Tuesday, August 19, 2008

Spit Sensor Spots Oral Cancer

An ultrasensitive optical protein sensor analyzes saliva.

Analyzing spit: Leyla Sabet, a member of the UCLA research team that built the new optical protein sensor, sits in front of the device. Based on a confocal microscope, the ultrasensitive system is being used by the researchers to detect biomarkers in saliva samples that are linked to oral cancer.

For the first time, an optical sensor, developed by researchers at the University of California, Los Angeles (UCLA), can measure proteins in saliva that are linked to oral cancer. The device is highly sensitive, allowing doctors and dentists to detect the disease early, when patient survival rates are high.

The researchers are currently working with the National Institute of Health (NIH) to push the technology to clinical tests so that it can be developed into a device that can be used in dentists' offices. Chih-Ming Ho, a scientist at UCLA and principal investigator for the sensor, says that it is a versatile instrument and can be used to detect other disease-specific biomarkers.

When oral cancer is identified in its early stages, patient survival rate is almost 90 percent, compared with 50 percent when the disease is advanced, says Carter Van Waes, chief of head and neck surgery at the National Institute on Deafness and Other Communication Disorders (NIDCD). The American Cancer Society estimates that there will be 35,310 new cases of oral cancer in the United States in 2008. Early forms are hard to detect just by visual examination of the mouth, says Van Waes, so physicians either have to perform a biopsy--remove tissue for testing--or analyze proteins in blood.

Detecting cancer biomarkers in saliva would be a much easier test to perform, but it is also technically more challenging: protein markers are harder to spot in saliva than in blood. To create the ultrasensitive sensor, researchers started with a glass substrate coated with a protein called streptavidin that enables other biomolecules to bind to the substrate and to one another. The researchers then added a molecule that would catch and bind the cancer biomarker--a protein in saliva called IL-8 that previous research has proved to be related to oral cancer. They also added molecules designed to keep the glass surface free of other proteins that might muddy detection of the biomarker. To visualize the target molecules, Ho's team then added a set of fluorescently tagged proteins designed to attach to the captured IL-8 markers.

Because saliva has a lower concentration of proteins than blood does, the team needed a highly sensitive method to detect the tagged proteins among the background noise, stray molecules in saliva that also fluoresce. So the researchers used a confocal microscope--an imaging system that employs a laser to collect the light generated from a sample--to analyze the saliva. Ho and his team found that focusing the laser light on a specific part of the sample resulted in a higher signal-to-noise ratio, allowing them to detect lower concentrations of the cancer biomarker.

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