Soft Bioelectronics Research Articles

Intelligent upper-limb exoskeleton integrated with soft bioelectronics and deep learning for intention-driven augmentation

The age and stroke-associated decline in musculoskeletal strength degrades the ability to perform daily human tasks using the upper extremities. Here, we introduce an intelligent upper-limb exoskeleton system that utilizes deep learning to predict human intention for strength augmentation. The embedded soft wearable sensors provide sensory feedback by collecting real-time muscle activities, which are simultaneously computed to determine the user’s intended movement. Cloud-based deep learning predicts four upper-limb joint motions with an average accuracy of 96.2% at a 500–550 ms response rate, suggesting that the exoskeleton operates just by human intention. In addition, an array of soft pneumatics assists the intended movements by providing 897 newtons of force while generating a displacement of 87 mm at maximum. The intent-driven exoskeleton can reduce human muscle activities by 3.7 times on average compared to the unassisted exoskeleton.

3D Printable Hydrogel Bioelectronic Interfaces for Healthcare Monitoring and Disease Diagnosis: Materials, Design Strategies, and Applications

AbstractIn recent years, additive manufacturing tools, such as 3D printing, has gained enormous attention in biomedical engineering for developing ionotropic devices, flexible electronics, skin‐electronic interfaces, and wearable sensors with extremely high precision and sensing accuracy. Such printed bioelectronics are innovative and can be used as multi‐stimuli response platforms for human health monitoring and disease diagnosis. This review systematically discusses the past, present, and future of the various printable and stretchable soft bioelectronics for precision medicine. The potential of various naturally and chemically derived conductive biopolymer inks and their nanocomposites with tunable physico‐chemical properties is also highlighted, which is crucial for bioelectronics fabrication. Then, the design strategies of various printable sensors for human body sensing are summarized. In conclusion, the perspectives on the future advanced bioelectronics are described, which will be helpful, particularly in the field of nano/biomedicine. An in‐depth knowledge of materials design to functional aspects of printable bioelectronics is demonstrated, with an aim to accelerate the development of next‐generation wearables.

Soft Bioelectronics for Neuroengineering: New Horizons in the Treatment of Brain Tumor and Epilepsy.

Soft bioelectronic technologies for neuroengineering have shown remarkable progress, which include novel soft material technologies and device design strategies. Such technological advances that are initiated from fundamental brain science are applied to clinical neuroscience and provided meaningful promises for significant improvement in the diagnosis efficiency and therapeutic efficacy of various brain diseases recently. System-level integration strategies in consideration of specific disease circumstances can enhance treatment effects further. Here, recent advances in soft implantable bioelectronics for neuroengineering, focusing on materials and device designs optimized for the treatment of intracranial disease environments, are reviewed. Various types of soft bioelectronics for neuroengineering are categorized and exemplified first, and then details for the sensing and stimulating device components are explained. Next, application examples of soft implantable bioelectronics to clinical neuroscience, particularly focusing on the treatment of brain tumor and epilepsy are reviewed. Finally, an ideal system of soft intracranial bioelectronics such as closed-loop-type fully-integrated systems is presented, and the remaining challenges for their clinical translation are discussed.

Functionalization of Natural-Derived Biogels for Soft Bioelectronics

Functionalization of Natural-Derived Biogels for Soft Bioelectronics

3D Printing of Robust High-Performance Conducting Polymer Hydrogel-Based Electrical Bioadhesive Interface for Soft Bioelectronics.

Electrical bioadhesive interface (EBI), especially conducting polymer hydrogel (CPH)-based EBI, exhibits promising potential applications in various fields, including biomedical devices, neural interfaces, and wearable devices. However, current fabrication techniques of CPH-based EBI mostly focus on conventional methods such as direct casting, injection, and molding, which remains a lingering challenge for further pushing them toward customized practical bioelectronic applications and commercialization. Herein, 3D printable high-performance CPH-based EBI precursor inks are developed through composite engineering of PEDOT:PSS and adhesive ionic macromolecular dopants within tough hydrogel matrices (PVA). Such inks allow the facile fabrication of high-resolution and programmable patterned EBI through 3D printing. Upon successive freeze-thawing, the as-printed PEDOT:PSS-based EBI simultaneously exhibits high conductivity of 1.2 S m-1, low interfacial impedance of 20 Ω, high stretchability of 349%, superior toughness of 109kJ m-3, and satisfactory adhesion to various materials. Enabled by these advantageous properties and excellent printability, the facile and continuous manufacturing of EBI-based skin electrodes is further demonstratedvia 3D printing, and the fabricated electrodes display excellent ECG and EMG signal recording capability superior to commercial products. This work may provide a new avenue for rational design and fabrication of next-generation EBI for soft bioelectronics, further advancing seamless human-machine integration.

