Circadian rhythms are endogenous self-sustained oscillations with 24h periods that regulate diverse physiological processes. Disruption of circadian rhythms is the first sign in patients with sleep disorders and it is used as diagnostic tool for these patients. Saliva melatonin measured in dim light conditions (DLMO) is a validated biomarker of circadian function used routinely in the Psychiatry and Sleep clinics worldwide. Current protocols for measuring DLMO require that patients remain in a specialized clinic for 24hrs and spit saliva in a tube every 30-60 min. However, because patients need to remain awake for 24hrs melatonin measurements in a hospital clinic setting are relative inaccurate because of sleep deprivation during the test period. Furthermore, patient hospitalization dramatically increases the costs of testing melatonin and decrease patient compliance for accepting the test. The overall focus of this project is to design and validate a novel multi-reservoir collecting saliva device that will allow to measure accurately DLMO levels and phase in a home setting.
Our specific aims are to design, fabricate and validate a Saliva Micro-Array Retainer (SR) to achieve multi-point passive saliva collection. This will allow accurately measurement of DLMO without the need of hospitalization. Our research is significant because will facilitate the utilization of DLMO measurements for sleep disorders and psychiatric patients. An increasing number of diseases is also linked to circadian clock dysregulation including autoimmune diseases (diabetes type I, rheumatoid arthritis, etc.) as well as different types of cancer where measurement of DLMO can become a key biomarker. These devices can also be used in the future for measuring a variety of other validated saliva biomarkers that are subject to circadian variation. In fact, over 50% of known saliva proteins are subject to significant daily variations and are direct targets of the circadian clock. With modifications (adaptation of a colorimetric assay in each chamber), SR has also a great potential to be adapted in the near future as a real time 24hrs monitoring device for all saliva biomarkers. This clinically oriented study is performed by an experienced multidisciplinary team including Drs. Petros Papagerakis (salivary function and circadian rhythms biologist), Chronis (mechanical engineering and MicroElectroMechanical Systems expert), Silvana Papagerakis (oral medicine specialist in clinical circadian research including patient recruitment in clinical trials), and Uswak (a senior oral health epidemiologist).

Public Health Relevance

The circadian clock is an endogenous mechanism that regulates our body?s functions such as sleep/wake status, saliva flow, metabolism, immunity, and hormone release. Several psychiatric diseases and sleep disorders are caused, at least in part, by malfunction of circadian clocks as documented by measuring saliva melatonin. However, the current available tests are expensive and require several 24hrs hospitalizations. Our aim is to manufacture a cost-effective personalized device that can collect saliva in real time for precise no invasive analysis of melatonin levels and phase changes to support diagnosis and treatment monitoring of these patients.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZDE1)
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Lopez, Orlando
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University of Michigan Ann Arbor
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Biomed Engr/Col Engr/Engr Sta
Ann Arbor
United States
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