Active Micro-Nano-Collaborative Bioelectronic Device for Advanced Electrophysiological Recording

The development of precise and sensitive electrophysiological recording platforms holds the utmost importance for research in the fields of cardiology and neuroscience.In recent years,active micro/nano-bioelectronic devices have undergone significant advancements,thereby facilitating the study of electrophysiology.The distinctive configuration and exceptional functionality of these active micro-nano-collaborative bioelectronic devices offer the potential for the recording of high-fidelity action potential signals on a large scale.In this paper,we review three-dimensional active nano-transistors and planar active micro-transistors in terms of their applications in electroexcitable cells,focusing on the evaluation of the effects of active micro/nano-bioelectronic devices on electrophysiological signals.Looking forward to the possibilities,challenges,and wide prospects of active micro-nano-devices,we expect to advance their progress to satisfy the demands of theoretical investigations and medical implementations within the domains of cardiology and neuroscience research.

Device design principles and bioelectronic applications for flexible organic electrochemical transistors

Organic electrochemical transistors(OECTs) exhibit significant potential for applications in healthcare and human-machine interfaces, due to their tunable synthesis, facile deposition, and excellent biocompatibility. Expanding OECTs to the fexible devices will significantly facilitate stable contact with the skin and enable more possible bioelectronic applications. In this work,we summarize the device physics of fexible OECTs, aiming to offer a foundational understanding and guidelines for material selection and device architecture. Particular attention is paid to the advanced manufacturing approaches, including photolithography and printing techniques, which establish a robust foundation for the commercialization and large-scale fabrication. And abundantly demonstrated examples ranging from biosensors, artificial synapses/neurons, to bioinspired nervous systems are summarized to highlight the considerable prospects of smart healthcare. In the end, the challenges and opportunities are proposed for fexible OECTs. The purpose of this review is not only to elaborate on the basic design principles of fexible OECTs, but also to act as a roadmap for further exploration of wearable OECTs in advanced bio-applications.

Tailoring Food Biopolymers into Biogels for Regenerative Wound Healing and Versatile Skin Bioelectronics

An increasing utilization of wound-related therapeutic materials and skin bioelectronics urges the development of multifunctional biogels for personal therapy and health management.Nevertheless,conventional dressings and skin bioelectronics with single function,mechanical mismatches,and impracticality severely limit their widespread applications in clinical.Herein,we explore a gelling mechanism,fabrication method,and functionalization for broadly applicable food biopolymers-based biogels that unite the challenging needs of elastic yet injectable wound dressing and skin bioelectronics in a single system.We combine our biogels with functional nanomaterials,such as cuttlefish ink nanoparticles and silver nanowires,to endow the biogels with reactive oxygen species scavenging capacity and electrical conductivity,and finally realized the improvement in diabetic wound microenvironment and the monitoring of electrophysiological signals on skin.This line of research work sheds light on preparing food biopolymers-based biogels with multifunctional integration of wound treatment and smart medical treatment.

Adhesive hydrogels for bioelectronics

Benefiting from the unique advantages of superior biocompatibility,strong stability,good biodegradability,and adjustable mechanical properties,hydrogels have attracted extensive research interests in bioelectronics.However,due to the existence of an interface between hydrogels and human tissues,the transmission of electrical signals from the human tissues to the hydrogel electronic devices will be hindered.The adhesive hydrogels with adhesive properties can tightly combine with the human tissue,which can enhance the contact between the electronic devices and human tissues and reduce the contact resistance,thereby improving the performance of hydrogel electronic devices.In this review,we will discuss in detail the adhesion mechanism of adhesive hydrogels and elaborate on the design principles of adhesive hydrogels.After that,we will introduce some methods of performance evaluation for adhesive hydrogels.Finally,we will provide a perspective on the development of adhesive hydrogel bioelectronics.

