Self-Healing Materials for Electronics Applications.

Self-healing materials have been attracting the attention of the scientists over the past few decades because of their effectiveness in detecting damage and their autonomic healing response. Self-healing materials are an evolving and intriguing field of study that could lead to a substantial increase in the lifespan of materials, improve the reliability of materials, increase product safety, and lower product replacement costs. Within the past few years, various autonomic and non-autonomic self-healing systems have been developed using various approaches for a variety of applications. The inclusion of appropriate functionalities into these materials by various chemistries has enhanced their repair mechanisms activated by crack formation. This review article summarizes various self-healing techniques that are currently being explored and the associated chemistries that are involved in the preparation of self-healing composite materials. This paper further surveys the electronic applications of self-healing materials in the fields of energy harvesting devices, energy storage devices, and sensors. We expect this article to provide the reader with a far deeper understanding of self-healing materials and their healing mechanisms in various electronics applications.

Self-Healing Functional Electronic Devices.

Electronic devices with various functions bring great convenience and revolutionize the way we live. They are inevitable to degrade over time because of physical or chemical fatigue and damage during practical operation. To make these devices have the ability to autonomously heal from cracks and restore their mechanical and electrical properties, self-healing materials emerged as the time requires for constructing robust and self-healing electronic devices. Here the development of self-healing electronic devices with different functions, for example, energy harvesting, energy storage, sensing, and transmission, is reviewed. The new application scenarios and existing challenges are explored, and possible strategies and perspectives for future practical applications are discussed.

An integrated interface for peripheral neural system recording and stimulation: system design, electrical tests and in-vivo results.

The prototype of an electronic bi-directional interface between the Peripheral Nervous System (PNS) and a neuro-controlled hand prosthesis is presented. The system is composed of 2 integrated circuits: a standard CMOS device for neural recording and a HVCMOS device for neural stimulation. The integrated circuits have been realized in 2 different 0.35µ m CMOS processes available from ams. The complete system incorporates 8 channels each including the analog front-end, the A/D conversion, based on a sigma delta architecture and a programmable stimulation module implemented as a 5-bit current DAC; two voltage boosters supply the output stimulation stage with a programmable voltage scalable up to 17V. Successful in-vivo experiments with rats having a TIME electrode implanted in the sciatic nerve were carried out, showing the capability of recording neural signals in the tens of microvolts, with a global noise of 7µ V r m s , and to selectively elicit the tibial and plantar muscles using different active sites of the electrode.

Sensing, Imaging, and Therapeutic Strategies Endowing by Conjugate Polymers for Precision Medicine.

Conjugated polymers (CPs) have promising applications in biomedical fields, such as disease monitoring, real-time imaging diagnosis, and disease treatment. As a promising luminescent material with tunable emission, high brightness and excellent stability, CPs are widely used as fluorescent probes in biological detection and imaging. Rational molecular design and structural optimization have broadened absorption/emission range of CPs, which are more conductive for disease diagnosis and precision therapy. This review provides a comprehensive overview of recent advances in the application of CPs, aiming to elucidate their structural and functional relationships. The fluorescence properties of CPs and the mechanism of detection signal amplification are first discussed, followed by an elucidation of their emerging applications in biological detection. Subsequently, CPs-based imaging systems and therapeutic strategies are illustrated systematically. Finally, recent advancements in utilizing CPs as electroactive materials for bioelectronic devices are also investigated. Moreover, the challenges and outlooks of CPs for precision medicine are discussed. Through this systematic review, it is hoped to highlight the frontier progress of CPs and promote new breakthroughs in fundamental research and clinical transformation.

Biomimetic Exogenous "Tissue Batteries" as Artificial Power Sources for Implantable Bioelectronic Devices Manufacturing.

Implantable bioelectronic devices (IBDs) have gained attention for their capacity to conformably detect physiological and pathological signals and further provide internal therapy. However, traditional power sources integrated into these IBDs possess intricate limitations such as bulkiness, rigidity, and biotoxicity. Recently, artificial "tissue batteries" (ATBs) have diffusely developed as artificial power sources for IBDs manufacturing, enabling comprehensive biological-activity monitoring, diagnosis, and therapy. ATBs are on-demand and designed to accommodate the soft and confining curved placement space of organisms, minimizing interface discrepancies, and providing ample power for clinical applications. This review presents the near-term advancements in ATBs, with a focus on their miniaturization, flexibility, biodegradability, and power density. Furthermore, it delves into material-screening, structural-design, and energy density across three distinct categories of TBs, distinguished by power supply strategies. These types encompass innovative energy storage devices (chemical batteries and supercapacitors), power conversion devices that harness power from human-body (biofuel cells, thermoelectric nanogenerators, bio-potential devices, piezoelectric harvesters, and triboelectric devices), and energy transfer devices that receive and utilize external energy (radiofrequency-ultrasound energy harvesters, ultrasound-induced energy harvesters, and photovoltaic devices). Ultimately, future challenges and prospects emphasize ATBs with the indispensability of bio-safety, flexibility, and high-volume energy density as crucial components in long-term implantable bioelectronic devices.

