are able to deliver images of distributions of small organic compounds like lipids and steroids. Since ME-SIMS and especially MetA-SIMS are capable of imaging biological surfaces with very high spatial resolution, these techniques could be very well suited for direct analysis of lipid distributions on single-cell surfaces. 

For ME-SIMS analysis, samples are covered with a thin layer of matrix by electrospray deposition yielding small (0.3—1 xm) matrix crystals ( g Note 5). 

ME-SIMS and MetA-SIMS Imaging Mass Spectrometry... 

IMS experiments can be performed using ME-SIMS or MetA-SIMS. In the cases described here, these experiments are conducted on a ToF-SIMS equipped with an In liquid metal ion gun. The experimental procedure for ME-SIMS and MetA-SIMS data acquisition is identical. 

Perform the ME-SIMS experiment in such a way that the analysis is conducted in the static SIMS regime. This can be achieved with a primary ion beam current of 450 pA, a primary pulse length of 30 ns, a spot diameter of 500 nm, and a primary ion energy of 15 kV. At 3 min per experiment this results in a primary ion dose of 4.9 x 10 ions/cm see Note 6). 

Following the procedures discussed in Section 3 images were acquired as shown in Fig. 11.1. In panel A ME-SIMS images of lymnaea Sta nalis brain tissue are shown and in panel B MetA-SIMS images of single neuroblastoma cells are shown. The plasma coating procedure in MetA SIMS enhances des-orption/ionization of membrane components such as lipids and sterols in SIMS imaging of tissues and cells. As shown... 

Since in SIMS imaging experiments only the top layer is sampled, the matrix layer shonld not be too thick and the analytes have to be able to migrate to the top surface layer. This combination is critical for a snccessful ME-SIMS experiment and therefore the ESD conditions have to be optimized carefully, in order to produce a fine mist of matrix droplets so the matrix arrives onto the sample surface in a wet environment. 

Large, intact molecules can be detected by SIMS analysis using etched Ag-substrates (Ag-SIMS) or matrix-enhanced SIMS (ME-SIMS). ME-SIMS [207] is a relatively new technique for the analysis of large molecules. As in MALDI-MS, in ME-SIMS the analyte molecules are prepared in a solid matrix, consisting of relatively small, organic molecules in high molar surplus. Molecular ions of organic mixtures can be detected up to masses of about 10000 Da. 

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