Development of an electrochemical impedance spectroscopy based biosensor for detection of ubiquitin C-Terminal hydrolase L1

Year over year, the incidence of traumatic brain injury (TBI) in the population is dramatically increasing; thus, timely diagnosis is crucial for improving patient outcomes in the clinic. Ubiquitin C-terminal hydrolase L1 (UCH-L1), a blood-based biomarker, has been approved by the FDA as a promising quantitative indicator of mild TBI that arises in blood serum shortly after injury. Current gold standard techniques for its quantitation are time-consuming and require specific laboratory equipment. Hence, development of a hand-held device is an attractive alternative. In this study, we report a novel system for rapid, one-step electrochemical UCH-L1 detection. Electrodes were functionalized with anti-UCH-L1 antibody, which was used as a molecular recognition element for selective sensing of UCH-L1. Electrochemical impedance spectroscopy (EIS) was used as a transduction method to quantify its binding. When the electrode was incubated with different concentrations of UCH-L1, impedance signal increased against a concentration gradient with high logarithmic correlation. Upon single-frequency analysis, a second calibration curve with greater signal to noise was obtained, which was used to distinguish physiologically relevant concentrations of UCH-L1. Notably, our system could detect UCH-L1 within 5 min, without a washing step nor bound/free separation, and had resolution across concentrations ranging from 1 pM to 1000 pM within an artificial serum sample. These attributes, together with the miniaturization potential afforded by an impedimetric sensing platform, make this platform an attractive candidate for scale-up as a device for rapid, on-site detection of TBI. These findings may aid in the future development of sensing systems for quantitative TBI detection.