SIMS Secondary Ion Mass Spectrometry

Secondary ion mass spectrometry (SIMS) is the technique with the highest spatial resolution within the family of mass spectrometry imaging techniques. It works by bombarding the sample surface with a beam of high-energy primary ions (such as Ga⁺, Bi₃⁺ or Cs⁺); the momentum of the primary ions ‘sputters’ atoms and molecules from the surface layer, some of which escape as charged secondary ions, which are then separated by the mass analyser according to their mass-to-charge ratio. The entire sputtering-ionisation process takes place in high vacuum or even ultra-high vacuum.

The greatest strengths of SIMS lie in its resolution and depth capability. The focused ion beam can reduce the beam spot size to the sub-micrometre (approximately 100 nm) scale, thereby enabling the observation of elemental and molecular distributions at the scale of organelles and even material grain boundaries; simultaneously, by sputtering the sample layer by layer, three-dimensional depth profiles can be obtained—something that is difficult to achieve with ambient-pressure soft ionisation techniques. It is extremely sensitive to inorganic elements, metals and semiconductor dopants, and occupies an irreplaceable position in materials science and the analysis of biomembrane lipids.

The drawbacks are equally evident. High-energy bombardment shatters molecules, resulting in secondary ion spectra dominated by fragments rather than intact molecular ions, making spectral interpretation more challenging than with soft ionisation; the sputtering process itself is destructive, as the sample is gradually eroded layer by layer, rendering it unsuitable for in situ observation of precious histological sections; furthermore, it is sensitive to salts and the matrix, requiring rigorous standards for quantification.

Comparison with New Ceyuan’s technical approach: the technical overview on the official website lists SIMS as one of the mass spectrometry imaging techniques. New Ceyuan’s MSI DPI (DESI + photochemical ionisation) and MSI LDPI (laser desorption + photochemical ionisation) follow an approach based on ambient pressure, soft ionisation and minimising sample damage —the former offers a resolution of 20–200 μm, whilst the latter provides 2–3 μm; although these do not match SIMS’s sub-micrometre limits, they offer the advantages of in situ analysis, repeatable sampling, and spectra that facilitate easier molecular identification.

The choice of technique depends on the specific problem at hand: if the focus is on elemental distribution and nanostructures, SIMS is more suitable; if the aim is to examine the spatial distribution of biomolecules without damaging the sample, ambient-pressure soft ionisation imaging is a more practical choice.

A side-by-side comparison of the main imaging techniques provides greater clarity: SIMS excels in sub-micrometre resolution and depth profiling, but produces abundant fragments and damages the sample; MALDI is suitable for macromolecules and high-throughput applications, but is subject to matrix interference in the low-mass region; DESI and LDPI utilise ambient-pressure soft ionisation, offering in situ analysis, clean spectra and easy molecular identification. New Source’s MSI DPI and MSI LDPI are prime examples of the latter approach, striking a balance between resolution, throughput and reproducibility in the imaging of biological and small molecules. When selecting a technique, researchers should first ask themselves: ‘Which molecules are we looking at? Do we need to preserve the sample? How high a level of detail is required?’ The answer will then become clear.