Drawn-on-Skin Sensors from Fully Biocompatible Inks toward High-Quality Electrophysiology.

The need to develop wearable devices for personal health monitoring, diagnostics, and therapy has inspired the production of innovative on-demand, customizable technologies. Several of these technologies enable printing of raw electronic materials directly onto biological organs and tissues. However, few of them have been thoroughly investigated for biocompatibility of the raw materials on the cellular, tissue, and organ levels or with different cell types. In addition, highly accurate multiday in vivo monitoring using such on-demand, in situ fabricated devices has yet to be done. Presented herein is the first fully biocompatible, on-skin fabricated electronics for multiple cell types and tissues that can capture electrophysiological signals with high fidelity. While also demonstrating improved mechanical and electrical properties, the drawn-on-skin ink retains its properties under various writing conditions, which minimizes the variation in electrical performance. Furthermore, the drawn-on-skin ink shows excellent biocompatibility with cardiomyocytes, neurons, mice skin tissue, and human skin. The high signal-to-noise ratios of the electrophysiological signals recorded with the DoS sensor over multiple days demonstrate its potential for personalized, long-term, and accurate electrophysiological health monitoring.

Wearable bioelectronics fabricated in situ on skins.

In recent years, wearable bioelectronics has rapidly expanded for diagnosing, monitoring, and treating various pathological conditions from the skin surface. Although the devices are typically prefabricated as soft patches for general usage, there is a growing need for devices that are customized in situ to provide accurate data and precise treatment. In this perspective, the state-of-the-art in situ fabricated wearable bioelectronics are summarized, focusing primarily on Drawn-on-Skin (DoS) bioelectronics and other in situ fabrication methods. The advantages and limitations of these technologies are evaluated and potential future directions are suggested for the widespread adoption of these technologies in everyday life.

Customizable, reconfigurable, and anatomically coordinated large-area, high-density electromyography from drawn-on-skin electrode arrays.

Accurate anatomical matching for patient-specific electromyographic (EMG) mapping is crucial yet technically challenging in various medical disciplines. The fixed electrode construction of multielectrode arrays (MEAs) makes it nearly impossible to match an individual's unique muscle anatomy. This mismatch between the MEAs and target muscles leads to missing relevant muscle activity, highly redundant data, complicated electrode placement optimization, and inaccuracies in classification algorithms. Here, we present customizable and reconfigurable drawn-on-skin (DoS) MEAs as the first demonstration of high-density EMG mapping from in situ-fabricated electrodes with tunable configurations adapted to subject-specific muscle anatomy. The DoS MEAs show uniform electrical properties and can map EMG activity with high fidelity under skin deformation-induced motion, which stems from the unique and robust skin-electrode interface. They can be used to localize innervation zones (IZs), detect motor unit propagation, and capture EMG signals with consistent quality during large muscle movements. Reconfiguring the electrode arrangement of DoS MEAs to match and extend the coverage of the forearm flexors enables localization of the muscle activity and prevents missed information such as IZs. In addition, DoS MEAs customized to the specific anatomy of subjects produce highly informative data, leading to accurate finger gesture detection and prosthetic control compared with conventional technology.

Wearable electronics for skin wound monitoring and healing.

Wound healing is one of the most complex processes in the human body, supported by many cellular events that are tightly coordinated to repair the wound efficiently. Chronic wounds have potentially life-threatening consequences. Traditional wound dressings come in direct contact with wounds to help them heal and avoid further complications. However, traditional wound dressings have some limitations. These dressings do not provide real-time information on wound conditions, leading clinicians to miss the best time for adjusting treatment. Moreover, the current diagnosis of wounds is relatively subjective. Wearable electronics have become a unique platform to potentially monitor wound conditions in a continuous manner accurately and even to serve as accelerated healing vehicles. In this review, we briefly discuss the wound status with some objective parameters/biomarkers influencing wound healing, followed by the presentation of various novel wearable devices used for monitoring wounds and accelerating wound healing. We further summarize the associated device working principles. This review concludes by highlighting some major challenges in wearable devices toward wound healing that need to be addressed by the research community.

