Method for improved secondary ion yields in cluster secondary ion mass spectrometry

A method to increase useful yields of organic molecules is investigated by cluster secondary ion mass spectrometry (SIMS). Glycerol drops were deposited onto various inkjet‐printed arrays and the organic molecules in the film were rapidly incorporated into the drop. The resulting glycerol/analyte drops were then probed with fullerene primary ions under dynamic SIMS conditions. High primary ion beam currents were shown to aid in the mixing of the glycerol drop, thus replenishing the probed area and sustaining high secondary ion yields. Integrated secondary ion signals for tetrabutylammonium iodide and cocaine in the glycerol drops were enhanced by more than a factor of 100 compared with an analogous area on the surface, and a factor of 1000 over the lifetime of the glycerol drop. Once the analyte of interest is incorporated into the glycerol microdrop, the solution chemistry can be tailored for enhanced secondary ion yields, with examples shown for cyclotrimethylenetrinitramine (RDX) chloride adduct formation. In addition, depositing localized glycerol drops may enhance analyte secondary ion count rates to high enough levels to allow for site‐specific chemical maps of molecules in complex matrices such as biological tissues. Published in 2010 by John Wiley & Sons, Ltd.     

Matrix‐enhanced secondary ion mass spectrometry: the influence of MALDI matrices on molecular ion yields of thin organic films

In this work the effect in secondary ion mass spectrometry (SIMS) of several frequently used matrix‐assisted laser desorption/ionisation (MALDI) matrices on the secondary ion intensities of low molecular weight (m/z 400–800) organic dyes and a pharmaceutical is tested. Matrix (10^?1 M) and analyte (10^?2 M) solutions were made in methanol. Mixtures with several concentration ratios were prepared from these solutions and spincoated on Si substrates prior to time‐of‐flight (TOF)‐SIMS analysis. In some cases the presence of the MALDI matrices caused a considerable increase in the positive secondary (protonated) molecular ion signals. Enhancements of a factor of 20 and more were recorded. Generally, of the matrices used, 2,5‐dihydroxybenzoic acid and 2,4,6‐trihydroxyacetophenone brought about the highest intensity increases. It was also shown that matrix‐enhanced (ME‐)SIMS is capable of lowering the detection limits for molecule ions. However, the enhancement effect is strongly influenced by the analyte/matrix combination and its concentration ratio. As a result, finding an optimal analyte/matrix mixture can be a very time‐consuming process. Mostly, the presence of the matrices causes changes in the relative ion intensities in the TOF‐S‐SIMS spectra. Compared to the spectra recorded from samples without matrices, only a few additional peaks, such as signals that originate directly from the applied matrix or adduct ions, are observed in the mass spectra. Sometimes molecule ions and some characteristic fragments at high m/z values, that cannot be recorded without matrix, do appear in the spectrum when a matrix is present. In the negative mode no enhancement effect is observed on applying the studied MALDI matrices. The results obtained from samples treated with MALDI matrices are also compared to SIMS results for the same samples after Ag and Au metallisation (MetA‐SIMS). For three of the four tested compounds Au MetA‐SIMS resulted in higher ion yields than ME‐SIMS. For both techniques possible mechanisms that can account for the enhancement effect are proposed. Copyright © 2005 John Wiley & Sons, Ltd.     

Lipid imaging with cluster time-of-flight secondary ion mass spectrometry

This brief article provides an overview of the current state of the art in biological imaging mass spectrometry using cluster time-of-flight secondary ion mass spectrometry (TOF–SIMS). Recent and spectacular improvements in terms of sensitivity of TOF–SIMS imaging methods have allowed many biological applications to recently be successfully tested, such as mapping of lipid disorders in human muscles of a patient suffering from dystrophy, localization of surfactins after the swarming of bacteria on a surface, or lipid mapping over whole-body animal sections.     

