Bioelectronic medicine: wearable and implantable electronics

Wearable and implantable electronics (WIEs) are more and more important and attractive to the public, and they have had positive influences on all aspects of our lives. As a bridge between wearable electronics and their surrounding environment and users, sensors are core components of WIEs and determine the implementation of their many functions. Although the existing sensor technology has evolved to a very advanced level with the rapid progress of advanced materials and nanotechnology, most of them still need external power supply, like batteries, which could cause problems that are difficult to track, recycle, and miniaturize, as well as possible environmental pollution and health hazards. In the past decades, based upon piezoelectric, pyroelectric, and triboelectric effect, various kinds of nanogenerators (NGs) were proposed which are capable of responding to a variety of mechanical movements, such as breeze, body drive, muscle stretch, sound/ultrasound, noise, mechanical vibration, and blood flow, and they had been widely used as self-powered sensors and micro-nanoenergy and blue energy harvesters. This review focuses on the applications of self-powered generators as implantable and wearable sensors in health monitoring, biosensor, human-computer interaction, and other fields. The existing problems and future prospects are also discussed.

60% of Americans live with at least one chronic disease. These diseases and their associated comorbidities are now the leading causes of death in the United States. The effective management of complex chronic diseases requires body-wide, long-term, accurate, and continuous monitoring of multiple physiological signals from wearable and implantable devices to precisely determine the pathological state. Wearable physiological signal monitoring can dramatically reduce the demand for physician visits and increase patients' engagement and treatment adherence rates. Specifically, battery-free wearables and implantable electronics reduce device volume and mechanical stiffness, significantly improving wear comfort, which is highly desirable for next-generation wearable and implantable electronics. However, battery-free wearables and implantable electronics still face many challenges, mainly wireless energy and data transfer. To address these challenges, my research has been involved in the exploration of rational system design concepts, material and device fabrication innovation, and tailored algorithms to enable smart battery-free wearables and implantable electronics targeting next-generation chronic disease management.Here, I would like to discuss two of my developed technology platforms to elaborate on the concept of battery-free wearable and implantable systems. First, I will describe an RFID-based body area sensor network technology platform. This technology uses electromagnetic waves and RF antennas as energy and data transmission media and has broad applications in sleep tracking, workout monitoring, chronic wound healing, and inflammation management. Second, I will describe a triboelectric transducer-based implantable battery-free device. This technology platform uses ultrasound waves and triboelectric transducers as energy and data transmission media and has broad applications in implantable sensing. Overall, the developed technology platforms can assess multiple health outcomes and treatment responses to various chronic diseases. Ultimately, this technology will help reduce the burden of chronic diseases, lower medical costs, and provide a better quality of life for patients. (1,2,3,4)

60% of Americans live with at least one chronic disease. These diseases and their associated comorbidities are now the leading causes of death in the United States. The effective management of complex chronic diseases requires body-wide, long-term, accurate, and continuous monitoring of multiple physiological signals from wearable and implantable devices to precisely determine the pathological state. Wearable physiological signal monitoring can dramatically reduce the demand for physician visits and increase patients' engagement and treatment adherence rates. Specifically, battery-free wearables and implantable electronics reduce device volume and mechanical stiffness, significantly improving wear comfort, which is highly desirable for next-generation wearable and implantable electronics. However, battery-free wearables and implantable electronics still face many challenges, mainly wireless energy and data transfer. To address these challenges, my research has been involved in the exploration of rational system design concepts, material and device fabrication innovation, and tailored algorithms to enable smart battery-free wearables and implantable electronics targeting next-generation chronic disease management.Here, I would like to discuss two of my developed technology platforms to elaborate on the concept of battery-free wearable and implantable systems. First, I will describe an RFID-based active living bioelectronic technology platform. This technology encompasses capabilities across the biogenic (bacteria), biomechanical (starch-based hydrogels), and bioelectrical properties (battery-free biosensors and stimulators) simultaneously and show promising results in managing skin inflammation. Second, I will describe a battery-free self-powered gait monitoring device. This technology platform uses triboelectric transducers to harvest biomechanical energy from walking and running. From a self-starting and highly efficient power management circuit, we realized a self-powered sustainable gait monitoring device that can evaluate gait steadiness, perform step counting, and analyze fall risks. Overall, the developed technology platforms can assess multiple health outcomes and treatment responses to various chronic diseases. Ultimately, this technology will help reduce the burden of chronic diseases, lower medical costs, and provide a better quality of life for patients. (1)