A Roadmap from Functional Materials to Plant Health Monitoring (PHM).

Soft bioelectronics have great potential for the early diagnosis of plant diseases and the mitigation of adverse outcomes such as reduced crop yields and stunted growth. Over the past decade, bioelectronic interfaces have evolved into miniaturized conformal electronic devices that integrate flexible monitoring systems with advanced electronic functionality. This development is largely attributable to advances in materials science, and micro/nanofabrication technology. The approach uses the mechanical and electronic properties of functional materials (polymer substrates and sensing elements) to create interfaces for plant monitoring. In addition to ensuring biocompatibility, several other factors need to be considered when developing these interfaces. These include the choice of materials, fabrication techniques, precision, electrical performance, and mechanical stability. In this review, some of the benefits plants can derive from several of the materials used to develop soft bioelectronic interfaces are discussed. The article describes how they can be used to create biocompatible monitoring devices that can enhance plant growth and health. Evaluation of these devices also takes into account features that ensure their long-term durability, sensitivity, and reliability. This article concludes with a discussion of the development of reliable soft bioelectronic systems for plants, which has the potential to advance the field of bioelectronics.

In situ 3D printing of liquid metal-hydrogel hybrid for multifunctional soft bioelectronics and devices

In situ 3D printing of liquid metal-hydrogel hybrid for multifunctional soft bioelectronics and devices

In Situ Nanomechanical Characterization Techniques for Soft Bioelectronic Interfaces and Their Building Blocks

AbstractSoft bioelectronic interfaces constitute a paradigm shift for biomedical devices. High‐resolution monitoring and stimulation of physiological processes in vivo are becoming possible with minimally invasive devices operated without inflicting tissue damage or discomfort over prolonged timescales. However, the development and commercialization of such interfaces still must address significant challenges. Biological tissue is subjected to continuous motion and the related device deformations can easily trigger fracture or delamination of the device components, putting long‐term durability of soft implants at risk. In this review, an overview of experimental techniques for testing mechanical properties and failure mechanisms of soft bioelectronic devices at the nanoscale while the deformation takes place (in situ) is provided. Through the tensile test, bending test, nanoindentation, and micropillar compression test, precise measurements of the mechanical properties of individual building blocks and the interfaces themselves can be obtained. Such parameters are crucial to design, model, and optimize the device's performance. Then, recent examples of how this information guides design and optimization of soft bioelectronic interfaces and devices for healthcare, robotics, and human–machine interfaces is provided. Last of all, future research that is needed to fully achieve long‐term soft bioelectronic interfaces for integration with the human body is discussed.

Cellulosic Nanofibers Utilizing a Silicone Elastomeric Core to Form Stretchable Paper

AbstractPaper, an inexpensive material with natural biocompatibility, non‐toxicity, and biodegradability, allows for affordable and cost‐effective substrates for unconventional advanced electronics, often called papertronics. On the other hand, polymeric elastomers have shown to be an excellent success for substrates of soft bioelectronics, providing stretchability in skin wearable technology for continuous sensing applications. Although both materials hold their unique advantageous characteristics, merging both material properties into a single electronic substrate reimagines paper‐based bioelectronics for wearable and patchable applications in biosensing, energy generation and storage, soft actuators, and more. Here, a breathable, light‐weighted, biocompatible engineered stretchable paper is reported via coaxial nonwoven microfibers for unconventional bioelectronic substrates. The stretchable papers allow intimate bioconformability without adhesive through coaxial electrospinning of a cellulose acetate polymer (sheath) and a silicone elastomer (core). The fabricated cellulose‐silicone fibers exhibit a greater percent strain than commercially available paper while retaining hydrophilicity, biocompatibility, combustibility, disposable, and other natural characteristics of paper. Moreover, the nonwoven stretchable cellulose‐silicone fibrous mat can adapt conventional printing and fabrication process for paper‐based electronics, an essential aspect of advanced bioelectronic manufacturing.

