Always in motion is the future.

—Yoda

It's tough to make predictions, especially about the future.

—Yogi Berra

In a nutshell, the story of time of flight secondary ion mass spectrometry (TOF-SIMS) is that it is a powerful analytical technique that has found great use since its invention due to its ability to analyze both inorganic and organic materials, its surface sensitivity, and its powerful imaging capabilities, but that it is flawed due to our fundamental lack of understanding of secondary ion formation mechanisms and, therefore, our inability to directly quantify its results and to identify unknowns. This last lack of ability to identify unknowns comes, in part, from the lack of a separation method prior to analysis and, in part, from the paucity of standard spectra. Creating clean standard spectra is made difficult by the lack of a separation method. The method also suffers from weak or nonspecific spectra from a wide range of materials, reducing its general applicability.

The strengths of TOF-SIMS have driven the proliferation of the technique. It has allowed scientists such as myself to convince laboratories around the world to purchase this fairly expensive equipment and leave the new toys in our care. The weaknesses of the method lead to a continuing need for our expert assistance in its use and in results interpretation. Every sample can be a challenge and a learning experience, every day a new adventure.

In a world with rapidly improving technologies, either TOF-SIMS will improve substantially going forward, or another method or set of methods will make it obsolete. This short chapter attempts to capture current developments that are poised to change and improve the prospects of TOF-SIMS going forward.

TOF-SIMS does indeed image chemical species on surfaces, but the lateral resolution of the method is hampered by instrumental limitations and by the static SIMS limit. Imaging using an ion beam that does not damage the sample is limited by the available spot sizes of those ion beams. Imaging using ion beams with the best spot sizes is limited by the damage they cause and the resulting static SIMS limit. Both are limited by ion yields of the species of interest, which means that even with an ion beam that does not leave a damaged surface, one can end up consuming a significant portion of the sample and be far from surface sensitive in the creation of a single image.

Image fusion is the trick of using information from multiple sources to construct an image. An example of this from the past was the fusion of X-ray photoelectron spectroscopy (XPS) results with atomic force microscopy (AFM) data (Artyushkova, Farrar, and Fulghum 2009). More to the current point, the higher lateral resolution of a secondary electron microscope (SEM) image has been used to sharpen the features of a relatively blurry ion image from a TOF-SIMS analysis (Milillo et al. 2015).

The trick is to use a multivariate statistical method to find the covariance in the data sets, and thus to associate the chemical features in one data set with the sharper contrast of the other. It is not clear that this will be easy to do on a regular basis going forward. There are two significant problems. First, SEM images or AFM images do not necessarily have contrast mechanisms that correspond to those in the secondary ion images. The techniques are after all measuring quite different properties of the surfaces in question. The applicability of the technique is liable to be sample specific. Second, it is entirely possible to create artifacts in the resulting images. Artifacts have been documented in the fusion of test data sets (Tyler 2015). Finally, a great effort must be made to line up the images prior to the attempt to fuse the images. As noted above, the speed with which calculations can be performed greatly increases its usefulness. As long as image fusion remains a difficult and time-consuming process, it will have little use. On the other hand, improvements in computing speeds and processes may lead to the automation of the most difficult parts of the image fusion process.

The advent of cluster ion sources has made a huge improvement in the utility of TOF-SIMS. Now, these sources need to be tailored to produce bright small spots that produce ever-greater secondary ion yields. The traditional TOF-SIMS instruments, in which the pulse length of the primary ion beam is critical, also need an ion source that produces homogeneous short pulses of primary ions. In this regard, the large distributions of ion sizes produced in the current generation of massive cluster ion sources are problematic.

The recent work with water clusters instead of Ar clusters appears to be promising in terms of improving secondary ion yields (Sheraz et al. 2015). Working with the idea that protonation is an important ionization mechanism, researchers have begun adding acids to the water clusters (Tian et. Al. 2015). This is clearly an active area of research.

Meanwhile, reported spot sizes for gas cluster ion guns have been steadily shrinking. Work has also shown that cluster size selection can be important to match with the sample to be analyzed. Smaller clusters will etch inorganic samples better than larger clusters, but the larger clusters have advantages for many samples. If the cluster sizes could be more narrowly chosen, or better focused in time as well as space, that would be a huge new advance for the field.

