Multimodal charting of molecular and functional cell states via in situ electro-sequencing.

Paired mapping of single-cell gene expression and electrophysiology is essential to understand gene-to-function relationships in electrogenic tissues. Here, we developed in situ electro-sequencing (electro-seq) that combines flexible bioelectronics with in situ RNA sequencing to stably map millisecond-timescale electrical activity and profile single-cell gene expression from the same cells across intact biological networks, including cardiac and neural patches. When applied to human-induced pluripotent stem-cell-derived cardiomyocyte patches, in situ electro-seq enabled multimodal in situ analysis of cardiomyocyte electrophysiology and gene expression at the cellular level, jointly defining cell states and developmental trajectories. Using machine-learning-based cross-modal analysis, in situ electro-seq identified gene-to-electrophysiology relationships throughout cardiomyocyte development and accurately reconstructed the evolution of gene expression profiles based on long-term stable electrical measurements. In situ electro-seq could be applicable to create spatiotemporal multimodal maps in electrogenic tissues, potentiating the discovery of cell types and gene programs responsible for electrophysiological function and dysfunction.

A three-dimensional liquid diode for soft, integrated permeable electronics.

Wearable electronics with great breathability enable a comfortable wearing experience and facilitate continuous biosignal monitoring over extended periods1-3. However, current research on permeable electronics is predominantly at the stage of electrode and substrate development, which is far behind practical applications with comprehensive integration with diverse electronic components (for example, circuitry, electronics, encapsulation)4-8. Achieving permeability and multifunctionality in a singular, integrated wearable electronic system remains a formidable challenge. Here we present a general strategy for integrated moisture-permeable wearable electronics based on three-dimensional liquid diode (3D LD) configurations. By constructing spatially heterogeneous wettability, the 3D LD unidirectionally self-pumps the sweat from the skin to the outlet at a maximum flow rate of 11.6 ml cm-2 min-1, 4,000 times greater than the physiological sweat rate during exercise, presenting exceptional skin-friendliness, user comfort and stable signal-reading behaviour even under sweating conditions. A detachable design incorporating a replaceable vapour/sweat-discharging substrate enables the reuse of soft circuitry/electronics, increasing its sustainability and cost-effectiveness. We demonstrated this fundamental technology in both advanced skin-integrated electronics and textile-integrated electronics, highlighting its potential for scalable, user-friendly wearable devices.

Strain-invariant stretchable radio-frequency electronics.

Wireless modules that provide telecommunications and power-harvesting capabilities enabled by radio-frequency (RF) electronics are vital components of skin-interfaced stretchable electronics1-7. However, recent studies on stretchable RF components have demonstrated that substantial changes in electrical properties, such as a shift in the antenna resonance frequency, occur even under relatively low elastic strains8-15. Such changes lead directly to greatly reduced wireless signal strength or power-transfer efficiency in stretchable systems, particularly in physically dynamic environments such as the surface of the skin. Here we present strain-invariant stretchable RF electronics capable of completely maintaining the original RF properties under various elastic strains using a 'dielectro-elastic' material as the substrate. Dielectro-elastic materials have physically tunable dielectric properties that effectively avert frequency shifts arising in interfacing RF electronics. Compared with conventional stretchable substrate materials, our material has superior electrical, mechanical and thermal properties that are suitable for high-performance stretchable RF electronics. In this paper, we describe the materials, fabrication and design strategies that serve as the foundation for enabling the strain-invariant behaviour of key RF components based on experimental and computational studies. Finally, we present a set of skin-interfaced wireless healthcare monitors based on strain-invariant stretchable RF electronics with a wireless operational distance of up to 30 m under strain.

Multi-project wafers for flexible thin-film electronics by independent foundries.

