Universal, Ultra-low Volume Cortisol Biosensor: From Point-of-care to Point-of-need Applications




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Frequent shift work by an individual causes disruption of the circadian rhythm and potentially, in the long run, result in increased health risks. Current biomarkers evaluating the presence of circadian rhythm disturbance include melatonin, cortisol, and monitoring body temperature. This requires 24- hour monitoring and as some of techniques like body temperature evaluation are indirect measures of the disturbances, they are often inconclusive. Therefore, it is imperative to design diagnostic sensors for rapid and non-invasive monitoring of biomarkers associated with circadian rhythm cycles. In this work, we have developed a hybrid flexible biosensor comprised of an aqueous and ionic interface integrated onto metallic gold microelectrodes for rapid and noninvasive monitoring of cortisol. This electrochemical sensor is calibrated for detection across multiple bio-fluids. Room temperature ionic liquid (RTIL), BMIM[BF4] (1-Butyl-3-methylimidazolium tetrafluoroborate) was used as the buffer to modulate the electrical double layer (EDL) to enhance the electrochemical signal response of the sensor. The sensor design and the surface chemistry were optimized using COMSOL simulations and FTIR (Fourier-transform infrared spectroscopy) respectively. Cortisol detection was achieved in the physiologically relevant ranges when tested in serum, blood, sweat, and, saliva using non-faradaic Electrochemical Impedance Spectroscopy (EIS) and performance parameters of the sensor were measured. The sensor’s response was tested against the only commercially available, salivary cortisol, point-of-care kit using regression analysis. Cross-reactive studies using prednisone indicated that the sensor is specific for cortisol. The sensor displayed a correlation value i.e. R2 > 0.95 between the signal response and the concentration of cortisol present in the system. Dynamic range of the sensor was across the physiologically relevant range of cortisol i.e.50-200 ng/mL for serum/blood, 1-40 ng/mL for saliva, and 10-150 ng/mL for sweat. Limit of detection for serum and sweat was 10 ng/mL and 1 ng/mL for saliva. In addition to this, we have also demonstrated that BMIM [BF4], can be used to modulate pH instability of buffers, sweat, urine, and saliva. We have observed that the sensor dynamics are conserved over the pH range of 4 through 8 in synthetic sweat, saliva, and urine. Our approach addresses the challenges associated with the variability of body buffer chemistry and its impact on monitoring cortisol.



Circadian rhythms, Impedance spectroscopy, Biosensors, Shift systems, Cortisol



©2019 Sayali Salil Upasham. All rights reserved.