An important feature of many other mass spectrometric methods is the ability to select an ion in a spectrum, and to produce a mass spectrum from that one ion. As an example, consider the unknown ion at 495 amu described in Chapter 6. In many mass spectrometry systems, one could select that ion, further fragment it, and examine the newly produced mass spectrum of just that species. This has two advantages. First, one can often reconstruct the structure of the ion from the fragments it produces, like putting together a jigsaw puzzle from its pieces. Second, the choice of an ion is a separation process in itself, and from a spectrum of a mixture one can isolate a spectrum of a specific species. Add to this a database of Mass spectrometry/Mass spectrometry (MS/MS) spectra, and one may never have a peak remain an unknown again.

As of this writing, both of the major TOF-SIMS instrument manufacturers are far along in the development of MS/MS capabilities. As a result of their recent announcements, one can state that of the improvements in TOF-SIMS one can foresee for the near future, this is both the most significant and the most certain. The methods they have chosen for doing MS/MS are completely different, and each has strengths and weaknesses.

IonTof’s solution for MS/MS is to couple a very different mass spectrometer from another instrument manufacturer into their system (Gilmore 2015). The concept, the brain child of Ian Gilmore of the National Physical Laboratory (NPL) labs in the UK, is to choose which spectrometer you want to use at the beginning of the analysis, and to either let the ions fly directly into the TOF MS or to divert the ions into an Orbitrap MS (Scigelova et al. 2011).

The Orbitrap’s advantages are:

1. It can (for the most expensive models) have enormous mass accuracy allowing direct identification of the formula for any ion one would be likely to produce in a SIMS instrument.

2. One can select ions for MS/MS analysis.

3. The typical MS/MS experiment performed in an Orbitrap is low energy collision induced dissociation (CID). The low energy CID is commonly used, especially for many biological applications, in particular proteomics, and, as a result, there is a very large database of low energy CID spectra to match results.

4. The Orbitrap will not be sensitive to the pulse length of the primary ion beam. This means one can, for example, optimize the beam for high lateral resolution and not worry about how what you do affects the mass resolution. One can also use Gas Cluster Ion Beam (GCIB) sources without worrying about the beam’s poor time focus.

The disadvantages of this approach are:

1. This solution comes with a high price tag. The high end Orbitrap is ~$600K, and that does not include what IonTof will charge to integrate it.

2. The Orbitrap itself is not large, but the electronics that accompanies it, and the space needed to separate things for proper maintenance are significant additions to the instrument’s footprint.

3. The low energy CID does not completely fragment ions, so that it may not be possible to completely determine the ion structure from the spectrum if one does not have a match in a database.

4. The repetition rate of the Orbitrap is low, 18 Hz in low-resolution mode, much slower if you are going for high mass resolution. The TOF-SIMS more normally operates on the order of 10 kHz. So one needs to slow the analysis down by three orders of magnitude to use the Orbitrap. Imaging experiments will thus take a long time. That may be OK if you have spent months preparing that one key tissue sample. For routine industrial analysis, it means you will rarely image with the Orbitrap and data rates will be low.

5. There will be inevitable losses in wrangling ions along an elongated path and in the process of injecting the ions into the Orbitrap. Some work may still be needed to optimize the transmission.

Phi took a completely different approach (Larson et al. 2015). They already had what they call the “high mass blanker” in place after the third electrostatic analyzer in their TRIFT TOF-MS, at a location where most of the mass separation has taken place. They decided to take that blanker, which was used to eliminate ions from a single amu that were more intense than you wanted at the detector, and to send those ions along a 45° trajectory into a high energy CID and from there into a linear TOF mass spectrometer.

The TOF approach has these advantages:

1. The PHI add on will cost “about the same as a typical Ion Gun” which will be on the order of half the Ion-Tof solution.

2. The addition should not change the footprint of the instrument.

3. This high energy CID should allow direct interpretation of the second MS to reconstruct an ion’s structure, since it generally produces a complete set of fragments of the ion.

