Ionization methods, SIMS

Although detailed methods depend on the instrument used, sources and ionization method are the major difference between SIMS and TIMS methods. SIMS methods... 

The compatibility is excellent with continuous ion sources such as ESI, dynamic SIMS, CF-FAB, ICP, El, Cl, etc. Sector instalments are not well-suited for pulsed ionization methods, although there are examples where MALDI sources have been utilized [225-229]. Sector instruments are usually larger and more expensive than other mass analyzers, such as TOFs, quadrupole filters, and traps. 

Concentrations of neuroactive steroids that are present in brain and plasma are normally very low. Therefore, several prepurification steps are generally required before analyzing these samples. It is necessary to improve detection limits and to introduce new methods of analyzing these samples directly from solution, without these labor-intensive and time-consuming prepurification procedures. Now, most neurosteroid analyses are performed by RIA or by GC/MS. The most sensitive GC/MS reported so far is GC/EC-NCI/MS, wherein MS in performed in the SIM mode. Neurosteroid sulfates can be directly analyzed by MS, without derivatization, by using soft ionization methods such as FAB and ESI. These methods are currently undergoing further refinement and development. 

A striking feature of the ILs is their low vapor pressure. This, on the other hand, is a factor hampering their investigation by MS. For example, a technique like electron impact (El) MS, based on thermal evaporation of the sample prior to ionization of the vaporized analyte by collision with an electron beam, has only rarely been applied for the analysis of this class of compounds. In contrast, nonthermal ionization methods, like fast atom bombardment (FAB), secondary ion mass spectrometry (SIMS), atmospheric pressure chemical ionization (APCI), ESI, and MALDI suit better for this purpose. Measurement on the atomic level after burning the sample in a hot plasma (up to 8000°C), as realized in inductively coupled plasma (ICP) MS, has up to now only rarely been applied in the field of IE (characterization of gold particles dissolved in IE [1]). This method will potentially attract more interest in the future, especially, when the coupling of this method with chromatographic separations becomes a routine method. 

The application of molecular SIMS as a sensitive ionization source for nonvolatile and thermally labile molecules compares favorably with other new ionization methods in mass spectrometry such as field desorption (FD), Californium-252 plasma desorption (PD), fast heavy ion induced desorption (FHIID), laser desorp-... 

Ionization Methods/Processes. The recent development of several new ionization methods in mass spectrometry has significantly improved the capability for the analysis of nonvolatile and thermally labile molecules [18-23]. Several of these methods (e.g., field desorption (FD), Californiun-252 plasma desorption (PD), fast heavy ion induced desorption (FHIID), laser-desorption (LD), SIMS, and fast atom bombardment (FAB) or liquid SIMS) desorb and ionize molecules directly from the solid state, thereby reducing the chance of thermal degradation. Although these methods employ fundamentally different excitation sources, similarities in their mass spectra, such as, the appearance of protonated, deprotonated, and/or cationized molecular ions, suggest a related ionization process. 

This paper focuses on special ionization methods such as secondary ion MS (SIMS) (1, 13, 24-28) and ZCf plasma desorption (PD), and on MS/MS methods for characterizing primary ions, such as surface induced dissociation (SID), laser photodissociation, and neutralization of multiply charged ions. A Hadamard transform method for more efficient recording of multiple MS-II spectra is also proposed. 

Fig. 5 Statistical evaluation of LC-MS-based methods for tropane alkaloids referred in this chapter. (a) Relative frequency of ionization methods. +APCI positive atmospheric pressure chemical ionization, +ESI positive electrospray ionization, FAB fast atom bombardment, +TSP positive thermospray, (b) Relative frequency of scan modes used. MS full scan MS, MS/MS tandem mass spectrometry (product ion scan), MRM multiple reaction monitoring, SIM selected ion monitoring, (c) Relative frequency of mass analysers used. EBQtQ2 double focusing sector field mass spectrometer, IT ion trap, QqQ triple quadrupole, SQ single quadrupole. Considered publications were found by PubMed data-based search and references cited in these articles...

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. 

A wide variety of desorption ionization methods is available [7] desorption chemical ionization (DCI), secondary-ion mass spectrometry (SIMS), fast-atom bombardment (FAB), liquid-SIMS, plasma desorption (PD), matrix-assisted laser desorption ionization (MALDI), and field desorption (FD). Two processes are important in the ionization mechanism, i.e., the formation of ions in the sample matrix prior to desorption, and rapid evaporation prior to ionization, which can be affected by very rapid heating or by sputtering by high-energy photons or particles. In addition, it is assumed that the energy deposited on the sample surface can cause (gas-phase) ionization reactions to occur near the interface of the solid or liquid and the vacuum (the so-called selvedge) or provide preformed ions in the condensed phase with sufficient kinetic energy to leave their environment. 