Tough and Water-Resistant Bioelastomers with Active-Controllable Degradation Rates.

Biodegradable electronic devices have gained significant traction in modern medical applications. These devices are generally desired to have a long enough working lifetime for stable operation and allow for active control over their degradation rates after usage. However, current biodegradable materials used as encapsulations or substrates for these devices are challenging to meet the two requirements due to the constraints of inadequate water resistance, poor mechanical properties, and passive degradation characteristics. Herein, we develop a novel biodegradable elastomer named POC-SS-Res by introducing disulfide linkage and resveratrol (Res) into poly(1,8-octanediol-co-citrate) (POC). Compared to POC, POC-SS-Res exhibits good water resistance and excellent mechanical properties in PBS, providing effective protection for devices. At the same time, POC-SS-Res offers the unique advantage of an active-controllable degradation rate, and its degradation products express low biotoxicity. Good biocompatibility of POC-SS-Res is also demonstrated. Bioelectronic components encapsulated with POC-SS-Res have an obvious prolongation of working lifetime in PBS compared to that encapsulated with POC, and its degradation rate can be actively controlled by the addition of glutathione (GSH).

Flexible Organic Electronic Ion Pump for Flow-Free Phytohormone Delivery into Vasculature of Intact Plants.

Plant vasculature transports molecules that play a crucial role in plant signaling including systemic responses and acclimation to diverse environmental conditions. Targeted controlled delivery of molecules to the vascular tissue can be a biomimetic way to induce long distance responses, providing a new tool for the fundamental studies and engineering of stress-tolerant plants. Here, a flexible organic electronic ion pump, an electrophoretic delivery device, for controlled delivery of phytohormones directly in plant vascular tissue is developed. The c-OEIP is based on polyimide-coated glass capillaries that significantly enhance the mechanical robustness of these microscale devices while being minimally disruptive for the plant. The polyelectrolyte channel is based on low-cost and commercially available precursors that can be photocured with blue light, establishing much cheaper and safer system than the state-of-the-art. To trigger OEIP-induced plant response, the phytohormone abscisic acid (ABA) in the petiole of intact Arabidopsis plants is delivered. ABA is one of the main phytohormones involved in plant stress responses and induces stomata closure under drought conditions to reduce water loss and prevent wilting. The OEIP-mediated ABA delivery triggered fast and long-lasting stomata closure far away from the delivery point demonstrating systemic vascular transport of the delivered ABA, verified delivering deuterium-labeled ABA.

Highly conformable chip-in-foil implants for neural applications.

Demands for neural interfaces around functionality, high spatial resolution, and longevity have recently increased. These requirements can be met with sophisticated silicon-based integrated circuits. Embedding miniaturized dice in flexible polymer substrates significantly improves their adaptation to the mechanical environment in the body, thus improving the systems' structural biocompatibility and ability to cover larger areas of the brain. This work addresses the main challenges in developing a hybrid chip-in-foil neural implant. Assessments considered (1) the mechanical compliance to the recipient tissue that allows a long-term application and (2) the suitable design that allows the implant's scaling and modular adaptation of chip arrangement. Finite element model studies were performed to identify design rules regarding die geometry, interconnect routing, and positions for contact pads on dice. Providing edge fillets in the die base shape proved an effective measure to improve die-substrate integrity and increase the area available for contact pads. Furthermore, routing of interconnects in the immediate vicinity of die corners should be avoided, as the substrate in these areas is prone to mechanical stress concentration. Contact pads on dice should be placed with a clearance from the die rim to avoid delamination when the implant conforms to a curvilinear body. A microfabrication process was developed to transfer, align, and electrically interconnect multiple dice into conformable polyimide-based substrates. The process enabled arbitrary die shape and size over independent target positions on the conformable substrate based on the die position on the fabrication wafer.

Wearable bioelectronic masks for wireless detection of respiratory infectious diseases by gaseous media.

