Tuesday, August 12, 2008

New Oral Fluid Technology for Cancer Detection

Source: ZD Net

Sensors to detect oral cancer in saliva
Posted by Roland Piquepaille @ 10:10 am

Categories: Health & Medicine, Engineering & Innovation

Tags: University Of California At Los Angeles, Team, Researcher, Protein, Sensor, Molecule, Cancer, Protein Sensor, Dr Wong, Team Management

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According to the American Cancer Society (ACS), there will be about 35,000 new cases of oral cancer in the U.S. this year. The ACS also estimates that ‘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.’ This is why a team of University of California at Los Angeles (UCLA) researchers supported by the National Institute of Health (NIH) has developed a very sensitive optical salivary sensor. Clinical tests should start soon. A simple and fast saliva test in your dentist office might one day replace blood tests and even biopsies. But read more…

You can see on the left “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.” (Credit: UCLA, via MIT’s Technology Review)

This sensor has been developed by Chih-Ming Ho, a professor of engineering at UCLA and several colleagues of the UCLA Micro Systems Laboratories, including researchers Leyla Sabet and Winny Tan. David Wong, professor of oral biology, and several members of his lab were also involved in this project.

According to the NIH news release, “the sensor can be integrated into a specially designed lab-on-a-chip, or microchip assay, and preprogrammed to bind a specific protein of interest, generating a sustained fluorescent signal as the molecules attach. A microscope then reads the intensity of the fluorescent light — a measure of the protein’s cumulative concentration in the saliva sample — and scientists gauge whether it corresponds with levels linked to developing disease.”

And is this optical sensor successful? “In their initial experiments, the scientists primed the optical protein sensor to detect the IL-8 protein, which at higher than normal concentration in saliva is linked to oral cancer. Using saliva samples from 20 people — half healthy, the others diagnosed with oral cancer — the sensor correctly distinguished in all cases between health and disease. Importantly, the sensor achieved a limit of detection for IL-8 that is roughly 100 times more sensitive than today’s blood-based Enzyme-Linked ImmunoSorbent Assay (ELISA) tests, the standard technique to measure protein in bodily fluid.”

Now, let’s turn to a Technology Review article, “Spit Sensor Spots Oral Cancer” (Brittany Sauser, August 6, 2008) to learn why it has been difficult to detect oral cancer biomarkers in saliva.”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.”

And what was Ho’s team next step? “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 lower signal-to-noise ratio, allowing them to detect lower concentrations of the cancer biomarker. Indeed, Ho says, the device is 100 times more sensitive than the standard protein-detection technique, ELISA.”

This research work has been published in Biosensors and Bioelectronics under the title “Optical protein sensor for detecting cancer markers in saliva” (Volume 24, Issue 2, 15 October 2008, Pages 266-271). Here is a quote from the abstract. “The ultra sensitive optical protein sensor presented in this paper has a wide number of applications in disease diagnoses. Measurements for detecting biomarkers in clinical sample are much more challenging than the measurements in buffer, due to high background noise contributed by large collections of non-target molecules. We used clinical saliva samples to validate the functionality of the optical protein sensor. Clinical detection of disease-specific biomarkers in saliva offers a non-invasive, alternative approach to using blood or urine.”

If you’re interested by this subject, you also should read a very good article coming from an unusual source, “On the tip of your tongue” by Anne-Marie McQueen (The National, United Arab Emirates, July 26, 2008). This article is more focused on David Wong’s research. “He and his team have already developed a saliva test for oral cancer and Sjogren’s Syndrome, a systemic disease in which the body’s immune system attacks the glands that produce saliva and tears. Dr Wong says they have promising early evidence that it will be possible – perhaps even within five years – to use saliva to detect biomarkers for more systemic diseases, like breast, lung and pancreatic cancers, as well as diabetes.”

And even if you like needles — which I don’t — “the benefits of saliva testing versus blood sampling or more invasive diagnostic tests are many, says Dr Wong. Saliva testing is easier, safer and less intrusive. Since its testing does not require specially trained personnel, there is no risk of exposing anyone to blood-born diseases. Also, oral fluids do not clot like blood, so they not require the same level of manipulation.”

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