A novel approach - electrical wiring of redox enzymes - provides a potentially powerful method of directly electrically sensing glucose, lactate and other oxidizable biomolecules. Biosensors based on the wired enzymes that were made in our laboratory show the following advantages: (a) no leachable components; (b) insensitivity to variation in the partial pressure of oxygen; (c) insensitivity to interferants such as ascorbate, urate, acetaminophen and bilirubin achieved through preelectrooxidation of the interferants; (d) miniaturization to 3microm electrode diameter and 20microm overall diameter; (e) 3-day stability in buffer with less than 5% signal variation; (f) subsecond response time; (g) high signal level at physiological biochemical concentration, e.g. 2mAcm-2 current density at 5mM glucose; (h) simplicity of production. Potential advantages are (1) applicability of mass manufacturing methods used in the fabrication of microelectronic components; (2) small and lightweight associated electronics. The wired enzyme electrodes have never been applied to medically important problems. In the first examination of the generality of the medical relevance of this approach we propose to develop (1) subcutaneously implantable glucose probes of <100microm diameter; (2) two neurosurgical tools; the first, a binary amperometric probe of 1mm diameter for simultaneous measurement of arterial and venous concentration of oxygen and lactate; and the second, a 200microm diameter microprobe for measuring lactate in the spinal fluid.
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