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.     

Effect of cocrystallization due to bile acid on molecular-ion sensitivity of biological phospholipids in Bi cluster time-of-flight secondary ion mass spectrometry measurements

Bi cluster time-of-flight secondary ion mass spectrometry (TOF-SIMS) is a useful method for evaluating organic surfaces. However, its ability to detect large molecules is limited. One of the problems is that the sensitivities of macromolecules are lower than those of small molecules because larger molecules tend to exhibit lower ionization efficiencies and/or higher probabilities of fragmentation. Matrix-enhanced (ME)-SIMS is a sensitivity enhancement technique for intact molecular ions. The crystal structure of a mixed substance composed of an analyte and a matrix is known to affect the sensitivity of the analysis target. In this study, the effect of cocrystallization, which occurs due to the presence of bile acid, on the molecular-ion sensitivity was investigated using Bi cluster TOF-SIMS. Biological phospholipids and bile acids, which exhibit surfactant behaviors, were selected as the evaluated molecules and additives, respectively. The mass spectra indicated that the secondary-ion yields of phospholipids with bile acid were substantially greater than those of the pristine lipid. Specifically, samples with an analyte/bile acid ratio of 1:100 achieved approximately 60–100-fold sensitivity enhancement of [M + H]⁺ and [2M + H]⁺ molecular ions than the sensitivity achieved with the pristine samples. In the evaluation of molecular distribution, higher signal counts of intact ions were obtained from the cocrystallization area, although less-fragmented ions were emitted from these regions. Consequently, the results indicate that the cocrystallization due to the presence of bile acid provides an effective crystal structure for facilitating emission of larger molecules.     

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.     

Secondary ion formation of low molecular weight organic dyes in time-of-flight static secondary ion mass spectrometry

Time-of-flight static secondary ion mass spectrometry (TOF-S-SIMS) was used to characterize thin layers of oxy- and thiocarbocyanine dyes on Ag and Si. Apart from adduct ions a variety of structural fragment ions were detected for which a fragmentation pattern is proposed. Peak assignments were confirmed by comparing spectra of dyes with very similar structures. All secondary ions were assigned with a mass accuracy better than 50 ppm. The intensity of molecular ions as well as fragment ions has been studied as a function of the type of organic dye, the substrate, the layer thickness and the type of primary ion. A large yield difference of two orders of magnitude was observed between the precursor ions of cationic carbocyanine dyes and the protonated molecules of the anionic dyes. Fragment ions, on the other hand, yielded similar intensities for both types of dye. As the dye layers deposited on an Ag substrate yielded higher secondary ion intensities than those deposited on a Si substrate, the Ag metal clearly acts as a promoting agent for secondary ion formation. The effect was more pronounced for precursor signals than for fragment ions. The promoting effect decreased as the deposited layer thickness of the organic dye layer was increased.     

Investigations on cluster and molecular ion formation by plasma mass spectrometry

The formation of molecular and cluster ions of different inorganic materials in plasma mass spectrometry – spark source mass spectrometry (SSMS), radiofrequency glow discharge mass spectrometry (rf GDMS), laser ionization mass spectrometry (LIMS), inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) – was investigated and compared. Similar abundance distributions of cluster ions were observed for a graphite sample, for boron nitride/ graphite and for metal oxide/graphite mixtures using different plasma mass spectrometric methods. A correlation of intensities of metal argide ions in ICP-MS with their bond dissociation energies was used to estimate unknown dissociation energies of molecular ionic species. For the elements of the 2nd or 3rd period in the periodic table, the intensities of most argon molecular ions (ArX⁺) measured by ICP-MS rise with increasing atomic number in a similar manner to the theoretically calculated bond dissociation energies of argon molecular ions.     

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.     

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.     

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.     

Influence of molecular environment on the analysis of phospholipids by time-of-flight secondary ion mass spectrometry

Understanding the influence of molecular environment on phospholipids is important in time-of-flight secondary ion mass spectrometry (TOF-SIMS) studies of complex systems such as cellular membranes. Varying the molecular environment of model membrane Langmuir-Blodgett (LB) films is shown to affect the TOF-SIMS signal of the phospholipids in the films. The molecular environment of a LB film of dipalmitoylphosphatidylcholine (DPPC) is changed by varying the film density, varying the sample substrate, and the addition of cholesterol. An increase in film density results in a decrease in the headgroup fragment ion signal at a mass-to-charge ratio of 184 (phosphocholine). Varying the sample substrate increases the secondary ion yield of phosphocholine as does the addition of proton-donating molecules such as cholesterol to the DPPC LB film. Switching from a model system of DPPC and cholesterol to one of dipalmitoylphosphatidylethanolamine (DPPE) and cholesterol demonstrates the ability of cholesterol to also mask the phospholipid headgroup ion signal. TOF-SIMS studies of simplistic phospholipid LB model membrane systems demonstrate the potential use of these systems in TOF-SIMS analysis of cells.     