Highly stretchable, deformation-stable wireless powering antenna for wearable electronics

Stretchable Silver‐Zinc Batteries Based on Embedded Nanowire Elastic Conductors

Powering biomedical devices is a major issue in the design of wearable and implantable electronics Chaimanonart et al. (2006); Chen et al. (2009); Kendir et al. (2004); Smith et al. (2002). Often, there is not space available for a battery that will last for the lifetime of the device, as batteries are limited both by total charge storage ability and number of recharge cycles Heller (2006). Replacement is often not an option, as the implant surgeries are both time consuming, require special expertise, and introduce the possibility of additional trauma to the patient. Percutaneous physical links Galbraith et al. (2007); Knutson et al. (2002) are prone to damage, because of the mismatch in material properties, scarring at the tissue interface Takura et al. (2006), and potential infections and skin irritation. In addition, these devices are difficult to keep sterile. An alternative is inductive links, which are coupled coils forming an air core transformer Hamici et al. (1996); Li et al. (2005); Liu et al. (2000); Sauer et al. (2005); Sivaprakasam et al. (2005); Theogarajan & Wyatt (2006); Wang, Liu, Sivaprakasam, Weiland & Humayun (2005). As diagrammed in Fig. 1, an inductive link consists of two components of electronics. Those located externally or physically detached from the subjects are referred as primary side electronics, e.g., external battery, power transmitter, power control units, etc. Those located under the skin (implanted electronics) or along with the subjects (wearable electronics) are referred as secondary electronics, including resonant amplifier, rectifier, regulators, and power management units. Power-transmission efficiency and system miniaturization are major design specifications to evaluate a power link. Given application related constraints, these specifications are inherently correlated and a careful trade-off analysis is required to achieve an optimal performance. This chapter is organized as follows. In Section 2, an introduction on power telemetry electronics is presented, followed by design analysis and simulation verifications. Section 3 focuses on inductor modeling, which correlates power efficiency with device size. Section 4 gives examples to quantify the achievable efficiency given design constraints. Design and Optimization of Inductive Power Link for Biomedical Applications

Body: Wearable electronics are increasingly important in healthcare applications for monitoring of the daily physical condition and diagnosis of an early stage of disorders. In particular, the wearable sensors on human skin can be utilized in real-time continuous monitoring systems because they provide comfortable wearing and consume less power. Pulse detection is one of the options and critical for high-risk groups of cardiovascular diseases such as angina, acute coronary syndrome, and myocardial infarction among the real-time monitoring of several physical parameters. Moreover, the pulse is easily detected from specific points on the human body such as carotid, temporal, fingertip, dorsal, and posterior tibial artery using skin-attachable sensor [Chen, et al. High durable, biocompatible and flexible piezoelectric pulse sensor using III-N thin film, Adv. Funct. Mater. 29, 1903162 (2019)]. Accurate sensing of the eyelid and eyeball movement is another new application. Brain disorders (e.g. Alzheimer's, Parkinson’s disease, and stroke) are accompanied by eye-related abnormal motions as early symptoms such as slow movements and the long interval between eye blinking. The diseases can be diagnosed in an early stage from the detection of unusual eye motions before they are seriously progressed. For both applications, the sensors should be light and small to attach on the human body, e.g. temple area. Recently developed thin-film piezoelectric skin-attachable sensor based on lead zirconate titanate (PZT) and ZnO inherently possess weakness for the wearable healthcare sensors. PZT contains lead, which is very harmful to the human body and environment by poisoning. A skin-attachable sensor should be containing toxic-free elements. ZnO sensor shows low sensitivity and resolution from the limitation of material, which demands additional signal processing for amplification of exact signal and minimization of the noise level. The benefit of non-toxicity is canceled by low sensitivity and extra work. As an alternative sensing element, III-N thin films are very promising to detect the physical motion of skin sensing due to their advantages of high sensitivity and durability, rapid response time, non-toxic nature on humans, lightweight, and low power consumption. Especially, single-crystalline gallium nitride (GaN) and aluminum-gallium nitride (AlGaN) piezoelectric thin films have been reported to show excellent output voltage, indicating outstanding sensitivity, rapid response time by a high electromechanical coupling factor, chemical and mechanical long-term stability, high thermal resistance, and excellent biocompatibility [Chen et al. Biocompatible and sustainable power supply for self-powered wearable and implantable electronics using flexible III-nitride thin-film-based piezoelectric generator, Nano Energy 57, 670 (2019)]. In this study, we developed and demonstrated skin-attachable GaN and AlGaN sensors for the detection of eye-lid motion to monitor the eye blinking and eyeball movements. Flexible III-N thin films were designed by layer transfer method from the rigid silicon substrate. They were analyzed by X-ray diffraction to reveal its single-crystalline quality without second phase or defects. The single sensor was applied to the temple area of the face for sensing of eye blinking and simple eyeball motion. Eye blinking is conducted with three different levels. Then, the multiple sensors were utilized with appropriate distance on the identical region to detect the transverse, longitudinal, diagonal, and rotational eyeball motions, which explain the abnormal eye movements. All the results from each sensor are distinguishable, which indicates that the sensors generated different values of output signals from each position with varied stimulates.

