SBIR-STTR Award

The purpose of this research is production and testing of a needle-implantable device for estimating long-term tissue availability of the hormone corticosterone in rats. This work contributes to the long-term goal of developing a similar device for measurement of the tissue availability of a broad range of compounds in both research and medical settings.The device operates on the diffusion-sink principle: A compartment is created in which the concentration of the compound of interest is maintained at a negligible level, by action of a binding protein with high affinity and specificity for that compound. Consequently, the compound continuously diffuses into the device at a rate that depends on its availablflty in the immediate environment and the diffusive resistance offered by the walls of the device. By measuring the accumulation of a compound by a subcutaneously implanted device over a suitable time interval, a direct estimate of its tissue availability is obtained. Compactness and high capacity are gained by using concentrated binding proteins purified by affinity chromatography.Potential applications of this device include measurement of tiine-integrated cortisol availability in clinical psychiatry for differential diagnosis of endogenous depression or melancholia.National Institute of Mental Health (NIMH)

The proposed research will test the utility in clinical psychiatric applications of a newly- developed method for measurement of the hormone cortisol. The new method uses an ultraminiature device, installed in the mouth of a subject, to continuously accumulate cortisol from the saliva. The rate of accumulation at any moment directly reflects the availability of this hormone to tissue. The total accumulation over some time (1 to 10 h) reflects the time integral of cortisol availability to tissue. This is advantageous since cortisol levels in the circulation and in the saliva fluctuate widely over short time intervals, and less than 10% of cortisol in blood is actually available to tissue. The new method represents both the most direct and the least invasive way of determining the actual degre of tissue exposure to cortisol. Brain hyperexposure to cortisol is implicated in the etiology of some forms of depression, and is thought to accompany sleep disorders, cognitive deficits, and psychotic features of depression. Further, abnormalities of cortisol regulation occur in a state-dependent way in depression, so that monitoring cortisol regulation regularly may allow prediction of the clinical course of the disease. If the new method proves to have diagnostic or predictive utility in psychiatry, widespread clinical use and commercial success are expected.National Institute of Mental Health (NIMH)