Respiratory infectious diseases (H1N1, H5N1, COVID-19, etc.) are pandemics that can continually spread in the air through micro-droplets or aerosols. However, the detection of samples in gaseous media is hampered by the requirement for trace amounts and low concentrations. Here, we develop a wearable bioelectronic mask device integrated with ion-gated transistors. Based on the sensitive gating effect of ion gels, our aptamer-functionalized transistors can measure trace-level liquid samples (0.3 µL) and even gaseous media samples at an ultra-low concentration (0.1 fg/mL). The ion-gated transistor with multi-channel analysis can respond to multiple targets simultaneously within as fast as 10 min, especially without sample pretreatment. Integrating a wireless internet of things system enables the wearable mask to achieve real-time and on-site detection of the surrounding air, providing an alert before infection. The wearable bioelectronic masks hold promise to serve as an early warning system to prevent outbreaks of respiratory infectious diseases.

A feedback control architecture for bioelectronic devices with applications to wound healing.

Bioelectronic devices can provide an interface for feedback control of biological processes in real-time based on sensor information tracking biological response. The main control challenges are guaranteeing system convergence in the presence of saturating inputs into the bioelectronic device and complexities from indirect control of biological systems. In this paper, we first derive a saturated-based robust sliding mode control design for a partially unknown nonlinear system with disturbance. Next, we develop a data informed model of a bioelectronic device for in silico simulations. Our controller is then applied to the model to demonstrate controlled pH of a target area. A modular control architecture is chosen to interface the bioelectronic device and controller with a bistable phenomenological model of wound healing to demonstrate closed-loop biological treatment. External pH is regulated by the bioelectronic device to accelerate wound healing, while avoiding chronic inflammation. Our novel control algorithm for bioelectronic devices is robust and requires minimum information about the device for broad applicability. The control architecture makes it adaptable to any biological system and can be used to enhance automation in bioengineering to improve treatments and patient outcomes.

An Oligonucleotide-Distortion-Responsive Organic Transistor for Platinum-Drug-Induced DNA-Damage Detection.

Organic transistor with DNA-damage evaluation ability can open up novel opportunities for bioelectronic devices. Even though trace amounts of drugs can cause cumulative gene damage in vivo, the extremely low occurrence proportion makes them hardly transduced into detectable electric signals. Here, an ultrasensitive DNA-damage sensor based on an oligonucleotide-distortion-responsive organic transistor (DROT) is reported by creating controllable conformation change of double-stranded DNA on the surface of organic semiconductors. In combination with interfacial charge redistribution and efficient signal amplification, the DROT provides an ultrasensitive single-site DNA-damage response with 20.5 s even upon 1 × 10-12 m cisplatin. The high generalizability of this DROT to three generations of classical platinum drugs and gene-relevant DNA damage is demonstrated. A biochip is further designed for intelligent damage analysis in complex environments, which holds the potential for high-throughput biotoxicity evaluation and drug screening in the future.

Carbon-based neural electrodes: promises and challenges.

Neural electrodes are primary functional elements of neuroelectronic devices designed to record neural activity based on electrochemical signals. These electrodes may also be utilized for electrically stimulating the neural cells, such that their response can be simultaneously recorded. In addition to being medically safe, the electrode material should be electrically conductive and electrochemically stable under harsh biological environments. Mechanical flexibility and conformability, resistance to crack formation and compatibility with common microfabrication techniques are equally desirable properties. Traditionally, (noble) metals have been the preferred for neural electrode applications due to their proven biosafety and a relatively high electrical conductivity. Carbon is a recent addition to this list, which is far superior in terms of its electrochemical stability and corrosion resistance. Carbon has also enabled 3D electrode fabrication as opposed to the thin-film based 2D structures. One of carbon's peculiar aspects is its availability in a wide range of allotropes with specialized properties that render it highly versatile. These variations, however, also make it difficult to understand carbon itself as a unique material, and thus, each allotrope is often regarded independently. Some carbon types have already shown promising results in bioelectronic medicine, while many others remain potential candidates. In this topical review, we first provide a broad overview of the neuroelectronic devices and the basic requirements of an electrode material. We subsequently discuss the carbon family of materials and their properties that are useful in neural applications. Examples of devices fabricated using bulk and nano carbon materials are reviewed and critically compared. We then summarize the challenges, future prospects and next-generation carbon technology that can be helpful in the field of neural sciences. The article aims at providing a common platform to neuroscientists, electrochemists, biologists, microsystems engineers and carbon scientists to enable active and comprehensive efforts directed towards carbon-based neuroelectronic device fabrication.

Neurosensory Prosthetics: An Integral Neuromodulation Part of Bioelectronic Device.

