Wearable, Skin-integrated Devices for Real-time Sweat Monitoring and Healthcare Management

Abstract

Over the past decades, wearable and skin-integrated electronics have been playing increasingly significant roles in various fields, particularly within the realm of biomedical applications, including healthcare monitoring, disease diagnosis and prevent, adjuvant therapy as well as drug delivery et al. Compared with these traditional rigid electronic devices, the cutting-edge wearable and skin-integrated electronics own the advantages of light weight, high flexibility, skin conformability, and biocompatibility, facilitating the process of personalized medicine and thus essentially improving life quality and prolonging lifetime. Regarding the measurement of biochemical signals, sweat acts as one of the most easily obtained biofluids and contains various biomarkers like glucose, lactate, pH, and inorganic ions, which can directly reflect body conditions and prevent diseases. To date, great efforts have been directed toward developing wearable sweat sensors with flexibility and wearability. However, research on some heart matters of wearable sweat monitoring devices, such as skin integrability, stretchability, power sources, data transmission and sweat collection, is still insufficient. In this thesis, we aim to develop wearable sweat and healthcare monitoring systems with high integrability. Apart from developing wearable and skin-integrated biosensors for real-time and in-situ health monitoring, we optimize the integrated system by every single module from structure design, wearable format, and power supplies to data transmission, intelligent safety warning and therapy.

Our research began with the epidermal self-powered glucose and lactate sensors based on enzymatic biofuel cells (EBFCs). Regardless of the applications, it remains a major challenge to find appropriate power sources for wearable electronics, as the weight and volume of batteries can greatly impact the miniaturization, flexibility, and biocompatibility of these devices. EBFCs represent a unique subset of fuel cells that use enzymes as catalysts to oxidize their fuel and transfer the chemical energy into electrical energy, leading to great biocompatibility, specificity, and low fabrication cost. EBFCs provide an alternative pathway for achieving self-powered sensors for in-situ monitoring the most common and abundant metabolites in sweat of glucose and lactate, as the outputs of EBFCs are proportional to the fuel concentration. As a result, we developed a stretchable self-powered sweat sensor with an epidermal format combined with advanced structure design and microfluidics, allowing for real-time and in-situ detection of lactate and glucose concentrations in sweat. The sensing modules of the EBFCs demonstrated a significant correlation for both lactate and glucose detection, with a determination coefficient (R2) of 0.98 and a sensitivity of 2.48 mV/mM for lactate as well as a R2 of 0.96 alongside a sensitivity of 0.11 mV/μM for glucose. Microfluidics of an advanced design, both thin and soft, has not merely expedited effective sweat collection but also provided exceptional mechanical qualities, maintaining a stable output performance, including scenarios of up to 30% stretching.

Aside from epidermal applications, EBFCs could also be applied as power sources for implantable devices because of their excellent biocompatibility and the abundant glucose content in human bodies. In this part, we developed high-performance, transient glucose enzymatic biofuel cells (TEBFCs) based on advanced transfer print technologies, which could avoid the risks of electrolyte leakage and rejection reaction and secondary damage for patients. In order to improve the output performance of the TEBFCs, the laser-induced graphene (LIG)/gold nanoparticles (Au NPs) composite electrodes were fabricated. The LIG electrodes with various patterns could be obtained on polyamide (PI) film and the LIG/Au NPs composites were modified by a one-step reduction method. The patterned electrodes were transferred to a poly(lactic-co-glycolic acid) (PLGA) substrate to achieve the transient function. With the help of these elements, the TEBFCs showcased a high open circuit potential (OCP) of 0.77 V and a maximum power density (MPD) of 483.1 µW/cm². Results from both in vitro and in vivo tests, underscoring its exceptional biocompatibility and transient performance, affirm the potential for extended TEBFC implantation in rats for energy harvesting.

Although EBFCs enable the self-powered sweat sensors and supply for implantable devices, their outputs are insufficient to support continuous long-distance data transmission of sensors and those electronics with complex functions (like sweat and healthcare monitoring). As a result, it is necessary to develop soft, thin, skin conformal and biocompatible power sources with high outputs to replace these bulky and rigid batteries for wearable electronics. We presented an ultrathin, garment-based system powered by sweat activated batteries (SABs) for real-time and in-situ sweat monitoring. The SAB cell, with a thickness of 1.25 mm, adjoins seamlessly with the skin, demonstrating notable biocompatibility and flexibility with a high capacity of 14.33 mAh and a MPD of 3.17 mW/cm2. The SABs can continuously power a wireless microelectronic for about three hours, enabling continuous monitoring of sweat and physiological metrics, including sweat sodium (Na⁺) concentration, pH, and skin impedance, which are wirelessly relayed to smartphone graphic user interfaces via a system based on Near Field Communication (NFC) technology.

For wearable sweat and healthcare monitoring devices, the ultimate aims are real-time monitoring of body conditions and alerting wearers when abnormal index occurs for preventing accidents and diseases. Therefore, we demonstrated a highly integrated intelligent system with simultaneous healthcare monitoring and safety warning. For comprehensively monitor health conditions and decode fresh sweat information during exercising, we developed an integrated sensor patch that enables detecting six parameters of ammonium ion (NH₄⁺), Na⁺, glucose, pH, skin impedance, and surface temperature. The system incorporated an innovative safety warning feature involving a miniaturized actuator that generated mechanical stimuli and was paired with six alterable-color LEDs. These LEDs corresponded to the six biosensors, thereby ensuring concurrent safety alerts for users. Moreover, the hydrophilic surface and pillars in the developed microfluidics system could enhance the sweat collection rate and filter impurities in sweat, respectively.

It is not only the real-time sweat monitoring that can reflect health information, but other body fluids, such as wound exudates, can also indicate the real-time health status of injured or post-surgery patients. We also developed wearable and skin-integrated devices with for monitoring wound exudates and processing personalized therapy according to the wound infection conditions. At first, we presented a stretchable magnesium-air battery based on dual-ions-conducting hydrogels for intelligent wound therapy. Benefitting from the advanced material and structure design, the stretchable battery was able to maintain high and stable output under 40% stretching. Combined with the stretchable battery, a self-adaptation wound dressing system was developed. The system could in-situ monitor the wound temperature and intelligently adjust the drug delivery rate and dosage spontaneously according to the wound conditions.

In conclusion, we have made significant developments in wearable and skin-integrated devices for sweat monitoring and healthcare management in various aspects of sweat sensors, power sources, sweat collection, intelligent alerts, wound exudates monitoring and personalized therapy. We believe that our efforts would accelerate the achievement of truly personalized medicine and we heartily hope that our research will improve the quality of life for everyone, prolong lifetime and reduce accidental death.

Date of Award	27 Aug 2024
Original language	English
Awarding Institution	City University of Hong Kong
Supervisor	Xinge YU (Supervisor)