Bioelectronic Devices Research Articles

Curvature-Matching Mechanics in Skin-Based Bioelectronics to Minimize Interfacial Stresses

Abstract A geometrical and mechanical design strategy is proposed for bioelectronics to improve wearability and comfort by reducing the magnitude of interfacial stresses and ensuring that the spatial stress distributions are below the somatosensory threshold for skin sensitivity. Conceptually, bioelectronic devices with soft polymeric encapsulations and internal rigid electronic components result in a mechanically hybrid composite structure, with intrinsically soft mechanics to facilitate integration with biological tissues through mechanical compliance. For accurate signal acquisition and sensing in curvilinear regions (e.g., limbs, chest, forehead), bioelectronic devices are pressed and bent to closely match the skin morphology, resulting in additional interfacial stresses. In the present work, we demonstrate how curvature-matching designs for the bioelectronic–skin interface can reduce the resulting normal and shear stresses generated from device adhesion and skin stretching during dynamic motions. Finite element modeling of the skin curvature, encapsulation, and internal electronic layouts was used to quantify the spatial distribution of the underlying stresses at the skin interface based on a mismatch curvature angle θ between the device and skin. The results show that curvature-matching designs for selected cases of θ = 30 deg and 60 deg can reduce the normal and shear stresses by up to 45% and 70%, respectively, even for a stretch of up to λ = 1.3. The proposed curvature-matching design strategy can inform the future design of user-specific bioelectronics to create anatomically compatible geometrical layouts that enhance mechanical compliance and enable physiological monitoring and integration in curved body structures.

Wireless Deep Brain Stimulation by Ultrasound-Responsive Molecular Piezoelectric Nanogenerators.

Implantable neural stimulation devices are becoming prevalent in bioelectronic medicine for the precise treatment of various clinical diseases. Nevertheless, the limited lifespan and buckling size of the implanted devices remain significant obstacles for chronic clinical application. In this study, we developed an ultrasound-driven battery-free neurostimulator based on a high-performance mini-sized nanogenerator and demonstrated its successful application for the deep-brain-stimulation (DBS) therapy of Parkinson's disease in a rat model. This soft piezoelectric-triboelectric hybrid nanogenerators (PTNG) are made of porous thin-films of molecular piezoelectric materials, which have great advantages of facile, scalable, low-temperature, and flexible processing. Without any bucky accessory control circuits, the subcutaneously implanted soft PTNG can function as a wirelessly powered neurostimulator, allowing for the adjustment of stimulation parameters through external programmable ultrasound pulses. This DBS electroceutical application of energy-harvesting thin-film devices based on molecular piezoelectric materials provides valuable insight into the development of a soft high-performance bioelectronic device.

Ga‐Based Liquid Metals: Versatile and Biocompatible Solutions for Next‐Generation Bioelectronics

AbstractThe utilization of gallium (Ga)‐based liquid metals (LMs) as functional materials in bioelectronics has been extensively explored over the past decade as a key to stimulation of biological systems and recording of biological signals. The motivation behind this class of electronics is driven by the opportunities to exploit mechanical properties similar to biological tissues. These bioelectronic devices are required to maintain functionality under deformation and, especially for implantable applications, should interface with biological tissues in a minimally invasive manner. LMs are attractive for such applications due to their ability to deform while retaining their electrical conductivity. Furthermore, unlike most liquids that form droplets to minimize surface energy, the ultrathin solid‐state oxide layer on the outer surface of LMs enables them to be shaped to specific 3D patterns. Unlike mercury, Ga‐based LMs are considered biocompatible due to their low toxicity and vapor pressure, highlighting their potential as advantageous materials for bioelectronics. This review comprehensively presents the fundamental aspects of these materials, with a focus on their effectiveness in stimulating and recording specific biological tissues, as well as their diverse applications as soft and stretchable electrodes in bioelectronics. Additionally, this review investigates additional strategies aimed at driving future advancements in this field.