Molecular weight determination of bulk polymer surfaces by static secondary ion mass spectrometry

The determination of molecular weights at surfaces of bulk polymer materials can be accomplished by static secondary ion mass spectrometry (SIMS) via fragments originating from repeat units and end groups. The intensity ratio of these fragments depends on the polymer chain length as seen for bisphenol-A-polycarbonate and perfluorinated polyethers (Krytox). A kinetic model of fragment ion formation explains the molecular weight dependent fragment intensities and links them to properties of the molecular weight distribution. In the most simple case one obtains the number average molecular weight <M_n> at the surface. This technique can be used for the determination of the molecular weight at bulk polymer surfaces such as a CD-ROM made from polycarbonate by injection molding.     

Sequence analysis for an unknown peptide by molecular secondary ion mass spectrometry

Positive and negative molecular secondary ion as well as metastable ion mass spectra for various peptides are investigated to clarify their fragmentation regularity. The fragmentation regularity is derived by considering all the possible bond cleavages at the peptide bond or at the adjacent bonds. It is demonstrated that the amino acid sequence for an unknown peptide can be determined by interpreting the positive and negative secondary ion and metastable ion mass spectra using this fragmentation regularity.     

Automated correlation and classification of secondary ion mass spectrometry images using a k-means cluster method

We present a novel method for correlating and classifying ion-specific time-of-flight secondary ion mass spectrometry (ToF-SIMS) images within a multispectral dataset by grouping images with similar pixel intensity distributions. Binary centroid images are created by employing a k-means-based custom algorithm. Centroid images are compared to grayscale SIMS images using a newly developed correlation method that assigns the SIMS images to classes that have similar spatial (rather than spectral) patterns. Image features of both large and small spatial extent are identified without the need for image pre-processing, such as normalization or fixed-range mass-binning. A subsequent classification step tracks the class assignment of SIMS images over multiple iterations of increasing n classes per iteration, providing information about groups of images that have similar chemistry. Details are discussed while presenting data acquired with ToF-SIMS on a model sample of laser-printed inks. This approach can lead to the identification of distinct ion-specific chemistries for mass spectral imaging by ToF-SIMS, as well as matrix-assisted laser desorption ionization (MALDI), and desorption electrospray ionization (DESI).     

Static secondary ion mass spectrometry for organic and inorganic molecular analysis in solids

The use of mass spectra in secondary ion mass spectrometry (S-SIMS) to characterise the molecular composition of inorganic and organic analytes at the surface of solid samples is investigated. Methodological aspects such as mass resolution, mass accuracy, precision and accuracy of isotope abundance measurements, influence of electron flooding and sample morphology are addressed to assess the possibilities and limitations that the methodology can offer to support the structural assignment of the detected ions. The in-sample and between-sample reproducibility of relative peak intensities under optimised conditions is within 10%, but experimental conditions and local hydration, oxidation or contamination can drastically affect the mass spectra. As a result, the use of fingerprinting for identification becomes compromised. Therefore, the preferred way of interpretation becomes the deductive structural approach, based on the use of the empirical desorption–ionisation model. This approach is shown to allow the molecular composition of inorganic and organic components at the surface of solids to be characterised. Examples of inorganic speciation and identification of organic additives with unknown composition in inorganic salt mixtures are given. The methodology is discussed in terms of foreseen developments with respect to the use of polyatomic primary ions.     

A discussion on mass resolution in secondary ion mass spectrometry

Mass resolution is a very important parameter for mass spectrometry. It is necessary to compare the mass resolution between the newly developed TOF-SIMS and the conventionally high-performance magnetic SIMS. However, the definitions of mass resolution for these two types of instruments are quite different. Whether it is possible to compare mass resolution and how to do such comparison is a challenge. This problem was raised officially during the 2012 ISO/TC 201 meeting at Tampa, Florida, the United States and the long-term cooperation with ISO started afterwards. The definition of mass resolution is one of the most important and fundamental problems for mass spectrometry and should attract significant attention. Here, some detail discussions on mass resolution as well as the related experimental studies in the past few years, including the collaborations with ISO/TC 201/SC6 and SC1 are summarized. This summary covers the common problem for almost all the current existing and still used definitions of mass resolution. A reasonable new definition for mass resolution considering the peak shape or resolution function has been proposed, which has also been confirmed by using experimental studies of the mass resolution comparison between TOF and magnetic SIMS. This study lays a foundation for the future mass resolution comparisons between different mass spectrometry.