The Smallest Sight: Researchers Zoom In on the Nanoscale

Researchers at the University of Rochester have created the highest resolution optical image ever, revealing structures as small as carbon nanotubes just a few billionths of an inch across. The new method should open the door to previously inaccessible chemical and structural information in samples as small as the proteins embedded in a cell’s membrane. The research appears in today’s issue of Physical Review Letters.

“This is the highest resolution optical spectroscopic measurement ever made,” says Lukas Novotny, professor of optics. “There are other methods that can see smaller structures, but none use light, which is rich in information. With this technique we have a detailed spectrum for every point on a surface.”

Since light is so rife with information (everything we know about the deep universe comes from teasing information from a tiny amount of light), Novotny and his colleague, visiting professor Achim Hartschuh, can determine what a piece of material is made of as well as its structure. Is the string of carbon rolled into a tube or just a string of atoms? Is a protein made of expected molecules and properly folded to be an effective medicine? And what could be the most rewarding result of the research-detecting properties of such small structures that were unknown before. Novotny and his team are also eager to learn if certain structures exhibit unknown characteristics, such as when carbon nanotubes, for instance, cross or interconnect.

The ultimate vision for the Raman microscopy project, however, is to refine the process to a point where it might revolutionize biology. “Identifying individual proteins right on the cell’s membrane has been the goal of this project from the start,” says Hartschuh. Garnering the cornucopia of information light provides from the proteins on a membrane would mean scientists could understand exactly how a cell’s membrane works, opening the door to designer medicines that could kill harmful cells, repair damaged cells, or even identify never-before-seen strains of disease.

The Rochester team’s technique, called near-field Raman microscopy, illuminates the nano-sized structures with light, allowing researchers to glean far more information than any other technique. Other ultra-high resolution imaging techniques, such as atomic force microscopes, only detect the presence of objects, they don’t “see” them. Though researchers have longed wished to use light at such magnification, the laws of physics make this extremely difficult. Light travels in waves, and if an object like a nanotube or a protein is much smaller than that wavelength, it’s like trying to pick up a poppy seed with a fork-the poppy seed falls between the tines. Some efforts have been made to force light to shorter wavelengths and through tiny apertures, but these methods have their own built-in limitations, including damage to the aperture itself.

Novotny and Hartschuh sharpen a gold wire to a point just a few billionths of an inch across. A laser then shines against the side of the gold tip, inciting electrons inside it to oscillate. These oscillations create a tiny bubble of electromagnetic energy at the tip, which interacts with the vibrations of the atoms in the sample. This interaction, called Raman scattering, releases packets of light from the sample at specific frequencies that can be detected and used to identify the chemical composition of the material.

In about two years, Novotny and Hartschuh think they will be able to refine the system, already with a resolution of 20 nanometers (billionths of a meter), so that they can image proteins, which are only 5 to 20 nanometers wide. To do that they will try to get the point of the gold tip sharper still, or even experiment with different shaped points. Then the trick will be keeping the tip “alive,” meaning using it without incurring the least damaging bump or scrape-a difficult task when hovering only a few nanometers above the scanned sample. If all goes well, the research team may try to push the technology even further to derive first-ever optical images of smaller molecules.

The research was supported by a grant from the National Science Foundation.