We must be getting close to the future that people have been foreseeing, because here’s a whole review on the topic of using atomic force microscopy to elucidate structures. It’s from the IBM Zürich group that has pioneered so much work in this area. Over just the time I’ve been writing this blog, that idea has gone from “Maybe someday” to “In some well-defined test cases” to “A few real-world examples known”, and now perhaps to “Hey, this might actually start working”.
Actually, it’s not just AFM. There’s also scanning tunneling microscopy (STM) and Kelvin probe force microscopy (KPFM), among other even more exotic ideas, and together you can get information that simply cannot be obtained by any other methods. Here they are in that order:
AFM is done typically by picking up a single CO molecule (from the carbon end) with the tip of the metal probe and scanning with the oxygen end across an adsorbed molecule (at liquid helium temperatures) at a constant height, about 4 Angstroms over the molecule itself. Often you go back and scan at several different tip heights. There are many other possible tips – xenon atoms, other diatomic molecules, halogen atoms, and so on. The cantilever holding the tip is oscillating (over about half an Angstrom) at a high frequency, and changes in this, induced by interactions with the molecule under study, are what get measured out (along with deflections in the angle that the CO molecule makes with the surface). The mechanism for these changes is just flat-out Pauli repulsion for the most part – electrons not wanting to occupy the same volume of space and getting out of each other’s way – although van der Waals and electrostatic forces can show up as well.
KPFM is pretty similar, except the readout is the voltage dependence of the position of the tip relative to the molecule, rather than changes in frequency of oscillation. You pick a voltage that gives you good signal/noise and scan around as with AFM. In practice, that gives you more of a pure electrostatic read on the surface, and it’s very useful for determining charge states and electron density in the sample. For example, fluorine is very close to the size of hydrogen, but they look dramatically different in KPFM because of the mass of electrons around the F atoms. Interpretation of the data, though, is not very straightforward, and often seems to involve matching up the experimental results to various calculations to try to see what’s going on.
And finally, in STM you apply a voltage to the tip and measure the changes in electric current between the tip and the sample as you scan, often by having the tip height change to keep a constant current level. At these distances, electrons are tunneling right across the gap, so this is sheer quantum mechanics all the way. If you pick the appropriate voltage, electrons can be temporarily attached to the lowest unoccupied molecular orbital (LUMO) of the test molecule (or detached from the highest-occupied, the HOMO, if you flip the voltage around), and the resulting images are absolutely terrifying for someone like me who came up thinking of these as mathematical abstractions.
At right is an example of these, with a CO tip used to show the bonds in the graphene-like molecule and then (in STM mode), its LUMO. As you can see, the resolution on these experiments is getting pretty good, and allows for an unequivocal assignment of the structure. Of course, an X-ray structure determination would almost certainly nail that down, too, but for that you have to have a purified sample and a good crystal. One interesting thing about AFM-type techniques is that you can scatter a mixed sample across the surface and take a look at the various things that might be in it, one molecule at a time.
At right is an illustration of something else that can really only be done under AFM conditions: actual atomic-level manipulation of the sample. Individual atoms can be pushed, twanged, or (as in this case) removed entirely. The result can be highly reactive intermediates (radicals, arynes, etc.) that can be studied directly at the liquid-helium temperatures involved. There are also opportunities to do on-surface reaction by heating followed by cooling down to AFM conditions, through photochemistry, etc. You can also study the interaction of individual molecules with each other
Now, it has to be said that there are not very many labs that are capable of these things at the moment, but that’s changing with the advent of more commercial apparatus and the spread of experienced workers in the field. What’s lacking? As the authors note, there’s a real need for techniques that might be able to read out functional groups and elements more directly. An even bigger challenge is that all the most spectacular results to date have been on planar or near-planar molecules, since these yield the most (and the most interpretable) data. You’re running your quantum fingers over the surface of things here, so the inside of a folded-up conformation is just not going to be available. And finally, there need to be improvements in the time it takes to get a measurement. It’s been stuck at roughly ten-minutes-per-molecule for a long time, but better time resolution would allow for a lot of new things to be picked up (and for better characterization of mixtures, and so on).
Update: here’s a Nature News article on the current developments in the field.