A Wearable Nanobiosensor for Automatic, Non-Invasive and Wireless Monitoring of Systemic Inflammation

Real-time monitoring of inflammatory proteins allows remote disease progression tracking and early intervention, thus improving patient outcomes and lowering economic burdens in chronic diseases. However, most current commercial protein sensing technologies rely on invasive blood draws, and require lengthy target incubation and labor-intensive washing steps to reach nanogram-level sensitivity. Although sweat is a non-invasive source for disease monitoring, wearable immunosensing is complex and sweat protein secretion is extremely underexplored, presenting a major challenge for personalized inflammation monitoring. Here, we present a wearable nanoengineered electrochemical biosensing technology that allows real-time and non-invasive analysis of a crucial inflammatory biomarker, C-reactive protein (CRP). Highly sensitive, selective, and fully automatic <i>in situ </i>inflammatory protein analysis across human activities was realized through seamless integration of a mesoporous graphene-gold nanoparticle modified immunosensor (coupled with thionine-tagged detector antibody-conjugated gold nanoparticles for signal transduction and amplification), autonomous sweat gland-driven microfluidics, and multimodal graphene sensor calibration. Through <i>in vitro</i> and <i>in vivo</i> clinical studies, we discovered the presence of CRP in chemically-induced human sweat and identified substantially elevated sweat CRP levels from patients with heart failure, chronic obstructive pulmonary disease, and active and past infections (e.g., COVID-19). We obtained a high correlation between sweat and blood CRP levels, demonstrating the potential of this technology toward non-invasive chronic disease management.