Diagnostics & Imaging Week

Researchers at Purdue University (West Lafayette, Indiana) are working on the development of what the university calls a new type of "ultra-sensitive" medical imaging technique using tiny nanorods which have gold as their major component.

Ji-Xin Cheng, an assistant professor of biomedical engineering at Purdue, said in an e-mail response to Diagnostics & Imaging Week that nanorods have actually been studied for about 10 years. But, he added: "We are the first to discover that nanorods [have] a very strong two-photon luminescence. This makes nanorods a new imaging agent."

The findings were detailed in a research paper that appeared online in mid-October in Proceedings of the National Academy of Sciences. The paper was written by researchers in Purdue's Weldon School of Biomedical Engineering and the Department of Chemistry.

The technique works by shining a laser through the skin to detect the gold nanorods which are injected into the bloodstream. In tests with mice, the nanorods yielded images nearly 60 times brighter than conventional fluorescent dyes, including rhodamine, which the university said is commonly used for a "wide range of biological imaging to study the inner workings of cells and molecules."

The gold rods are about 20 nanometers wide and 60 nanometers long, or roughly 200 times smaller than a red blood cell, the university said.

Cheng wrote that the researchers use a two-photon fluorescence microscope, excitation with a femtosecond Ti: sapphire laser to view the nanorods.

Although it "may take some time" before the nanorods can be tested in humans, according to Cheng, their use represents a possible way to overcome barriers in developing advanced medical imaging techniques that use light to analyze blood vessels and underlying tissues. The gold nanorods fluoresce red.

"One obstacle is that light visible spectrum does not pass through tissue very well," said Alexander Wei, an associate professor of chemistry who worked with Cheng and other Purdue researchers, including Philip Low, a professor of chemistry.

The university in a statement said that imaging methods might be developed using laser pulses in longer wavelengths of light, beyond the visible range in a region of the spectrum called near infrared. Purdue said the gold nanorods are "ideal" for a type of imaging called two-photon fluorescence, which it said "provides higher contrast and brighter images than conventional fluorescent imaging methods."

"There is a window of light in the near infrared wavelengths from about 800 to 1,300 nanometers, which could be harnessed for new imaging technologies," Wei said.

The gold rods with a certain "aspect ratio" of length to width shine brightly when illuminated by light in that spectral region.

Photons are the individual particles that make up light, and in two-photon fluorescence, two photons hit the nanorod at the same time. Because of the two-photon effect, the method might enable scientists to develop advanced "non-linear optical techniques" that could provide better contrast than conventional technologies.

Cheng said that while these methods may ultimately not prove to be better, the gold nanorods clearly have "some unique advantages."

"First, the TPL is very strong, as strong as semiconductor nanoparticles," Cheng wrote. "Second, being different from [a] semiconductor, gold is non-toxic. [Third], there is neither photobleaching nor photoblinking, which other imaging agents may suffer from."

"To be able to detect cells at an early stage of disease such as cancer, it is important to have a reliable technique that has sensitivity at the single-particle level," Wei said. "The gold nanorods demonstrate that Cheng's non-linear imaging methods are capable of this level of detection."

The research has been funded by the National Institutes of Health (Bethesda, Maryland).