Soft bioelectronics for the management of cardiovascular diseases

Soft bioelectronics for the management of cardiovascular diseases

Soft Bioelectronics for Therapeutics.

Soft bioelectronics play an increasingly crucial role in high-precision therapeutics due to their softness, biocompatibility, clinical accuracy, long-term stability, and patient-friendliness. In this review, we provide a comprehensive overview of the latest representative therapeutic applications of advanced soft bioelectronics, ranging from wearable therapeutics for skin wounds, diabetes, ophthalmic diseases, muscle disorders, and other diseases to implantable therapeutics against complex diseases, such as cardiac arrhythmias, cancer, neurological diseases, and others. We also highlight key challenges and opportunities for future clinical translation and commercialization of soft therapeutic bioelectronics toward personalized medicine.

Multifunctional Filler-Free PEDOT:PSS Hydrogels with Ultrahigh Electrical Conductivity Induced by Lewis-Acid-Promoted Ion Exchange.

Highly conductive hydrogels with biotissue-like mechanical properties are of great interest in the emerging field of hydrogel bioelectronics due to their good biocompatibility, deformability, and stability. Fully polymeric hydrogels may exhibit comparable Young's modulus to biotissues. However, most of these filler-free hydrogels have a low electrical conductivity of <10 Scm-1 , which limits their wide applications of them in digital circuits or bioelectronic devices. In this work, a series of metal-halides-doped poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) hydrogels with an ultrahigh electrical conductivity up to 547 Scm-1 is reported, which is 1.5 times to 104 times higher than previously reported filler-free polymeric hydrogels. Theoretical calculation demonstrated that the ion exchange between PEDOT:PSS and the metal halides played an important role to promote phase separation in the hydrogels, which thus leads to ultrahigh electrical conductivity. The high electrical conductivity resulted in multifunctional hydrogels with high performance in thermoelectrics, electromagnetic shielding, Joule heating, and sensing. Such flexible and stretchable hydrogels with ultrahigh electrical conductivity and stability upon various deformations are promising for soft bioelectronics devices and wearable electronics.

Single-Step Transfer-Printing Microfabrication of Soft Bioelectronics Using PDMS with Tuned Adhesion Forces

Recent soft and stretchable bioelectronics for various wearable applications generally require special equipment and facilities for microelectromechanical systems (MEMS). As an alternative, simple photolithography-free microfabrication methods have been proposed based on transfer printing onto soft substrates; however, limitations remain in that precise control is involved for modulating adhesion forces. In this study, a simple, rapid, cost-effective transfer-printing-based microfabrication process is demonstrated without requiring any MEMS process or sophisticated transfer control. We utilized ethoxylated polyethylenimine (PEIE) to tune the adhesion properties of polydimethylsiloxane (PDMS) such that thin sensor patterns fabricated by laser-machined gold leaves are easily transferred from the low-adhesion donor PDMS onto the high-adhesion receiver PDMS layer. The microfabrication steps were optimized based on the electrical and mechanical analysis of the transferred patterns, thereby enabling stable fabrication of thin gold lines of 100 μm width. An additional advantage of the sticky PDMS (sPDMS) is presented for stronger bonding of the cover layer and gold layer around the opening windows, which may allow for greater long-term stability in aqueous conditions. The sPDMS also enables adhesive-free attachment to the skin without losing its adhesion forces over repeated applications. The feasibility of the simple microfabrication process is verified by successfully demonstrating a multifunctional wearable patch for electrical (electromyography) and mechanical (strain) monitoring. This process provides a complete set of efficient microfabrication procedures for soft bioelectronics, from metal deposition to patterning and selective encapsulation, which can be utilized in a wide range of multifunctional and wearable physiological monitoring.

Recent Progress on Transparent Microelectrode-Based Soft Bioelectronic Devices for Neuroscience and Cardiac Research.

