SERS Advances Disease Diagnosis

Scientists at Duke University have developed a new noninvasive optical technique that uses a laser to peer into the genetic material of cells, enabling the detection of early-stage cancer and other diseases.

The method uses metallic nanoparticles dubbed “molecular sentinels” to advance the technique known as surface-enhanced Raman scattering, or SERS. Leading the Duke team was Tuan Vo-Dinh, who has pioneered the practical application of SERS over the past 20 years. He is the R. Eugene and Susie E. Goodson Distinguished Professor of Biomedical Engineering and director of The Fitzpatrick Institute for Photonics at Duke University.

"[Laser technology] is capable of yielding the critical information bridging molecular structure and physiological function, which is the most important process in the understanding, treatment and prevention of disease,” Vo-Dinh said.

He and his colleagues from Duke have attached the "molecular sentinels" to snippets of DNA to detect early signs of disease at the DNA and RNA level. When light is directed at samples from the cell, the nanoparticle can “report” back about the conditions inside.

When laser light is directed at a sample, the target molecule vibrates and scatters back its own unique light, often referred to as the Raman scatter. Typically, this Raman response is extremely weak. However, when the target molecule is coupled with a metal nanoparticle, the Raman response is greatly enhanced by the SERS effect -- often by more than a million times, Vo-Dinh said.

“This technology can be used to directly detect chemical species and biological species with exquisite sensitivity, or to monitor the environment inside single cells,” Vo-Dinh said. “Put another way, the nanoprobes play the role of molecular sentinels patrolling the sample solution by switching their warning light on and off when a significant event occurs.”

Using this approach, researchers have already been able to “read” the gene sequences of infectious agents such as HIV and the early biomarkers of other diseases, such as the BRCA1 and ERB2 breast cancer genes.

Duke researchers also have developed optical sensors that, when excited by laser light, can probe physiological parameters, including pH levels, biochemical markers such as cancer-causing metabolites attached to DNA, and molecular pathways such as apoptosis.

“These nanosensors are leading to a new generation of tools that can detect the earliest signs of disease at the single-cell level in a systems biology approach and have the potential to drastically change our fundamental understanding of the life process itself,” Vo-Dinh said.

Duke bioengineers have already developed methods for using light, including lasers, for performing biopsies without actually having to remove any tissue from patients. Known as laser-induced fluorescence, physicians can use the technique to spot precancerous or cancerous cells simply by shining light from the fiber tip inserted into an endoscope, for example, during a routine procedure in the gastrointestinal tract.

“We are also studying the use of laser-induced fluorescence to detect other types of cancer as well, such as that of the skin and brain,” Vo-Dinh said. “These optical biopsy technologies could revolutionize medical diagnostics since the measurements are performed in a matter of seconds, and no tissue needs to be removed.”

For more information, visit: www.duke.edu