Desorption Ionization Methods

Desorption ionization methods are those techniques in which sample molecules are emitted directly from a condensed phase into the vapor phase as ions. The primary use is for large, nonvolatile, or ionic compounds. There can be significant disadvantages. Desorption methods generally do not use available sample efficiently. Oftentimes, the information content is limited. For unknown compounds, the methods are used primarily to provide molecular weight, and in some cases to obtain an exact mass. However, even for this purpose, it should be used with caution because the molecular ion or the quasimo-lecular ion may not be evident. The resulting spectra are often complicated by abundant matrix ions. 

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In either case, the use of a DEP allows to extend the temperature range for evaporation. In addition, it reduces thermal degradation as a result of heating the analyte faster than its thermal decomposition usually proceeds, and therefore expands the range of applications for El and Cl to some extent. Whatsoever, employing direct exposure probes is by far no replacement of real desorption ionization methods. [52,53]... 

Direct analysis of solid samples or analytes present on solid surfaces without any sample preparation has always been a topic of interest. Desorption electrospray ionization (DESI) is an atmospheric pressure desorption ionization method introduced by Cooks et al., producing ions directly from the surface to be analyzed, which are then sampled with the mass spectrometer [22, 37]. DESI is based on charged liquid droplets that are directed by a high velocity gas jet (in the order of 300 m s ) to the surface to be analyzed. Analytes are desorbed from the surface and analyzed by mass spectrometer (Eig. 1.15). 

Electrospray (ESI) is an atmospheric pressure ionization source in which the sample is ionized at an ambient pressure and then transferred into the MS. It was first developed by John Fenn in the late 1980s [1] and rapidly became one of the most widely used ionization techniques in mass spectrometry due to its high sensitivity and versatility. It is a soft ionization technique for analytes present in solution therefore, it can easily be coupled with separation methods such as LC and capillary electrophoresis (CE). The development of ESI has a wide field of applications, from small polar molecules to high molecular weight compounds such as protein and nucleotides. In 2002, the Nobel Prize was awarded to John Fenn following his studies on electrospray, for the development of soft desorption ionization methods for mass spectrometric analyses of biological macromolecules. ... 

Hillenkamp F, Karas M (1990) Mass spectrometry of peptides and proteins by matrix-assisted ultraviolet laser desorption/ionization. Methods Enzymol 193 280-295... 

Without authentic standards or a spectroscopic detection scheme, compound identification is difficult. Our choice of a desorption/ionization method is potassium ionization of desorbed species (K+IDS) with mass spectrometric detection (n. 12) which provides a rapid qualitative tool for compound identification. Using K+IDS, molecular weight data is available and fragmentation is minimal. Ions appear as M[K], the mass of the analyte plus 39 Da, the mass of potassium. Hence, structure identification is possible based on a knowledge of starting materials and the molecular weight data afforded by K+IDS. 

The above example shows how we use SFC to furnish accurate quantitative data. In addition, SFC is used to insure that desorption/ionization methods do not yield artifacts particularly when analyzing reactive monomers. Under K+IDS, the sample under study may be exposed to high temperatures giving rise to decomposition products or the re-association of thermal fragments. Using SFC, the sample integrity is preserved. 

The Laser Desorption Ionization (LDI) was investigated by Franz Hillenkamp and Michael Karas [2, 3], LDI involved sample bombardment with short and intense pulses from a laser light to effect both desorption and ionization of the analyte molecules. It has become a soft desorption ionization method for mass spectrometric analyses of biological macromolecules and small molecular compounds. The MALDI technique was improved by Koichi Tanaka. 

Matrix-free direct laser desorption ionization of analyte has been studied on different kinds of surfaces without real success because degradation of the sample is usually observed. However, good results were obtained with the method called surface-activated laser desorption ionization (SALDI) [43] which uses graphite as the surface. But the use of porous silicon as a new surface is more promising and has led to the development of a new method called desorption ionization on silicon (DIOS) [44], Unlike the other matrix-free laser desorption ionization methods, DIOS allows ion formation from analyte with little or no degradation. 

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. 

John B. Fenn, Koichi Tanaka For their development of soft desorption ionization methods for mass spec-trometric analyses of biological macromolecules. ... 

Ventura, F. Characterization of surfactants in water by desorption ionization methods, in Environmental Analysis Techniques, Applications, Quality Assurance, Vol. 13, ed. D. Barceld, Elsevier, Amsterdam 1993, p.481. 

A brief list of ionization methods is given in Table 1. (One may quibble a bit about the dates given in the table, but we believe these are more or less accurate.) Up xmtil about 1970, the only ionization method in common use was electron impact (El). Field ionization (FI) was developed in the 1950s, but it was never very popular, and chemical ionization (Cl) was just getting started. These three methods (El, Cl, FI) depend upon vaporization of the sample by heating, which pretty much limits polymer applications to small, stable oligomers or to polymer degradation products (formed by pyrolysis or other methods). Field desorption (FD-MS), invented in 1969, was the first "desorption/ionization" method. FD- and FI-MS are often very useful (particularly for analysis of less polar polymers), but they have never been in widespread use. 

The 1970s and 1980s saw the advent of several new "soft" desorption/ ionization methods, many of which are now well-established in analytical mass spectrometry. The term "desorption/ionization" refers to a method in which the desorption (vaporization) and ionization steps occur essentially simultaneously. MALDI and several other techniques listed in Table 1 have important applications in polymer analysis. 

