Secondary Ion Mass Spectrometry Experiments Research Articles

Enzymatically modified peptide surfaces: towards general electrochemical sensor platform for protein kinase catalyzed phosphorylations

We hereby present an electrochemical approach for monitoring the three protein kinases sarcoma-related kinase (Src), extracellular signal-regulated kinase 1 (Erk1), and cyclin A-dependent kinase 2 (CDK2/cyclin A). The electrochemical sensor is based on the ability of kinases to transfer a redox-labeled phosphoryl group to surface-bound peptides that are highly specific substrates for the particular protein kinase (EGIYDVP, EPLTPSG, and HHASPRK, respectively). The detection method relies on the use of 5'-γ-ferrocenoyl-ATP (Fc-ATP) as a co-substrate for peptide phosphorylation. The peptides themselves are attached to a Au substrate, which acts as the working electrode. In this process a Fc-phosphoryl group is transferred to the peptide and the presence of the redox active Fc group is detected electrochemically. All peptide films were fully characterized by cyclic voltammetry (CV), square wave voltammetry (SWV), and electrochemical impedance spectroscopy (EIS). Particular attention was given to the electron transfer rates, k(ET), in peptide films after Fc-phosphorylation which were found to be on the order of seconds. The slow ET kinetics is presumably a result of the negative charge on the phosphoryl group. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) and X-ray photoelectron spectroscopy (XPS) experiments based on the peptide modified Au surfaces reveal significant ferrocene and phosphate group content introduced using the kinase-catalyzed phosphorylation reaction.

Mass spectrometry imaging: Towards a lipid microscope?

Biological imaging techniques are the most efficient way to locally measure the variation of different parameters on tissue sections. These analyses are gaining increasing interest since 20 years and allow observing extremely complex biological phenomena at lower and lower time and resolution scale. Nevertheless, most of them only target very few compounds of interest, which are chosen a priori, due to their low resolution power and sensitivity. New chemical imaging technique has to be introduced in order to overcome these limitations, leading to more informative and sensitive analyses for biologists and physicians. Two major mass spectrometry methods can be efficiently used to generate the distribution of biological compounds over a tissue section. Matrix-Assisted Laser Desorption/Ionisation-Mass Spectrometry (MALDI-MS) needs the co-crystallization of the sample with a matrix before to be irradiated by a laser, whereas the analyte is directly desorbed by a primary ion bombardment for Secondary Ion Mass Spectrometry (SIMS) experiments. In both cases, energy used for desorption/ionization is locally deposited -some tens of microns for the laser and some hundreds of nanometers for the ion beam- meaning that small areas over the surface sample can be separately analyzed. Step by step analysis allows spectrum acquisitions over the tissue sections and the data are treated by modern informatics software in order to create ion density maps, i.e., the intensity plot of one specific ion versus the ( x, y) position. Main advantages of SIMS and MALDI compared to other chemical imaging techniques lie in the simultaneous acquisition of a large number of biological compounds in mixture with an excellent sensitivity obtained by Time-of-Flight (ToF) mass analyzer. Moreover, data treatment is done a posteriori, due to the fact that no compound is selectively marked, and let us access to the localization of different lipid classes in only one complete acquisition.

Segregation surface in binary solid solutions

Analytic equations describing the concentration profile, surface energy, and adsorption for a binary solid solution with the emergence of one of the components to the surface (surface segregation) were obtained using a unique approach, a modified van der Waals approximation. The calculation results were compared with the experimental secondary ion mass spectrometry data on Cu-Ge and Cu-Al metallic binary solutions; agreement was satisfactory.

Stable Glass Transformation to Supercooled Liquid via Surface-Initiated Growth Front

Highly stable glasses of tris-naphthylbenzene transform into a liquid when annealed above the glass transition temperature T_{g}. In contrast to the predictions of standard models, the observed transformation is spatially inhomogeneous. Secondary ion mass spectrometry experiments on isotopically labeled multilayer films show that the liquid grows into the stable glass with sharp growth fronts initiated at the free surface and at the interface with the substrate. For the free surface, the growth velocity is constant in time and has the same temperature dependence as self-diffusion in the equilibrium supercooled liquid. These stable glasses are packed so efficiently that surfaces and interfaces are required to initiate the transformation to the liquid even well above T_{g}.

