Electrochemical detection methods have been popular in the medical diagnostics field. Several well-known devices such as the self-monitoring blood glucose meter have relied on electrochemical techniques for their sensitivity, and ability to make direct measurements without optical labels. Currently, no point-of-care or handheld diagnostic tool exists to quantify the severity of a traumatic brain injury (TBI). We have shown that enzymatic detection of norepinephrine (NE), a biomarker which can indicate TBI severity, using impedance-based electrochemical techniques can achieve the required sensitivity, ~100 pg/mL. Furthermore, the first steps have been taken to quantify NE in whole blood solutions and to optimize the technique for a handheld device.