Longitudinal Tracking of Calprotectin and Interleukin-6 in Sweat and Saliva Using a Sweat Wearable Device
Authors: Shahub Sarah , Mahesh Kumar Ruchita , Ramasubramanya Annapoorna , Lin Kai-Chun , Muthukumar Sriram , Prasad Shalini 
Published: August 2024

Introduction: This work demonstrates an electrochemical sensor for the application of continuous, noninvasive measurement of inflammation in sweat and saliva through the biomarkers Calprotectin and Interleukin-6 (IL-6), respectively. Calprotectin and IL-6 play a part in the systemic inflammation inherent to chronic inflammatory conditions, such as Inflammatory Bowel Disease (IBD), rheumatoid arthritis, cystic fibrosis, etc. Sweat and saliva represent comparable external mediums through which inflammation can be tracked continuously and noninvasively.

Materials and Methods: Calprotectin and IL-6 were measured in sweat and saliva for 2 chronically inflamed subjects and 10 healthy subjects over a two-day period. Sweat measurements were performed using a wearable, skin-based electrochemical sensor utilizing electrochemical impedance spectroscopy (EIS) to quantify Calprotectin and IL-6 concentrations continuously in passively expressed sweat. Calprotectin and IL-6 levels were measured in real time and transmitted to a wireless device application. Figure 1 illustrates the sensor and wearable device design and composition alongside an application interface displaying the wearer's Calprotectin levels measured in real time. Synchronously collected saliva was measured for Calprotectin and IL-6 to characterize the relationship between sweat and saliva expression, establish the relationship between Calprotectin and IL-6 expression as markers of chronic inflammation, and investigate the sweat and salivary diurnal patterns of marker expression for inflamed and healthy subjects. In addition, we tracked sweat Calprotectin over a 40-hour period for chronically inflamed and healthy subjects with varying levels of inflammation and treatments.

Results and Discussion: Between sweat and saliva, Calprotectin and IL-6 demonstrated a strong linear relationship (R2>0.7), and strong to moderate linear relationships between Calprotectin and IL-6 in sweat and saliva, respectively. Bland-Altman analysis and Deming regression analysis determined a low incidence of outliers and similar ranges of Calprotectin and IL-6 expression between sweat and saliva. Diurnal analysis exhibited significantly higher sweat Calprotectin and higher median Calprotectin measured in the morning-afternoon than measured in the evening among chronically inflamed and healthy subjects, respectively. Among sweat IL-6 measured in the morning-afternoon and evening, chronically inflamed individuals expressed higher median sweat IL-6 in the morning-afternoon, while healthy individuals expressed higher median IL-6 in the evening. Temporal results of 40-hour tracking of sweat Calprotectin demonstrated higher basal Calprotectin in a medicated over unmedicated inflamed subject, and higher basal Calprotectin of inflamed subjects over a healthy subject.

Conclusion: Calprotectin and IL-6 demonstrated strong positive linear relationships between saliva and sweat expression of each marker and strong to moderate linear relationships between the markers in sweat and saliva, along with a low incidence of outliers and a similar range of expression between sweat and saliva. Diurnal patterns were characterized for chronically inflamed and healthy individuals for Calprotectin and IL-6 in sweat, and continuous tracking of inflammation in sweat was demonstrated with the wearable sensor device.

Figure 1