Direct reprogramming of cardiomyocytes into cardiac Purkinje-like cells.

Currently, there are no treatments that ameliorate cardiac cell death, the underlying basis of cardiovascular disease. An unexplored cell type in cardiac regeneration is cardiac Purkinje cells; specialized cells from the cardiac conduction system (CCS) responsible for propagating electrical signals. Purkinje cells have tremendous potential as a regenerative treatment because they may intrinsically integrate with the CCS of a recipient myocardium, resulting in more efficient electrical conduction in diseased hearts. This study is the first to demonstrate an effective protocol for the direct reprogramming of human cardiomyocytes into cardiac Purkinje-like cells using small molecules. The cells generated were genetically and functionally similar to native cardiac Purkinje cells, where expression of key cardiac Purkinje genes such as CNTN2, ETV1, PCP4, IRX3, SCN5a, HCN2 and the conduction of electrical signals with increased velocity was observed. This study may help to advance the quest to finding an optimized cell therapy for heart regeneration.

Rubbery Electronics Fully Made of Stretchable Elastomeric Electronic Materials.

Stretchable electronics outperform existing rigid and bulky electronics and benefit a wide range of species, including humans, machines, and robots, whose activities are associated with large mechanical deformation and strain. Due to the nonstretchable nature of most electronic materials, in particular semiconductors, stretchable electronics are mostly realized through the strategies of architectural engineering to accommodate mechanical stretching rather than imposing strain into the materials directly. On the other hand, recent development of stretchable electronics by creating them entirely from stretchable elastomeric electronic materials, i.e., rubbery electronics, suggests a feasible a venue. Rubbery electronics have gained increasing interest due to the unique advantages that they and their associated manufacturing technologies have offered. This work reviews the recent progress in developing rubbery electronics, including the crucial stretchable elastomeric materials of rubbery conductors, rubbery semiconductors, and rubbery dielectrics. Thereafter, various rubbery electronics such as rubbery transistors, integrated electronics, rubbery optoelectronic devices, and rubbery sensors are discussed.

Air/water interfacial assembled rubbery semiconducting nanofilm for fully rubbery integrated electronics.

A rubber-like stretchable semiconductor with high carrier mobility is the most important yet challenging material for constructing rubbery electronics and circuits with mechanical softness and stretchability at both microscopic (material) and macroscopic (structural) levels for many emerging applications. However, the development of such a rubbery semiconductor is still nascent. Here, we report the scalable manufacturing of high-performance stretchable semiconducting nanofilms and the development of fully rubbery transistors, integrated electronics, and functional devices. The rubbery semiconductor is assembled into a freestanding binary-phased composite nanofilm based on the air/water interfacial assembly method. Fully rubbery transistors and integrated electronics, including logic gates and an active matrix, were developed, and their electrical performances were retained even when stretched by 50%. An elastic smart skin for multiplexed spatiotemporal mapping of physical pressing and a medical robotic hand equipped with rubbery multifunctional electronic skin was developed to show the applications of fully rubbery-integrated functional devices.

Ultra-conformal drawn-on-skin electronics for multifunctional motion artifact-free sensing and point-of-care treatment.

An accurate extraction of physiological and physical signals from human skin is crucial for health monitoring, disease prevention, and treatment. Recent advances in wearable bioelectronics directly embedded to the epidermal surface are a promising solution for future epidermal sensing. However, the existing wearable bioelectronics are susceptible to motion artifacts as they lack proper adhesion and conformal interfacing with the skin during motion. Here, we present ultra-conformal, customizable, and deformable drawn-on-skin electronics, which is robust to motion due to strong adhesion and ultra-conformality of the electronic inks drawn directly on skin. Electronic inks, including conductors, semiconductors, and dielectrics, are drawn on-demand in a freeform manner to develop devices, such as transistors, strain sensors, temperature sensors, heaters, skin hydration sensors, and electrophysiological sensors. Electrophysiological signal monitoring during motion shows drawn-on-skin electronics' immunity to motion artifacts. Additionally, electrical stimulation based on drawn-on-skin electronics demonstrates accelerated healing of skin wounds.