Disposable sensors based on biodegradable polylactic acid piezoelectret films and their application in wearable electronics

Conformal transistor array based on solution-processed organic crystals, which can provide sensory and scanning features for monitoring, biofeedback, and tracking of physiological function, presents one of the most promising technologies for future large-scale low-cost wearable and implantable electronics. However, it is still a huge challenge for the integration of solution-processed organic crystals into conformal FETs owing to a generally existing swelling phenomenon of the elastic materials and the lack of the corresponding device fabrication technology. Here, we present a promising route to fabricate a conformal field-effect transistor (FET) array based on solution-processed TIPS-pentacene single-crystal micro/nanowire array. By simply drop-casting the organic solution on an anti-solvent photolithography-compatible electrode with bottom-contact coplanar configuration, the transistor array can be formed and can conform onto uneven objects. Excellent electrical properties with device yield as high as 100%, field-effect mobility up to 0.79 cm2V−1s−1, low threshold voltage, and good device uniformity are demonstrated. The results open up the capability of solution-processed organic crystals for conformal electronics, suggesting their substantial promise for next-generation wearable and implantable electronics.

Monitoring human health in real-time using wearable and implantable electronics (WIE) has become one of the most promising and rapidly growing technologies in the healthcare industry. In general, these electronics are powered by batteries that require periodic replacement and maintenance over their lifetime. To prolong the operation of these electronics, they should have zero post-installation maintenance. On this front, various energy harvesting technologies to generate electrical energy from ambient energy sources have been researched. Many energy harvesters currently available are limited by their power output and energy densities. With the miniaturization of wearable and implantable electronics, the size of the harvesters must be miniaturized accordingly in order to increase the energy density of the harvesters. Additionally, many of the energy harvesters also suffer from limited operational parameters such as resonance frequency and variable input signals. In this work, low frequency motion energy harvesting based on reverse electrowetting-ondielectric (REWOD) is examined using perforated high surface area electrodes with 38 µm pore diameters. Total available surface area per planar area was 8.36 cm2 showing a significant surface area enhancement from planar to porous electrodes and proportional increase in AC voltage density from our previous work. In REWOD energy harvesting, high surface area electrodes significantly increase the capacitance and hence the power density. An AC peak-to-peak voltage generation from the electrode in the range from 1.57-3.32 V for the given frequency range of 1-5 Hz with 0.5 Hz step is demonstrated. In addition, the unconditioned power generated from the harvester is converted to a DC power using a commercial off-theshelf Schottky diode-based voltage multiplier and low dropout regulator (LDO) such that the sensors that use this technology could be fully self-powered. The produced charge is then converted to a proportional voltage by using a commercial charge amplifier to record the features of the motion activities. A transceiver radio is also used to transmit the digitized data from the amplifier and the built-in analog-to-digital converter (ADC) in the micro-controller. This paper proposes the energy harvester acting as a self-powered motion sensor for different physical activities for wearable and wireless healthcare devices.

