glasses, watches, wristbands, or belts, are either fully or partially composed of planar and rigid materials, which require the use of obtrusive, hard supports or additional bendable strips to be mounted on the human body. Therefore, clinical devices that use the existing wearables cause discomfort and limit monitoring of human physiological data in the laboratory. This is the big limitation factor to overcome despite the ever-growing market for wearables in broader screenings outside of the clinic. By this account, it is necessary to replace the bulky and rigid plastics and metal components in the sensors and electronics with skin-like materials for enhanced wearability and functionality.The concept of WFHE poses a possible solution to address the aforementioned difficulties by providing user comfort, compliant mechanics, soft integration, multifunctionality, and smart diagnostics with embedded machine learning algorithms. Specifically, such electronics would provide stable and intimate contact to the soft human skin without adding any mechanical and thermal loadings or causing skin breakdown. Current development strategies and approaches for advanced WFHE focus on soft, flexible form factors, nonirritating and nontoxic characteristics, fully autonomous energy components, seamless wireless communications, Recent advances in soft materials and system integration technologies have provided a unique opportunity to design various types of wearable flexible hybrid electronics (WFHE) for advanced human healthcare and humanmachine interfaces. The hybrid integration of soft and biocompatible materials with miniaturized wireless wearable systems is undoubtedly an attractiveprospect in the sense that the successful device performance requires high degrees of mechanical flexibility, sensing capability, and user-friendly simplicity. Here, the most up-to-date materials, sensors, and system-packaging technologies to develop advanced WFHE are provided. Details of mechanical, electrical, physicochemical, and biocompatible properties are discussed with integrated sensor applications in healthcare, energy, and environment. In addition, limitations of the current materials are discussed, as well as key challenges and the future direction of WFHE. Collectively, an all-inclusive review of the newly developed WFHE along with a summary of imperative requirements of material properties, sensor capabilities, electronics performance, and skin integrations is provided. Wearable Flexible Hybrid ElectronicsThe ORCID identification number(s) for the author(s) of this article can be found under https://doi.

Researchers report advances in materials and designs for skin-integrated devices capable of measuring acoustic signatures.

Combination of optogenetics and pharmacology represents a unique approach to dissect neural circuitry with high specificity and versatility. However, conventional tools available to perform these experiments, such as optical fibers and metal cannula, are limited due to their tethered operation and lack of biomechanical compatibility. To address these issues, a miniaturized, battery-free, soft optofluidic system that can provide wireless drug delivery and optical stimulation for spatiotemporal control of the targeted neural circuit in freely behaving animals is reported. The device integrates microscale inorganic light-emitting diodes and microfluidic drug delivery systems with a tiny stretchable multichannel radiofrequency antenna, which not only eliminates the need for bulky batteries but also offers fully wireless, independent control of light and fluid delivery. This design enables a miniature (125 mm ), lightweight (220 mg), soft, and flexible platform, thus facilitating seamless implantation and operation in the body without causing disturbance of naturalistic behavior. The proof-of-principle experiments and analytical studies validate the feasibility and reliability of the fully implantable optofluidic systems for use in freely moving animals, demonstrating its potential for wireless in vivo pharmacology and optogenetics.

Traditionally, electronics have been designed with static form factors to serve designated purposes. This approach has been an optimal direction for maintaining the overall device performance and reliability for targeted applications. However, electronics capable of changing their shape, flexibility, and stretchability will enable versatile and accommodating systems for more diverse applications. Here, we report design concepts, materials, physics, and manufacturing strategies that enable these reconfigurable electronic systems based on temperature-triggered tuning of mechanical characteristics of device platforms. We applied this technology to create personal electronics with variable stiffness and stretchability, a pressure sensor with tunable bandwidth and sensitivity, and a neural probe that softens upon integration with brain tissue. Together, these types of transformative electronics will substantially broaden the use of electronics for wearable and implantable applications.

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Optogenetics is a powerful technique that allows target-specific spatiotemporal manipulation of neuronal activity for dissection of neural circuits and therapeutic interventions. Recent advances in wireless optogenetics technologies have enabled investigation of brain circuits in more natural conditions by releasing animals from tethered optical fibers. However, current wireless implants, which are largely based on battery-powered or battery-free designs, still limit the full potential of in vivo optogenetics in freely moving animals by requiring intermittent battery replacement or a special, bulky wireless power transfer system for continuous device operation, respectively. To address these limitations, here we present a wirelessly rechargeable, fully implantable, soft optoelectronic system that can be remotely and selectively controlled using a smartphone. Combining advantageous features of both battery-powered and battery-free designs, this device system enables seamless full implantation into animals, reliable ubiquitous operation, and intervention-free wireless charging, all of which are desired for chronic in vivo optogenetics. Successful demonstration of the unique capabilities of this device in freely behaving rats forecasts its broad and practical utilities in various neuroscience research and clinical applications.

This Protocol Extension describes the fabrication and technical procedures for implementing ultrathin, flexible optofluidic neural probe systems that provide targeted, wireless delivery of fluids and light into the brains of awake, freely behaving animals. As a Protocol Extension article, this article describes an adaptation of an existing Protocol that offers additional applications. This protocol serves as an extension of an existing Nature Protocol describing optoelectronic devices for studying intact neural systems. Here, we describe additional features of fabricating self-contained platforms that involve flexible microfluidic probes, pumping systems, microscale inorganic LEDs, wireless-control electronics, and power supplies. These small, flexible probes minimize tissue damage and inflammation, making long-term implantation possible. The capabilities include wireless pharmacological and optical intervention for dissecting neural circuitry during behavior. The fabrication can be completed in 1-2 weeks, and the devices can be used for 1-2 weeks of in vivo rodent experiments. To successfully carry out the protocol, researchers should have basic skill sets in photolithography and soft lithography, as well as experience with stereotaxic surgery and behavioral neuroscience practices. These fabrication processes and implementation protocols will increase access to wireless optofluidic neural probes for advanced in vivo pharmacology and optogenetics in freely moving rodents.This protocol is an extension to: Nat. Protoc. 8, 2413-2428 (2013); doi:10.1038/nprot.2013.158; published online 07 November 2013.

Billions of neurons in the brain coordinate together to control trillions of highly convoluted synaptic pathways for neural signal processing. Optogenetics is an emerging technique that can dissect such complex neural circuitry with high spatiotemporal precision using light. However, conventional approaches relying on rigid and tethered optical probes cause significant tissue damage as well as disturbance with natural behavior of animals, thus preventing chronic in vivo optogenetics. A microscale inorganic LED (μ-ILED) is an enabling optical component that can solve these problems by facilitating direct discrete spatial targeting of neural tissue, integration with soft, ultrathin probes as well as low power wireless operation. Here we review recent state-of-the art μ-ILED integrated soft wireless optogenetic tools suitable for use in freely moving animals and discuss opportunities for future developments.