Wearable Devices for Single-Cell Sensing and Transfection.

Wearable healthcare devices are mainly used for biosensing and transdermal delivery. Recent advances in wearable biosensors allow for long-term and real-time monitoring of physiological conditions at a cellular resolution. Transdermal drug delivery systems have been further scaled down, enabling wide selections of cargo, from natural molecules (e.g., insulin and glucose) to bioengineered molecules (e.g., nanoparticles). Some emerging nanopatches show promise for precise single-cell gene transfection in vivo and have advantages over conventional tools in terms of delivery efficiency, safety, and controllability of delivered dose. In this review, we discuss recent technical advances in wearable micro/nano devices with unique capabilities or potential for single-cell biosensing and transfection in the skin or other organs, and suggest future directions for these fields.

Invited Article: Emerging soft bioelectronics for cardiac health diagnosis and treatment.

Cardiovascular diseases are among the leading causes of death worldwide. Conventional technologies for diagnosing and treating lack the compliance and comfort necessary for those living with life-threatening conditions. Soft electronics presents a promising outlet for conformal, flexible, and stretchable devices that can overcome the mechanical mismatch that is often associated with conventional technologies. Here, we review the various methods in which electronics have been made flexible and stretchable, to better interface with the human body, both externally with the skin and internally with the outer surface of the heart. Then, we review soft, wearable, noninvasive heart monitors designed to be attached to the chest or other parts of the body for mechano-acoustic and electrophysiological sensing. A common method of treatment for various abnormal heart rhythms involves catheter ablation procedures and we review the current soft bioelectronics that can be placed on the balloon or head of the catheter. Cardiac mapping is integral to determine the state of the heart; we discuss the various parameters for sensing aside from electrophysiological sensing, such as temperature, pH, strain, and tactile sensing. Finally, we review the soft devices that harvest energy from the natural and spontaneous beating of the heart by converting its mechanical motion into electrical energy to power implants.

Metal oxide semiconductor nanomembrane-based soft unnoticeable multifunctional electronics for wearable human-machine interfaces.

Wearable human-machine interfaces (HMIs) are an important class of devices that enable human and machine interaction and teaming. Recent advances in electronics, materials, and mechanical designs have offered avenues toward wearable HMI devices. However, existing wearable HMI devices are uncomfortable to use and restrict the human body's motion, show slow response times, or are challenging to realize with multiple functions. Here, we report sol-gel-on-polymer-processed indium zinc oxide semiconductor nanomembrane-based ultrathin stretchable electronics with advantages of multifunctionality, simple manufacturing, imperceptible wearing, and robust interfacing. Multifunctional wearable HMI devices range from resistive random-access memory for data storage to field-effect transistors for interfacing and switching circuits, to various sensors for health and body motion sensing, and to microheaters for temperature delivery. The HMI devices can be not only seamlessly worn by humans but also implemented as prosthetic skin for robotics, which offer intelligent feedback, resulting in a closed-loop HMI system.

Stretchable elastic synaptic transistors for neurologically integrated soft engineering systems.

Artificial synaptic devices that can be stretched similar to those appearing in soft-bodied animals, such as earthworms, could be seamlessly integrated onto soft machines toward enabled neurological functions. Here, we report a stretchable synaptic transistor fully based on elastomeric electronic materials, which exhibits a full set of synaptic characteristics. These characteristics retained even the rubbery synapse that is stretched by 50%. By implementing stretchable synaptic transistor with mechanoreceptor in an array format, we developed a deformable sensory skin, where the mechanoreceptors interface the external stimulations and generate presynaptic pulses and then the synaptic transistors render postsynaptic potentials. Furthermore, we demonstrated a soft adaptive neurorobot that is able to perform adaptive locomotion based on robotic memory in a programmable manner upon physically tapping the skin. Our rubbery synaptic transistor and neurologically integrated devices pave the way toward enabled neurological functions in soft machines and other applications.