Mussel‑Inspired Redox‑Active and Hydrophilic Conductive Polymer Nanoparticles for Adhesive Hydrogel Bioelectronics

Conductive polymers(CPs)are generally insoluble,and developing hydrophilic CPs is significant to broaden the applications of CPs.In this work,a mussel-inspired strategy was proposed to construct hydrophilic CP nanoparticles(CP NPs),while endowing the CP NPs with redox activity and biocompatibility.This is a universal strategy applicable for a series of CPs,including polyaniline,polypyrrole,and poly(3,4-ethylenedioxythiophene).The catechol/quinone contained sulfonated lignin(LS)was doped into various CPs to form CP/LS NPs with hydrophilicity,conductivity,and redox activity.These CP/LS NPs were used as versatile nanofillers to prepare the conductive hydrogels with long-term adhesiveness.The CP/LS NPs-incorporated hydrogels have a good conductivity because of the uniform distribution of the hydrophilic NPs in the hydrogel network,forming a well-connected electric path.The hydrogel exhibits long-term adhesiveness,which is attributed to the mussel-inspired dynamic redox balance of catechol/quinone groups on the CP/LS NPs.This conductive and adhesive hydrogel shows good electroactivity and biocompatibility and therefore has broad applications in electrostimulation of tissue regeneration and implantable bioelectronics.

Flexible energy storage devices for wearable bioelectronics

With the growing market of wearable devices for smart sensing and personalized healthcare applications,energy storage devices that ensure stable power supply and can be constructed in flexible platforms have attracted tremendous research interests.A variety of active materials and fabrication strategies of flexible energy storage devices have been intensively studied in recent years,especially for integrated self-powered systems and biosensing.A series of materials and applications for flexible energy storage devices have been studied in recent years.In this review,the commonly adopted fabrication methods of flexible energy storage devices are introduced.Besides,recent advances in integrating these energy devices into flexible self-powered systems are presented.Furthermore,the applications of flexible energy storage devices for biosensing are summarized.Finally,the prospects and challenges of the self-powered sensing system for wearable electronics are discussed.

Opportunities and challenges for developing closed-loop bioelectronic medicines

The peripheral nervous system plays a major role in the maintenance of our physiology. Several peripheral nerves intimately regulate the state of the brain, spinal cord, and visceral systems. A new class of therapeutics, called bioelectronic medicines, are being developed to precisely regulate physiology and treat dysfunction using peripheral nerve stimulation. In this review, we first discuss new work using closed-loop bioelectronic medicine to treat upper limb paralysis. In contrast to open-loop bioelectronic medicines, closed-loop approaches trigger ‘on demand' peripheral nerve stimulation due to a change in function(e.g., during an upper limb movement or a change in cardiopulmonary state). We also outline our perspective on timing rules for closedloop bioelectronic stimulation, interface features for non-invasively stimulating peripheral nerves, and machine learning algorithms to recognize disease events for closed-loop stimulation control. Although there will be several challenges for this emerging field, we look forward to future bioelectronic medicines that can autonomously sense changes in the body, to provide closed-loop peripheral nerve stimulation and treat disease.

Semi-Implantable Bioelectronics

Developing techniques to effectively and real-time monitor and regulate the interior environment of biological objects is significantly important for many biomedical engineering and scientific applications, including drug delivery, electrophysiological recording and regulation of intracellular activities. Semi-implantable bioelectronics is currently a hot spot in biomedical engineering research area, because it not only meets the increasing technical demands for precise detection or regulation of biological activities, but also provides a desirable platform for externally incorporating complex functionalities and electronic integration. Although there is less definition and summary to distinguish it from the well-reviewed non-invasive bioelectronics and fully implantable bioelectronics, semi-implantable bioelectronics have emerged as highly unique technology to boost the development of biochips and smart wearable device. Here, we reviewed the recent progress in this field and raised the concept of “Semi-implantable bioelectronics”, summarizing the principle and strategies of semi-implantable device for cell applications and in vivo applications, discussing the typical methodologies to access to intracellular environment or in vivo environment, biosafety aspects and typical applications. This review is meaningful for understanding in-depth the design principles, materials fabrication techniques, device integration processes, cell/tissue penetration methodologies, biosafety aspects, and applications strategies that are essential to the development of future minimally invasive bioelectronics.

