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Skirting Light's Traditional Limit

By Robert M. Frederickson

May 12, 2005 |  Small is big in today’s biology. New research is breaking traditional barriers that limited the ability to use optical microscopy to detect features with dimensions similar to or greater than visible light wavelengths and new nanomaterials are allowing us to detect vanishingly small levels of molecules of interest.

While conventional light-based imaging methods are limited to about 200 nanometers, the new work suggests that a combination of illumination, detection and computing technologies can circumvent this limitation. National Institute of Standards and Technology (NIST) research suggests a newfangled version of the optical microscope might be able to image features down to 10 nanometers — a mere fraction of the wavelength of visible light and within the realm of molecules and atoms.

NIST scientists used violet light with a wavelength of 436 nanometers to image features as small as 40 nanometers, about five times smaller than possible with conventional optical microscopy. Called phase-sensitive, scatter-field optical imaging, the computer-intensive technique uses a set of engineered light waves optimized for particular properties (such as angular orientation and polarization). How this illumination field — engineered differently to highlight the particular geometry of each type of specimen — scatters after striking the target can reveal the tiniest of details.

Patterned structures, both solid-date and biological, are particularly sensitive to imaging by this technique, suggesting potential applications for the manufacturing of chips and other nanoscale products. Work is underway to extend the technology to less-structured elements. “It is quite surprising, that imaging 10 nm sized features with light 400 nm in wavelength can be done and good signal to noise achieved without great difficulty,” according to project leader Rick Silver.

In other recent work published in the Proceedings of the National Academy of Science, researchers have found that tailored nanoparticles, known as nanoshells,  enhance chemical sensing sensitivity by as much as 10 billion times. These particles can be 10,000 times more effective at Raman scattering than traditional methods.

Raman scattering is used by chemists, medical researchers and those involved in drug discovery to determine the chemical makeup of a compound of interest. When light hits a compound, a small fraction of the light that is scattered interacts in a way that can provide clues to chemical makeup.

Nearly thirty years ago it was found that a roughened metallic surface could enhance the weak sensitivity of Raman scattering by a factor of a million. But this so-called “surface-enhancement effect” was difficult to control and reproduce. Researchers have now shown that metallic nanoshells can overcome these problems. Lead researcher Naomi Halas, of Rice University, noted the nanoshells were effective in magnifying the Raman signal of the analyte, and also were found to act individually as an independent Raman enhancer.

About the size of a virus, the spherical nanoshells are made up of a core of nonconducting glass covered by a metallic shell, typically either gold or silver. The metal shell “captures” passing light and focuses it, a property that directly leads to the enormous Raman enhancements observed. Importantly, the thickness of the metallic sheath of the nanoshells can be varied, allowing the particles to be tuned for light of specific wavelengths.

Discovered by Halas at Rice in the 1990s, nanoshells are already being developed for applications including cancer diagnosis, cancer therapy, diagnosis and testing for proteins associated with Alzheimer’s disease, drug delivery and rapid whole-blood immunoassay. Nanospectra Biosciences was formed in September 2001 to commercialize life science applications of Nanoshells.
The finding that individual nanoshells can greatly enhance the Raman effect opens the door for biosensor designs that use a single nanoshell, something that could prove useful for engineers who are trying to probe the chemical processes within very small structures such as individual cells, or for the detection of very small amounts of a material, like a few molecules of a deadly biological pathogen or noxious chemical agent.

Robert M. Frederickson is a biotech writer based in Seattle. E-mail:

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