Implantable Electronic Systems Research Articles

Catheter-Free Urodynamics Testing: Current Insights and Clinical Potential.

Lower urinary tract dysfunction not only interferes with the health-related quality of life of patients but may also lead to acute kidney injury and infections. To assess the bladder, urodynamic studies (UDS) have been implemented but the use of catheters leads to discomfort for the patient. Catheter-free long-term UDS would be useful and a potential solution could be ambulatory wireless devices that communicate via telemetry. Such sensors can detect pressure or volume. Numerous types of potential catheter-free sensors have been proposed for bladder monitoring. Despite substantial innovation in the manufacturing of implantable biomedical electronic systems, such sensors have remained at the laboratory stage due to a number of critical challenges. These challenges primarily concern hermeticity and biocompatibility, sensitivity and artifacts, drift, telemetry, and energy management. Having overcome these challenges, catheter-free ambulatory urodynamic monitoring could combine a synchronized intravesical pressure sensor with a volume analyzer but only the steps of cystometry and volume measurement are currently sufficiently reproducible to simulate UDS results. The measurement of volume by infrared optical sensors, in the form of abdominal patches, appears to be promising and studies are underway to market a telemetric ambulatory urodynamic monitoring system that includes an intravesical pressure sensor. There has been considerable progress in wearable and conformable electronics on many fronts, and continued collaboration between engineers and urologists could quickly overcome current challenges. In addition, to the diagnosis of UDS, such sensors could be useful in the development of a long-term closed-loop neuromodulation system. In this review, we explore the various types of catheter-free bladder sensors, inherent challenges and solutions to overcome these challenges, and the clinical potential of such long-term implantable sensors.

Wireless, Fully Implantable and Expandable Electronic System for Bidirectional Electrical Neuromodulation of the Urinary Bladder.

Current standard clinical options for patients with detrusor underactivity (DUA) or underactive bladder─the inability to release urine naturally─include the use of medications, voiding techniques, and intermittent catheterization, for which the patient inserts a tube directly into the urethra to eliminate urine. Although those are life-saving techniques, there are still unfavorable side effects, including urinary tract infection (UTI), urethritis, irritation, and discomfort. Here, we report a wireless, fully implantable, and expandable electronic complex that enables elaborate management of abnormal bladder function via seamless integrations with the urinary bladder. Such electronics can not only record multiple physiological parameters simultaneously but also provide direct electrical stimulation based on a feedback control system. Uniform distribution of multiple stimulation electrodes via mesh-type geometry realizes low-impedance characteristics, which improves voiding/urination efficiency at the desired times. In vivo evaluations using live, free-moving animal models demonstrate system-level functionality.

Fully implantable batteryless soft platforms with printed nanomaterial-based arterial stiffness sensors for wireless continuous monitoring of restenosis in real time

Atherosclerosis is a common cause of coronary artery disease and a significant factor in broader cardiovascular diseases, the leading cause of death. While implantation of a stent is a prevalent treatment of coronary artery disease, a frequent complication is restenosis, where the stented artery narrows and stiffens. Although early detection of restenosis can be achieved by continuous monitoring, no available device offers such capability without surgeries. Here, we report a fully implantable soft electronic system without batteries and circuits, which still enables continuous wireless monitoring of restenosis in real-time with a set of nanomembrane strain sensors in an electronic stent. The low-profile system requires minimal invasive implantation to deploy the sensors into a blood vessel through catheterization. The entirely printed, nanomaterial-based set of soft membrane strain sensors utilizes a sliding mechanism to offer enhanced sensitivity and detection of low strain while unobtrusively integrating with an inductive stent for passive wireless sensing. The performance of the soft sensor platform is demonstrated by wireless monitoring of restenosis in an artery model and an ex-vivo study in a coronary artery of ovine hearts. The capacitive sensor-based artery implantation system offers unique advantages in wireless, real-time monitoring of stent treatments and arterial health for cardiovascular disease.