Electrospray droplet impact/secondary ion mass spectrometry: cluster ion formation

The electrospray droplets that are sampled through an orifice into the vacuum chamber are accelerated by 10 kV and impact on the stainless steel substrate. The mass and the kinetic energy of electrospray droplets are roughly estimated to be a few 10(6) u and approximately 10(6) eV, respectively. The molecular ion M(+.) and the protonated molecule [M+H](+) are observed as secondary ions for chrysene and coronene deposited on the metal substrate (no matrix used). The ionization may take place in the shock wave generated by the high-momentum coherent collision between the droplet projectile and the solid sample. Cluster ions of H(+)(H(2)O)(n) and CF(3)COO(-)(H(2)O)(n), with n up to approximately 150, were observed as secondary ions formed by the electrospray droplet impact ionization (EDI) for 10(-2) M trifluoroacetic acid (TFA) aqueous solution. This indicates that the charged droplets that collide with the metal substrate with the kinetic energy of approximately 10(6) eV do not vaporize completely but are disintegrated into many tiny microdroplets. The ion signal intensity anomalies (i.e. magic numbers) were observed for the cluster ions of H(3)O(+)(H(2)O)(n) and CF(3)COO(-)(H(2)O)(n) for 10(-2) M TFA aqueous solution and of Cs(+)(H(2)O)(n), I(-)(H(2)O)(n), Cs(+)(CsI)(n), and I(-)(CsI)(n) for 10(-2) M CsI aqueous solution.     

Relationships between cluster secondary ion mass intensities generated by different cluster primary ions

Measurements are described to evaluate the constitution of secondary ion mass spectra for both monatomic and cluster primary ions. Previous work shows that spectra for different primary ions may be accurately described as the product of three material-dependent component spectra, two being raised to increasing powers as the cluster size increases. That work was for an organic material and, here, this is extended to (SiO₂) _t OH⁻ clusters from silicon oxide sputtered by 25 keV Bi _n ⁺ cluster primary ions for n = 1, 3, and 5 and 1 ≤ t ≤ 15. These results are described to a standard deviation of 2.4% over 6 decades of intensity by the product of a constant with a spectrum, H _SiOH/*, and a power law spectrum in t. This evaluation is extended, using published data for Si _t ⁺ sputtered from Si by 9 and 18 keV Au⁻ and Au₃⁻, with confirmation that the spectra are closely described by the product of a constant with a spectrum, H _Si^*, and a simple spectrum that is an exponential dependence on t, both being raised to appropriate powers. This is confirmed with further published data for 6, 9, 12, and 18 keV Al⁻ and Al₂⁻ primary cluster ions. In all cases, the major effect of intensity is then related to the deposited energy of the primary ion at the surface. The constitution of SIMS spectra, for monatomic and cluster primary ion sources, is shown, in all cases, to be consistent with the product of a constant with two component spectra raised to given powers.     

Characterization of high explosive particles using cluster secondary ion mass spectrometry

The use of secondary ion mass spectrometry (SIMS) for the detection and spatially resolved analysis of individual high explosive particles is described. A C(8) (-) carbon cluster primary ion beam was used in a commercial SIMS instrument to analyze samples of high explosives dispersed as particles on silicon substrates. In comparison with monatomic primary ion bombardment, the carbon cluster primary ion beam was found to greatly enhance characteristic secondary ion signals from the explosive compounds while causing minimal beam-induced degradation. The resistance of these compounds to degradation under ion bombardment allows explosive particles to be analyzed under high primary ion dose bombardment (dynamic SIMS) conditions, facilitating the rapid acquisition of spatially resolved molecular information. The use of cluster SIMS combined with computer control of the sample stage position allows for the automated identification and counting of explosive particle distributions on silicon surfaces. This will be useful for characterizing the efficiency of transfer of particulates in trace explosive detection portal collectors and/or swipes utilized for ion mobility spectrometry applications.     

