A smartwatch was developed for noninvasive stress biomarker data acquisition that provides real-time feedback to the wearer.

Active biofluid management is central to the realization of wearable bioanalytical platforms that are poised to autonomously provide frequent, real-time, and accurate measures of biomarkers in epidermally-retrievable biofluids (e.g., sweat). Accordingly, here, a programmable epidermal microfluidic valving system is devised, which is capable of biofluid sampling, routing, and compartmentalization for biomarker analysis. At its core, the system is a network of individually-addressable microheater-controlled thermo-responsive hydrogel valves, augmented with a pressure regulation mechanism to accommodate pressure built-up, when interfacing sweat glands. The active biofluid control achieved by this system is harnessed to create unprecedented wearable bioanalytical capabilities at both the sensor level (decoupling the confounding influence of flow rate variability on sensor response) and the system level (facilitating context-based sensor selection/protection). Through integration with a wireless flexible printed circuit board and seamless bilateral communication with consumer electronics (e.g., smartwatch), contextually-relevant (scheduled/on-demand) on-body biomarker data acquisition/display was achieved.

We devised a strategy for high-fidelity, wearable biomarker data acquisition and sensor integration with consumer electronics.

To achieve the mission of personalized medicine, centering on delivering the right drug to the right patient at the right dose, therapeutic drug monitoring solutions are necessary. In that regard, wearable biosensing technologies, capable of tracking drug pharmacokinetics in noninvasively retrievable biofluids (e.g., sweat), play a critical role, because they can be deployed at a large scale to monitor the individuals’ drug transcourse profiles (semi)continuously and longitudinally. To this end, voltammetry-based sensing modalities are suitable, as in principle they can detect and quantify electroactive drugs on the basis of the target’s redox signature. However, the target’s redox signature in complex biofluid matrices can be confounded by the immediate biofouling effects and distorted/buried by the interfering voltammetric responses of endogenous electroactive species. Here, we devise a wearable voltammetric sensor development strategy—centering on engineering the molecule–surface interactions—to simultaneously mitigate biofouling and create an “undistorted potential window” within which the target drug’s voltammetric response is dominant and interference is eliminated. To inform its clinical utility, our strategy was adopted to track the temporal profile of circulating acetaminophen (a widely used analgesic and antipyretic) in saliva and sweat, using a surface-modified boron-doped diamond sensing interface (cross-validated with laboratory-based assays, R² ∼ 0.94). Through integration of the engineered sensing interface within a custom-developed smartwatch, and augmentation with a dedicated analytical framework (for redox peak extraction), we realized a wearable solution to seamlessly render drug readouts with minute-level temporal resolution. Leveraging this solution, we demonstrated the pharmacokinetic correlation and significance of sweat readings. Significance To achieve the mission of personalized medicine, centering on delivering the right drug to the right patient at the right dose, therapeutic drug monitoring solutions are necessary. By devising a surface engineering strategy, we created a voltammetric sensing interface, featuring an “undistorted potential window,” within which the target electroactive drug’s voltammetric response is dominant and interference is eliminated, rendering reliable target quantification in noninvasively retrievable biofluids (sweat and saliva). Leveraging this sensing interface, a fully integrated, wearable solution was constructed to seamlessly render drug readouts with minute-level temporal resolution. To inform its clinical utility, the solution was utilized to demonstrate noninvasive pharmacokinetic monitoring of a pharmaceutical (here, acetaminophen, a widely used analgesic and antipyretic) in a wearable format.

Recent advances in microelectronics, microfluidics, and electrochemical sensing platforms have enabled the development of an emerging class of fully integrated personal health monitoring devices that exploit sweat to noninvasively access biomarker information. Despite such advances, effective sweat sampling remains a significant challenge for reliable biomarker analysis, with many existing methods requiring active stimulation (e.g., iontophoresis, exercise, heat). Natural perspiration offers a suitable alternative as sweat can be collected with minimal effort on the part of the user. To leverage this phenomenon, we devised a thin hydrogel micropatch (THMP), which simultaneously serves as an interface for sweat sampling and a medium for electrochemical sensing. To characterize the performance of the THMP, caffeine and lactate were selected as two representative target molecules. We demonstrated the suitability of the sampling method to track metabolic patterns, as well as to render sample-to-answer biomarker data for personal monitoring (through coupling with an electrochemical sensing system). To inform its potential application, this biomarker sampling and sensing system is incorporated within a distributed terminal-based sensing network, which uniquely capitalizes on the fingertip as a site for simultaneous biomarker data sampling and user identification.