Noninvasive wearable electroactive pharmaceutical monitoring for personalized therapeutics.

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.

Soft strain-insensitive bioelectronics featuring brittle materials.

Advancing electronics to interact with tissue necessitates meeting material constraints in electrochemical, electrical, and mechanical domains simultaneously. Clinical bioelectrodes with established electrochemical functionalities are rigid and mechanically mismatched with tissue. Whereas conductive materials with tissue-like softness and stretchability are demonstrated, when applied to electrochemically probe tissue, their performance is distorted by strain and corrosion. We devise a layered architectural composite design that couples strain-induced cracked films with a strain-isolated out-of-plane conductive pathway and in-plane nanowire networks to eliminate strain effects on device electrochemical performance. Accordingly, we developed a library of stretchable, highly conductive, and strain-insensitive bioelectrodes featuring clinically established brittle interfacial materials (iridium-oxide, gold, platinum, and carbon). We paired these bioelectrodes with different electrochemical probing methods (amperometry, voltammetry, and potentiometry) and demonstrated strain-insensitive sensing of multiple biomarkers and in vivo neuromodulation.