Choice of Ionization Method. Both TSP and DLI can only operate to give Cl spectra while the MBI can be operated under El, Cl (choice of reagent gases), NCI. FAB and SIMS. The ability to obtained El spectra has been stressed for library searches since under soft ionization conditions the spectra usually exhibit only protonated molecule ions and adduct ions with the reagent species and little or no fragmentation. In this respect, the... 

In addition to some early applications in bioanalysis, ambient ionization mass spectrometry has been used as an imaging tool to study drug distribution in tissue sections. Most of the work reported so far involved the use of DESI as the ambient ionization method. Compared to other mass spectrometry-based tissue imaging techniques such as MALDI and SIMS, DESI allows tissue samples to be analyzed under ambient conditions without sample preparation, which simplifies the procedure and prevents the redistribution of analytes during matrix deposition. A major drawback of DESI as an imaging tool is its relatively low spatial resolution (typically 250 pm) and therefore cannot be used for cellular or subcellular imaging. 

Newer ionization methods such as FAB-MS and SIMS have been developed in which derivatization is unnecessary. With the aid of FAB-MS, it has been possible for the first time to obtain data on such structural parameters as molecular mass, homogene. /, sequences, composition branching and linkage. This method has been successfully applied to glycolipid structure analysis (30,31). 

Derivatization of samples with an equimolar mixture of labeled and unlabeled reagents to produce ion clusters has been applied recently to the characterization of the bleomycins by FD and FAB mass spectrometry. A variation of this technique utilizes a mixture of labeled and unlabeled reagent gases pyridine/[ Hs]pyridine, trimethylchlorosilane (TMCS)/ [ HsJTMCS, tetramethylsilane (TMS)/[ HizITMS," and NHa/N Ha in conjunction with Cl mass spectral analyses. The isotope cluster technique also may be exploited with the newer ionization methods of SIMS and FAB through the addition of appropriate counter-ions (for example, Ag " ). 

Together with SIMS (Chapter 8), and prior to the advent of MALDl technique (Chapter 10), FAB was the most important ionization method that allowed the analysis of intact polymer molecules, and therefore the MS literature on synthetic polymers in the last fifteen years is in sizeable part based on FAB analysis. 

A variety of volatilization/ionization methods have been applied to polymers a recent review or key paper is cited here for each. Extensive reviews that include mass spectrometry of pol5mrers can be found in Analytical Chemistry Other to )ical reviews are field desorption, laser desorption, plasma desorption, fast-atom bombardment, pyrolysis, and electrospray ionization. The present review will focus on polymer characterization using secondary-ion mass spectrometry (SIMS) in the high mass range comparison with other methods will be presented where appropriate. 

The versatility of mass spectrometry for metabolomic studies is based on the different sample introduction techniques, the various ionization methods, the ability to collect both MS and MS/MS spectra frequently, including accurate mass measurement, as well as performing SIM and SRM (Section 3.3.3.1). Acquisition of MS/MS spectra and their incorporation in the construction of searchable libraries, which include different fragmentation and structural information from the libraries of El... 

Some ionization techniques (El, FAB, and SIMS) are compatible with all mass analyzers. PD, LD, and MALDI are most suited to TOF analyses. Atmospheric pressure ionization methods (TSP, ESI, APCI) are best coupled with quadrupole and ion trap instruments. Sector and FTICR instruments can also operate with chromatographic interfaces however, a significant reduction of pressure in the system is required. Consequently, in FTICR, the ion source and the ICR cells must be separated by a distance of about 1 m. Powerful ion optics is required for the transmission of ions for these long distances. This inconvenience, however, is offset by the advantages of FTICR, such as extremely high resolution and the ability to store the ions of interest for long periods. 

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. 

Of the two related techniques, FAB found far greater use in studies of enantioselective discrimination as compared to other desorption/ionization methods, such as MALDI and secondary ion mass spectrometry (SIMS). Chan and coworkers demonstrated enantiodiscrimina-tion of amino acids by a-, P-, and y-cyclodextrins using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) [28]. The observed levels of enantioselectivity were found to be dependent on the size of cyclodextrin cavities, as well as on the length and functionality of the amino acid side chain. Vairamani and coworkers demonstrated discrimination of amino acid methyl esters using various monosaccharide hosts by liquid secondary ion mass spectrometry (LSIMS) [29]. It is curious that more work has not been done using these sources. MALDI, in particular, is a simple and straightforward technique. Various researchers have demonstrated the observation of noncovalent complexes [30-32], for example, between peptides and proteins, but relatively little work has been performed that focuses on studying enantioselective noncovalent interactions by MALDI-MS. 

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