Characterization of Surface and Bulk Properties of an Electrochemical Biosensor for Reliable Detection of Inflammatory Biomarkers
Authors: Jagannath Badrinath , Muthukumar Sriram , Prasad Shalini 
Published: February 2020

Sweat based diagnostics has gained a lot of precedence in the last few years owing to the availability of plenty of biomarkers and the compatibility for integration with semiconductor electronics as wearable devices. In this work, we leverage electrochemical aspects of a novel electrolyte system to develop a robust biosensor for the detection of inflammatory biomarkers in sweat for real-time monitoring during an inflammation. Sweat contains pro and anti-inflammatory cytokines, whose levels can be monitored to aid for monitoring the prognosis and recovery during an inflammation. Two well-known inflammatory biomarkers, interleukin-6 (IL-6) and interleukin-10 (IL-10), that are pro and anti-inflammatory respectively, have been chosen for this study for monitoring inflammatory levels in real-time. Typically, the levels of pro-inflammatory cytokines increase rapidly with the onset of an inflammation while the levels of anti-inflammatory cytokines increase at a later stage to suppress the levels of pro-inflammatory cytokines. In order to achieve robust sensor metrics, the sensor surface has been engineered through the use of novel electrolyte system called room temperature ionic liquid (RTIL) for achieving highly sensitive electrochemical response to the target analyte of interest. RTIL encapsulates the capture probe antibody, thereby, providing a signal response only to the specific target biomolecule. Furthermore, RTILs enhance the electrochemical response of the electrode/biomolecular interface by forming a compact electrical double layer (EDL), thereby, tuning the EDL for sensitive and specific detection of target analyte. The modulation of the EDL interface due to biomolecular interaction can be captured as surface effect phenomena which is reflective of direct quantification of the biomolecular concentration. These surface effects are distinguished from the bulk effects in impedance spectroscopy. The RTIL prevents non-specific interaction by forming a surrounding around the capture probe, thereby, any changes in signal is captured as bulk phenomena and not a surface interaction, which typically is the measuring signal for specific capture probe-analyte interaction. A limit of detection of 0.2 pg/mL has been achieved for pro-inflammatory cytokines with a dynamic range of 0.2- 200 pg/mL. Specificity tests demonstrated no/minimal signal response that lies within the noise threshold for non-specific molecules. Furthermore, combinatorial studies of the target analyte in the presence of interferent molecules demonstrated impedance signal response specific to the target molecule, confirming the robust specificity of the sensor. Additionally, the sensor, in a wearable form-factor can monitor the levels of cytokines continuously. The developed sensor system presents new avenues in diagnostic wearables for determining the extent of inflammation by reporting concentration of pro and anti-inflammatory cytokines expressed as a ratio in real-time.