Bioelectronic medicines (BEMs) constitute a branch of bioelectronic devices (BEDs), which are a class of therapeutics that combine neuroscience with molecular biology, immunology, and engineering technologies. Thus, BEMs are the culmination of thought processes of scientists of varied fields and herald a new era in the treatment of chronic diseases. BEMs work on the principle of neuromodulation of nerve stimulation. Examples of BEMs based on neuromodulation are those that modify neural circuits through deep brain stimulation, vagal nerve stimulation, spinal nerve stimulation, and retinal and auditory implants. BEDs may also serve as diagnostic tools by mimicking human sensory systems. Two examples of in vitro BEDs used as diagnostic agents in biomedical applications based on in vivo neurosensory circuits are the bioelectronic nose and bioelectronic tongue. The review discusses the ever-growing application of BEDs to a wide variety of health conditions and practices to improve the quality of life.

PEDOT:PSS-Based Bioelectronic Devices for Recording and Modulation of Electrophysiological and Biochemical Cell Signals.

To understand the physiology and pathology of electrogenic cells and the corresponding tissue in their full complexity, the quantitative investigation of the transmission of ions as well as the release of chemical signals is important. Organic (semi-) conducting materials and in particular organic electrochemical transistor are gaining in importance for the investigation of electrophysiological and recently biochemical signals due to their synthetic nature and thus chemical diversity and modifiability, their biocompatible and compliant properties, as well as their mixed electronic and ionic conductivity featuring ion-to-electron conversion. Here, the aim is to summarize recent progress on the development of bioelectronic devices utilizing polymer polyethylenedioxythiophene: poly(styrene sulfonate) (PEDOT:PSS) to interface electronics and biological matter including microelectrode arrays, neural cuff electrodes, organic electrochemical transistors, PEDOT:PSS-based biosensors, and organic electronic ion pumps. Finally, progress in the material development is summarized for the improvement of polymer conductivity, stretchability, higher transistor transconductance, or to extend their field of application such as cation sensing or metabolite recognition. This survey of recent trends in PEDOT:PSS electrophysiological sensors highlights the potential of this multifunctional material to revolve current technology and to enable long-lasting, multichannel polymer probes for simultaneous recordings of electrophysiological and biochemical signals from electrogenic cells.

Nanobiohybrid Material-Based Bioelectronic Devices.

Biomolecules, especially proteins and nucleic acids, have been widely studied to develop biochips for various applications in scientific fields ranging from bioelectronics to stem cell research. However, restrictions exist due to the inherent characteristics of biomolecules, such as instability and the constraint of granting the functionality to the biochip. Introduction of functional nanomaterials, recently being researched and developed, to biomolecules have been widely researched to develop the nanobiohybrid materials because such materials have the potential to enhance and extend the function of biomolecules on a biochip. The potential for applying nanobiohybrid materials is especially high in the field of bioelectronics. Research in bioelectronics is aimed at realizing electronic functions using the inherent properties of biomolecules. To achieve this, various biomolecules possessing unique properties have been combined with novel nanomaterials to develop bioelectronic devices such as highly sensitive electrochemical-based bioelectronic sensing platforms, logic gates, and biocomputing systems. In this review, recently reported bioelectronic devices based on nanobiohybrid materials are discussed. The authors believe that this review will suggest innovative and creative directions to develop the next generation of multifunctional bioelectronic devices.

Standalone operation of an EGOFET for ultra-sensitive detection of HIV.

A point-of-care (POC) device to enable de-centralized diagnostics can effectively reduce the time to treatment, especially in case of infectious diseases. However, many of the POC solutions presented so far do not comply with the ASSURED (affordable, sensitive, specific, user-friendly, rapid and robust, equipment free, and deliverable to users) guidelines that are needed to ensure their on-field deployment. Herein, we present the proof of concept of a self-powered platform that operates using the analysed fluid, mimicking a blood sample, for early stage detection of HIV-1 infection. The platform contains a smart interfacing circuit to operate an ultra-sensitive electrolyte-gated field-effect transistor (EGOFET) as a sensor and facilitates an easy and affordable readout mechanism. The sensor transduces the bio-recognition event taking place at the gate electrode functionalized with the antibody against the HIV-1 p24 capsid protein, while it is powered via paper-based biofuel cell (BFC) that extracts the energy from the analysed sample itself. The self-powered platform is demonstrated to achieve detection of HIV-1 p24 antigens in fM range, suitable for early diagnosis. From these developments, a cost-effective digital POC device able to detect the transition from "healthy" to "infected" state at single-molecule precision, with no dependency on external power sources while using minimal components and simpler approach, is foreseen.