For S5mthetic polymers, the most popular desorption/ionization method has been matrix-assisted laser desorption/ionization (MALDI-MS, Chapter 10). Several other techniques have important applications in polymer analysis. The more widely used methods are covered in this book electrospray (Chapter 4), field ionization/desorption (Chapter 6), fast atom bombardment (Chapter 7), secondary ion mass spectrometry (Chapter 8), and laser desorption (Chapters 9 and 11). 

In the past several years, a number of new ionization methods in mass spectrometry have been introduced. These new techniques have extended mass spectrometric analysis to a wide variety of labile (thermally unstable), highly polar, and higher molecular weight materials. Field ionization (FI) and field desorption (FD) are two of the pioneering techniques in this list of alternative ionization methods. FI-MS, which was introduced for organic molecules in 1954, was the first soft ionization method. (Soft ionization refers to processes that produce high relative abundances of molecular, or quasimolecular, ions.) FD-MS, which was invented in 1969, was the first desorption/ionization method. (Desorption/ionization refers to processes in which die vaporization/ desorption, and ionization steps occur essentially simultaneously.)... 

The number of El/ED-MS publications rose rapidly in the early to mid-1970s, reaching a peak in the late 1970s. A noticeable drop in FI/ED use occurred after 1983 because of the advent of fast atom bombardment (EAB-MS), and later other desorption/ionization methods. A high percentage of FI/FD-MS articles have come from Germany, which is not surprising in view of the early development of the techniques in Borm. 

As with most ionization methods, FI and FD mass spectra are most often acquired for compounds of mass <1000 Da (1 kDa). There are many examples in the literature, however, of FI/FD mass spectra for compounds/polymers in the mass range 1-5 kDa. Based on a few literature examples, the maximum practical FD mass range would appear to be 10-15 kDa thus FD-MS is a technique of intermediate mass range capability. Molecular ions can be obtained at higher masses than have been reported, for example, for El-MS and CI-MS. However, some desorption/ionization methods, such as MALDI- and ESI-MS, have demonstrated higher mass capabilities. 

At any length, those who think of FI-MS and FD-MS as pioneering techniques diat are no longer useful should rethink their position. It is premature to put these methods on the endangered species list. FI-MS and FD-MS have some attractive features that make them both complementary to other desorption/ionization methods and unique in their applications. 

In general all desorption/ionization methods, including FAB, are intended to produce ions of high mass and to minimize the fragmentation processes. 

Analysis of sulfotyrosine peptides and locahzation of sulfotyrosine positions in the presence of multiple potential sulfation sites can be a challenging task, in particular, if multiple sulfotyrosines are present in a single peptide chain, which is the case with most N-terminal chemokine receptor peptides. While mass spectrometry analysis of protein phosphorylation on a proteomics scale is well established, this is not the case for protein tyrosine sulfation. Due to the inherent lability of the sulfotyrosine sulfoester bond, partial or complete loss of the sulfotyrosine modification is generally observed as a neutral loss of SO3 (AMr = -80 Da) under standard mass spectrometry conditions. In particular, irrespective of the desorption/ionization method employed, positive... 

DART is different from the other snrface desorption ionization methods in that an excited gas stream, typically helinm (sometimes N2 or Ne), is nsed to ionize the analytes (Figure 2.18). The neutral gas atoms (or molecules), flowing at low velocity (1-5 L/min), are snbjected to a corona discharge that creates a mixtnre of ions, electrons, and excited (metastable) gas atoms (or molecules). All charged species are... 

Although a number of innovative desorption ionization methods have been developed, none of these techniques has been commonly employed throughout the mass spectrometry community owing to the nonroutine nature of the experiments and the need for specialized instrumentation and sp>ecially trained per-... 

Ion cyclotron resonance (ICR) mass spectrometers have become increasingly popular with the use of Fourier transform (FT) techniques, the development of superconducting magnets, and the importance of pulsed desorption ionization methods and are now in the forefront of mass spectrometer development. 

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. 

Mass spectrometry (MS) is a method where the mass of the molecules that have been ionized can be measmed using a mass spectrometer. MS has become a key tool in proteomics research because it can analyze and identify compounds that are present at extremely low concentrations (as little as 1 pg) in very complex mixtmes by analyzing its unique signatme. A critical concern in MS is that the methods used for ionization can be so harsh that they may generate very little product to measme at the end. The development of soft desorption ionization methods by John Fenn and Koichi Tanaka [26], which allowed the application of MS to biomolecules on a wide scale, earned them a share of the Nobel Prize in chemistry in 2002. 

Four of the most commonly used desorption/ionization methods for MSI are secondary ion mass spectrometry (SIMS), desorption electrospray ionization (DESI), matrix-assisted laser desorption/ionization (MALDI), and laser ablation (LA) with post-ionization. Other desorption/ionization approaches such as laser desorption/ionization (LDI) see Chapter 9, (12)), desorption/ionization on silicon (DIOS) (13), electrospray ionization (ESI) (14), and nanostructure-initiator mass spectrometry (NIMS) (15, 16) also have great potential in MSI. Importantly, many mass spectrometers equipped with a MALDI ion source can be used with related ionization processes such as LDI, DIOS, LA, and laser-NIMS. Erequently, a specific ion source arrangement is optimized for a specific mass analyzer for example, MALDI is often interfaced to a time-of-flight (TOF) mass analyzer (described below) although it can also be used with ICR-based instruments. 

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