Matrix cluster ions

Fig. 9.6. In LSIMS and FAB, sample-matrix cluster ion formation and desolvation processes occur on a longer time scale. Adapted from Ref. [24] by permission. John Wiley Sons, 1995.

MALDI is the dominant ionization source choice for MSI however, it is not without drawbacks. The application of MALDI matrix on top of the tissue surface complicates the analysis by adding potentially isobaric matrix cluster ions that may obscure the drug compound. Careful selection of MALDI matrix can reduce the matrix effect. An alternative would be to either use the water native to the tissue as a matrix such as with IR-MALDI or altogether eliminate the need for matrix. DESI is an atmospheric pressure technique that permits the direct analysis of surface samples, including tissue sections, with minimal sample preparation (Takats et al., 2004 Cooks et al., 2006). In contrast to MALDI—MSI, no matrix is required however, the spatial resolution for DESI—MSI is worse when compared to MALDI or SIMS imaging experiments. 

Although many different compounds have been suggested as MALDI matrices, the analysis of lipids with their low molecular weights requires certain special properties of the matrix. For example, it is important that the yields of matrix (or matrix cluster) ions generated by laser irradiation are as low as possible. This is the reason why compounds that undergo photoreactions (especially matrices derived from cinnamic acid such as sinapinic add) should not be used, in order to avoid saturation of the detector by matrix-derived ions. 

Figure 3.11 summarizes such key experimental points. As a first point, we have to choose the appropriate ionization method for the detection of small metabolites, we have alternative choices other than MALDI, such as secondary ion mass spectrometry (SIMS) [15], nanostructure-initiator mass spectrometry (NIMS) [20,21], desorption/ionization on silicon (DIOS) [22], nanoparticle-assisted laser desorptiopn/ ionization (nano-PALDI) [23], and even laser desorption/ionization (LDI) [24,25]. We consider that MALDI is stiU the most versatile method, particularly due to the soft ionization capability of intact analyte. However, other methods each have unique advantages for example, SIMS and nano-PALDI have achieved higher spatial resolution than conventional MALDI-IMS, and above aU, these mentioned alternative methods are all matrix-free methods, and thus can exclude the interruption of the matrix cluster ion. Next, if MALDI is chosen, experimenters should choose a suitable matrix compound, solvent composition, and further matrix application method for their target analyte. All these factors are critical to obtain sufficient sensitivity because they affect efficiency of analyte extraction, condition of cocrystallization, and, above all, analyte-ionization efficiency. In addition, based on the charge state of the analyte molecule, suitable MS polarity (i.e., positive/ negative ion detection mode) should be used in MS measurement. Below, we shall describe the key experimental points for MALDI-IMS applications of representative metabolites. 

Molecular ions are observed in spectra from rare earth metals with ion intensities similar to non-rare earth samples. Table 37C.2 lists typical intensity relationships observed in rare earth metal spectra for oxygen, fluorine, and carbon impurities and their associated matrix cluster ion intensities. Although the source of these ions relative to the solid sample has been studied by Muheim (1972, 1973), certain facets of their character remain clouded. Their intensities tend to be erratic and depend upon many parameters such as non-metallic impurity content, residual gas level in the spectrometer ion source chamber, contaminants on the surface of the metal sample, chemical environment, etc. The analytical usefulness of these cluster ion signals has not been established. 

Matrix effects and inhomogeneous sample charging seriously hinder quantitative analysis of SIMS on technical catalysts. Although full quantitation is almost impossible in this area, the interpretation of SIMS data on a more qualitative base nevertheless offers unique possibilities. Molecular cluster ions may be particularly informative about compounds present in a catalyst. 

FAB matrix spectra are generally characterized by a series of matrix (Ma) cluster ions accompanied by some more abundant fragment ions in the lower m/z range. In positive-ion FAB, [Ma +H] cluster ions predominate, while [Ma -H] cluster ions are preferably formed in negative-ion FAB (Fig. 9.7). The principal ion series... 

Example The Bunte salt [ 3( 2)158-803] Na yields a very useful negative-ion FAB spectrum from NBA matrix (Fig. 9.11). NBA forms [Ma-H] and Ma " ions. The salt anion contributes the base peak at m/z 337.3. [Ch-2A] m/z 697.5, and [2C-I-3A] m/z 1057.6, cluster ions are observed in addition, their isotopic patterns being in good agreement with theoretical expectation. It is noteworthy that the matrix adduct at m/z 513.4 is a negative radical ion. 

Barber et al. introduced FAB in 1981. In this technique, bombardment of a liquid target surface by a beam of fast atoms such as xenon or argon, causes the continuous desorption of ions that are characteristic of the liquid. In a typical FAB spectrum, the analyte ion is usually formed as protonated or cationized ions in positive FAB, and deprotonated ions in negative FAB mode. A few fragmented ions may also be formed. The spectrum usually contains peaks from the matrix, such as protonated matrix clusters of glycerol if it is used as the matrix solvent. FAB utilizes a liquid matrix such as glycerol. The matrix is used to enhance sensitivity and ion current stability. 

Carbide cluster ions (MC + - M = matrix element) have been measured by investigating them directly from the solid carbides (B4C,46 SiC) or by analyzing metal oxide/graphite mixtures (for M = rare earth element,3 Si,46 Th or U36). Figure 9.60 shows the distribution of silicon carbide cluster ions (SiC +) in laser ionization mass spectrometry by the direct analysis of compact SiC in comparison to the carbide cluster ion distribution of LaC + and SrC + in spark source mass spectrometry, by investigating a metal oxide/graphite mixture. 

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