This application aims to develop a portable, diagnostic system useable by minimally trained personnel in the field for the diagnosis of pulmonary diseases using saliva as a sample specimen. The ultimate goal of the project is to create a universal platform for performing systemic diagnosis using saliva. The device will be fully integrated and self-contained. A saliva specimen will be loaded onto a disposable microfluidic card containing all the necessary components and reagents to process the sample and measure multiple clinically relevant analytes with an optical fiber microarray. The results will be read optically and reported both via a liquid crystal display and over a wireless network. Pulmonary diseases will be targeted including asthma, chronic obstructive pulmonary disease (COPD)/emphysema, cystic fibrosis, and acute pneumonia. Saliva samples from both diseased and control patients will be obtained and analyzed using a variety of fluorescent-based assays. The initial phase will be carried out in an outpatient clinic setting, where patients will be followed at regular intervals when stable and during exacerbations of their disease. Samples will be collected and analyzed at baseline and during clinically unstable conditions allowing analysis of change from baseline as well as single sample correlations with clinical status. To directly test our overall hypothesis that saliva contains substances that correlate with disease, we will also collect and analyze key representative respiratory secretions and compare these results with those obtained from salivary analysis. Analytes that correlate with disease will be selected and converted into bead-based sensors for use with optical fiber microarrays. Analytes to be examined will include DNA/RNA, proteins such as cytokines, and small molecules and ions. All sample preparation and pre-treatments will be incorporated onto a microfluidic cassette. The disposable cassette will be integrated with the sensor array, enabling many clinical parameters to be measured simultaneously. The array will be interrogated by a portable optical reader that will be designed and integrated with the microfluidic cassette and the optical fiber array. We will demonstrate efficacy of the system at the lab bench and later provide one Alpha and three Beta units to the clinical investigators for pilot studies and expanded field trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DE017788-05
Application #
7797591
Study Section
Special Emphasis Panel (ZDE1-GH (49))
Program Officer
Burgoon, Penny W
Project Start
2006-09-01
Project End
2013-02-28
Budget Start
2010-03-01
Budget End
2013-02-28
Support Year
5
Fiscal Year
2010
Total Cost
$1,895,390
Indirect Cost
Name
Tufts University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
073134835
City
Medford
State
MA
Country
United States
Zip Code
02155
Khanna, Prarthana; Walt, David R (2015) Salivary diagnostics using a portable point-of-service platform: a review. Clin Ther 37:498-504
Little, Frédéric F; Delgado, Diana M; Wexler, Philip J et al. (2014) Salivary inflammatory mediator profiling and correlation to clinical disease markers in asthma. PLoS One 9:e84449
Nie, Shuai; Henley, W Hampton; Miller, Scott E et al. (2014) An automated integrated platform for rapid and sensitive multiplexed protein profiling using human saliva samples. Lab Chip 14:1087-98
Nie, Shuai; Benito-Pena, Elena; Zhang, Huaibin et al. (2013) Multiplexed salivary protein profiling for patients with respiratory diseases using fiber-optic bundles and fluorescent antibody-based microarrays. Anal Chem 85:9272-80
Oblath, Emily A; Henley, W Hampton; Alarie, Jean Pierre et al. (2013) A microfluidic chip integrating DNA extraction and real-time PCR for the detection of bacteria in saliva. Lab Chip 13:1325-32
Nie, Shuai; Benito-Peña, Elena; Zhang, Huaibin et al. (2013) Multiplexed fluorescent microarray for human salivary protein analysis using polymer microspheres and fiber-optic bundles. J Vis Exp :
Zhang, Huaibin; Nie, Shuai; Etson, Candice M et al. (2012) Oil-sealed femtoliter fiber-optic arrays for single molecule analysis. Lab Chip 12:2229-39
Thomadaki, K; Helmerhorst, E J; Tian, N et al. (2011) Whole-saliva proteolysis and its impact on salivary diagnostics. J Dent Res 90:1325-30
Siqueira, W L; Margolis, H C; Helmerhorst, E J et al. (2010) Evidence of intact histatins in the in vivo acquired enamel pellicle. J Dent Res 89:626-30
White, M R; Helmerhorst, E J; Ligtenberg, A et al. (2009) Multiple components contribute to ability of saliva to inhibit influenza viruses. Oral Microbiol Immunol 24:18-24

Showing the most recent 10 out of 17 publications