Pseudo-doping effect on structural and electrical properties of polyaniline-camphorsulfonic acid

Electroconductive polymers (ECP) are critical for the design of soft electronic and bioelectronic devices. Polyaniline:camphorsulfonic acid (PANI:CSA) is an example of a biocompatible and affordable ECP, whose electroconductivity is highly dependent on chain organization/conformation. PANI:CSA aggregation ordering is overlooked in most works, but it can greatly impact the performance of PANI:CSA-based devices and limit their applicability. A simple and cheap method to avoid random coil aggregation of PANI:CSA is to select solvents with pseudo-doping properties. This work presents a novel alternative solvent system, based on trifluoroethanol (TFE) and hexafluoropropanol (HFP) mixtures, capable of being removed without hampering the structural and electrical properties of PANI:CSA. For the first time, we present a systematic study that compares the performance of solvent systems containing different amounts of TFE and HFP, which, unlike m-cresol, the golden-standard of pseudo-doping, are easy to remove without compromising the ECP’s electroconductivity and biocompatibility. We also evaluate the influence of the processing method, drop-casting vs spin-coating, on the structural and electrical properties of the obtained samples. Samples obtained by spin-coating show a more consistent improvement in electroconductivity (σ(TFE) = 61 S cm−1, σ(TFE:HFP (50:50 vol)) = 70 S cm−1) and more intense near-infrared (NIR) absorption bands. Atomic force microscopy (AFM), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) indicate that samples processed with HFP and m-cresol have higher benzenoid content, lower random coil aggregation and more efficient CSA doping. The solvent system comprised of equal parts of TFE and HFP was found to simultaneously enhance the electrical properties and structural ordering of PANI:CSA. We believe our results are critical for the fabrication of PANI-based next generation bioelectronic devices.

Advances in P(VDF-TrFE) Composites: A Methodical Review on Enhanced Properties and Emerging Electronics Applications

Piezoelectric polymers are a class of material that belong to carbon–hydrogen-based organic materials with a long polymer chain. They fill the void where single crystals and ceramics fail to perform. This characteristic of piezoelectric polymers made them unique. Their piezoelectric stress constant is higher than ceramics and the piezoelectric strain is lower compared to ceramics. This study’s goal is to present the most recent information on poly(vinylidene fluoride) with trifluoroethylene P(VDF-TrFE), a major copolymer of poly(vinylidene fluoride) PVDF with piezoelectric, pyroelectric, and ferroelectric characteristics. The fabrication of P(VDF-TrFE) composites and their usage in a variety of applications, including in actuators, transducers, generators, and energy harvesting, are the primary topics of this work. The report provides an analysis of how the addition of fillers improves some of the features of P(VDF-TrFE). Commonly utilized polymer composite preparation techniques, including spinning, Langmuir–Blodgett (LB), solution casting, melt extrusion, and electrospinning are described, along with their effects on the pertinent characteristics of the polymer composite. A brief discussion on the literature related to different applications (such as bio-electronic devices, sensors and high energy-density piezoelectric generators, low mechanical damping, and easy voltage rectifiers of the polymer composite is also presented.

Flexible, ultrathin bioelectronic materials and devices for chronically stable neural interfaces

AbstractAdvanced technologies that can establish intimate, long‐lived functional interfaces with neural systems have attracted increasing interest due to their wide‐ranging applications in neuroscience, bioelectronic medicine, and the associated treatment of neurodegenerative diseases. A critical challenge of significance remains in the development of electronic platforms that offer conformal contact with soft brain tissue for the sensing or stimulation of brain activities and chronically stable operation in vivo, at scales that range from cellular‐level resolution to macroscopic areas. This review summarizes recent advances in this field, with an emphasis on the use of demonstrated concepts, constituent materials, engineered designs, and system integration to address the current challenges. The article begins with an overview of recent bioelectronic platforms with unique form factors, ranging from filamentary probes to conformal sheets and three‐dimensional frameworks for alleviating the mechanical mismatch between interface materials and neural tissues. Next, active interfaces which utilize inorganic/organic semiconductor‐enabled devices are reviewed, highlighting various working principles of recording mechanisms including capacitively and conductively coupled sensing enabled by high transistor matrices at high spatiotemporal resolution. The subsequent section presents approaches to biological integration which use active materials for multiplexed addressing, local amplification and multimodal operation with high‐channel‐count and large‐scale electronic systems in a safe fashion that provides multi‐decade stable performance in both animal models and human subjects. The advances summarized in this review will guide the future direction of this technology and provide a basis for next‐generation chronic neural interfaces with long‐lived high‐performance operation.