The human body has an abundance of available energy from the mechanical movements of walking, jumping, and running. Many devices such as electromagnetic, piezoelectric, and triboelectric energy harvesting devices have been demonstrated to convert body mechanical energy into electricity, which can be used to power various wearable and implantable electronics. However, the complicated structure, high cost of production/maintenance, and limitation of wearing and implantation sites restrict the development and commercialization of the body energy harvesters. Here, we present a body-integrated self-powered system (BISS) that is a succinct, highly efficient, and cost-effective method to scavenge energy from human motions. The biomechanical energy of the moving human body can be harvested through a piece of electrode attached to skin. The basic principle of the BISS is inspired by the comprehensive effect of triboelectrification between soles and floor and electrification of the human body. We have proven the feasibility of powering electronics using the BISS in vitro and in vivo. Our investigation of the BISS exhibits an extraordinarily simple, economical, and applicable strategy to harvest energy from human body movements, which has great potential for practical applications of self-powered wearable and implantable electronics in the future.

Conformal organic single‐crystal circuit on 3D curved surfaces, which can provide sensory and scanning features for monitoring, biofeedback, and tracking of physiological function, presents one of the most promising technologies for high‐performance wearable and implantable electronics. However, the present organic single‐crystal circuits remain limited on rigid planar substrates, by the lack of fabrication techniques for mechanically elastic and flexible electrodes to conform to 3D curved surfaces. Here, a novel electrode design for the formation of a wafer‐scale coplanar electrode, together with only one individual flexible rubrene nanobelt, to achieve the 3D conformal single‐crystal transistors and circuits for the first time is proposed. Excellent electrical properties with device yield as high as 93.2%, field‐effect mobility up to 23.9 cm2 V−1 s−1, near‐zero threshold voltage, inverter gain over 23, and the extreme circuit stability with zero hysteresis are shown. The results open up the capability of organic single crystals for conformal circuits and reveal the strong potential of the new‐type electrode for future large‐scale wearable and implantable electronics.

Biocompatible and sustainable power supply for self-powered wearable and implantable electronics using III-nitride thin-film-based flexible piezoelectric generator

Deformable lithium-ion batteries (LIBs) have attracted increasingly widespread attention due to their enormous prospects for powering flexible electronics. In recent years, technological advances in manufacturing deformable LIBs at the material and device levels have promoted the rapid and sustainable development in energy storage. Despite recent advances, there is so far no review to make a comprehensive introduction focusing on the topic of deformable LIBs for future wearable and implantable electronics. This review systematically summarizes the recent progresses in deformable LIBs and their applications in various scenarios. Specifically, we classify the deformable LIBs into several categories such as stretchable LIBs, self-healing LIBs, shape memory LIBs, biodegradable LIBs, etc. Initially, the fundamentals of LIBs, such as their components and working mechanism, are introduced. Then, various strategies for constructing deformable LIBs are discussed in detail, with a particular focus on stretchable LIBs. Subsequently, the latest advances in the application of deformable LIBs in wearable/implantable electronic systems are summarized. To finalize, the challenges and prospects are outlined to promote further development in this booming field. This review has the potential to inspire researchers working on the development of high-performance deformable energy storage devices and to contribute to the future development of flexible electronics.

Thermoelectric nanogenerators (TENGs) are promising sustainable energy devices that utilize thermoelectric (TE) effect of nanomaterials to convert a temperature gradient into electrical energy. Compared to bulk thermoelectric generators (TEGs) that are commercially available, TENGs are more flexible and power‐dense, owing to their tuneable nanostructures. Hence, smaller TENGs are better suited for small form‐factor applications like wearable electronics, internet of things (IoT) devices, and self‐powered sensors. However, the higher complexity and cost of TENGs than TEGs inhibit their widespread adoption. This review appraises the latest advances in TENG materials, design, and fabrication in optimizing the performance of TENGs, making TENGs more viable for real‐world applications. More precisely, this work examines how nanostructure engineering, nanomaterial compositing, and post‐synthesis treatment approaches have enhanced the TE properties of common and promising TE materials, including tellurides, selenides, metal oxides, metal alloys, silicon, carbon nanomaterials, and organic compounds. Given that the TE material is a key component in TENGs, this review highlights how to optimize other vital parameters, including the TENG configuration, contact interface, form factor, heat sink use, and folded shape for specific applications. Lastly, critical attributes of TENGs used in wearable electronics, sensors, implantable electronics, solar energy conversion, and waste heat recovery are analyzed.