Recent Advances in Organ Specific Wireless Bioelectronic Devices:Perspective on Biotelemetry and Power Transfer Using Antenna Systems

The integration of electronics and biology has spawned bioelectronics and opened exciting opportunities to fulfill the unmet needs of therapeutic treatments.Recent developments in nanoelectronics and soft and biocompatible materials have shown potential applicability to clinical practices,including physiological sensing,drug delivery,cardiovascular monitoring,and brain stimulation.To date,most bioelectronic devices require wired connections for electrical control,making their implantation complicated and inconvenient for patients.As an alternative,wireless technology is proliferating to create bioelectronics that offer noninvasive control,biotelemetry,and wireless power transfer(WPT).This review paper provides a comprehensive overview of wireless bioelectronics and ongoing developments in their applications for organ-specific treatments,including disorders and dysfunctions.The main emphasis is on delineating the key features of antennas,namely their radiation characteristics,materials,integration with rest of the electronics,and experimental setup.Although the recent progress in wireless mediated bioelectronics is expected to enhance the control of its functionalities,there are still numerous challenges that need to be addressed for commercialization,as well as to address everexpanding and evolving future therapeutic targets.

Intelligent structured nanocomposite adhesive for bioelectronics and soft robots

The remarkable functionality of biological systems in detecting and adapting to various environmental conditions has inspired the design of the latest electronics and robots with advanced features.This review focuses on intelligent bio-inspired strategies for developing soft bioelectronics and robotics that can accommodate nanocomposite adhesives and integrate them into biological surfaces.The underlying principles of the material and structural design of nanocomposite adhesives were investigated for practical applications with excellent functionalities,such as soft skin-attachable health care sensors,highly stretchable adhesive electrodes,switchable adhesion,and untethered soft robotics.In addition,we have discussed recent progress in the development of effective fabrication methods for micro/nanostructures for integration into devices,presenting the current challenges and prospects.

Long-Range Electronic Effect-Promoted Ring-Opening Polymerization of Thioctic Acid to Produce Biomimetic Ionic Elastomers for Bioelectronics

Poly(disulfide)s have been widely used in flexible wearable electronics,smart materials,and drug delivery.The synthesis of poly(disulfide)s usually utilizes external stimuli or toxic initiators to promote the polymerization.Here,we indicated that the long-range electronic effect can significantly alter the reactivity of the disulfide group.Accordingly,we established deprotonation-promoted ring-opening polymerization of thioctic acid(TA)as a highly effective and simple method to synthesize poly(disulfide)s due to the long-range electronic effect and nucleophilic carboxylate.Without external stimuli and initiators,simple mixing of TA and deprotonation reagent,choline bicarbonate,in different ratios at room temperature rapidly produced a series of high molecular weight(up to 772 kDa)ionic liquid crystal poly(disulfide)s elastomers with room temperature self-healing ability,adjustable conductivity(2.39×10^(−2)∼0.28×10^(−2)S m^(−1)),degradability,biocompatibility,antibacterial property,and tissue-like softness(Young’s moduli ranging from 18.2±6.0 to 111.1±36.7 kPa).The experiments and density functional theory calculations also revealed the principle of long-range electronic effect to establish a new synthetic strategy of poly(disulfide)s with superior properties favorable for bioelectronics.

Chemical Approaches to Emerging Advancements in Deformable Bioelectronics:Synthesis,Device Concepts,Performance,and Applications

This mini review examines the current advances and future prospects of chemical approaches in deformable bioelectronics,emphasizing their transformative potential in healthcare and other sectors.The mini review outlines novel fabrication strategies that rely on chemical principles to create adaptable,comfortable,and durable bioelectronic devices that are capable of seamlessly integrating into the dynamic biological environment.The discussion also extends to the integration of innovative device concepts that enhance the outcomes in both sensing and modulation functionalities.Performance-enhancing strategies that use chemistry to refine the sensitivity and precision of these devices are also highlighted.Moreover,the mini review explores the emerging applications of chemically enhanced bioelectronic devices in healthcare,reflecting the potential of this field to revolutionize patient care and improve health monitoring.In the outlook section,this mini review investigates the promising future of transient and living bioelectronics,emphasizing the pivotal role of chemical approaches in their development.It additionally covers the potential of chemical techniques in powering bioelectronic devices using biological systems and discusses the prospective applications of chemically synthesized bioelectronic devices outside of healthcare.While the field has made substantial progress,this mini review also identifies challenges that must be addressed,thus underlining the necessity for continued research and chemical innovation in bioelectronics.