Theoretical Study of the Role of Chemistry and Substrate Characteristics in C60 keV Bombardment of Si, SiC, and Diamond by Molecular Dynamics Simulations

This article presents a theoretical study aimed at understanding the reactive nature of carbon in secondary ion mass spectrometry experiments of Si with keV C60+. Molecular dynamics simulations are performed to model the bombardment of three different substrates, Si, SiC, and diamond, with normal incident C60 at kinetic energies ranging from 5 to 20 keV. Projectile atoms form strong covalent bonds with both Si and C and, therefore, are incorporated into the target material. Although these substrates have the same diamond lattice structure, they differ greatly in their cohesive energy and number density. The yield is found to be a factor of two times greater on SiC than on Si or diamond. The mesoscale energy deposition footprint model is used to understand the reasons for the differing behaviors of the substrates as a result of C60 bombardment.

Comparing the fragmentation chemistry of gas-phase adducts of poly(dimethylsiloxane) oligomers with metal and organic ions

Gas-phase ions of poly(dimethylsiloxane) oligomers were formed by electrospray ionization either by protonating them in solution with formic acid or by generating adducts of the oligomers with the metal ions Li+, Na+, K+, and Ag+ as well as with the organic cations NH4+, CH3CH2NH3+, and protonated glycine, aspartic acid, and 1,2-diphenylethylamine. The collision-induced fragmentation of the oligomeric ions was strongly dependent on the nature of the charging species. Ag+ adducts dissociated in a manner previously observed in secondary ion mass spectrometry experiments generating a series of linear and cyclic fragment ions, while Li+ adducts fragmented to form two ions: an adduct of the metal ion with the oligomer end-group and one with the remaining oligomer. Na+ and K+ adducts simply dissociate to form the bare metal ion. The organic species, to varying extents, transfer the proton to the oligomer to form a protonated poly(siloxane) ion. These protonated oligomers then dissociate at very low laboratory-frame collision energy along the siloxane backbone by loss of a silanol. These backbone fragments can then lose a methyl group to form a second series of fragment ions. Suggestions for probable mechanistic pathways for these processes are presented.

Correction of secondary ion mass spectrometry profiles for atom diffusion measurements

A simple method is proposed in order to correct experimental secondary ion mass spectrometry (SIMS) profiles. This method uses only one parameter which is experimentally accessible. It is tested in the case of As SIMS profiles in Si(001) acquired with three different primary ion beam energies: 1, 3, and 9 keV. This method is shown to give consistent corrections. The correction of SIMS profiles measured in a same sample with different analysis conditions leads to the same As distribution.

C60 secondary ion mass spectrometry with a hybrid-quadrupole orthogonal time-of-flight mass spectrometer.

A hybrid quadrupole orthogonal time-of-flight mass spectrometer optimized for matrix-assisted laser desorption ionization (MALDI) and electrospray ionization has been equipped with a C 60 cluster ion source. This configuration is shown to exhibit a number of characteristics that improve the performance of traditional time-of-flight secondary ion mass spectrometry (TOF-SIMS) experiments for the analysis of complex organic materials and, potentially, for chemical imaging. Specifically, the primary ion beam is operated as a continuous rather than a pulsed beam, resulting in up to 4 orders of magnitude greater ion fluence on the target. The secondary ions are extracted at very low voltage into 8 mTorr of N 2 gas introduced for collisional focusing and cooling purposes. This extraction configuration is shown to yield secondary ions that rapidly lose memory of the mechanism of their birth, yielding tandem mass spectra that are identical for SIMS and MALDI. With implementation of ion trapping, the extraction efficiency is shown to be equivalent to that found in traditional TOF-SIMS machines. Examples are given, for a variety of substrates that illustrate mass resolution of 12,000-15,600 with a mass range for inorganic compounds to m/ z 40,000. Preliminary chemical mapping experiments show that with added sensitivity, imaging in the MS/MS mode of operation is straightforward. In general, the combination of MALDI and SIMS is shown to add capabilities to each technique, providing a robust platform for TOF-SIMS experiments that already exists in a large number of laboratories.

Fluorine-doped SiO 2 and fluorocarbon low- k dielectrics investigated by SIMS

In this work, we present secondary ion mass spectrometry (SIMS) investigations of the incorporation of fluorine into thin SiO 2 films adapted as low- k dielectrics in the metal-oxide-semiconductor (MOS) devices. The insulating SiOF oxides with the thickness ranging from 1 up to 15 nm have been prepared by plasma-enhanced chemical vapor deposition (PECVD) and/or by reactive ion etching (RIE) methods on 〈1 0 0〉 oriented p-Si substrates with the use of either CF 4 or CHF 3 source of the plasma. SIMS experiments were performed using ultra-low energy (1 keV) argon ion beam and quadrupole mass analyzer. Depth profiles of the resulting dielectric films illustrate: (i) the incorporation of F into the SiO 2 matrix is accomplished by either the CHF 3 or CF 4 plasmas; (ii) no etching of SiO 2 matrix is observed by using of CHF 3; (iii) CHF 3 is a source of fluorocarbon film deposition on top of the SiO 2 that prevents the SiO 2 etching; and (iv) fluorine quantifications done based on implantation criteria give the maximum concentrations within the films from 6.0 × 10 18 to 2.4 × 10 20 atoms/cm 3 depending on the different fluoridation conditions. The F concentration in SiO 2 increases with the r.f. power of CF 4 or with decreasing a gas pressure of CHF 3 plasma.