Resorbable barrier polymers for flexible bioelectronics

Resorbable, implantable bioelectronic devices are emerging as powerful tools to reliably monitor critical physiological parameters in real time over extended periods. While degradable magnesium-based electronics have pioneered this effort, relatively short functional lifetimes have slowed clinical translation. Barrier films that are both flexible and resorbable over predictable timelines would enable tunability in device lifetime and expand the viability of these devices. Herein, we present a library of stereocontrolled succinate-based copolyesters which leverage copolymer composition and processing method to afford tunability over thermomechanical, crystalline, and barrier properties. One copolymer composition within this library has extended the functional lifetime of transient bioelectronic prototypes over existing systems by several weeks–representing a considerable step towards translational devices.

Piezoelectric nanogenerators for self-powered wearable and implantable bioelectronic devices.

One of the recent innovations in the field of personalized healthcare is the piezoelectric nanogenerators (PENGs) for various clinical applications, including self-powered sensors, drug delivery, tissue regeneration etc. Such innovations are perceived to potentially address some of the unmet clinical needs, e.g., limited life-span of implantable biomedical devices (e.g., pacemaker) and replacement related complications. To this end, the generation of green energy from biomechanical sources for wearable and implantable bioelectronic devices gained considerable attention in the scientific community. In this perspective, this article provides a comprehensive state-of-the-art review on the recent developments in the processing, applications and associated concerns of piezoelectric materials (synthetic/biological) for personalized healthcare applications. In particular, this review briefly discusses the concepts of piezoelectric energy harvesting, piezoelectric materials (ceramics, polymers, nature-inspired), and the various applications of piezoelectric nanogenerators, such as, self-powered sensors, self-powered pacemakers, deep brain stimulators etc. Important distinction has been made in terms of the potential clinical applications of PENGs, either as wearable or implantable bioelectronic devices. While discussing the potential applications as implantable devices, the biocompatibility of the several hybrid devices using large animal models is summarized. This review closes with the futuristic vision of integrating data science approaches in developmental pipeline of PENGs as well as clinical translation of the next generation PENGs. STATEMENT OF SIGNIFICANCE: Piezoelectric nanogenerators (PENGs) hold great promise for transforming personalized healthcare through self-powered sensors, drug delivery systems, and tissue regeneration. The limited battery life of implantable devices like pacemakers presents a significant challenge, leading to complications from repititive surgeries. To address such a critical issue, researchers are focusing on generating green energy from biomechanical sources to power wearable and implantable bioelectronic devices. This comprehensive review critically examines the latest advancements in synthetic and nature-inspired piezoelectric materials for PENGs in personalized healthcare. Moreover, it discusses the potential of piezoelectric materials and data science approaches to enhance the efficiency and reliability of personalized healthcare devices for clinical applications.

Self-healable stretchable printed electronic cryogels for in-vivo plant monitoring

A key challenge in bioelectronics is to establish and improve the interface between electronic devices and living tissues, enabling a direct assessment of biological systems. Sensors integrated with plant tissue can provide valuable information about the plant itself as well as the surrounding environment, including air and soil quality. An obstacle in developing interfaces to plant tissue is mitigating the formation of fibrotic tissues, which can hinder continuous and accurate sensor operation over extended timeframes. Electronic systems that utilize suitable biocompatible materials alongside appropriate fabrication techniques to establish plant-electronic interfaces could provide for enhanced environmental understanding and ecosystem management capabilities. To meet these demands, this study introduces an approach for integrating printed electronic materials with biocompatible cryogels, resulting in stable implantable hydrogel-based bioelectronic devices capable of long-term operation within plant tissue. These inkjet-printed cryogels can be customized to provide various electronic functionalities, including electrodes and organic electrochemical transistors (OECTs), that exhibit high electrical conductivity for embedded conducting polymer traces (up to 350 S/cm), transconductance for OECTs in the mS range, a capacitance of up to 4.2 mF g−1 in suitable structures, high stretchability (up to 330% strain), and self-healing properties. The biocompatible functionalized cryogel-based electrodes and transistors were successfully implanted in plant tissue, and ionic activity in tomato plant stems was collected for over two months with minimal scar tissue formation, making these cryogel-based printed electronic devices excellent candidates for continuous, in-situ monitoring of plant and environmental status and health.

