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Seeing a Virus in Three Dimensions

Posted by tothewire on January 13, 2009

A Breakthrough in Imaging: Seeing a Virus in Three Dimensions

The end of the cantilever arm, with virus particles attached.

NYTIMES 

For the first time, researchers at an I.B.M. laboratory have captured a three-dimensional image of a virus.

The technique used by the I.B.M. scientists has some similarity to magnetic resonance imaging, or M.R.I., now routinely used by physicians to peer inside the human body. But the results were 100 million times better in terms of resolution with the new technique, magnetic resonance force microscopy, or M.R.F.M. The team of researchers, based at the computer maker’s Almaden Research Center in San Jose, Calif., reports in the The Proceedings of the National Academy of Sciences that they have captured a 3-D image of a tobacco mosaic virus with a spatial resolution down to four nanometers.

Techniques like atomic force and scanning tunneling microscopes have provided images of individual atoms. (An atom is about one-tenth of a nanometer in diameter). But these techniques are more destructive of biological samples because they send a stream of electrons at the target in order to get an image. And these microscopes cannot peer beneath the surface of the Lilliputian structures. The researchers said that many of their ideas had evolved from earlier work on atomic force microscopes. “The one thing that has always intrigued me, is, can we take the same idea and do it in three dimensions?” said Daniel Rugar, an I.B.M. physicist who helped design the first M.R.F. microscope in 1993. “We’d like to be able to take pictures of atomic structures like molecules. That’s been our motivation.”

The development of M.R.F.M. as a three-dimensional microscope actually began in 1991 with publication of a speculative paper by a theoretical physicist, John A. Sidles, who was then searching for new tools to help design drugs to combat the AIDS virus. After reading about atomic force microscope research at I.B.M., Dr. Sidles, who is a professor of orthopedics at the University of Washington School of Medicine, called Dr. Rugar and proposed a related tool that measured minute magnetic fields to construct images of biological structures.

“He realized that many of the diseases that they see are molecular-based,” Dr. Rugar said. In research in 2004, Dr. Rugar and others were able to make an image of a single electron with the new technique. The new achievement is the dimensionality of the image.

Magnetic resonance force microscopy employs an ultrasmall cantilever arm as a platform for specimens that are then moved in and out of proximity to a tiny magnet. At extremely low temperatures the researchers are able to measure the effect of a magnetic field on the protons in the hydrogen atoms found in the virus.

By repeatedly flipping the magnetic field, the researchers are able to cause a minute vibration in the cantilever arm which can then be measured by a laser beam. By moving the virus through the magnetic field it is possible to build up a 3-D image from many two-dimensional samples.

The researchers said they believed the tool would be of interest to structural biologists who are trying to unravel the structure and the interactions of proteins.

It would be particularly useful for biological samples that cannot be crystallized for X-ray analysis. Although the structure of DNA molecules has already been characterized by other means, it will be possible to use the system both to look at the components that make up the basic DNA structure as well as to make images of interactions among biomolecules, Dr. Rugar said.

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