Transparent microelectrodes have emerged as promising tools to combine electrical and optical sensing and modulation modalities in many areas of biological and biomedical research. Compared to conventional opaque microelectrodes, they offer a number of specific advantages that can enable advances in functionality and performance. In addition to optical transparency, the mechanical softness feature is desired to minimize foreign body responses, increase biocompatibility, and avoid loss of functionality. In this review, we present recent research from the past several years on transparent microelectrode-based soft bioelectronic devices with an emphasis on their material properties and advanced device designs, as well as multimodal application scenarios for neuroscience and cardiology. First, we introduce material candidates with proper electrical, optical, and mechanical properties for soft transparent microelectrodes. We then discuss examples of soft transparent microelectrode arrays tailored to combine electrical recording and/or stimulation with optical imaging and/or optogenetic modulation of the brain and the heart. Next, we summarize the most recent progress on soft opto-electric devices integrating transparent microelectrodes with microscale light-emitting diodes and/or photodetectors into single and hybrid microsystems as powerful tools to explore the brain and heart functions. A brief overview of possible future directions of soft transparent microelectrode-based biointerfaces is provided to conclude the review.

Screen-Printable Functional Nanomaterials for Flexible and Wearable Single-Enzyme-Based Energy-Harvesting and Self-Powered Biosensing Devices

HighlightsScreen-printable functional nanocomposite inks are engineered for flexible, single-enzyme-based energy-harvesting, and self-powered biosensing devices.A BFC powered by the same biosubstrate (glucose) is developed to harvest energy in a biofluid model and act as a self-powered electrochemical glucose.Customized inks are advantageous in terms of integrating with flexible materials, which can be integrated with a wide range of wearables and soft bioelectronics.

A Nonswelling Hydrogel with Regenerable High Wet Tissue Adhesion for Bioelectronics.

Reducing the swelling of tissue-adhesive hydrogels is crucial for maintaining stable tissue adhesion and inhibiting tissue inflammation. However, reported strategies for reducing swelling always result in a simultaneous decrease in the tissue adhesive strength of the hydrogel. Furthermore, once the covalent bonds break in the currently reported hydrogels, they cannot be rebuilt, and the hydrogel loses its tissue adhesive ability. In this work, a nonswelling hydrogel (named as "PAACP") possessing regenerable high tissue adhesion is synthesized by copolymerizing and crosslinking poly(vinyl butyral) with acrylic acid, gelatin, and chitosan-grafted N-acetyl-l-cysteine. The tissue adhesive strength of the obtained PAACP reaches 211.4kPa, which is approximately ten times higher than that of the reported nonswelling hydrogels, and the hydrogel can be reused for multiple cycles. The as-prepared hydrogel shows great potential in soft bioelectronics, as muscle fatigue is successfully monitored via the electrode array and strain sensor integrated on PAACP substrates. The success of these bioelectronics offers potential applicability in the long-term diagnosis of muscle-related health conditions and prosthetic manipulations.

A Review of Soft Electronic Devices Based on Flexible and Stretchable Materials for Cardiac Monitoring

Purpose of the study: The number one killer, cardiovascular disease, has sharply increased in recent years. For early diagnosis and prevention, continuous cardiac monitoring is crucial, and flexible, stretchable electronic devices have become essential instruments to record cardiac activity. Bioelectronics has greatly improved from recent developments in soft, ultrathin bioelectronics that have been made possible by breakthroughs in soft materials and novel device designs.&#x0D; Methodology: This study focuses on flexible and stretchable materials as well as design strategies for current developments in soft electronics-based wearable and implantable devices for cardiac monitoring.&#x0D; Main Findings: The mechanical deformability in soft bioelectronics has enabled researchers to obtain high-quality bio-signals and reduce long-term negative effects in vivo. They provide close, long-term integration with cardiac tissues due to their thin and soft characteristics, allowing for continuous, high-quality, and wide coverage in cardiac monitoring.&#x0D; Applications of this study: This review is anticipated to provide timely and significant information for prospective audiences in the fields of material science and biomedical engineering, who seek a concise summary of key technologies, as well as biomedical fields who may be interested in the clinical implications of soft bioelectronics for cardiac healthcare.&#x0D; Novelty/Originality of this study: The materials, fabrication techniques, and device designs for flexible and stretchable electronics are reviewed with a particular emphasis on flexible and soft materials.

