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A library of soft, stretchable, strain-insensitive bioelectronics was made using brittle interfacial materials. 

A microneedle-based aptamer biosensor was developed to minimally-nvasively measure the drug levels in real time. 

The awareness of individuals’ biological status is critical for creating interactive and adaptive environments that can actively assist the users to achieve optimal outcomes. Accordingly, specialized human–machine interfaces—equipped with bioperception and interpretation capabilities—are required. To this end, we devised a multimodal cryptographic bio-human–machine interface (CB-HMI), which seamlessly translates the user’s touch-based entries into encrypted biochemical, biophysical, and biometric indices. As its central component, the CB-HMI features thin hydrogel-coated chemical sensors and inference algorithms to noninvasively and inconspicuously acquire biochemical indices such as circulating molecules that partition onto the skin (here, ethanol and acetaminophen). Additionally, the CB-HMI hosts physical sensors and associated algorithms to simultaneously acquire the user’s heart rate, blood oxygen level, and fingerprint minutiae pattern. Supported by human subject studies, we demonstrated the CB-HMI’s capability in terms of acquiring physiologically relevant readouts of target bioindices, as well as user-identifying and biometrically encrypting/decrypting these indices in situ (leveraging the fingerprint feature). By upgrading the common surrounding objects with the CB-HMI, we created interactive solutions for driving safety and medication use. Specifically, we demonstrated a vehicle-activation system and a medication-dispensing system, where the integrated CB-HMI uniquely enabled user bioauthentication (on the basis of the user’s biological state and identity) prior to rendering the intended services. Harnessing the levels of bioperception achieved by the CB-HMI and other intelligent HMIs, we can equip our surroundings with a comprehensive and deep awareness of individuals’ psychophysiological state and needs. 

Wearable technologies for personalized monitoring require sensors that track biomarkers often present at low levels. Cortisol—a key stress biomarker—is present in sweat at low nanomolar concentrations. Previous wearable sensing systems are limited to analytes in the micromolar-millimolar ranges. To overcome this and other limitations, we developed a flexible field-effect transistor (FET) biosensor array that exploits a previously unreported cortisol aptamer coupled to nanometer-thin-film In 2 O 3 FETs. Cortisol levels were determined via molecular recognition by aptamers where binding was transduced to electrical signals on FETs. The physiological relevance of cortisol as a stress biomarker was demonstrated by tracking salivary cortisol levels in participants in a Trier Social Stress Test and establishing correlations between cortisol in diurnal saliva and sweat samples. These correlations motivated the development and on-body validation of an aptamer-FET array–based smartwatch equipped with a custom, multichannel, self-referencing, and autonomous source measurement unit enabling seamless, real-time cortisol sweat sensing. 

To track dynamically varying and physiologically relevant biomarker profiles in sweat, autonomous wearable platforms are required to periodically sample and analyze sweat with minimal or no user intervention. Previously reported sweat sensors are functionally limited to capturing biomarker information at one time-point/period, thereby necessitating repeated user intervention to increase the temporal granularity of biomarker data. Accordingly, we present a compact multi-compartment wearable system, where each compartment can be activated to autonomously induce/modulate sweat secretion ( via iontophoretic actuation) and analyze sweat at set time points. This system was developed following a hybrid-flex design and a vertical integration scheme—integrating the required functional modules: miniaturized iontophoresis interfaces, adhesive thin film microfluidic-sensing module, and control/readout electronics. The system was deployed in a human subject study to track the diurnal variation of sweat glucose levels in relation to the daily food intake. The demonstrated autonomous operation for diurnal sweat biomarker data acquisition illustrates the system's suitability for large-scale and longitudinal personal health monitoring applications. 

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.

 

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.

 

Lithium is a drug widely employed for the treatment of bipolar disorder owing to its high efficacy in mood management and suicide prevention. However, this efficacy is often undermined by misdosing and nonadherence, and diligent drug monitoring is required during treatment. Standard lithium monitoring involves invasive blood collections and laboratory analysis with low time granularity. Recent advances in sensor technology have enabled the development of personalized drug‐monitoring devices that analyze biomarker information noninvasively. Herein, based on the fact that the analyte partition onto the fingertip with a high flux, a touch‐based noninvasive monitoring modality for managing lithium pharmacotherapy is devised. The system is built based on a thin organohydrogel‐mounted lithium ion‐selective electrode (TOH‐ISE). The TOH coating provides a stable environment for sensing. Through the utilization of a water/glycerol bi‐solvent matrix, the gel exhibits dehydration‐resist properties, rendering a controlled micro‐environment for ISE conditioning, and subsequently minimizing signal drift. To illustrate the clinical application of the solution, the system is tested on a subject prescribed lithium. The system successfully detected the increase in circulating drug levels following medication intake. Collectively, the results indicate the devised solution is capable to facilitate lithium adherence monitoring and has broader potential for optimizing lithium pharmacotherapy.