Performance improvement of poly(lactic acid) films for bioelectronics with eco-friendly supercritical fluids combined with activated-carbon technique

The rise of bioelectronics has sparked significant interest in exploring biocompatible and environmentally friendly materials including Poly(lactic acid) (PLA), which is the only biologically derived material capable of large-scale production. However, its suitability as an electronic material is limited due to inadequate electrical, optical, and mechanical properties arising from inherent impurities. In this study, lower molecular weight PLA was dissolved in chloroform and spin-coated into ultra-thin (1.689 μm) films as dielectric layer in capacitor devices. We explored the low-temperature supercritical fluid-activated carbon adsorption technique (LTSCF-AC) to remove residual solvent molecules from PLA film and thus improve its comprehensive properties. The leakage current decreased by about 70 times, and the capacitance values decreased and become more stable at different frequencies. The extremely thin PLA film exhibits excellent optical and mechanical properties. In particular, following LTSCF-AC treatment, optical transmittance and refractive index of PLA films improved significantly. Additionally, the Young's modulus increased by 61.5% while tensile strength and elongation at break doubled compared to their initial values. These simultaneous enhancements of insulation, transparency, deformation resistance, and tensile strength highlight the huge potential of low-temperature and eco-friendly LTSCF-AC in improving the performance of PLA. These advancements not only broaden the application of PLA in bioelectronics but also providing new avenues for improving bioelectronic devices.

Recent Advances in Bioelectronics for Localized Drug Delivery.

The last decade has witnessed remarkable advancements in bioelectronics, ushering in a new era of wearable and implantable devices for drug delivery. By utilizing miniaturized system design and/or flexible materials, bioelectronics illustrates ideal integration with target organs and tissues, making them ideal platforms for localized drug delivery. Furthermore, the development of electrically assisted drug delivery systems has enhanced the efficiency and safety of therapeutic administration, particularly for the macromolecules that encounter additional challenges in penetrating biological barriers. In this review, a concise overview of recent progress in bioelectronic devices for in vivo localized drug delivery, with highlights on the latest trends in device design, working principles, and their corresponding functionalities, is provided. The reported systems based on their targeted delivery locations as wearable systems, ingestible systems, and implantable systems are categorized. Each category is introduced in detail by highlighting the special requirements for devices and the corresponding solutions. The remaining challenges in this field and future directions are also discussed.

Short-Range Charge Transfer in DNA Base Triplets: Real-Time Tracking of Coherent Fluctuation Electron Transfer.

The short-range charge transfer of DNA base triplets has wide application prospects in bioelectronic devices for identifying DNA bases and clinical diagnostics, and the key to its development is to understand the mechanisms of short-range electron dynamics. However, tracing how electrons are transferred during the short-range charge transfer of DNA base triplets remains a great challenge. Here, by means of ab initio molecular dynamics and Ehrenfest dynamics, the nuclear-electron interaction in the thymine-adenine-thymine (TAT) charge transfer process is successfully simulated. The results show that the electron transfer of TAT has an oscillating phenomenon with a period of 10 fs. The charge density difference proves that the charge transfer proportion is as high as 59.817% at 50 fs. The peak position of the hydrogen bond fluctuates regularly between -0.040 and -0.056. The time-dependent Marcus-Levich-Jortner theory proves that the vibrational coupling between nucleus and electron induces coherent electron transfer in TAT. This work provides a real-time demonstration of the short-range coherent electron transfer of DNA base triplets and establishes a theoretical basis for the design and development of novel biological probe molecules.

