(295b) Advancing Personalized Healthcare through Wearable Biosensors

The evolution of personalized healthcare is significantly propelled by advancements in wearable bioelectronic systems, which enable non-invasive, real-time monitoring of vital biomarkers through biofluids like sweat. These systems hold the promise of transforming healthcare by facilitating continuous health status assessments outside clinical settings, thereby aligning interventions with individual health needs. However, the practical realization of these technologies faces hurdles in autonomous biofluid access, the development of highly sensitive and selective sensors for a comprehensive biomarker spectrum, sustainable energy sources for operation, and the scalability of manufacturing processes (Figure 1)¹.

Electrochemical Detection of Essential Biomarkers.

Central to overcoming the challenges in personalized healthcare monitoring is the creation of novel sensors capable of detecting a wide range of biomarkers, including electrolytes, metabolites, amino acids, proteins, and hormones. The most mature sensor technologies in this domain, enzymatic sensors and ion-selective electrodes, are adept at detecting a handful of metabolites and electrolytes but are limited in their scope. Consequently, the monitoring of many key biomarkers necessitates the adoption of alternate or novel sensing technologies. This research propels the development of electrochemical sensors employing advanced techniques such as imprinted polymers (MIPs), aptamers, and antibodies to bridge this gap.

These sensors, integrated with scalable fabrication methods such as laser engraving, inkjet printing, and additive manufacturing, afford unprecedented sensitivity, selectivity, accessibility, and scalability. Specifically, the use of laser-engraved graphene (LEG) electrodes and microfluidics, patterned using a CO² laser cutter, exemplifies low-cost scalability while maintaining high performance. This approach not only enhances the feasibility of widespread application but also marks a significant advancement in sensor technology.

The utilization of molecularly imprinted polymers (MIPs) alongside antibody-based sensors marks a transformative advancement in biosensing². MIPs, synthesized to mimic natural antibody functions, bind specific biomarkers with high fidelity, mirroring the selectivity and sensitivity of biological systems but without their inherent limitations. These 'artificial antibodies' were engineered through a process where functional monomers form a complex around a template molecule, which, once polymerized and the template removed, leaves behind a cavity perfectly shaped for the target biomarker. When integrated with laser-engraved graphene (LEG) electrodes, this approach facilitates the precise detection of a wide range of biomarkers directly from biofluids such as sweat. This combination not only leverages the conductivity and surface area advantages of LEG but also utilizes the selectivity of MIPs, enabling the monitoring of essential health indicators like amino acids and vitamins with unparalleled accuracy.

The antibody-based CRP sensor platform integrates laser-engraved graphene electrodes with microfluidics on a patch, designed for the real-time monitoring of the inflammatory biomarker C-reactive protein (CRP)³. Utilizing gold nanoparticles (AuNPs) conjugated with antibodies and redox-active tags, this system amplifies the electrochemical signal upon CRP binding, ensuring highly sensitive detection. The microfluidic design facilitates efficient sweat sampling and mixing directly on the skin, enabling the CRP antigen-antibody reaction to occur seamlessly within the device. Clinical studies conducted on patients have demonstrated the platform's efficacy, showcasing its potential for non-invasive chronic disease management by providing accurate, real-time inflammatory status monitoring through sweat analysis, thus heralding a significant advance in personalized healthcare monitoring.

Sustainable Powering of Wearables.

The autonomous operation of wearable health monitoring devices requires a reliable and continuous power source. Energy harvesting from the body, through biofuel cells (BFCs)⁴ that convert metabolites like lactate into electricity, and triboelectric nanogenerators (TENGs)⁵ that convert motion into electrical energy, presents a sustainable approach for powering wearable devices for fitness monitoring applications. However, these methods typically rely on exercise for sweat or power generation, limiting the applicability of wearable devices for continuous health monitoring, especially in sedentary or low-activity scenarios.

Addressing the limitations of body-powered systems, this research harnesses ambient light as an ubiquitous energy source. The development of flexible perovskite solar cells (FPSCs) offers a compelling solution, demonstrating high power conversion efficiency under both indoor and outdoor lighting conditions⁶. Distinguished from conventional silicon solar cells, FPSCs exhibit flexibility, robustness, and an optimal spectral response to indoor lighting, making them ideal for wearable applications. This energy-harvesting approach eliminates the dependency on physical activity for power generation, significantly enhancing the operational capability of wearable devices for continuous monitoring across various user activity levels.

The high power output of the FPSCs, coupled with a powerful low power electronic system, enables the platform to perform autonomous sweat extraction via iontophoresis and conduct all commonly used types of electrochemical measurements. This integration facilitates the interfacing and multiplexing of various sensors, allowing for comprehensive biomarker analysis. Moreover, data transmission is achieved wirelessly over Bluetooth Low Energy (BLE), ensuring seamless communication. By leveraging ambient light for power and enabling autonomous sweat extraction, this system markedly extends the wearable devices' operational capability for continuous monitoring, irrespective of the user's activity level. In a demonstrative application, biomarker levels (glucose, pH, sodium, skin temperature, sweat rate) were simultaneously monitored for over 12 hours using this battery-free device while a subject engaged in various daily activities, including exercise and desk work. This breakthrough underscores the potential of FPSC-powered wearable devices in realizing the vision of continuous, unobtrusive health monitoring, thereby advancing personalized healthcare through innovative technology.

By integrating novel wearable sensor technologies for metabolic and nutritional analysis with advanced energy harvesting methods for sustainable powering, this research lays the groundwork for the next generation of wearable health monitoring platforms. These platforms promise to enable the continuous, autonomous monitoring of a broad spectrum of health biomarkers, powered sustainably by our bodies and the environment.

References († indicates equal contributions)

1. Min, J.^†, Tu, J.^†, Xu, C^†., Lukas, H^†. et al. Skin-Interfaced Wearable Sweat Sensors for Precision Medicine. Rev. 123, 5049–5138 (2023).
2. Wang, M.^†, Yang, Y.^†, Min, J.^† et al. A wearable electrochemical biosensor for the monitoring of metabolites and nutrients. Biomed. Eng. 6, 1225-1235 (2022).
3. Tu, J., Min, J. et al. A wireless patch for the monitoring of C-reactive protein in sweat, Biomed. Eng. 7, 1293–1306 (2023).
4. Yu, Y., Nassar, J., Xu, C., Min, J. et al. Biofuel-powered soft electronic skin with multiplexed and wireless sensing for human-machine interfaces. Robot. 5, eaaz7946 (2020).
5. Song, Y.^†, Min, J^†. et al. Wireless battery-free wearable sweat sensor powered by human motion. Adv. 6, eaay9842 (2020).
6. Min, J.^†, Demchyshyn, S.^† et al. An autonomous wearable biosensor powered by a perovskite solar cell. Electron. 6, 630-641 (2023).

Figure 1. Insights into Wearable Sweat Sensing Technologies for Customized Health Management