Single-Molecule Bioelectronic Sensors with AI-Aided Data Analysis:Convergence and Challenges

Single-molecule bioelectronic sensing,a groundbreaking domain in biological research,has revolutionized our understanding of molecules by revealing deep insights into fundamental biological processes.The advent of emergent technologies,such as nanogapped electrodes and nanopores,has greatly enhanced this field,providing exceptional sensitivity,resolution,and integration capabilities.However,challenges persist,such as complex data sets with high noise levels and stochastic molecular dynamics.Artificial intelligence(AI)has stepped in to address these issues with its powerful data processing capabilities.AI algorithms effectively extract meaningful features,detect subtle changes,improve signal-to-noise ratios,and uncover hidden patterns in massive data.This review explores the synergy between AI and single-molecule bioelectronic sensing,focusing on how AI enhances signal processing and data analysis to boost accuracy and reliability.We also discuss current limitations and future directions for integrating AI,highlighting its potential to advance biological research and technological innovation.

Microfluidics-derived microfibers in flexible bioelectronics

Flexible electronics have attracted extensive attention across a wide range of fields due to their potential for preventive medicine and early disease detection.Microfiber-based textiles,encountered in everyday life,have emerged as promising platforms with integrated sensing capabilities.Microfluidic technology has been recognized as a promising avenue for the development of flexible conductive microfibers and has made significant achievements.In this review,we provide a comprehensive overview of the state-of-the-art advancements in microfiber-based flexible electronics fabricated using microfluidic platforms.Firstly,the fundamental strategies of the microfluidic fabrication of conductive microfibers with different structures and morphologies are introduced.Subsequently,attention is then directed towards the diverse applications of these microfibers in bioelectronics.Finally,we offer a forwardlooking perspective on the future challenges about microfluidic-derived microfibers in flexible bioelectronics.

Chemical Strategies of Tailoring PEDOT:PSS for Bioelectronic Applications:Synthesis,Processing and Device Fabrication

Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(PEDOT:PSS)has been the most prominent conducting polymer due to its outstanding electrical properties,chemical stability,biocompatibility,and commercial availability.In this mini review,we aimto comprehensively outline the chemical approaches employed in tailoring PEDOT:PSS for bioelectronic applications.We open our discussion by showcasing various synthetic techniques and commercially accessible forms of PEDOT:PSS,providing practical advice and approaches to greatly enhance its electrical properties,and presenting diverse chemical designs and processing methods that are essential for converting PEDOT:PSS into different form factors,such as fibers,gels,and films,for integration a range of device structures.Additionally,we explore several burgeoning applications of PEDOT:PSS in bioelectronics,ranging from wearable health monitoring to implantable neural interfaces,underscoring its essential impact on improving device efficiency and biological compatibility,as it opens avenues for innovative diagnostic and therapeutic techniques in the realm of precision medicine.Concluding with an outlook,the review presents insights into the ongoing challenges and future research paths for PEDOT:PSS in the ever-evolving landscape of bioelectronics.We emphasize the need for continued innovation in materials science and engineering to further harness the full potential of this dynamic domain.

Neuromodulation of the peripheral nervous system:Bioelectronic technology and prospective developments

The peripheral nervous system(PNS)is a fascinatingly complex and crucial component of the human body,responsible for transmitting vital signals throughout the body's intricate network of nerves.Its efficient functioning is paramount to our health,with any dysfunction often resulting in serious medical conditions,including motor disorders,neurological diseases,and psychiatric disorders.Recent strides in science and technology have made neuromodulation of the PNS a promising avenue for addressing these health issues.Neuromodulation involves modifying nerve activity using a range of techniques,such as electrical,chemical,optical,and mechanical stimulation.Bioelectronics plays a critical role in this effort,allowing for precise,controlled,and sustained stimulation of the PNS.This paper provides an overview of the PNS,discusses the current state of neuromodulation devices,and presents emerging trends in the field,including advances in wireless power transfer and materials,that are shaping the future of neuromodulation.

