Kilo-electron volt collision-induced dissociation (keV-CID) enables the compositional identification and structural elucidation of molecules, metabolites and degradation products with 2D/3D visualization by mass spectrometry imaging (MSI). TOF-SIMS tandem MS imaging has been brought to bear for unambiguous molecular visualization in single cell-omics [1], natural product chemistry [2], metabolomics [3,4], surface modification [5], biocompatibility, high performance polymers and composites [6], 2D materials [7], electronic devices [8], catalysis [9], forensic and failure analysis, bio-medicine and pharmaceuticals [10-12]. Here, we will introduce and explore the advantages of surface-induced dissociation (SID) to assist molecular identifications together with the CID spectra. In contrast to the CID which promotes cleavage at every molecular bond, the SID is more subtle in that the bond cleavages result predominantly in the observation of functional group chemistry. While the SID and CID are generated at the same kinetic energy, the molecular energetics are distinct which can have a pronounced effect on the calibration and, hence, the putative peaks used for precursor identification.

References

[1] C.E. Chini, et al, Biointerph. 13 (2018) 03B409.

[2] A. Mikhael, et al, Rapid Comm. Mass Spectrom. (2020) DOI: 10.1002/rcm.8740.

[3] T. Fu, et al, Anal. Chem. 90 (2018) 7535-7543.

[4] T. Fu, et al, Nat. Sci. Rep. 9 (2018) 1928-1938.

[5] G.L. Fisher, et al, Anal. Chem. 88 (2016) 6433-6440.

[6] S. Iida, et al, Bunseki 2018(2) (2018) 52-57 (Japanese).

[7] G.L. Fisher, et al, Microscop. Microanal. 23 (2017) 843-848.

[8] S. Iida, et al, Rapid Comm. Mass Spectrom. (2019) DOI: 10.1002/rcm.8640.

[9] S. Oh, et al, Chem. Mater. 32 (2020) 8512-8521.

[10] A.L. Bruinen, et al, in Imaging Mass Spectrometry: Methods and Protocols, L.M. Cole, Ed. (Springer, 2017) p. 165-173.

[11] N. Ogrinc Potočnik, et al, Anal. Chem. 89 (2017) 8223.

[12] Y. Shi, et al, J. Proteome Res. 18 (2019) 1669-1678.

The continuing development of primary ion beams has arguably been the single most important driver of improvements in secondary ion mass spectrometry (SIMS). This is particularly evident in the analysis of molecular ions, leading to new applications in life sciences.¹ Polyatomic primary ions have greatly extended the sensitivity, depth resolution, and mass range of the technique for molecular analysis.^2,3 While benefits clearly arise from the novel physics associated with keV impact of large clusters on molecular materials, more recently the chemistry has also been shown to play an important role in the SIMS ionisation mechanism(s).^4,5

Here we highlight some of our recent work involving water gas cluster ion beams (GCIBs). We explore the effect of different GCIB chemistry on the secondary ion yields from a range of samples, spanning from pure metal surfaces and single-component drugs to biological tissues. We also attempt to determine the composition of GCIBs containing mixtures of Ar, CO₂, and H₂O, and relate that to SIMS performance to help understand the underlying mechanisms of ion formation.

References:

(1) Yang, J.; Gilmore, I. Application of Secondary Ion Mass Spectrometry to Biomaterials, Proteins and Cells: A Concise Review. Mater. Sci. Technol. 2015, 31 (2), 131–136. https://doi.org/10.1179/1743284714Y.0000000613.

(2) Toyoda, N.; Matsuo, J.; Aoki, T.; Yamada, I.; Fenner, D. B. Secondary Ion Mass Spectrometry with Gas Cluster Ion Beams. Nucl. Instrum. Methods Phys. Res. Sect. B Beam Interact. Mater. At. 2002, 190 (1–4), 860–864. https://doi.org/10.1016/S0168-583X(02)00463-9.

(3) Angerer, T. B.; Blenkinsopp, P.; Fletcher, J. S. High Energy Gas Cluster Ions for Organic and Biological Analysis by Time-of-Flight Secondary Ion Mass Spectrometry. Int. J. Mass Spectrom. 2015, 377, 591–598. https://doi.org/10.1016/j.ijms.2014.05.015.

(4) Moritani, K.; Nagata, S.; Tanaka, A.; Goto, K.; Inui, N. Large Molecular Cluster Formation from Liquid Materials and Its Application to ToF-SIMS. Quantum Beam Sci. 2021, 5 (2), 10. https://doi.org/10.3390/qubs5020010.

(5) Lagator, M.; Berrueta Razo, I.; Royle, T.; Lockyer, N. P. Sensitivity Enhancement Using Chemically Reactive Gas Cluster Ion Beams in Secondary Ion Mass Spectrometry (SIMS). Surf. Interface Anal. 2022, sia.7054. https://doi.org/10.1002/sia.7054.

In recent years, the advent of cluster ion beam technology has enabled us to perform high mass molecular ion imaging and organic depth profiling for various types of organic materials. However, when conducting these measurements using commercial time-of-flight secondary ion mass spectrometry (TOF-SIMS) instruments, a significant amount of manual operation is required, leading to considerable effort during the measurements. The primary issue is that optimizing the measurement conditions, such as neutralization and analyzer settings, for each insulating material requires human intervention due to differences in dielectric properties and thickness. Recently, by combining pulsed low-energy electron and pulsed low-energy ion beams, we have successfully achieved fixed neutralization conditions for the majority of insulating materials [1]. Furthermore, we have developed a functionality that allows the computer to optimize the analyzer conditions for each sample, eliminating the need for human intervention. In this presentation, we will introduce our new function and discuss unmanned analysis for insulating samples.

[1] Patent WO2022047190A1.