Research Project
2656506
DESCRIPTION (Adapted from Applicant's Abstract): The investigators will build a fiber optic sensor for measuring Zn2+ in biological fluids, with emphasis on the extracellular fluid of the brain. This zinc sensor will be useful for basic research as well as for the particular clinical application of monitoring intracerebral zinc in head-injured patients at risk for zinc-induced neuron death. Mounting evidence indicates that synaptically-released Zn2+ contributes to the death of neurons in ischemia, stroke, convulsions, and (according to our new data) traumatic head injury. All of these conditions involve co- release of massive amounts of Zn2+ and glutamate, a cell-killing combination. Early detection of such zinc+glutamate "flooding" in hospitalized brain-injured patients could allow rapid therapeutic intervention, reducing neuron loss. To create zinc sensors, the investigators will use a new ion-sensing technology developed for oceanography. The new technique ("EnZin") uses a zinc-dependent native enzyme for detecting zinc. MicroFab's biochip and micro-optical fabrication methods will be used to adapt this enzymatic method to a minimally-invasive, implantable ion-sensor for rapid, on-line monitoring of zinc in vivo. Extensions of the technology can potentially deliver subminiature, multi-element, multi-antigen fiber optic probes. In Phase I, they will establish proof-of-principle, detection limits, and calibrations. Phase II will conclude with a prototype sensor for pre- market alpha testing in animals. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE
