A Breathable, Passive-Cooling, Non-Inflammatory, and Biodegradable Aerogel Electronic Skin for Wearable Physical-Electrophysiological-Chemical Analysis.

Real-time monitoring of human health can be significantly improved by designing novel electronic skin (E-skin) platforms that mimic the characteristics and sensitivity of human skin. A high-quality E-skin platform that can simultaneously monitor multiple physiological and metabolic biomarkers without introducing skin discomfort or irritation is an unmet medical need. Conventional E-skins are either monofunctional or made from elastomeric films that do not include key synergistic features of natural skin, such as multi-sensing, breathability, and thermal management capabilities in a single patch. Herein, a biocompatible and biodegradable E-skin patch based on flexible gelatin methacryloyl aerogel (FGA) for non-invasive and continuous monitoring of multiple biomarkers of interest is engineered and demonstrated. Taking advantage of cryogenic temperature treatment and slow polymerization, FGA is fabricated with a highly interconnected porous structure that displays good flexibility, passive-cooling capabilities, and ultra-lightweight properties that make it comfortable to wear for long periods of time. It also provides numerous permeable capillary channels for thermal-moisture transfer, ensuring its excellent breathability. Therefore, the engineered FGA-based E-skin can simultaneously monitor body temperature, hydration, and biopotentials via electrophysiological sensors and detect glucose, lactate, and alcohol levels via electrochemical sensors. This work offers a previously unexplored materials strategy for next-generation E-skin platforms with superior practicality.

Wearable microneedle-based electrochemical aptamer biosensing for precision dosing of drugs with narrow therapeutic windows.

Therapeutic drug monitoring is essential for dosing pharmaceuticals with narrow therapeutic windows. Nevertheless, standard methods are imprecise and involve invasive/resource-intensive procedures with long turnaround times. Overcoming these limitations, we present a microneedle-based electrochemical aptamer biosensing patch (µNEAB-patch) that minimally invasively probes the interstitial fluid (ISF) and renders correlated, continuous, and real-time measurements of the circulating drugs' pharmacokinetics. The µNEAB-patch is created following an introduced low-cost fabrication scheme, which transforms a shortened clinical-grade needle into a high-quality gold nanoparticle-based substrate for robust aptamer immobilization and efficient electrochemical signal retrieval. This enables the reliable in vivo detection of a wide library of ISF analytes-especially those with nonexistent natural recognition elements. Accordingly, we developed µNEABs targeting various drugs, including antibiotics with narrow therapeutic windows (tobramycin and vancomycin). Through in vivo animal studies, we demonstrated the strong correlation between the ISF/circulating drug levels and the device's potential clinical use for timely prediction of total drug exposure.

A touch-based multimodal and cryptographic bio-human-machine interface.

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 human­machine interfaces­equipped with bioperception and interpretation capabilities­are required. To this end, we devised a multimodal cryptographic bio-human­machine 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 aptamer-field-effect transistor sensing system for noninvasive cortisol monitoring.

Wearable technologies for personalized monitoring require sensors that track biomarkers often present at low levels. Cortisol­a key stress biomarker­is 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 In2O3 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 array­based smartwatch equipped with a custom, multichannel, self-referencing, and autonomous source measurement unit enabling seamless, real-time cortisol sweat sensing.

Microengineered poly(HEMA) hydrogels for wearable contact lens biosensing.

Microchannels in hydrogels play an essential role in enabling a smart contact lens. However, microchannels have rarely been created in commercial hydrogel contact lenses due to their sensitivity to conventional microfabrication techniques. Here, we report the fabrication of microchannels in poly(2-hydroxyethyl methacrylate) (poly(HEMA)) hydrogels that are used in commercial contact lenses with a three-dimensional (3D) printed mold. We investigated the corresponding capillary flow behaviors in these microchannels. We observed different capillary flow regimes in these microchannels, depending on their hydration level. In particular, we found that a peristaltic pressure could reinstate flow in a dehydrated channel, indicating that the motion of eye-blinking may help tears flow in a microchannel-containing contact lens. Colorimetric pH and electrochemical Na+ sensing capabilities were demonstrated in these microchannels. This work paves the way for the development of microengineered poly(HEMA) hydrogels for various biomedical applications such as eye-care and wearable biosensing.

A programmable epidermal microfluidic valving system for wearable biofluid management and contextual biomarker analysis.

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.

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.

A wearable freestanding electrochemical sensing system.

To render high-fidelity wearable biomarker data, understanding and engineering the information delivery pathway from epidermally retrieved biofluid to a readout unit are critical. By examining the biomarker information delivery pathway and recognizing near-zero strained regions within a microfluidic device, a strain-isolated pathway to preserve biomarker data fidelity is engineered. Accordingly, a generalizable and disposable freestanding electrochemical sensing system (FESS) is devised, which simultaneously facilitates sensing and out-of-plane signal interconnection with the aid of double-sided adhesion. The FESS serves as a foundation to realize a system-level design strategy, addressing the challenges of wearable biosensing, in the presence of motion, and integration with consumer electronics. To this end, a FESS-enabled smartwatch was developed, featuring sweat sampling, electrochemical sensing, and data display/transmission, all within a self-contained wearable platform. The FESS-enabled smartwatch was used to monitor the sweat metabolite profiles of individuals in sedentary and high-intensity exercise settings.

Design Framework and Sensing System for Noninvasive Wearable Electroactive Drug Monitoring.

Wearable drug monitoring targeting epidermally retrievable biofluids (e.g., sweat) can enable a variety of applications, including drug compliance/abuse monitoring and personalized therapeutic drug dosing. In that regard, voltammetry-based approaches are suitable because they uniquely leverage the electroactive nature of target drug molecules for quantification, eliminating the reliance on the availability of recognition elements. However, to adapt such approaches for the envisioned application, three main challenges must be addressed: (1) constructing a sensitive voltammetric sensing interface with high signal-to-background ratio, (2) decoupling the confounding effect of endogenous electroactive species (naturally present in complex biofluid matrices) and baseline variation, and (3) realizing wireless voltammetric excitation and signal acquisition/transmission. To this end, first, a framework for the quantification of electroactive drugs is presented, which centers on the evaluation and determination of suitable sensing electrodes and characterization of the interference from a panel of physiologically relevant electroactive species. This framework was utilized to establish the design space and operational settings for the development of a coupled sensing system and analytical framework to render sample-to-answer drug readouts in complex biofluid matrices. The presented design framework and sensing system can serve as a basis for future wearable sensor development efforts aiming to monitor electroactive species such as pharmaceutical molecules.

Natural Perspiration Sampling and in Situ Electrochemical Analysis with Hydrogel Micropatches for User-Identifiable and Wireless Chemo/Biosensing.

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.

A wearable electrofluidic actuation system.

We report a wearable electrofluidic actuation system, which exploits the alternating current electrothermal (ACET) effects to engineer biofluid flow profiles on the body. The wearable ACET flow is induced with the aid of corrosion-resistant electrode configurations (fabricated on a flexible substrate) and custom-developed, wirelessly programmable high frequency (MHz) excitation circuitry. Various tunable flow profiles are demonstrated with the aid of the devised flexible ACET electrode configurations, where the induced profiles are in agreement with the ACET theory and simulation. The demonstrated capabilities rendered by the presented system create new degrees of freedom for implementing advanced bioanalytical operations for future lab-on-the-body platforms.

A rapid and low-cost fabrication and integration scheme to render 3D microfluidic architectures for wearable biofluid sampling, manipulation, and sensing.

The large-scale deployment of wearable bioanalytical devices for general population longitudinal monitoring necessitates rapid and high throughput manufacturing-amenable fabrication schemes that render disposable, low-cost, and mechanically flexible microfluidic modules capable of performing a variety of bioanalytical operations within a compact footprint. The spatial constraints of previously reported wearable bioanalytical devices (with microfluidic operations confined to 2D), their lack of biofluid manipulation capability, and the complex and low-throughput nature of their fabrication process inherently limit the diversity and frequency of end-point assessments and prevent their deployment at large scale. Here, we devise a simple, scalable, and low-cost "CAD-to-3D Device" fabrication and integration scheme, which renders 3D and complex microfluidic architectures capable of performing biofluid sampling, manipulation, and sensing. The devised scheme is based on laser-cutting of tape-based substrates, which can be programmed at the software-level to rapidly define microfluidic features such as a biofluid collection interface, microchannels, and VIAs (vertical interconnect access), followed by the vertical assembly of pre-patterned layers to realize the final device. To inform the utility of our fabrication scheme, we demonstrated three representative devices to perform sweat collection (with visualizable secretion profile), sample filtration, and simultaneous biofluid actuation and sensing (using a sandwiched-interface). Our devised scheme can be adapted for the fabrication and manufacturing of current and future wearable bioanalytical devices, which in turn will catalyze the large-scale production and deployment of such devices for general population health monitoring.

Amylose-Derived Macrohollow Core and Microporous Shell Carbon Spheres as Sulfur Host for Superior Lithium-Sulfur Battery Cathodes.

Porous carbon can be tailored to great effect for electrochemical energy storage. In this study, we propose a novel structured spherical carbon with a macrohollow core and a microporous shell derived from a sustainable biomass, amylose, by a multistep pyrolysis route without chemical etching. This hierarchically porous carbon shows a particle distribution of 2-10 µm and a surface area of 672 m2 g-1. The structure is an effective host of sulfur for lithium-sulfur battery cathodes, which reduces the dissolution of polysulfides in the electrolyte and offers high electrical conductivity during discharge/charge cycling. The hierarchically porous carbon can hold 48 wt % sulfur in its porous structure. The S@C hybrid shows an initial capacity of 1490 mAh g-1 and retains a capacity of 798 mAh g-1 after 200 cycles at a discharge/charge rate of 0.1 C. A capacity of 487 mAh g-1 is obtained at a rate of 3 C. Both a one-step pyrolysis and a chemical-reagent-assisted pyrolysis are also assessed to obtain porous carbon from amylose, but the obtained carbon shows structures inferior for sulfur cathodes. The multistep pyrolysis and the resulting hierarchically porous carbon offer an effective approach to the engineering of biomass for energy storage. The micrometer-sized spherical S@C hybrid with different sizes is also favorable for high-tap density and hence the volumetric density of the batteries, opening up a wide scope for practical applications.