Conductive Hydrogel for Flexible Bioelectronic Device: Current Progress and Future Perspective

AbstractConductive hydrogels (CHs) for flexible bioelectronic devices have raised great attention due to their tunable mechanical performances, adhesion, anti‐swelling, and biocompatibility. This review summarizes the current development of conductive hydrogel‐based flexible bioelectronic devices in the aspect of classifications and applications. Firstly, the conductive hydrogels are classified into two kinds according to the types of conductivity: ionic conductive hydrogels and electronic conductive hydrogels (hydrogel based on pure conductive materials, introducing conductive micro/nano‐materials). Secondly, the applications of conductive hydrogels for bioelectronic device, like wearable devices (strain sensor, body fluid detector, serviced in extreme environment), tissue engineering (skin, heart, nerve, muscle), and other applications (bionic robot, cancer treatment), are highly illustrated. Finally, a depth outlook is given, which aims to promote the development of this field in the future.

Soft implantable printed bioelectronic system for wireless continuous monitoring of restenosis

Atherosclerosis is a prominent cause of coronary artery disease and broader cardiovascular diseases, the leading cause of death worldwide. Angioplasty and stenting is a common treatment, but in-stent restenosis, where the artery re-narrows, is a frequent complication. Restenosis is detected through invasive procedures and is not currently monitored frequently for patients. Here, we report an implantable vascular bioelectronic device using a newly developed miniaturized strain sensor via microneedle printing methods. A capillary-based printing system achieves high-resolution patterning of a soft, capacitive strain sensor. Ink and printing parameters are evaluated to create a fully printed sensor, while sensor design and sensing mechanism are studied to enhance sensitivity and minimize sensor size. The sensor is integrated with a wireless vascular stent, offering a biocompatible, battery-free, wireless monitoring system compatible with conventional catheterization procedures. The vascular sensing system is demonstrated in an artery model for monitoring restenosis progression. Collectively, the artery implantable bioelectronic system shows the potential for wireless, real-time monitoring of various cardiovascular diseases and stent-integrated sensing/treatments.

Tracking kidney transplant fitness.

An implantable bioelectronic device detects the early signs of kidney transplant rejection in rats.

Magnetoelectrics enables large power delivery to mm-sized wireless bioelectronics.

To maximize the capabilities of minimally invasive implantable bioelectronic devices, we must deliver large amounts of power to small implants; however, as devices are made smaller, it becomes more difficult to transfer large amounts of power without a wired connection. Indeed, recent work has explored creative wireless power transfer (WPT) approaches to maximize power density [the amount of power transferred divided by receiver footprint area (length × width)]. Here, we analyzed a model for WPT using magnetoelectric (ME) materials that convert an alternating magnetic field into an alternating voltage. With this model, we identify the parameters that impact WPT efficiency and optimize the power density. We find that improvements in adhesion between the laminated ME layers, clamping, and selection of material thicknesses lead to a power density of 3.1 mW/mm2, which is over four times larger than previously reported for mm-sized wireless bioelectronic implants at a depth of 1 cm or more in tissue. This improved power density allows us to deliver 31 and 56 mW to 10 and 27-mm2 ME receivers, respectively. This total power delivery is over five times larger than similarly sized bioelectronic devices powered by radiofrequency electromagnetic waves, inductive coupling, ultrasound, light, capacitive coupling, or previously reported magnetoelectrics. This increased power density opens the door to more power-intensive bioelectronic applications that have previously been inaccessible using mm-sized battery-free devices.

Highly uniform resistive switching characteristics of KGM resistive memory through air plasma technology

In this study, a highly stable resistive switching behavior was obtained by utilizing konjac glucomannan, a biomaterial, as a dielectric layer through a solution-based process, and the ITO bottom electrode was modified by using an air plasma technique. Electrical results showed that the pretreatment device did not observe significant switching characteristics (∼101). The device, which underwent additional plasma treatment, was recognized for its significant improvements in this area, demonstrating a reduced set voltage (Vset = 0.37 V) with a 6% coefficient of variation, more than 200 consecutive cycles, and up to 90% electrical yield. Moreover, the treated device exhibited a dramatically higher memory window (>104) due to the relatively low off-state current. According to the XPS and UPS analysis, the work function increased from an untreated 4.3 to 5.79 eV as the treatment time increased to 180 s. The conductive filaments, which stemmed from oxygen vacancies, were introduced through plasma treatment to enhance the proportion of oxygen vacancies in the ITO films, thereby creating a stable and consistent filament path. Consequently, the systematic and reproducible resistive switching phenomenon was intensified. The reported results confirmed that the reliability and uniformity in bioelectronic devices can be accomplished through a simple and effective plasma technique. This approach paved the way for alternative applications of these devices.

