In secondary ion mass spectrometry (SIMS), reactive species are commonly used to enhance secondary ion yields.¹ Electronegative primary ion species or reactive gas flooding with electronegative elements is used to enhance the emission of positive secondary ions ². For the emission of negative secondary ions, electropositive primary ions or flooding with reactive electropositive elements is used ^3,4. Compared to non-reactive species, secondary ion yields can be increase by several orders of magnitude. The enhancement of secondary ion yields by combining ion bombardment with simultaneous reactive gas flooding was limited up to now to monatomic primary ion species. However, it has been found to be independent of the primary ion species, i.e. similar yields have been obtained for Cs⁺, Ga^+3,4, He⁺ and Ne⁺.⁵

In this presentation, we are going to explore to what extent cesium flooding can be extended to cluster ion bombardment on inorganic matter. Such cluster ion bombardment is becoming more and more popular because of reduced fragmentation during the analysis of organic matter. For C₆₀⁺ bombardment combined with cesium flooding on silicon, results show that the useful yield of negative secondary ions can be increased by more than three orders of magnitude, which is comparable to what has been observed previously for Ga⁺ bombardment combined with Cs flooding. For polymers, similar experiments have been carried out for Ar₄₀₀₀⁺ bombardment combined with cesium flooding on polycarbonate. Compared to monatomic primary ions or small cluster ions, massive Ar clusters produce less fragmentation and depth profiling of polymers, which could not be profiled successfully with other primary ions, became possible. We will show that, for this kind of samples, cesium flooding does not enhance the ionization probability, but will reduce charging effects and/or fragmentation of polymers. The influence of primary current, cluster size and cluster composition and the validity for other sample materials will be discussed in detail.

References:

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2. Frache, G.; Adib, B. E.; Audinot, J. N.; Migeon, H. N. Surf. Interface Anal.2011,43 (1-2), 639-642.

3. Philipp, P.; Wirtz, T.; Migeon, H. N.; Scherrer, H. Int. J. Mass Spectrom.2006,253 (1-2), 71-78.

4. Philipp, P.; Wirtz, T.; Migeon, H. N.; Scherrer, H. Appl. Surf. Sci.2006,252 (19), 7205-7207.

5. Pillatsch, L.; Vanhove, N.; Dowsett, D.; Sijbrandij, S.; Notte, J.; Wirtz, T. Appl. Surf. Sci.2013,282 (0), 908-913.

Over the years the collaboration between Orsay and EA Schweikert groups from TAMU explored the advantages of Nano-Particle (NP) projectiles for surface analysis. Our studies led to the Pegase project [1], founded by NSF (Grant CHE-0750377) and installed in TAMU, which accelerates under 130 Kv NPs delivered by a liquid metal ion source. The results obtained with this platform demonstrate the interest of this new probe for micro and nano-structured surface analysis. The Pegase project allowed the design of a new more ambitious instrument, taking into account the results obtained at higher energies in the MeV range [2], named ANDROMEDE which has benefited from an “Equipement d’Excellence” grant (ANR-10-EQPX-23). This project is now being achieved. The goal is to create a new instrument for the mass spectrometry analysis of nano-objects present on a surface with a spatial resolution around the µm. Molecular information (mass and structure) will be obtained from the impact of a NP accelerated in the MeV range by a single stage electrostatic accelerator. The principal device of this new instrument is a rising generation of ion sources NAPIS (Nano Particle Ion Source) installed in the terminal. The dedicated instrument will be a ToF mass spectrometer with high mass resolution incorporating the localization of the NP impacts with micrometre accuracy. This last point is developed in collaboration with the TAMU group from their Electron Emission Microscope [3] which is modified to obtain an image in positive mode from the H⁺ emission .

We shall recall the main results leading to the project. The Andromede project [4] enters its final step and will be described and the first results presented. The commissioning of the accelerator designed by NEC (National Electrostatics Corporation, Middleton, Wisconsin USA) has been performed. A maximum voltage of 4160 MV was reached. The terminal voltage of 4 MV was left unattended without any problem during 15 hours. The accelerator is equipped with two interchangeable ion sources. The ECR source Microgan™ is provided by Pantechnik. The advantage of this source lies in the adjustment of the magnetic field which permits to produce high multicharged atomic ions (with a minimum B configuration) or large intact molecular ions (without minimum B). OrsayPhysics developed the ionic column NAPIS which provides beams of gold atomic ions, clusters and nanoparticles composed of several hundred atoms.

In this study, we adapted the external calibration method, a general method to calibrate a MALDI-TOF spectrum, to perform mass calibration on a ToF-SIMS spectrum in delay extraction mode obtained by Ar GCIB. Irganox1010 was used as an external calibrant for mass calibration of trypsinized proteins obtained by Ar GCIB. Based on systematic tests with internal or external calibration together with and without the delay extraction, we conclude that the external calibration in the delay extraction mode could be a useful method to improve mass resolution and mass accuracy of ToF-SIMS spectrum obtained by argon GCIB.

【Introduction】 Large cluster ion projectiles of the secondary ion mass spectroscopy (SIMS) have improved the problem of molecular fragmentation and enhanced the emission of the molecular ion. The secondary ion intensity, when excluding analyzer-related factors, can be determined from the sputtering yield and ionization probability. The sputtering yield increases with the incident ion energy, which must be trade-off against molecular fragmentation. The ionization probability is influenced by the properties of the bombarding primary ion beams as well as the chemical nature of the sample surface during the collision with the primary ion. Thus, selecting the appropriate primary ion species may flexibly modify the sample surface by primary particles, enhancing the secondary ion intensities. It has been reported that some protein molecules are ionized without fragmentation and emitted into a vacuum upon impact when using molecules with a dipole moment as the cluster’s constituents, e.g. water [1] and SO₂ cluster[2], which suggested that both solvation and charge transfer processes can take place during cluster collision and play important roles in the soft-ionization of bio-molecules. In this study, we have investigated the secondary ion emission from aspartic acid film bombarded by hydrogen-bonded clusters, e.g. (H₂O)_n⁺, (D₂O)_n⁺ and (CH₃OH)_n⁺.

