Passive Sweat Based Electrochemical Sensor for Rapid Detection of IL-6

Abstract

Introduction: Portable, on demand biosensing has become a key element for rapid detection of disease, particularly conditions that progress rapidly, such as infections and trauma in response to injury. Severe infections or internal traumas caused by injury can rapidly progress from the moment of onset, often before a patient has started to show symptoms, leading to progressive organ damage. In order to promptly get access to treatment, rapid testing for infection/trauma is necessary for individuals who experience a physical injury. When a person undergoes a traumatic injury, the immune system releases inflammatory cytokines, such as Interleukin-6 (IL6), in response. These cytokines induce inflammation at the site of injury as a defense mechanism against infection and further injury. The inflammatory cytokines are excreted through sweat at levels detectable by an electrochemical sensor. Using a portable, sweat-collecting electrochemical sensor, we have developed a sweat-based sensor that can detect IL6 within ultralow volumes of sweat (1-5 ul) at concentrations as low as 1 pg/ml, for rapid, noninvasive detection of infection and traumatic injury. Materials and Methods: The electrochemical sensor consists of zinc oxide electrodes on a flexible substrate. IL6 antibodies were immobilized onto the sensor surface using a thiol linker chemistry. Sensor response was measured using Electrochemical Impedance Spectroscopy (EIS) of synthetic sweat dosed with concentrations of IL6 within their physiological ranges. The spike dosing results were verified by a human study, where subjects induced IL6 elevation in their sweat. Results and Discussion: Sensor response to IL6 spike doses in synthetic sweat showed a dose dependent response to concentration of IL6, as illustrated by the Nyquist plot for sensor response to IL6 in Figure 1. These results were verified by the sensor response to pre- and post-exercise sweat of human subjects, which demonstrates an increase in IL6 levels after 10 minutes of anaerobic exercise for all subjects. This increase in IL6 post-exercise was shown to be significant for all subjects with 95% confidence using a paired T test. Conclusion: This study presents a noninvasive electrochemical sensor for rapid and early detection of infection or traumatic injury in response to a physical injury. The sensor exhibits a dose dependent response to IL6, a marker expressed at the time of injury. Sensor capability was demonstrated with human sweat pre- and post-exercise, in order to simulate the conditions following a traumatic injury, for which a significant increase in sensor response post-exercise was observed. Figure 1. Nyquist plot of Electrochemical Impedance Spectroscopy assay of IL6 in synthetic sweat. Figure 1