Flexible and large-area electronics rely on thin-film transistors (TFTs) to make displays1-3, large-area image sensors4-6, microprocessors7-11, wearable healthcare patches12-15, digital microfluidics16,17 and more. Although silicon-based complementary metal-oxide-semiconductor (CMOS) chips are manufactured using several dies on a single wafer and the multi-project wafer concept enables the aggregation of various CMOS chip designs within the same die, TFT fabrication is currently lacking a fully verified, universal design approach. This increases the cost and complexity of manufacturing TFT-based flexible electronics, slowing down their integration into more mature applications and limiting the design complexity achievable by foundries. Here we show a stable and high-yield TFT platform for the fabless manufacturing of two mainstream TFT technologies, wafer-based amorphous indium-gallium-zinc oxide and panel-based low-temperature polycrystalline silicon, two key TFT technologies applicable to flexible substrates. We have designed the iconic 6502 microprocessor in both technologies as a use case to demonstrate and expand the multi-project wafer approach. Enabling the foundry model for TFTs, as an analogy of silicon CMOS technologies, can accelerate the growth and development of applications and technologies based on these devices.

Water-responsive supercontractile polymer films for bioelectronic interfaces.

Connecting different electronic devices is usually straightforward because they have paired, standardized interfaces, in which the shapes and sizes match each other perfectly. Tissue-electronics interfaces, however, cannot be standardized, because tissues are soft1-3 and have arbitrary shapes and sizes4-6. Shape-adaptive wrapping and covering around irregularly sized and shaped objects have been achieved using heat-shrink films because they can contract largely and rapidly when heated7. However, these materials are unsuitable for biological applications because they are usually much harder than tissues and contract at temperatures higher than 90 °C (refs. 8,9). Therefore, it is challenging to prepare stimuli-responsive films with large and rapid contractions for which the stimuli and mechanical properties are compatible with vulnerable tissues and electronic integration processes. Here, inspired by spider silk10-12, we designed water-responsive supercontractile polymer films composed of poly(ethylene oxide) and poly(ethylene glycol)-α-cyclodextrin inclusion complex, which are initially dry, flexible and stable under ambient conditions, contract by more than 50% of their original length within seconds (about 30% per second) after wetting and become soft (about 100 kPa) and stretchable (around 600%) hydrogel thin films thereafter. This supercontraction is attributed to the aligned microporous hierarchical structures of the films, which also facilitate electronic integration. We used this film to fabricate shape-adaptive electrode arrays that simplify the implantation procedure through supercontraction and conformally wrap around nerves, muscles and hearts of different sizes when wetted for in vivo nerve stimulation and electrophysiological signal recording. This study demonstrates that this water-responsive material can play an important part in shaping the next-generation tissue-electronics interfaces as well as broadening the biomedical application of shape-adaptive materials.

A microscale soft ionic power source modulates neuronal network activity.

Bio-integrated devices need power sources to operate1,2. Despite widely used technologies that can provide power to large-scale targets, such as wired energy supplies from batteries or wireless energy transduction3, a need to efficiently stimulate cells and tissues on the microscale is still pressing. The ideal miniaturized power source should be biocompatible, mechanically flexible and able to generate an ionic current for biological stimulation, instead of using electron flow as in conventional electronic devices4-6. One approach is to use soft power sources inspired by the electrical eel7,8; however, power sources that combine the required capabilities have not yet been produced, because it is challenging to obtain miniaturized units that both conserve contained energy before usage and are easily triggered to produce an energy output. Here we develop a miniaturized soft power source by depositing lipid-supported networks of nanolitre hydrogel droplets that use internal ion gradients to generate energy. Compared to the original eel-inspired design7, our approach can shrink the volume of a power unit by more than 105-fold and it can store energy for longer than 24 h, enabling operation on-demand with a 680-fold greater power density of about 1,300 W m-3. Our droplet device can serve as a biocompatible and biological ionic current source to modulate neuronal network activity in three-dimensional neural microtissues and in ex vivo mouse brain slices. Ultimately, our soft microscale ionotronic device might be integrated into living organisms.

Chiral assemblies of pinwheel superlattices on substrates.

The unique topology and physics of chiral superlattices make their self-assembly from nanoparticles highly sought after yet challenging in regard to (meta)materials1-3. Here we show that tetrahedral gold nanoparticles can transform from a perovskite-like, low-density phase with corner-to-corner connections into pinwheel assemblies with corner-to-edge connections and denser packing. Whereas corner-sharing assemblies are achiral, pinwheel superlattices become strongly mirror asymmetric on solid substrates as demonstrated by chirality measures. Liquid-phase transmission electron microscopy and computational models show that van der Waals and electrostatic interactions between nanoparticles control thermodynamic equilibrium. Variable corner-to-edge connections among tetrahedra enable fine-tuning of chirality. The domains of the bilayer superlattices show strong chiroptical activity as identified by photon-induced near-field electron microscopy and finite-difference time-domain simulations. The simplicity and versatility of substrate-supported chiral superlattices facilitate the manufacture of metastructured coatings with unusual optical, mechanical and electronic characteristics.