Using Wool Keratin as a Structural Biomaterial and Natural Mediator to Fabricate Biocompatible and Robust Bioelectronic Platforms.

The design and fabrication of biopolymer-incorporated flexible electronics have attracted immense interest in healthcare systems, degradable implants, and electronic skin. However, the application of these soft bioelectronic devices is often hampered by their intrinsic drawbacks, such as poor stability, inferior scalability, and unsatisfactory durability. Herein, for the first time, using wool keratin (WK) as a structural biomaterial and natural mediator to fabricate soft bioelectronics is presented. Both theoretical and experimental studies reveal that the unique features of WK can endow carbon nanotubes (CNTs) with excellent water dispersibility, stability, and biocompatibility. Therefore, well-dispersed and electroconductive bio-inks can be prepared via a straightforward mixing process of WK and CNTs. The as-obtained WK/CNTs inks can be directly exploited to design versatile and high-performance bioelectronics, such as flexible circuits and electrocardiogram electrodes. More impressively, WK can also be a natural mediator to connect CNTs and polyacrylamide chains to fabricate a strain sensor with enhanced mechanical and electrical properties. With conformable and soft architectures, these WK-derived sensing units can be further assembled into an integrated glove for real-time gesture recognition and dexterous robot manipulations, suggesting the great potential of the WK/CNT composites for wearable artificial intelligence.

Conductive and antibacterial dual-network hydrogel for soft bioelectronics.

Conductive hydrogels have shown significant potential for use in soft bioelectronics due to their unique similarities to biological tissue, including high water content, low modulus, and conductivity. However, their high water content makes them susceptible to absorbing microorganisms and promoting bacterial growth, which can trigger an immune response. Besides, the adhesion and biocompatibility of the hydrogel are not satisfactory, seriously limiting the conductive hydrogel's high-performance applications in human healthcare monitoring. Herein, the problem is addressed by introducing borax through a swelling and a semi-dehydration method into the interpenetrated network of a polyvinyl alcohol and poly(acrylic acid) hydrogel. The hydrogel exhibits both outstanding antibacterial (>99.99% toward E. coli and S. aureus) activity and high ionic conductivity, in addition to tissue-like softness, strong wet-tissue adhesion (600 J m-2 for skin), environmental stability, and excellent biocompatibility. Furthermore, the as-prepared hydrogel can serve as a biosensing conductor, showing high-quality recording and monitoring of real-time tiny yet complex muscle movements during speaking and realizing neuromodulation through low-current electronic stimulation (40 μA) of a rat's nerve. Simultaneously, the hydrogel also exhibits the capacity to accelerate wound healing. Therefore, the proposed antibacterial conductive hydrogel is a safer option for next-generation bioelectronic materials in human healthcare.

PEDOT:PSS hydrogels with high conductivity and biocompatibility for in situ cell sensing.

Conducting polymer hydrogels, especially poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) hydrogels, show great promise in soft bioelectronics due to their high conductivity and the ability of electrical coupling with tissues for sensing and stimulation. However, it is challenging to solve the problem of poor biocompatibility of PEDOT:PSS hydrogels due to the existing harsh preparation methods with the use of toxic and harmful reagents. Herein, we report the synthesis of PEDOT:PSS hydrogels with positively charged conductive polymers as a cross-linker and the application of PEDOT:PSS hydrogels as in situ electrochemical sensors for living cells. The conductivities of PEDOT:PSS hydrogels prepared using this method without any toxic or harmful reagents can reach up to 3265 S m-1. The facile synthesis approach with a simple mixture of PEDOT:PSS aqueous solution and the monomers of conductive polymers at room temperature also enables the printability of PEDOT:PSS hydrogels to fabricate patterned electrodes. Moreover, all the proposed PEDOT:PSS hydrogels demonstrated good biocompatibility. The in situ electrochemical detection of dopamine secreted from PC12 cells cultured within PEDOT:PSS hydrogels suggests that our PEDOT:PSS hydrogels with high conductivity and biocompatibility offer great potential for the integration of biosensors within 3D cell culture.