Many years ago, as a budding young science writer, I attended a press conference at a physics meeting and heard John Sidles of the University of Washington describe a promising new imaging technique: magnetic resonance force microscopy (MRFM). He made a strong case that such a technique was needed, particularly for 3D imaging single biological molecules such as proteins at the atomic level, which can’t really be done using more conventional methods like X-ray crystallography. MRFM was pretty much in its infancy at the time, but Sidles’ lucid, impassioned championing of it stuck with me all these years.
I don’t know what Sidles is up to these days, but the other impassioned scientist at that long-ago press conference was Dan Rugar of IBM Almaden Research Center, and he’s been fighting the good fight on behalf of MRFM ever since. Rugar was a featured speaker during this morning’s session on bio-Imaging, detailing the progress made to date on MRFM and outlining the challenges that (still) remain. Sidles had said it would take a good 10-15 years of R&D before the technique was ready for prime-time; looks like he was right. But it might just be on the brink of success at long last.
MRFM basically combines the concepts of magnetic resonance imaging (MRI) and atomic force microscopy (AFM) to detect the magnetic signal from electrons in a given sample. Electrons have a property known as “spin,” causing it take like itsy-bitsy bar magnet, and either attract or repel the magnetic tip of an ultrathin cantilever made of silicon.
The interaction between the electron spin and the magnetic tip causes the cantilever to vibrate ever so slightly in response. A nearby coil generates a high-frequency magnetic field, causing the electron spin to “flip” back and forth between the “up” and “down” positions, alternating attraction and repulsion, causing the cantilever’s frequency to change ever so slightly. This slight change can be measured very precisely by a laser beam (courtesy of an interferometer). The data can then be processed in a computer to produce a final image.
It’s a complex system with lots of different pieces, each with its own set of technical challenges. Why is MRFM so necessary? Well, proteins, for example, tend to fold in very complex patterns that directly impact how they function, but to date, researchers have been quite limited in their ability to observe biomolecules (and atoms, for that matter) in three dimensions. In nanotechnology and materials science, the ability to precisely locate specific atoms — to map a material’s structure at the atomic level in 3D — would give deeper insights into how to tailor them to exhibit preferred properties. (Materials derive most of their unique properties from atomic structure.)
Various incarnations of Rugar’s MRFM instrument have been used to image the structure of tobacco mosaic virus and dengue virus, as well as hydrogen molecules in a multi-walled carbon nanotube. In 2004, Rugar’s team made a critical breakthrough when they directly detected the faint magnetic signal from a single electron buried inside a solid sample — a 10 million times improvement over conventional MRI machines used to image organs in the human body. It’s still not the desired 3D snapshot of a single atom or molecule, it’s a strong proof of principle that MRFM is capable of achieving atomic-scale imaging. His team has also demonstrated one-dimensional imaging of a sample with 24-nanometer resolution.
Among the more enabling advances for bringing MRI to the nanometer scale was fabrication of an ultrasensitive silicon cantilever — a miniature diving board 1000 times thinner than a human hair capable of vibrating about 5000 times a second, with a powerful magnetic tip. (Rugar has his cantilevers tailor-fabricated by B.W. Chui’s group at Stanford University.)
It hasn’t been easy to get this far, and daunting obstacles still remain, but Rugar is still optimistic that the ultimate goal can be achieved through perseverance and sheer ingenuity — and the payoff could be revolutionary if/when that happens. “Throughout history, the ability to see matter more clearly has always enabled important new discoveries and insights,” Rugar said of these latest advances back in 2004. “This new capability should ultimately lead to fundamental advances in nanotechnology and biology.”
Science is like that most of the time: you grind away at the minutiae year after drudge-filled year, until you finally reach a tipping point and make the Big Breakthrough. It’s been a long wait for Rugar, Sidles and their many collaborators. Here’s hoping MRFM finds its way into widespread lab use very soon, so they can finally break out the bubbly to celebrate much-deserved success.