Nonlinear decision-making with enzymatic neural networks.

Artificial neural networks have revolutionized electronic computing. Similarly, molecular networks with neuromorphic architectures may enable molecular decision-making on a level comparable to gene regulatory networks1,2. Non-enzymatic networks could in principle support neuromorphic architectures, and seminal proofs-of-principle have been reported3,4. However, leakages (that is, the unwanted release of species), as well as issues with sensitivity, speed, preparation and the lack of strong nonlinear responses, make the composition of layers delicate, and molecular classifications equivalent to a multilayer neural network remain elusive (for example, the partitioning of a concentration space into regions that cannot be linearly separated). Here we introduce DNA-encoded enzymatic neurons with tuneable weights and biases, and which are assembled in multilayer architectures to classify nonlinearly separable regions. We first leverage the sharp decision margin of a neuron to compute various majority functions on 10 bits. We then compose neurons into a two-layer network and synthetize a parametric family of rectangular functions on a microRNA input. Finally, we connect neural and logical computations into a hybrid circuit that recursively partitions a concentration plane according to a decision tree in cell-sized droplets. This computational power and extreme miniaturization open avenues to query and manage molecular systems with complex contents, such as liquid biopsies or DNA databases.

Large-area display textiles integrated with functional systems.

Displays are basic building blocks of modern electronics1,2. Integrating displays into textiles offers exciting opportunities for smart electronic textiles-the ultimate goal of wearable technology, poised to change the way in which we interact with electronic devices3-6. Display textiles serve to bridge human-machine interactions7-9, offering, for instance, a real-time communication tool for individuals with voice or speech difficulties. Electronic textiles capable of communicating10, sensing11,12 and supplying electricity13,14 have been reported previously. However, textiles with functional, large-area displays have not yet been achieved, because it is challenging to obtain small illuminating units that are both durable and easy to assemble over a wide area. Here we report a 6-metre-long, 25-centimetre-wide display textile containing 5 × 105 electroluminescent units spaced approximately 800 micrometres apart. Weaving conductive weft and luminescent warp fibres forms micrometre-scale electroluminescent units at the weft-warp contact points. The brightness between electroluminescent units deviates by less than 8 per cent and remains stable even when the textile is bent, stretched or pressed. Our display textile is flexible and breathable and withstands repeated machine-washing, making it suitable for practical applications. We show that an integrated textile system consisting of display, keyboard and power supply can serve as a communication tool, demonstrating the system's potential within the 'internet of things' in various areas, including healthcare. Our approach unifies the fabrication and function of electronic devices with textiles, and we expect that woven-fibre materials will shape the next generation of electronics.

High-frequency and intrinsically stretchable polymer diodes.

Skin-like intrinsically stretchable soft electronic devices are essential to realize next-generation remote and preventative medicine for advanced personal healthcare1-4. The recent development of intrinsically stretchable conductors and semiconductors has enabled highly mechanically robust and skin-conformable electronic circuits or optoelectronic devices2,5-10. However, their operating frequencies have been limited to less than 100 hertz, which is much lower than that required for many applications. Here we report intrinsically stretchable diodes-based on stretchable organic and nanomaterials-capable of operating at a frequency as high as 13.56 megahertz. This operating frequency is high enough for the wireless operation of soft sensors and electrochromic display pixels using radiofrequency identification in which the base-carrier frequency is 6.78 megahertz or 13.56 megahertz. This was achieved through a combination of rational material design and device engineering. Specifically, we developed a stretchable anode, cathode, semiconductor and current collector that can satisfy the strict requirements for high-frequency operation. Finally, we show the operational feasibility of our diode by integrating it with a stretchable sensor, electrochromic display pixel and antenna to realize a stretchable wireless tag. This work is an important step towards enabling enhanced functionalities and capabilities for skin-like wearable electronics.