Development of Bioelectronic Devices Using Bionanohybrid Materials for Biocomputation System.

Bioelectronic devices have been researched widely because of their potential applications, such as information storage devices, biosensors, diagnosis systems, organism-mimicking processing system cell chips, and neural-mimicking systems. Introducing biomolecules including proteins, DNA, and RNA on silicon-based substrates has shown the powerful potential for granting various functional properties to chips, including specific functional electronic properties. Until now, to extend and improve their properties and performance, organic and inorganic materials such as graphene and gold nanoparticles have been combined with biomolecules. In particular, bionanohybrid materials that are composed of biomolecules and other materials have been researched because they can perform core roles of information storage and signal processing in bioelectronic devices using the unique properties derived from biomolecules. This review discusses bioelectronic devices related to computation systems such as biomemory, biologic gates, and bioprocessors based on bionanohybrid materials with a selective overview of recent research. This review contains a new direction for the development of bioelectronic devices to develop biocomputation systems using biomolecules in the future.

Analysis of the Bipolar Resistive Switching Behavior of a Biocompatible Glucose Film for Resistive Random Access Memory.

Resistive random access memory (RRAM) devices are fabricated through a simple solution process using glucose, which is a natural biomaterial for the switching layer of RRAM. The fabricated glucose-based RRAM device shows nonvolatile bipolar resistive switching behavior, with a switching window of 103 . In addition, the endurance and data retention capability of glucose-based RRAM exhibit stable characteristics up to 100 consecutive cycles and 104 s under constant voltage stress at 0.3 V. The interface between the top electrode and the glucose film is carefully investigated to demonstrate the bipolar switching mechanism of the glucose-based RRAM device. The glucose based-RRAM is also evaluated on a polyimide film to verify the possibility of a flexible platform. Additionally, a cross-bar array structure with a magnesium electrode is prepared on various substrates to assess the degradability and biocompatibility for the implantable bioelectronic devices, which are harmless and nontoxic to the human body. It is expected that this research can provide meaningful insights for developing the future bioelectronic devices.

Generation of electrical power under human skin by subdermal solar cell arrays for implantable bioelectronic devices.

Medical electronic implants can significantly improve people's health and quality of life. These implants are typically powered by batteries, which usually have a finite lifetime and therefore must be replaced periodically using surgical procedures. Recently, subdermal solar cells that can generate electricity by absorbing light transmitted through skin have been proposed as a sustainable electricity source to power medical electronic implants in bodies. However, the results to date have been obtained with animal models. To apply the technology to human beings, electrical performance should be characterized using human skin covering the subdermal solar cells. In this paper, we present electrical performance results (up to 9.05mW/cm2) of the implantable solar cell array under 59 human skin samples isolated from 10 cadavers. The results indicate that the power densities depend on the thickness and tone of the human skin, e.g., higher power was generated under thinner and brighter skin. The generated power density is high enough to operate currently available medical electronic implants such as pacemakers that require tens of microwatt.

Improvement Strategies, Cost Effective Production, and Potential Applications of Fungal Glucose Oxidase (GOD): Current Updates.

Fungal glucose oxidase (GOD) is widely employed in the different sectors of food industries for use in baking products, dry egg powder, beverages, and gluconic acid production. GOD also has several other novel applications in chemical, pharmaceutical, textile, and other biotechnological industries. The electrochemical suitability of GOD catalyzed reactions has enabled its successful use in bioelectronic devices, particularly biofuel cells, and biosensors. Other crucial aspects of GOD such as improved feeding efficiency in response to GOD supplemental diet, roles in antimicrobial activities, and enhancing pathogen defense response, thereby providing induced resistance in plants have also been reported. Moreover, the medical science, another emerging branch where GOD was recently reported to induce several apoptosis characteristics as well as cellular senescence by downregulating Klotho gene expression. These widespread applications of GOD have led to increased demand for more extensive research to improve its production, characterization, and enhanced stability to enable long term usages. Currently, GOD is mainly produced and purified from Aspergillus niger and Penicillium species, but the yield is relatively low and the purification process is troublesome. It is practical to build an excellent GOD-producing strain. Therefore, the present review describes innovative methods of enhancing fungal GOD production by using genetic and non-genetic approaches in-depth along with purification techniques. The review also highlights current research progress in the cost effective production of GOD, including key advances, potential applications and limitations. Therefore, there is an extensive need to commercialize these processes by developing and optimizing novel strategies for cost effective GOD production.