Flexible bioelectronic innovation for personalized health management

1|INTRODUCTION With the rapid developments in intelligent medical care and interdisciplinary science,innovative flexible bioelectronics(FBEs)are emerging for monitoring health,diagnosing and treating diseases,and even cancer therapy.FBEs subvert physical form and break through the bottleneck of traditional rigid electronics.

Chemically revised conducting polymers with inflammation resistance for intimate bioelectronic electrocoupling

Conducting polymers offer attractive mixed ionic-electronic conductivity,tunable interfacial barrier with metal,tissue matchable softness,and versatile chemical functionalization,making them robust to bridge the gap between brain tissue and electronic circuits.This review focuses on chemically revised conducting polymers,combined with their superior and controllable electrochemical performance,to fabricate long-term bioelectronic implants,addressing chronic immune responses,weak neuron attraction,and long-term electrocommunication instability challenges.Moreover,the promising progress of zwitterionic conducting polymers in bioelectronic implants(≥4 weeks stable implantation)is highlighted,followed by a comment on their current evolution toward selective neural coupling and reimplantable function.Finally,a critical forward look at the future of zwitterionic conducting polymers for in vivo bioelectronic devices is provided.

Gelatin-Based Metamaterial Hydrogel Films with High Conformality for Ultra-Soft Tissue Monitoring

Implantable hydrogel-based bioelectronics(IHB)can precisely monitor human health and diagnose diseases.However,achieving biodegradability,biocompatibility,and high conformality with soft tissues poses significant challenges for IHB.Gelatin is the most suitable candidate for IHB since it is a collagen hydrolysate and a substantial part of the extracellular matrix found naturally in most tissues.This study used 3D printing ultrafine fiber networks with metamaterial design to embed into ultra-low elastic modulus hydrogel to create a novel gelatin-based conductive film(GCF)with mechanical programmability.The regulation of GCF nearly covers soft tissue mechanics,an elastic modulus from 20 to 420 kPa,and a Poisson’s ratio from-0.25 to 0.52.The negative Poisson’s ratio promotes conformality with soft tissues to improve the efficiency of biological interfaces.The GCF can monitor heartbeat signals and respiratory rate by determining cardiac deformation due to its high conformability.Notably,the gelatin characteristics of the biodegradable GCF enable the sensor to monitor and support tissue restoration.The GCF metamaterial design offers a unique idea for bioelectronics to develop implantable sensors that integrate monitoring and tissue repair and a customized method for endowing implanted sensors to be highly conformal with soft tissues.

Potential of eNose Technology for Monitoring Biological CO_(2) Conversion Processes

Electronic nose(eNose) is a modern bioelectronic sensor for monitoring biological processes that convert CO_(2) into valueadded products, such as products formed during photosynthesis and microbial fermentation. eNose technology uses an array of sensors to detect and quantify gases, including CO_(2), in the air. This study briefly introduces the concept of eNose technology and potential applications thereof in monitoring CO_(2) conversion processes. It also provides background information on biological CO_(2) conversion processes. Furthermore, the working principles of eNose technology vis-à-vis gas detection are discussed along with its advantages and limitations versus traditional monitoring methods. This study also provides case studies that have used this technology for monitoring biological CO_(2) conversion processes. eNose-predicted measurements were observed to be completely aligned with biological parameters for R~2 values of 0.864, 0.808, 0.802, and 0.948. We test eNose technology in a variety of biological settings, such as algae farms or bioreactors, to determine its effectiveness in monitoring CO_(2) conversion processes. We also explore the potential benefits of employing this technology vis-à-vis monitoring biological CO_(2) conversion processes, such as increased reaction efficiency and reduced costs versus traditional monitoring methods. Moreover, future directions and challenges of using this technology in CO_(2) capture and conversion have been discussed. Overall, we believe this study would contribute to developing new and innovative methods for monitoring biological CO_(2) conversion processes and mitigating climate change.