【Experimental】 The water and methanol cluster beams were generated by bubbling argon with adjusting the flow rate of the argon carrier gas through a reservoir filled with water and methanol liquid at room temperature. The sample was a thin film of aspartic acid (HOOCCH₂CH(COOH)NH₂ (C₄H₇NO₄), MW: 133). An aqueous solution of the chemical (1 g/L) was dropped on a silicon substrate and dried in vacuum.

【Results and discussion】 A proton (hydrogen or deuterium) attached intact ion (C₄H₈NO₄ and C₄H₇NO₄D) appeared in the secondary ion mass (SIM) spectra even under the (D₂O)_n⁺ bombardment. This result indicates that the proton exchange reaction in several picoseconds at the cluster-surface collision should dominate the intact ion formation. We have also investigated D₂O ion dose dependence of SIM spectra. The intact ion components including deuterium atoms (C₄H_8-xNO₄D_x, x=1~5) appeared in the SIM spectra with increasing D₂O cluster ion dose. The dosage dependence of C₄H_8-xNO₄D_x components show different tendency between x=1~3 group and x=4,5 group, which suggests different reactivity at the carboxyl end and amino end for the proton exchange reactions via hydrogen bond network.

[1] K. Hiraoka et al, J. Mass. Spectrom. Soc. Jpn. 58, 175 (2010).

[2] C. R. Gebhardt, et al, Angew. Chem. Int. Ed. 48, 4162 (2009).

The influence of the matrix effect on secondary ion yield presents a very significant challenge in quantitative SIMS analysis, for example in determining the relative concentrations of metabolites that characterize normal biological activities or disease progression [1-5]. Not only the sample itself, but also the choice of primary ion beam may influence the extent of ionisation suppression/enhancement due to the local chemical environment.

In this study an assessment of ionisation matrix effects was carried out on model systems using C₆₀⁺, Ar_n⁺_, (H₂O)_n⁺ and (H₂O/Ar)_n⁺ cluster ion beams. The analytes ranged from binary to multi-component mixtures in biologically relevant matrices. 20 keV ion beams were compared with a range of cluster sizes n=1000-10,000. The component secondary ion yields were assessed for matrix effects using different primary ion beams and sample composition. The presence of water in the cluster beam was associated with a reduction in the observed matrix effects suggesting chemically modified ion beams may provide a route to more quantitative SIMS analysis of complex biological systems.

[1] J. S. Fletcher, H. L. Kotze, E. G. Armitage, N. P. Lockyer, and J. C. Vickerman, “Evaluating the challenges associated with time-of-fight secondary ion mass spectrometry for metabolomics using pure and mixed metabolites,” Metabolomics, Dec. 2012.

[2] E. A. Jones, N. P. Lockyer, J. Kordys, and J. C. Vickerman, “Suppression and enhancement of secondary ion formation due to the chemical environment in static-secondary ion mass spectrometry.,” J. Am. Soc. Mass Spectrom. (2007) 18, 1559–67.

[3] S. Keskin, A. Piwowar, J. Hue, K. Shen, and N. Winograd, “Relative ion yields in mammalian cell components using C 60 SIMS,” Surf. Interface Anal. (2013) 45, 244–247.

[4] G. Karras, N.P. Lockyer “Quantitative Surface Analysis of a Binary Drug Mixture - Suppression Effects in the Detection of Sputtered Ions and Post-Ionized Neutrals” J. Am. Soc. Mass Spectrom. (2014) 25, 832-840.

[5] A.G. Shard, S.J. Spencer, S.A. Smith, R. Havelund and I.S. Gilmore, “The matrix effect in organic secondary ion mass spectrometry“ Int. J. Mass Spectrom. (2015) 377, 599-609

N-substituted benzylpyridinium salts or “thermometer molecules” were used to measure the internal energy of the secondary ion produced by argon cluster projectiles. During the bombardment process, energy from the primary ion beam is transferred to the secondary ions. ‘Hot’ secondary ions fragment in the gas phase, resulting in complex mass spectra and reduced molecular ion yields. The efficiency of this energy transfer is unknown, therefore a series of thermometer molecules, with well-defined internal energy thresholds, were employed to measure the internal energies of secondary ions produced from argon cluster primary ion beams with various E/n values.

In this experiment, the molecular ion-to-fragment ratios for the series of thermometer molecules were measured for argon cluster primary ion beams with E/n values ranging from 0.8 to 4 (n=3). For each thermometer molecule, the survival rate of the molecular ion was plotted and fitted with an error function and the E/n value at maximum dissociation was calculated. The internal energy of the secondary ions was found to be linear with the primary ion beam E/n value. The data suggests an efficient transfer of energy from the cluster projectiles to the secondary ions. Improved relative molecular ion yields were observed for large argon clusters at low energies despite reduced total ion yield. These results are consistent with the work published by Seah.¹

Data from the argon clusters projectiles was compared to the bismuth cluster ion beam and CID tandem MS. Diclofenac, a nonsteroidal anti-inflammatory drug with thermometer-like properties, was also analyzed. The ability to detect intact drug molecules in cells and tissues is essential to the advancement of SIMS in the pharmaceutical sector. Therefore, it is important to understand how the selected ion beam parameters affect the quality of the spectral data.

[1] Seah, M. P. "Universal equation for argon gas cluster sputtering yields." The Journal of Physical Chemistry C 117.24 (2013): 12622-12632.