Article
Impact of PHI TOF-SIMS instruments on scientific discovery
Introduction
The time-of-flight secondary ion mass spectrometry (TOF-SIMS) community continues to grow. A Google Scholar search for “TOF-SIMS” articles published in 2025 yielded 7,350 results, a 40% increase over the results from 2024. This surge reflects the expanding adoption of TOF-SIMS across diverse research fields and the increasing recognition of its value for high-resolution chemical imaging and surface analysis.
The year 2025 brought a wave of innovation in both instrumentation and application. Building on last year’s momentum, researchers leveraged PHI nanoTOF TOF-SIMS instruments to address persistent challenges in battery technology, biological imaging, SIMS methodology, and materials characterization. This review spotlights several of these landmark studies that collectively illustrate the growing impact and versatility of TOF-SIMS.
Biological Imaging: In Situ Cryo-Sectioning for Subcellular Analysis
Seydoux et al.1 introduced an accessible workflow for subcellular TOF-SIMS imaging of hydrated biological specimens. Their in-situ cryo-etching method uses a gas cluster ion beam and a custom titanium mask to section frozen samples directly inside the nanoTOF II TOF-SIMS instrument, eliminating the need for chemical fixation or costly cryotransfer systems. Figure 1 shows the ion image of a cross sectioned seed using this new approach. With TOF-SIMS imaging, they were able to see the seed coat (c), albumen (a), and the protein body (p).
Figure 1. Subcellular imaging of Arabidopsis seed (Seydoux et al., bioRxiv 2025).
Advances in Battery Materials: Reinventing the Sodium Anode
A major breakthrough in sodium battery technology was achieved by Wang et al.,2 who introduced a reconstructed sodium metal anode (RSMA) featuring a three-dimensional ion-conductive network. By embedding NaPF₆ and conductive polymers within the metal bulk, the RSMA enables uniform, high-dimensional plating and stripping of sodium ions. This design overcomes the limitations of traditional two-dimensional deposition, suppressing dendrite formation, and dramatically improving cycling stability. TOF-SIMS also played a crucial role in characterizing the solid electrolyte interphase (SEI), showing the improvements gained by the RSMA. In particular, they used TOF-SIMS 3D imaging, acquired from their nanoTOF II system, to show the stability of the anode, shown in Figure 2.
Figure 2. 3D rendering for NaO⁻, CH₂O⁻, NaF⁻, and PO₃⁻ secondary ions in SEI (Wang et al., Sci. Adv. 2025).
Data Correction and Visualization: Depth Correction in 3D TOF-SIMS Imaging
Brunet, Gorman, and Kraft3 addressed a common challenge in 3D TOF-SIMS imaging: distortion along the z-axis when profiling contoured samples such as cells. Their depth correction strategy, performed with the nanoTOF II TOF-SIMS, uses total ion count images to model the sample’s surface morphology at each profiling step, enabling accurate adjustment of voxel positions in 3D renderings. Figure 3 shows the uncorrected and depth corrected images using this technique.
Figure 3. Depth corrected 3D 19F⁻ image of HEK cell (Brunet et al., Biomolecules 2025).
Parallel Imaging MS/MS of Lead Soaps in Paint Cross Sections
A notable advance in the application of TOF-SIMS to cultural heritage science was demonstrated by Garcia et al.4 Their work showcases the use of the nanoTOF II parallel imaging tandem mass spectrometry (MS/MS) to unambiguously identify and localize lead soaps in embedded paint cross sections at high spatial resolution. Figure 4 shows the ion images of a paint sample (A), the TOF-SIMS spectrum of lead oxide, hydroxide, hypochlorite, and an unknown lead peak at m/z 463.2, in addition to the tandem MS spectrum of the m/z 463.2 peak (C). The researchers were able to identify the loss of a fatty acid and subsequently identified the m/z 463.2 peak as palmitic acid lead soap.
Figure 4. Parallel MS/MS imaging of palmitic acid lead soap (Garcia et al., Anal. Chem. 2025).
Methodological Innovation: Hybrid Sputtering for Multilayer Films (Our Lab)
Finally, we’d like to highlight research conducted in our own analytical lab at ULVAC PHI. While Ar‑GCIB enables low‑damage, high‑resolution profiling of organic layers, its intrinsically low sputter yield on inorganics restricts its usefulness for hybrid stacks commonly found in optical coatings, perovskite solar cells, and polymer‑electrolyte fuel cells. To overcome this, Iida et al.5 developed a hybrid sputtering approach using the nanoTOF 3 TOF-SIMS that alternates low‑energy Cs⁺ ions with Ar‑GCIB, using each sputter gun where it performs best. The Cs⁺ phase of the depth profile efficiently removes inorganic layers and stabilizes negative ion yields, while the subsequent GCIB phase smooths the surface and preserves organic molecular information, allowing more accurate reconstruction of buried interfaces.
This method was validated on thin‑film structures such as 40 nm Al overlayers on PC and PET substrates, where Ar‑GCIB alone could not fully remove the metal even after extended sputtering. In contrast, the hybrid sequence removed the inorganic overlayer reliably and produced high‑quality polymer spectra nearly identical to GCIB‑only conditions. The approach enabled sharp interface resolution and restored molecular signals that would otherwise be lost with monoatomic sputtering alone (Figure 5). These results demonstrate that hybrid sputtering provides a practical, high‑fidelity solution for profiling increasingly common hybrid material stacks, combining the speed and effectiveness of Cs⁺ sputtering with the chemical gentleness of GCIB.
Figure 5. Depth profiling results of Al films on PC substrates (Iida et al., JVST B 2025).
Outlook
The studies highlighted in this review exemplify the expanding reach of TOF-SIMS, from battery interfaces and multilayer films to subcellular imaging, data analysis, and cultural heritage science. Methodological advances such as hybrid sputtering, in situ cryo-sectioning, and parallel MS/MS imaging are enabling researchers to tackle previously inaccessible questions, while improved data correction techniques are enhancing the fidelity of 3D chemical maps.
References
- Seydoux et al., In situ GCIB Cryo-Sectioning Enables Subcellular Cryo-ToF-SIMS Imaging of Arabidopsis Seeds. bioRxiv 2025.11.28.691143.
DOI: 10.1101/2025.11.28.691143 - Chutao Wang et al., Reinvented sodium anode by creating a metal-bulk storage matrix with an expanded 3D plating/stripping mechanism. Sci.Adv. 11, eadw5701 (2025). DOI:10.1126/sciadv. adw5701
- Brunet et al., Depth Correction of TOF-SIMS Depth Profiling Images Using the Total Ion Count Images. Biomolecules 2025, 15(9), 1237.
DOI: 10.3390/biom15091237 - Garcia et al., ToF-SIMS Parallel Imaging MS/MS of Lead Soaps in Embedded Paint Cross Sections. Anal. Chem. 2025, 97, 2, 1054–1058
DOI: 10.1021/acs.analchem.4c05523 - Iida et al., Hybrid sputtering approach for reliable TOF-SIMS depth profiling of inorganic-organic multilayer films. J. Vac. Sci. Technol. B, 2025 DOI: 10.1116/6.0005000