Atomic force microscopy and surface plasmon resonance investigation of fibronectin interactions with group B streptococci

The interactions of fibronectin (Fn) with group B streptococci (GBS) were investigated using the atomic force microscope (AFM) and surface plasmon resonance (SPR) biosensing. Submonolayer amounts of Fn were immobilized onto the AFM tip by two different methods, using either a sulfosuccinimidyl-4-(N-maleimidomethyl) cycholhexane-1-carboxylate (SMCC) linker or a pyridyldithio poly(ethylene glycol) succinimidylpropionate (NHS-PEG-PDP) linker. Each step of both immobilization methods was characterized using x-ray photoelectron spectroscopy. Time-of-flight secondary ion mass spectrometry experiments indicated both methods produced Fn immobilized in a similar conformation. AFM force-distance curves from live GBS plated onto polystyrene exhibited several types of interactions between the Fn functionalized AFM tip and the surface of capsule-deficient GBS (no interactions, interactions with the cell wall, Fn unfolding, large specific unbinding events, and small specific unbinding events). From analysis of the force-distance curves that exhibited only a single specific unbinding event, the work of adhesion and rupture force for the SMCC immobilized Fn tips (11,131 pN nm and 213 pN) were larger than the corresponding values for the NHS-PEG-PDP immobilized Fn tips (8115 pN nm and 189 pN). The unbinding event occurred at distances approximately 100 nm further from the surface with the NHS-PEG-PDP immobilized Fn tip compared to SMCC immobilized Fn tip. The SPR experiments of soluble Fn with adsorbed serine protease C5a peptidase (Scp), the surface protein on GBS that binds Fn, showed that both low (millimolar) and high binding (nanomolar) affinity interactions were present. However, the low binding affinity interactions dominated the adsorption process and, with increasing Fn solution concentration, the amount of Scp bound to Fn via the high binding affinity interaction decreased. These data confirm that Scp binds only to adsorbed Fn at the Fn concentrations typically present in blood plasma.

Effect of Cluster Size in Kiloelectronvolt Cluster Bombardment of Solid Benzene

Emission of benzene molecules by 5-keV cluster bombardment of a range of carbon projectiles from C6H6 to C180 is studied by a coarse-grained molecular dynamics (MD) technique. This approach permits calculations that are not feasible using more complicated potential energy functions, particularly as the interesting physics associated with the ion impact event approaches the mesoscale. These calculations show that the highest ejection yields are associated with clusters that deposit their incident energy 15-20 A below the surface. The highest yield for the projectiles is produced by the C20 and C60 projectiles. The results from the MD simulations are also compared favorably to an analytical model based on fluid dynamics to describe the energy deposition. The analytical model is then utilized to extend the range of the calculations to higher incident energies. The issue of the relative amount of chemical fragmentation and intact molecular desorption is also examined for the benzene crystal. These results show that damage accumulation at high-incident fluence should not be problematic and that it should be possible to perform molecular depth profiling via secondary ion mass spectrometry experiments. In general, the approach presented here illustrates the power of combining a simplified MD method with analytical strategies for describing a length scale that is difficult to achieve with traditional MD calculations.

C60, Buckminsterfullerene: its impact on biological ToF‐SIMS analysis

AbstractThe desire to apply the analytical abilities of the time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) experiment to increasingly diverse samples, particularly those of a biological nature, has provided the impetus for development of new technologies to overcome some of the inherent difficulties associated with such studies. Of these, one of the most important is the widespread introduction of polyatomic ion beams to increase the secondary ion yields of the higher mass, more chemically characteristic species. The introduction of the C60 ion beam for routine analysis has made arguably the greatest impact, providing new possibilities for analysing molecular compounds present both on the surface and in some cases in the bulk of samples such as biological tissue sections and single cells. Copyright © 2006 John Wiley & Sons, Ltd.

Impurity dimers in superconducting B-doped diamond: Experiment and first-principles calculations

On the basis of first-principles calculations and experimental secondary ion mass spectroscopy, electrical transport, and Raman measurements performed on homoepitaxial diamond, we find that at high concentrations boron atoms tend to segregate in dimers. The study of the electronic, vibrational, and electron-phonon coupling properties, corroborated by Raman measurements, shows that boron dimers may be associated to the broad Raman peak around $500\phantom{\rule{0.3em}{0ex}}{\mathrm{cm}}^{\ensuremath{-}1}$ as well as to some of the gap states which have been reported in the literature, and that they are both electrically and vibrationally inactive with respect to the electron-phonon coupling driving the superconducting transition in metallic diamond. These results bear important consequences on the evolution of the critical temperature with the impurity concentration in B-doped diamond.

Desorption of organic overlayers by Ga and C 60 bombardment

This paper reviews our recent work on computer simulations of Ga and C 60 bombardment of thin organic overlayers deposited on metal substrate. A multilayer of benzene, a monolayer of PS4 on Ag{1 1 1} and a self-assembled monolayer of octanethiol molecules on Au{1 1 1} were irradiated with 15 keV monoatomic (Ga) and polyatomic (C 60) projectiles that are recognized as valuable sources for desorption of high mass particles in secondary ion and neutral mass spectrometry (SIMS/SNMS) experiments. The results indicate that the sputtering yield decreases with the increase of the binding energy and the average kinetic energy of parent molecules is shifted toward higher kinetic energy. Although the total sputtering yield of organic material is larger for 15 keV C 60, the impact of this projectile leads to a significant fragmentation of ejected species. As a result, the yield of the intact molecules is comparable for C 60 and Ga projectiles. Our results indicate that the chemical analysis of thin organic films performed by detection of sputtered neutrals will not benefit from the use of C 60 projectiles.

Epitaxy and characterisation of dilute III–As1−yNy on GaAs and InP

Epitaxial growth and characterisation of Ga1−xInxAs1−yNy films and quantum wells are presented. Starting with the epitaxy on GaAs, recent results on the local bonding of nitrogen in Ga1−xInxAs1−yNy are reviewed, revealing that bonding of nitrogen is controlled by an interplay between bond cohesive energy and reduction of local strain. Thus, III–N bonding can be changed from Ga–N to In–N by post-growth thermal annealing. For high In-content Ga1−xInxAs1−yNy on InP it is demonstrated that only small amounts of Ga are necessary to cause the bonding of the nitrogen atoms to at least one Ga neighbour. The epitaxy on InP substrates, equivalent to a drastic increase in indium content, allows an extension of optical transitions to longer wavelengths. The feasibility of high In-content Ga1−xInxAs1−yNy pseudomorphic quantum wells on InP is shown. The deterioration of the photoluminescence properties with increasing nitrogen incorporation can be partially compensated by thermal annealing. Within the resolution limits of the secondary ion mass spectrometry experiments, no annealing-induced loss of nitrogen was observed. The indium-rich strained Ga0.22In0.78As0.99N0.01 quantum wells are shown to exhibit room-temperature photoluminescence at wavelengths up to 2.3 μm. Finally quantum well lasers emitting at wavelengths beyond 2 μm are demonstrated.

Coincidental emission of molecular ions from keV carbon cluster impacts

We report here experimental data for the emission of one and two phenylalanine (Ph) molecular ions per impact from 10 to 21 keV impacts of coronene (C 24H 12), C 60, and gramicidin S (C 60N 12O 10H 92) projectiles as a function of projectile mass, energy, and geometry. Secondary ion mass spectrometry (SIMS) experiments were conducted using event-by-event bombardment and detection. With this method, individual projectile impacts and the resulting secondary ions are recognized as singular events resolved in time and space. The target surface was an equa-molar mixture of phenylalanine (Ph H, C 9H 11NO 2) and deuterated phenylalanine (Ph D, C 9H 3D 8NO 2). This allowed for the detection of two co-emitted [M-H] − phenylalanine ions in a dual time-of-flight instrument. In contrast to the linear dependence yield of Ph versus energy for single Ph ion emission, the yield for two Ph ion emission versus energy is nonlinear within the experimental energy range. For the co-emission of two Ph ions, C 60 was found to be more efficient than coronene at equal velocities.

