SBIR-STTR Award

We will build implantable, fiberoptic, zinc sensors for neurology and neuroscience. These sensors will utilize proprietary, genetically engineered proteins (on optical fibers) to provide real-time monitoring of intracranial Zn2+. The sensors are needed both for basic research on zinc-containing neurons and in the emergency room/ICU for monitoring acutely brain-injured patients. Monitoring intracranial Zn2+ is clinically important because the Zn2+/- ion is a contributing cause of excitotoxic neuron injury. In head trauma, ischemia, and seizures, merely chelating extracellular zinc substantially reduces the number of neurons showing degenerative changes after the insult. Our clinical zinc sensor is designed to be inserted through a ventriculostomy, beside the traditional intracranial pressure probe. In acutely brain-injured patients, rising levels of Zn2+ would alert surgical, ER or ICU staff to intervene aggressively with zinc-release blockers, zinc chelators, zinc channel blockers, or other therapies against zinc-mediated neurotoxicity. For the basic neuroscience laboratory, our fiberoptic sensors will allow the real-time monitoring of the synaptic release of zinc into the extracellular milieu. Just as older methods for monitoring transmitter release (voltametry, microdialysis) revolutionized our understanding of classical transmitters, so too can optical monitoring of Zn2+ release inform our understanding of zinc-modulated synaptic function.

We will deliver to basic and clinical neuroscientists the tools they need to measure "free" (rapidly- exchangeable) zinc in biological fluids. As it turns out, the health of brain tissue in vivo or in vitro is just as sensitive to the free zinc concentration, or "pZn," as it is to the free proton concentration, or "pH." We have developed the first, practical pZn Meter, a fluorimetric instrument, with both in-cuvette and optical fiber probe measuring modalities. Our customers will include: (i) neuroscientists interested in synaptic and intracellular zinc signaling, (ii) clinicians treating victims of stroke, head trauma, cardiac arrest, and seizures, where zinc is now understood to be one of the worst of the toxins injuring brain cells, and (iii), biologists growing or studying cells in vitro who want to monitor (and control) the pZn of their media. Collectively, these markets represent about 80,000 customers, with consumables of ~ $500/yr (scientists) to ~$10,000/yr (clinicians). In Phase I, we built prototype, fluorimetric zinc measurement tools, and we used them to establish the value for physiological pZn in the brain (7.7 +/- 0.3). In Phase II we shall capitalize on our knowledge of the physiological value of pZn and our access to proprietary zinc-sensing fluorescent molecules and: (i) complete development of a solution-based fluorimetric pZn Meter, "tuned" to measure physiological pZn, (ii) develop and optimize cuvettes with the zinc-sensing fluorescent molecules attached to the walls, for "semi-automatic" pZn determinations, (iii) develop an evanescent wave illumination for the cuvette, so that the fluorimetric zinc assays can be done even with "dirty" solutions in the cuvette, (iv) adapt the evanescent wave+ surface assay to an optical fiber "zintrode," (v) perfect the attachment and sensing chemistry on zintrodes so that they can be used for medium-term (days-weeks) in situ recording of intracranial pZn