Scalable production of high-performing woven lithium-ion fibre batteries.

Fibre lithium-ion batteries are attractive as flexible power solutions because they can be woven into textiles, offering a convenient way to power future wearable electronics1-4. However, they are difficult to produce in lengths of more than a few centimetres, and longer fibres were thought to have higher internal resistances3,5 that compromised electrochemical performance6,7. Here we show that the internal resistance of such fibres has a hyperbolic cotangent function relationship with fibre length, where it first decreases before levelling off as length increases. Systematic studies confirm that this unexpected result is true for different fibre batteries. We are able to produce metres of high-performing fibre lithium-ion batteries through an optimized scalable industrial process. Our mass-produced fibre batteries have an energy density of 85.69 watt hour per kilogram (typical values8 are less than 1 watt hour per kilogram), based on the total weight of a lithium cobalt oxide/graphite full battery, including packaging. Its capacity retention reaches 90.5% after 500 charge-discharge cycles and 93% at 1C rate (compared with 0.1C rate capacity), which is comparable to commercial batteries such as pouch cells. Over 80 per cent capacity can be maintained after bending the fibre for 100,000 cycles. We show that fibre lithium-ion batteries woven into safe and washable textiles by industrial rapier loom can wirelessly charge a cell phone or power a health management jacket integrated with fibre sensors and a textile display.

Porous Conductive Textiles for Wearable Electronics.

Over the years, researchers have made significant strides in the development of novel flexible/stretchable and conductive materials, enabling the creation of cutting-edge electronic devices for wearable applications. Among these, porous conductive textiles (PCTs) have emerged as an ideal material platform for wearable electronics, owing to their light weight, flexibility, permeability, and wearing comfort. This Review aims to present a comprehensive overview of the progress and state of the art of utilizing PCTs for the design and fabrication of a wide variety of wearable electronic devices and their integrated wearable systems. To begin with, we elucidate how PCTs revolutionize the form factors of wearable electronics. We then discuss the preparation strategies of PCTs, in terms of the raw materials, fabrication processes, and key properties. Afterward, we provide detailed illustrations of how PCTs are used as basic building blocks to design and fabricate a wide variety of intrinsically flexible or stretchable devices, including sensors, actuators, therapeutic devices, energy-harvesting and storage devices, and displays. We further describe the techniques and strategies for wearable electronic systems either by hybridizing conventional off-the-shelf rigid electronic components with PCTs or by integrating multiple fibrous devices made of PCTs. Subsequently, we highlight some important wearable application scenarios in healthcare, sports and training, converging technologies, and professional specialists. At the end of the Review, we discuss the challenges and perspectives on future research directions and give overall conclusions. As the demand for more personalized and interconnected devices continues to grow, PCT-based wearables hold immense potential to redefine the landscape of wearable technology and reshape the way we live, work, and play.

Wireless Battery-free and Fully Implantable Organ Interfaces.

Advances in soft materials, miniaturized electronics, sensors, stimulators, radios, and battery-free power supplies are resulting in a new generation of fully implantable organ interfaces that leverage volumetric reduction and soft mechanics by eliminating electrochemical power storage. This device class offers the ability to provide high-fidelity readouts of physiological processes, enables stimulation, and allows control over organs to realize new therapeutic and diagnostic paradigms. Driven by seamless integration with connected infrastructure, these devices enable personalized digital medicine. Key to advances are carefully designed material, electrophysical, electrochemical, and electromagnetic systems that form implantables with mechanical properties closely matched to the target organ to deliver functionality that supports high-fidelity sensors and stimulators. The elimination of electrochemical power supplies enables control over device operation, anywhere from acute, to lifetimes matching the target subject with physical dimensions that supports imperceptible operation. This review provides a comprehensive overview of the basic building blocks of battery-free organ interfaces and related topics such as implantation, delivery, sterilization, and user acceptance. State of the art examples categorized by organ system and an outlook of interconnection and advanced strategies for computation leveraging the consistent power influx to elevate functionality of this device class over current battery-powered strategies is highlighted.

E-Tattoos: Toward Functional but Imperceptible Interfacing with Human Skin.