4. The PHI MS/MS operation runs at the speed of the TOF-SIMS, and you can as easily image a fragment in the MS/MS spectrum as an ion in the original spectrum.

5. The mass resolution is decent at around 3K, not enough to ID formulae, but enough to give reasonable guesses and to allow decent separation in most cases.

6. The sensitivity of the second MS appears to be high.

The disadvantages are:

1. There is little by way of high-energy CID databases. The analyst will be forced to interpret the CID spectra directly to make identifications, a likely time consuming process for the analyst. The energy of the collision is not a choice. The instrument design forces collisions to take place at 1.5 KeV.

2. The mass selection is limited to 1 amu. This means that if there are multiple peaks at the same nominal mass, they will all end up with their fragments in the second MS. The separation one looks for from the MS/MS is thus incomplete.

3. To get a decent mass resolution, you will need to have a short pulse from the primary ion beam. This is a bit of a problem for massive Ar cluster sources, which produce the most spectacular high mass spectra. This is of particular concern in the analysis of biological samples.

At the moment there is little effort being made to expand of TOF-SIMS spectral libraries or to rigorously study sputter induced ion formation mechanisms. One impact of the new MS/MS technologies may be to advance both of these efforts. The second MS spectrum may be captured in growing libraries, and the study of the structures of the various fragments in TOF-SIMS spectra via MS/MS may also lead to insights into the mechanisms that lie behind the technique. This, in turn, may allow for a more focused (pun intended) effort in producing ion sources that further enhance the variety of materials with decent ion yields and meaningful spectra in a TOF-SIMS. Spectral libraries, better understanding of ion formation, and ever advancing ion sources are the keys to the growth of this technique. The success of this method in an ever-growing variety of applications seems likely.

TOF-SIMS remains a technique with seemingly enormous potential that seems just out of reach. From a practical tool today for specific uses in surface analysis, it may well become much more common and easily used. Only time will tell.

References

Artyushkova, K., J.O. Farrar, and J.E. Fulghum. 2009. “Data Fusion of XPS and AFM Images for Chemical Phase Identification in Polymer Blends.” Surface and Interface Analysis 41, no. 2, pp. 119–26. doi:10.1002/sia.2968

Gilmore, I.S. 2015. “A Revolution in Chemical Imaging—More Techniques, More Power, More Data, and More Answers.” In SIMS XX, 20th International Conference on Secondary Ion Mass Spectrometry. Seattle, WA.

Milillo, T., R. Hard, B. Yatzor, M.E. Miller, and J. Gardella. 2015. “Image Fusion Combining SEM and ToF-SIMS Images.” Surface and Interface Analysis 47, no. 3, pp. 371–76. doi:10.1002/sia.5719

Larson, P.E., G.L. Fisher, J.S. Hammond, R.M.A. Heeren, and S. Bryan. 2015. “A New Instrument with Parallel TOF-SIMS and MS/MS Data Acquisition.” In SIMS XX, 20th International Conference on Secondary Ion Mass Spectrometry. Seattle, WA.

Scigelova, M., M. Hornshaw, A. Giannakopulos, and A. Makarov. 2011. “Fourier Transform Mass Spectrometry.” Molecular and Cellular Proteomics 10, no. 7, p. M111.009431. doi:10.1074/mcp.M111.009431

Sheraz, S., I.B. Razo, T.P. Kohn, N.P. Lockyer, and J.C. Vickerman. 2015. “Enhancing Ion Yields in TOF-SIMS—A Comparative Study of Argon and Water Cluster Primary Beams.” Analytical Chemistry 87, no. 4, pp. 2367—74. doi:10.1021/ac504191m

Tian, H., A. Wucher, N. Winograd 2015. “Projectile Assisted Surface Chemistry: A Possible Route to Enhance Molecular Second Ion Yields?” In SIMS XX, 20th International Conference on Secondary Ion Mass Spectrometry. Seattle, WA.

Tyler, B.J. 2015. “Mass Spectrometry Image Fusion: What Works and What Doesn’t.” In SIMS XX, 20th International Conference on Secondary Ion Mass Spectrometry. Seattle, WA.