Sandia Handheld Instrument Assesses Dental Disease

April 23, 2007 // Published as a news service by IHS

Using a disposable lab-on-a-chip cartridge, the device makes use of a molecular sieve made out of a polyacrylamide gel.

The location of the sieve in the microfluidic chips is determined using photo-lithographical methods adapted from the semiconductor industry.

A "lab on a chip" refers to an entire laboratory on an area the size of a computer chip, requiring only minute amounts of material to perform automated chemical analysis, said Sandia.

The gel is porous, with very small openings. A low electrical current measured in micro-amps is passed through the gel and a process called electrophoresis moves charged proteins through it, according to Sandia.

The gel has a gelatin-like consistency and, by permitting the easy passage of smaller molecules and slowing the passage of larger ones, quickly separates proteins contained in the saliva.

Prior to this separation, the proteins are brought into contact with specific antibodies chosen on their ability to bind to the biomarkers. The antibodies are pre-labeled with fluorescent molecules attached to them.

Interrogation by laser of these combined molecules - fluorescent antibody and fluorescent antibody bound to the biomarker - determines the amount of biomarker present, indicating the degree of periodontitis.

"The gold standard for any medical test is when instruments are used to examine human patients," said Sandia researcher Amy Herr.

"The pilot study allowed us to compare our results to accepted clinical measurements. Then we could statistically validate both the periodontal disease biomarker and the new microfluidic instrument. We achieved faster and more reproducible results because we combined steps that ordinarily require time-consuming manual handling by many people, into a single automated device."

Because the amount of sample fluid needed for testing is so small, Herr said she sees further applications in other disease areas - including potentially improved diagnosis of prostate and breast cancer - as well as rapid measurements of serum in animal models employed in vaccine development research.

"This technology also has great promise for Sandia's efforts in homeland defense," said Sandia researcher Anup Singh. "We have ongoing efforts to use the diagnostic platform to detect biotoxins and other markers in bodily fluids to be able to diagnose exposure to a biological agent."

While components of the saliva-detection technique were reported earlier by Sandia, this is the first comprehensive study of Sandia's integrated clinical method.

Aiding dental practitioners, the pocket-sized device measures the state of biomarkers to determine how much the disease has been set back. Its progress may be cloaked, silently advancing or retreating without showing any signs, according to Sandia.

"Periodontitis can be episodic in nature," said Herr. "You need to know the stage of disease progression to diagnose and treat the illness most effectively. The enzyme [biomarker] that we monitored decreased or stabilized if the treatment was working well."

Often, owing to the time and expense involved, practitioners formerly had not been able to perform extensive biochemical investigations, said Sandia.

The work, funded by the National Institute of Dental and Craniofacial Research (NIDCR) - one of 20 institutes in the National Institutes of Health - is the first application using microliters of saliva, a painlessly and easily secured fluid, said Sandia. The real-life alternative was quasi-subjective physiological measurements, such as gum recession and gum bleeding on probing, to diagnose periodontitis.

Unlike Sandia's MicroChemLab - its patented version of a lab on a chip - which reports multiple protein signatures in fluids of interest, the clinical diagnostic instrument described in PNAS is a lab on a chip designed to quantify the amount of a specific protein (or panel of proteins) present in particular biological fluids. Monitoring quantities of specific proteins makes the tool useful as a clinical diagnostic, said Sandia.

Source: Sandia National Laboratories.