The human body continuously emits physiological and psychological information from head to toe. Wearable electronics capable of noninvasively and accurately digitizing this information without compromising user comfort or mobility have the potential to revolutionize telemedicine, mobile health, and both human-machine or human-metaverse interactions. However, state-of-the-art wearable electronics face limitations regarding wearability and functionality due to the mechanical incompatibility between conventional rigid, planar electronics and soft, curvy human skin surfaces. E-Tattoos, a unique type of wearable electronics, are defined by their ultrathin and skin-soft characteristics, which enable noninvasive and comfortable lamination on human skin surfaces without causing obstruction or even mechanical perception. This review article offers an exhaustive exploration of e-tattoos, accounting for their materials, structures, manufacturing processes, properties, functionalities, applications, and remaining challenges. We begin by summarizing the properties of human skin and their effects on signal transmission across the e-tattoo-skin interface. Following this is a discussion of the materials, structural designs, manufacturing, and skin attachment processes of e-tattoos. We classify e-tattoo functionalities into electrical, mechanical, optical, thermal, and chemical sensing, as well as wound healing and other treatments. After discussing energy harvesting and storage capabilities, we outline strategies for the system integration of wireless e-tattoos. In the end, we offer personal perspectives on the remaining challenges and future opportunities in the field.

Materials and Structural Designs toward Motion Artifact-Free Bioelectronics.

Bioelectronics encompassing electronic components and circuits for accessing human information play a vital role in real-time and continuous monitoring of biophysiological signals of electrophysiology, mechanical physiology, and electrochemical physiology. However, mechanical noise, particularly motion artifacts, poses a significant challenge in accurately detecting and analyzing target signals. While software-based "postprocessing" methods and signal filtering techniques have been widely employed, challenges such as signal distortion, major requirement of accurate models for classification, power consumption, and data delay inevitably persist. This review presents an overview of noise reduction strategies in bioelectronics, focusing on reducing motion artifacts and improving the signal-to-noise ratio through hardware-based approaches such as "preprocessing". One of the main stress-avoiding strategies is reducing elastic mechanical energies applied to bioelectronics to prevent stress-induced motion artifacts. Various approaches including strain-compliance, strain-resistance, and stress-damping techniques using unique materials and structures have been explored. Future research should optimize materials and structure designs, establish stable processes and measurement methods, and develop techniques for selectively separating and processing overlapping noises. Ultimately, these advancements will contribute to the development of more reliable and effective bioelectronics for healthcare monitoring and diagnostics.

Permeable Bioelectronics toward Biointegrated Systems.

Bioelectronics integrates electronics with biological organs, sustaining the natural functions of the organs. Organs dynamically interact with the external environment, managing internal equilibrium and responding to external stimuli. These interactions are crucial for maintaining homeostasis. Additionally, biological organs possess a soft and stretchable nature; encountering objects with differing properties can disrupt their function. Therefore, when electronic devices come into contact with biological objects, the permeability of these devices, enabling interactions and substance exchanges with the external environment, and the mechanical compliance are crucial for maintaining the inherent functionality of biological organs. This review discusses recent advancements in soft and permeable bioelectronics, emphasizing materials, structures, and a wide range of applications. The review also addresses current challenges and potential solutions, providing insights into the integration of electronics with biological organs.

Electrochemical and Electrical Biosensors for Wearable and Implantable Electronics Based on Conducting Polymers and Carbon-Based Materials.

Bioelectronic devices are designed to translate biological information into electrical signals and vice versa, thereby bridging the gap between the living biological world and electronic systems. Among different types of bioelectronics devices, wearable and implantable biosensors are particularly important as they offer access to the physiological and biochemical activities of tissues and organs, which is significant in diagnosing and researching various medical conditions. Organic conducting and semiconducting materials, including conducting polymers (CPs) and graphene and carbon nanotubes (CNTs), are some of the most promising candidates for wearable and implantable biosensors. Their unique electrical, electrochemical, and mechanical properties bring new possibilities to bioelectronics that could not be realized by utilizing metals- or silicon-based analogues. The use of organic- and carbon-based conductors in the development of wearable and implantable biosensors has emerged as a rapidly growing research field, with remarkable progress being made in recent years. The use of such materials addresses the issue of mismatched properties between biological tissues and electronic devices, as well as the improvement in the accuracy and fidelity of the transferred information. In this review, we highlight the most recent advances in this field and provide insights into organic and carbon-based (semi)conducting materials' properties and relate these to their applications in wearable/implantable biosensors. We also provide a perspective on the promising potential and exciting future developments of wearable/implantable biosensors.

