Probing Hidden Chemistries with Light

Scott McCain (left) and David Bradyby Monte Basgall
As part of a new computerized approach to chemical analysis, researchers at the Fitzpatrick Institute for Photonics are developing a way to use near-infrared laser beams as probes to measure levels of alcohol in a person's bloodstream.
The method could prove to have a number of advantages over conventional breathalyzers, according to Scott McCain, a graduate student working on the project.
"Unlike with breathalyzer examinations, with our sensors the subject doesn't have to be awake and aware," he said. "So an unconscious person could be brought into a hospital emergency room and, in 10 seconds, our approach could reveal how much alcohol -- or cocaine, marijuana or anything else -- is present in the person's bloodstream."
So far, the group has successfully used the approach to detect alcohol in a test liquid that duplicates the optical effects of passing a laser beam through human skin. McCain reported the findings in the June 2006 issue of the journal Applied Spectroscopy.
"We've also started doing some studies in rats and mice," he said. "We eventually want to do human studies, where we would shoot a laser beam into a person's arm and analyze the scattered light that comes out."
Measuring alcohol levels via blood testing remains the "gold standard" for sobriety testing, McCain acknowledged. "But clinical testing is obviously very invasive, and it's also not very practical for continuous monitoring," he said. "So we think our system, when perfected, would offer some practical advantages."
The group also sees potential for using the technique to detect a variety of other substances of medical interest, such as glucose or cholesterol, in a person's bloodstream. "If we can fully develop this technology, it would have lots of applications," McCain said.
Another goal, he said, is to make their detectors "cheaper and smaller and use less power."
The photonics center research group in which McCain works is led by David Brady, the Addy Family Professor of Electrical and Computer Engineering at the Pratt School of Engineering.
Brady sees the work in detecting alcohol as just an initial phase of his group's broader research thrust to harness the power of computers to extract unusually precise information from extremely low levels of light.
"We feel like we've developed a very general sensing approach that allows much more accurate molecular or chemical analysis," he said. "For example, we could make a map of chemicals in body tissues and determine where pathologies are occurring. We're also working on techniques like real-time analysis of the dynamics of molecules in a cell."
A key to their approach is an unusually complex form of spectroscopy, a general technique that scientists use to decipher chemical details about materials by decoding the ways substances interact with light waves.
"What we've discovered is a new analytical method for doing spectroscopy," said Michael Gehm, a postdoctoral investigator with Brady's group who led a feasibility analysis of the technology. Gehm reported the findings in the May 1, 2006, issue of the journal Applied Optics.
In a normal spectrometer, light is passed through the material to be analyzed, where it interacts with the substances' atoms and molecules. The modified light is then separated into a spectrum of component wavelengths (colors) in the same way that sunlight passing through water vapor in the air produces a rainbow.
The light typically is forced through a narrow slit, then its different wavelengths are separated using a device called a "diffraction grating", which spreads the light apart based upon its wavelength. The light is then focused onto a digital camera where every pixel of the camera measures a different wavelength.
But slit-based spectrometers are inadequate for the kind of analysis Brady and his colleagues are focusing on, because the emerging light is too dim and diffused.
For example, the researchers' prototype alcohol detector uses spontaneous Raman spectroscopy, a technique developed nearly a century ago. This method makes use of less than 1 percent of the laser light that is scattered by the sample. That small portion of light, however, is scattered in a very unique way by the various molecules in the sample material.
"The light gives a kick to the molecules and sets them vibrating, which changes the energy of the light," said McCain. Those changes reveal themselves as different telltale lines of color. The lines are so specific that "the patterns for various different compounds -- for example, ethyl alcohol, glucose, Tylenol and hemoglobin -- are all going to be different," he said.
While Raman spectroscopy can thus provide unusually precise analytical information, the light signals it processes are "inherently very weak," McCain added.
That weakening has a number of causes. The incoming laser beam must first pass through the skin in order to stimulate a Raman effect among molecules of alcohol or other substances in the bloodstream. The much-dimmer Raman light fomented by that laser beam must then pass through internal tissues again to reach a spectroscopic detector back outside the body.
During that torturous passage, "light bounces around and becomes difficult to work with," McCain said. That's because skin contains a variety of different kinds of cells in a matrix of water, and each cell has its own unique optical properties than can make the resulting light signals difficult to read, he said.
If such weak and scattered light is analyzed with a standard slit-type spectrometer, it is impossible to force the light into the narrow slit. Even a tightly focused laser beam is scattered thousands of times by the tissue making it a difficult to measure. "It becomes this big blob," McCain said.
To get around these problems, the group has replaced a slit-style spectrometer with one that incorporates a complicated two-dimensional patterned mask. This allows the spectrometer to handle 10-100 times the amount of light than with a slit-based system. After some processing on the computer to decode the measured image, a spectrum with sharp peaks is recovered.
By a clever choice of masks, reconstructions of the spectrum can be done in less than a second on an average desktop computer. The enhanced sensitivity gained by the increased light throughput can lead to systems of greater sensitivity, lower power, lower exposure times, more inexpensive components, or a combination of these based on the design.
Because it uses such pinpoint computer analysis, the group's technology also provides the equivalent of digital control, Brady said. "What you really want is a digital chemistry platform, and we've gone a long way toward developing that," Brady added.