The realization of long-wavelength(λ ≤2.3 µm)Ga1−xInxAs1−yNy quantum wells on InP by molecular-beam epitaxy

The epitaxial growth and characterization of diluteGa1−xInxAs1−yNy films and quantum wells are presented. Starting with the epitaxyon GaAs, recent results on the local bonding of nitrogen inGa1−xInxAs1−yNy are reviewed, revealing that bonding of nitrogen is controlled by an interplaybetween bond cohesive energy and reduction of local strain. Thus, III–N bonding inGa1−xInxAs1−yNy can be changed from Ga–N to In–N by post-growth thermal annealing. Nitrogen loss due tothe annealing process is not observed. We then adopted this concept for the epitaxy on InPsubstrates, which is equivalent to a drastic increase in indium content of theGa1−xInxAs1−yNy systemand thus an extension to longer wavelengths. The low-energy shift of quaternary pseudomorphicallystrained Ga0.4In0.6As1−yNy double quantum wells upon nitrogen incorporation is reported. The deterioration of thephotoluminescence characteristics in terms of reduced peak intensity and increasedlinewidth with increasing nitrogen incorporation can be partially compensated by rapidthermal annealing, which is accompanied by a blueshift with respect to the as-grownsamples. Within the resolution limits of our secondary ion mass spectrometry experiments,no annealing-induced loss of nitrogen was observed even for the high indium contentGa1−xInxAs1−yNy quantum well structures. The results on indium-rich highly strainedGa0.22In0.78As0.99N0.01 quantumwells on InP substrate are reported, showing room temperature photoluminescence at wavelengths up to2.3 µm. Wefinally conclude with the demonstration of multi quantum well lasers emitting at wavelengths beyond2 µm.

Monte Carlo simulations of antibody adsorption and orientation on charged surfaces.

Monte Carlo simulations were performed to study the adsorption and orientation of antibodies on charged surfaces based on both colloidal and all-atom models. The colloidal model antibody consists of 12 connected beads representing the 12 domains of an antibody molecule. The structure of the all-atom antibody model was taken from the protein databank. The effects of the surface charge sign and density, the solution pH and ionic strength on the adsorption and orientation of different colloidal model antibodies with different dipole moments were examined. Simulation results show that both the 12-bead and the all-atom models of the antibody, for which the dipole moment points from the Fc to (Fab)2 fragments, tend to have the desired "end-on" orientation on positively charged surfaces and undesired "head-on" orientation on negatively charged surfaces at high surface charge density and low solution ionic strength where electrostatic interactions dominate. At low surface charge density and high solution ionic strength where van der Waals interactions dominate, 12-bead model antibodies tend to have "lying-flat" orientation on surfaces. The orientation of adsorbed antibodies results from the compromise between electrostatic and van der Waals interactions. The dipole moment of an antibody is an important factor for antibody orientation on charged surfaces when electrostatic interactions dominate. This charge-driven protein orientation hypothesis was verified by our simulations results in this work. It was further confirmed by surface plasmon resonance biosensor and time-of-flight secondary ion mass spectrometry experiments reported elsewhere.

Sputtering of a polycyclic hydrocarbon molecule: TOF–SIMS experiments and molecular dynamic simulations

This study focuses on the desorption and ionization processes of an aromatic molecule containing several phenyl rings, 1,2,3,4-tetraphenylnaphthalene (TPN), adsorbed on a Au surface, via the comparison of experimental secondary ion mass spectrometry (SIMS) data and molecular dynamic (MD) simulations. The mass spectra and kinetic energy distribution (KED) measurements were obtained using both TOF–SIMS and MD simulation methods. For entire TPN molecules, a good agreement is observed between the calculated and experimental KEDs, except for high energies, where they start diverging. This difference is partly caused by the unimolecular dissociation of internally excited molecules over larger time intervals than those considered in the simulation. In turn, using an internal energy threshold to remove the most excited molecules from the calculated KEDs provides a better agreement with the experiment. The MD simulations also show that molecules surrounding the impact point of the projectile are sputtered with more kinetic energy and shorter emission times than molecules located farther away from it. The distinct emission mechanisms inducing these different energy spectra are identified by the analysis of the simulation results.

Sputtering simulations of organic overlayers on metal substrates by monoatomic and clusters projectiles

This paper reviews our recent work on computer simulations of monoatomic and cluster bombardment of metal and organic surfaces. The investigated surfaces are irradiated with keV monoatomic (C, Ar, Ga) and polyatomic (C 60) projectiles that are recognized as valuable sources for desorption of high mass particles in secondary ion and neutral mass spectrometry (SIMS/SNMS) experiments. The analysis of the results reveals that the C 60 ion beam enables to perform chemical imaging with higher sensitivity, better depth resolution, and lower contamination than monoatomic projectiles with similar kinetic energy. For monoatomic projectiles, the development of a linear collision cascade is the predominant mechanism responsible for the ejection of particles. In contrast, strongly nonlinear, collective processes occur during C 60 bombardment. These nonlinear processes lead to the enhanced removal of material and the formation of a macroscopic crater. This paper presents theoretical insight into possible mechanisms responsible for the observed behavior with the emphasis on the phenomena important to the SIMS/SNMS community.