Matrix‐assisted laser ablation production of gold cluster ions from Au‐coated photonic crystals

A new strategy was explored to generate pure gold cluster ions, Au_n^+/?, from gold films deposited on solid substrates via a matrix‐assisted laser ablation technique. The gold films deposited on SiO₂‐particle‐assembled photonic crystals were demonstrated to be the most ideal compared with the films deposited on various glass slides. Dropped with a matrix of 2‐(4‐hydroxyphenylazo) benzoic acid and bombarded by nitrogen pulse laser (355 nm), they could release a series of Au_n⁺ with n more than 110 or Au_n^? with n more than 60 according to the data obtained by inline time‐of‐flight mass spectrometry. The gold‐deposited photonic crystal substrates could be stored at room temperature for at least 6 months. The method is hence steady and convenient in use. Copyright © 2012 John Wiley & Sons, Ltd.     

Structural analysis of secondary ions by post-source decay in time-of-flight secondary ion mass spectrometry

Tandem mass spectrometry measurements have been achieved using time-of-flight secondary ion mass spectrometry (TOF-SIMS) and a post source decay (PSD)-like method. The performance of the method has been demonstrated on model molecules with well-known fragmentation pathways. Several lipids have been fragmented including the phosphocholine ion, phosphatidylcholines, cholesterol and vitamin E. Pure samples were analyzed, and the results compared with those obtained with the same compounds on a quadrupole-TOF hybrid mass spectrometer. Then, the structures of some lipids which are currently observed in the TOF-SIMS imaging of mammalian tissue sections were verified.     

Biological tissue imaging with time-of-flight secondary ion mass spectrometry and cluster ion sources

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) using liquid metal ion guns (LMIGs) is now sensitive enough to produce molecular-ion images directly from biological tissue samples. Primary cluster ions strike a spot on the sample to produce a mass spectrum. An image of this sample is achieved by rastering the irradiated point over the sample surface. The use of secondary ion mass spectrometry for mapping biological tissue surfaces provides unique analytical capabilities; in particular, it enables in a single acquisition a large variety of biological compounds to be localised on a micrometer scale and scrutinised for colocalisations. Without any treatment of the sample, this method is fully compatible with subsequent and complementary analyses like fluorescence microscopy, histochemical staining, or even matrix-assisted laser desorption/ionisation imaging. Basic physical concepts, required instrumentation (ion source and mass analyzer), sample preparation methods, image acquisition, image processing, and emerging biological applications will be described and discussed.     

Proton-bound cluster ions in ion mobility spectrometry

Gaseous oxygen and nitrogen bases, both singly and as binary mixtures, have been introduced into ion mobility spectrometers to study the appearance of protonated molecules, and proton-bound dimers and trimers. At ambient temperature it was possible to simultaneously observe, following the introduction of molecule A, comparable intensities of peaks ascribable to the reactant ion (H₂O)_nH⁺, the protonated molecule AH⁺ and AH⁺ · H₂O, and the symmetrical proton bound dimer A₂H⁺. Mass spectral identification confirmed the identifications and also showed that the majority of the protonated molecules were hydrated and that the proton-bound dimers were hydrated to a much lesser extent. No significant peaks ascribable to proton-bound trimers were obtained no matter how high the sample concentration. Binary mixtures containing molecules A and B, in some cases gave not only the peaks unique to the individual compounds but also peaks due to asymmetrical proton bound dimers AHB⁺. Such ions were always present in the spectra of mixtures of oxygen bases but were not observed for several mixtures of oxygen and nitrogen bases. The dimers, which were not observable, notable for their low hydrogen bond strengths, must have decomposed in their passage from the ion source to the detector, i.e. in a time less than ∼5 ms. When the temperature was lowered to −20 °C, trimers, both homogeneous and mixed, were observed with mixtures of alcohols. The importance of hydrogen bond energy, and hence operating temperature, in determining the degree of solvation of the ions that will be observed in an ion mobility spectrometer is stressed. The possibility is discussed that a displacement reaction involving ambient water plays a role in the dissociation.     