Materials-Driven Soft Wearable Bioelectronics for Connected Healthcare.

In the era of Internet-of-things, many things can stay connected; however, biological systems, including those necessary for human health, remain unable to stay connected to the global Internet due to the lack of soft conformal biosensors. The fundamental challenge lies in the fact that electronics and biology are distinct and incompatible, as they are based on different materials via different functioning principles. In particular, the human body is soft and curvilinear, yet electronics are typically rigid and planar. Recent advances in materials and materials design have generated tremendous opportunities to design soft wearable bioelectronics, which may bridge the gap, enabling the ultimate dream of connected healthcare for anyone, anytime, and anywhere. We begin with a review of the historical development of healthcare, indicating the significant trend of connected healthcare. This is followed by the focal point of discussion about new materials and materials design, particularly low-dimensional nanomaterials. We summarize material types and their attributes for designing soft bioelectronic sensors; we also cover their synthesis and fabrication methods, including top-down, bottom-up, and their combined approaches. Next, we discuss the wearable energy challenges and progress made to date. In addition to front-end wearable devices, we also describe back-end machine learning algorithms, artificial intelligence, telecommunication, and software. Afterward, we describe the integration of soft wearable bioelectronic systems which have been applied in various testbeds in real-world settings, including laboratories that are preclinical and clinical environments. Finally, we narrate the remaining challenges and opportunities in conjunction with our perspectives.

Self-powered, light-controlled, bioresorbable platforms for programmed drug delivery.

Degradable polymer matrices and porous scaffolds provide powerful mechanisms for passive, sustained release of drugs relevant to the treatment of a broad range of diseases and conditions. Growing interest is in active control of pharmacokinetics tailored to the needs of the patient via programmable engineering platforms that include power sources, delivery mechanisms, communication hardware, and associated electronics, most typically in forms that require surgical extraction after a period of use. Here we report a light-controlled, self-powered technology that bypasses key disadvantages of these systems, in an overall design that is bioresorbable. Programmability relies on the use of an external light source to illuminate an implanted, wavelength-sensitive phototransistor to trigger a short circuit in an electrochemical cell structure that includes a metal gate valve as its anode. Consequent electrochemical corrosion eliminates the gate, thereby opening an underlying reservoir to release a dose of drugs by passive diffusion into surrounding tissue. A wavelength-division multiplexing strategy allows release to be programmed from any one or any arbitrary combination of a collection of reservoirs built into an integrated device. Studies of various bioresorbable electrode materials define the key considerations and guide optimized choices in designs. In vivo demonstrations of programmed release of lidocaine adjacent the sciatic nerves in rat models illustrate the functionality in the context of pain management, an essential aspect of patient care that could benefit from the results presented here.

Biosymbiotic platform for chronic long-range monitoring of biosignals in limited resource settings.

Remote patient monitoring is a critical component of digital medicine, and the COVID-19 pandemic has further highlighted its importance. Wearable sensors aimed at noninvasive extraction and transmission of high-fidelity physiological data provide an avenue toward at-home diagnostics and therapeutics; however, the infrastructure requirements for such devices limit their use to areas with well-established connectivity. This accentuates the socioeconomic and geopolitical gap in digital health technology and points toward a need to provide access in areas that have limited resources. Low-power wide area network (LPWAN) protocols, such as LoRa, may provide an avenue toward connectivity in these settings; however, there has been limited work on realizing wearable devices with this functionality because of power and electromagnetic constraints. In this work, we introduce wearables with electromagnetic, electronic, and mechanical features provided by a biosymbiotic platform to realize high-fidelity biosignals transmission of 15 miles without the need for satellite infrastructure. The platform implements wireless power transfer for interaction-free recharging, enabling long-term and uninterrupted use over weeks without the need for the user to interact with the devices. This work presents demonstration of a continuously wearable device with this long-range capability that has the potential to serve resource-constrained and remote areas, providing equitable access to digital health.