Insightful Light: Raman Spectroscopy May Offer Doctors, Dentists and Forensic Scientists a Better Tool for Molecular Detection

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From CT, PET and MRI to the original X, a vast alphabetical arsenal of tools tells doctors what is going on inside the body. But despite their successes, these tools often fail to detect the subtle changes that signal the imminent onset of illness. Mischief at the molecular level often evades doctors' current imaging and detection abilities. So for sensing such changes, biomedical scientists are taking a tip from chemists. Using a method known as Raman spectroscopy, medical detectives are moving ever closer to exploiting the power of light to improve disease detection.


Long used in labs, spectroscopy employs light and other types of electromagnetic radiation to analyze matter. The various spectroscopic techniques reveal a molecule's unique chemical fingerprint by measuring the wavelengths of light that the molecule absorbs or emits, or by tracking how radiation scatters after interacting with a molecule. For 30 years, scientists have been eager to harness the power of Raman spectroscopy, a type of scattering spectroscopy, to image the body at the level of individual molecules. The method holds promise for pinpointing the beginnings of dental cavities and tumors. And it could even help forensic investigators nab killers sooner by lifting latent fingerprints from corpses.

A variety of researchers, from dentists and doctors to chemists, now report some of the first successes using Raman spectroscopy to probe chemicals and minerals within and on living--and dead--bodies. "Raman spectroscopy is a very powerful tool," says Cristina Zavaleta, a molecular imaging radiologist at Stanford University. But, she adds, the technique still needs some time to develop.

In recent years, scientists have rapidly overcome many of the hitches holding up the widespread use of Raman-based instruments. That progress leads many to speculate that within a few years doctors and dentists could be wheeling new, Raman-based tools into the examining room, or detectives could even be driving them to the scene of a murder.

Imaging humans' insides

In Raman spectroscopy, scientists shoot a laser light at a target molecule and measure how the wavelengths of scattered light, in the form of photons, coming off the target compare with the laser's original wavelength. Only one in 10 million of the photons hitting the target shows an increase or decrease in wave-length. Detecting these rare photons is the challenge--and ultimately the payoff--for scientists seeking to harness the Raman effect for clinical applications.


The wavelength change is called the Raman effect in honor of Indian physicist Chandrasekhara Venkata Raman, who first showed in the 1920s that measuring the changes in wavelengths of scattered photons can help scientists identify a compound's molecular makeup. He won the Nobel Prize in physics in 1930 for his work. Currently, geologists, chemists and archaeologists use the technique to study minerals in the soil, identify new materials and determine the pigments in ancient paintings, manuscripts and other artifacts.

"At this point, Raman spectroscopy is good for surface scans," says David Batchelder, a Raman researcher from the University of Leeds in England. Unlike X-rays and CT scans, existing Raman tools have yet to let doctors look inside the body. "To penetrate deep into tissues," Batchelder says, "the equipment has to be very good."

But Stanford University researchers, including Zavaleta, are on track to engineer inward-probing Raman tools. The key, the scientists discovered, is in using nanoparticles. By wrapping cancer antibodies around gold nanoparticles, the team used Raman spectroscopyto detect tumors in a living mouse.

Zavaleta and colleagues injected the nanoparticles into the mouse. Each specific antibody attached to a specific type of tumor cell. When the researchers shone laser light across the animal's body, the cells with attached antibody-coated nanoparticles showed a change in wavelength compared with the laser. …