Flavonoid–matrix cluster ions in MALDI mass spectrometry

The behaviour of 2,5‐dihydroxybenzoic acid (2,5‐DHB) matrix under matrix‐assisted laser desorption/ionisation (MALDI) conditions was investigated, and the formation of 2,5‐DHB cluster ions, mainly dehydrated 2,5‐DHB ions, is reported. Interestingly, in the mass spectra of this compound, besides dimers and trimers, protonated tetramers, pentamers, hexamers and heptamers were also found with significant abundance. The MALDI behaviour of four flavonoids, quercetin, myricetin, luteolin and kaempferol, using 2,5‐DHB as matrix, was also investigated. The mass spectra of the flavonoids studied revealed a number of flavonoid–2,5‐DHB cluster ions (mainly with the dehydrated 2,5‐DHB). The number of clusters formed is dependent on the structure of the analyte. For luteolin and kaempferol, in particular, evidence was found for the formation of cluster ions involving retro Diels Alder fragments and intact flavonoids molecules, as well as the corresponding protonated retro Diels Alder fragments with dehydrated DHB molecules. All ion compositions were attributed taking into account high accuracy mass measurements and tandem mass spectrometry experiments. Copyright © 2009 John Wiley & Sons, Ltd.     

Cluster ions in the secondary ion mass spectrometry of choline and acetylcholine halides

Liquid secondary ion mass spectra of choline and acetylcholine halides exhibit several series of cluster ions whose origins were investigated using B/E and B²/E linked-scan techniques. In the case of choline halides three series of cluster ions were identified as (Me₃$ \mathop {\rm N}\limits^ + $CH₂CH₂OH + nM), (Me₃$ \mathop {\rm N}\limits^ + $CH₂CH₂OMe + nM) and (Me₃N$ \mathop {\rm N}\limits^ + $CH₂CH₂OH · Me₃$ \mathop {\rm N}\limits^ + $CH₂CH₂O^? + nM), while (CH₃COOCH₂CH₂$ \mathop {\rm N}\limits^ + $Me₃ + nM), (Me₃$ \mathop {\rm N}\limits^ + $CH₂CH₂OH + nM) and (CH₂ = CH$ \mathop {\rm N}\limits^ + $Me₃ + nM) were observed in the spectra of acetylcholine halides. For these cluster ions, bimolecular reactions induced on ion bombardment under secondary ion mass spectrometric conditions are discussed.     

Identification of human calculi with time‐of‐flight secondary ion mass spectrometry

Time‐of‐flight secondary ion mass spectrometry was used to study four human calculi and to compare the results with those from twelve commercially available urinary calculi minerals including three organic compounds (L‐cystine, uric acid and sodium urate). Phase identification of calcium phosphate compounds was carried out by considering the relative ion abundances of [Ca₂O]⁺ and [CaPO₂]⁺. Deprotonated [M–H]^? and protonated [M+H]⁺ uric acid were detected and used for component recognition in pure uric acid and in the mixed samples of struvite, calcium oxalate and uric acid. Iodine related to the medical history of a patient was also detected. Copyright © 2009 John Wiley & Sons, Ltd.     

Analysis of bone minerals by time-of-flight secondary ion mass spectrometry: a comparative study using monoatomic and cluster ions sources

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) is an important tool for the analysis of bone minerals at implant surfaces. Most studies have been performed with monoatomic primary ion sources such as Ga(+) with poor secondary molecular ion production efficiency and only elemental distributions and minor fragments of bone minerals have been reported. By using cluster ion sources, such as Au(1-3) (+) and Bi(1-3) (+), identification of larger hydroxyapatite species at m/z 485, 541, 597 and 653, identified as Ca(5)P(3)O(12), Ca(6)P(3)O(13), Ca(7)P(3)O(14) and Ca(8)P(3)O(15), respectively, became possible. The ions appear to be fragments of the hydroxyapatite unit cell Ca(10)(PO(4))(6)(OH)(2). Each ion in the series is separated by 55.9 m/z units, corresponding to CaO, and this separation might reflect the columnar nature of the unit cell.