DNA nanopores as artificial membrane channels for bioprotonics

Biological membrane channels mediate information exchange between cells and facilitate molecular recognition. While tuning the shape and function of membrane channels for precision molecular sensing via de-novo routes is complex, an even more significant challenge is interfacing membrane channels with electronic devices for signal readout, which results in low efficiency of information transfer - one of the major barriers to the continued development of high-performance bioelectronic devices. To this end, we integrate membrane spanning DNA nanopores with bioprotonic contacts to create programmable, modular, and efficient artificial ion-channel interfaces. Here we show that cholesterol modified DNA nanopores spontaneously and with remarkable affinity span the lipid bilayer formed over the planar bio-protonic electrode surface and mediate proton transport across the bilayer. Using the ability to easily modify DNA nanostructures, we illustrate that this bioprotonic device can be programmed for electronic recognition of biomolecular signals such as presence of Streptavidin and the cardiac biomarker B-type natriuretic peptide, without modifying the biomolecules. We anticipate this robust interface will allow facile electronic measurement and quantification of biomolecules in a multiplexed manner.

(Invited) smart Wearable Electronics for Chronic Disease Management

60% of Americans live with at least one chronic disease. These diseases and associated comorbidities are now the leading causes of death in the United States. Effective management of complex chronic diseases requires body-wide, long-term, accurate, and continuous monitoring of multiple physiological signals from wearable devices to precisely determine the pathological state. These wearable physiological signal monitoring can dramatically reduce the demand of physician visiting and increase patients’ engagement and treatment adherence rate. Although wearable bioelectronic devices have shown huge potential in chronic disease management, existing technology still mostly relies on rigid chip components, where the interface between chips and skin/tissue has been a bottleneck that limits the system performance (noise, robustness etc). To address these challenges, my research has been involved in the exploration of rational system design concepts, material and device fabrication innovation, and tailored algorithms to enable smart wearable electronics that targets next-generation chronic disease management.Here I would like to discuss two of my developed technology platforms to elaborate the concept of smart wearables. First, I will describe a body area sensor network technology platform. In the system design concept side, this technology utilizes a novel wireless hybridization strategy and an unconventional detuned RFID working regime that provide an ideal skin interface. In the material/device side, this system integrates several skin-conforming polymer-based soft devices (ring oscillators, RF diodes, antennas, transistors etc.) as an integrated soft multimode sensing sticker. (1,2) Next, I will describe a wireless closed-loop smart bandage that can accelerate and monitor the wound healing process. (3) Such smart bandage also integrates new design concepts (wireless, battery-free design that combines both sensing and stimulation), novel materials (low-impedance, high-toughness, and tunable adhesion hydrogel as skin interface) and closed-loop control algorithms. Overall, the developed technology platform could assess multiple health outcomes and treatment responses to various chronic diseases. Ultimately, this technology will help to reduce chronic disease burden, lower medical costs, and provide a better quality of life for patients.

Controlling swelling in mixed transport polymers through alkyl side-chain physical cross-linking

Semiconducting conjugated polymers bearing glycol side chains can simultaneously transport both electronic and ionic charges with high charge mobilities, making them ideal electrode materials for a range of bioelectronic devices. However, heavily glycolated conjugated polymer films have been observed to swell irreversibly when subjected to an electrochemical bias in an aqueous electrolyte. The excessive swelling can lead to the degradation of their microstructure, and subsequently reduced device performance. An effective strategy to control polymer film swelling is to copolymerize glycolated repeat units with a fraction of monomers bearing alkyl side chains, although the microscopic mechanism that constrains swelling is unknown. Here we investigate, experimentally and computationally, a series of archetypal mixed transporting copolymers with varying ratios of glycolated and alkylated repeat units. Experimentally we observe that exchanging 10% of the glycol side chains for alkyl leads to significantly reduced film swelling and an increase in electrochemical stability. Through molecular dynamics simulation of the amorphous phase of the materials, we observe the formation of polymer networks mediated by alkyl side-chain interactions. When in the presence of water, the network becomes increasingly connected, counteracting the volumetric expansion of the polymer film.