Achievements and Challenges for Real-Time Sensing of Analytes in Sweat within Wearable Platforms

Physiological sensors in a wearable form have rapidly emerged on the market due to technological breakthroughs and have become nearly ubiquitous with the Apple Watch, FitBit, and other wearable devices. While these wearables mostly monitor simple biometric signatures, new devices that can report on the human readiness level through sensing molecular biomarkers are critical to optimizing the human factor in both commercial sectors and the Department of Defense. The military is particularly interested in real-time, wearable, minimally invasive monitoring of fatigue and human performance to improve the readiness and performance of the war fighter. However, very few devices have ventured into the realm of reporting directly on biomarkers of interest. Primarily this is because of the difficulties of sampling biological fluids in real-time and providing accurate readouts using highly selective and sensitive sensors. When additional restrictions to only use sweat, an excretory fluid, are enforced to minimize invasiveness, the demands on sensors becomes even greater due to the dilution of the biomarkers of interest, as well as variability in salinity, pH, and other physicochemical variables which directly impact the read-out of real-time biosensors. This Account will provide a synopsis not only on exemplary demonstrations and technological achievements toward implementation of real-time, wearable sweat sensors but also on defining problems that still remain toward implementation in wearable devices that can detect molecular biomarkers for real world applications. First, the authors describe the composition of minimally invasive biofluids and then identify what biomarkers are of interest as biophysical indicators. This Account then reviews demonstrated techniques for extracting biofluids from the site of generation and transport to the sensor developed by the authors. Included in this discussion is a detailed description on biosensing recognition elements and transducers developed by the authors to enable generation of selective electrochemical sensing platforms. The authors also discuss ongoing efforts to identify biorecognition elements and the chemistries necessary to enable high affinity, selective biorecognition elements. Finally, this Account presents the requirements for wearable, real-time sensors to be (1) highly stable, (2) portable, (3) reagentless, (4) continuous, and (5) responsive in real-time, before delving into specific methodologies to sense classes of biomarkers that have been explored by academia, government laboratories, and industry. Each