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“Periodontitis can be episodic in nature,” says 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.
The work, funded by the National Institute of Dental and Craniofacial Research — one of 20 institutes in the National Institutes of Health — is the first application using microliters of saliva, a painlessly and easily secured fluid. The real-life alternative to diagnose periodontitis has been quasi-subjective physiological measurements, such as gum recession and gum bleeding upon probing.
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 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.
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. 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. 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 for 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 disease.
Sandia authors of the study, in addition to Herr and Singh, the NIDCR project primary investigator, include Anson Hatch, Daniel Throckmorton, James Brennan, and Huu Tran, as well as Will Giannobile of the School of Dentistry at the University of Michigan, Ann Arbor.
Technical contact: Anup Singh, (925) 294-1260, aksingh@sandia.gov
Technical contact: Amy Herr, (925) 294-3738, aeherr@sandia.gov
Media contact: Neal Singer, (505) 845-7078, nsinger@sandia.gov