Biodegradable Molybdenum (Mo) and Tungsten (W) Devices: One Step Closer towards Fully-Transient Biomedical Implants

Close monitoring of vital physiological parameters is often key in following the evolution of certain medical conditions (e.g., diabetes, infections, post-operative status or post-traumatic injury). The allocation of trained medical staff and specialized equipment is, therefore, necessary and often translates into a clinical and economic burden on modern healthcare systems. As a growing field, transient electronics may establish fully bioresorbable medical devices capable of remote real-time monitoring of therapeutically relevant parameters. These devices could alert remote medical personnel in case of any anomaly and fully disintegrate in the body without a trace. Unfortunately, the need for a multitude of biodegradable electronic components (power supplies, wires, circuitry) in addition to the electrochemical biosensing interface has halted the arrival of fully bioresorbable electronically active medical devices. In recent years molybdenum (Mo) and tungsten (W) have drawn increasing attention as promising candidates for the fabrication of both energy-powered active (e.g., transistors and integrated circuits) and passive (e.g., resistors and capacitors) biodegradable electronic components. In this review, we discuss the latest Mo and W-based dissolvable devices for potential biomedical applications and how these soluble metals could pave the way towards next-generation fully transient implantable electronic systems.

Stress-Released Amorphous Oxide/Carbon Nanotube CMOS Amplifier Circuits for Skin-Compatible Electronics

Recently, there has been a great interest for realizing flexible, cheap, smart, and disposable bioelectronics and implantable electronic systems that can collect various types of in vivo biological signals from the body. In these cases, highly flexible amplifier circuits are often demanded as a basic building block for the realization of the bioelectronic systems with high signal-to-noise ratio. Here, we report highly flexible amorphous indium–gallium–zinc oxide (a-IGZO)/single-walled carbon nanotube (SWCNT) thin-film-transistor-based hybrid-type complementary metal oxide semiconductor (CMOS) amplifiers by introducing a stress-diffusive mesa-island structure. The hybrid amplifier showed stable operation under extremely stressed conditions (bending radius of 125 μm, 10000 cycles) without significant degradation, exhibiting a maximum gain of ∼21.6 dB at 0.1–5 kHz with a gain loss of −9.9 dB/dec over 10 kHz. Additionally, to ensure the viability of the developed stress-released CMOS circuits, we provided a circuit level physical modeling and synthetic analysis using structural and electrical characterizations along with multidomain finite-element analysis (FEA) and AIM-Spice simulation, verifying the acts of the materials and device architecture as a way of highly reliable and outperforming skin-compatible amplifier circuits. The results reported here imply that further neutral layer generation and its intermediate location can be controlled by device architectures and component materials, offering extremely reliable and high performance CMOS amplifier circuits for large-scaled skin-compatible on-chip applications.

Sporadic high pacing and shock impedance on remote monitoring in hybrid implantable cardioverter-defibrillator systems: Clinical impact and management

Sporadic high impedance values without other anomalies detected by remote monitoring of hybrid cardiac implantable electronic device systems have been described recently. The clinical significance and related hazard of this phenomenon are not fully understood. The purpose of this study was to describe the prevalence, management, and outcomes associated with hybrid implantable cardioverter-defibrillator (ICD) systems. We collected data on patients with sporadic high lead impedance alert on remote monitoring who had undergone implantation with a hybrid ICD system between January 2015 and December 2019. Pacing thresholds, sensing and impedance values, and temporal pattern of impedance values were collected by remote monitoring, at implantation, and during an in-office visit. Among 92 patients receiving a hybrid ICD, 15 (16.3%) had high impedance alert on remote monitoring (14 Boston Scientific and 1 St. Jude Medical ICD canisters paired with Medtronic or Biotronik DF-1 leads). Four patients had a cardiac resynchronization therapy-defibrillator (CRT-D), 7 a dual-chamber ICD, and 4 a single-chamber ICD. Three patients presented with high atrial lead impedance, 7 high right ventricular lead impedance, 1 high left ventricular impedance, and 2 high shock impedance values. All patients underwent follow-up by remote monitoring. Sporadic high impedance values were not associated with an adverse outcome or need for revision in all but 1 patient, who had continuously increasing pacing thresholds due to lead microfracture. In the absence of clear signs of lead fracture or connection issues, sporadic high pacing and shock impedance in hybrid implantable defibrillator systems can be safely managed by close follow-up.

Biodegradable Materials for Sustainable Health Monitoring Devices.

The recent advent of biodegradable materials has offered huge opportunity to transform healthcare technologies by enabling sensors that degrade naturally after use. The implantable electronic systems made from such materials eliminate the need for extraction or reoperation, minimize chronic inflammatory responses, and hence offer attractive propositions for future biomedical technology. The eco-friendly sensor systems developed from degradable materials could also help mitigate some of the major environmental issues by reducing the volume of electronic or medical waste produced and, in turn, the carbon footprint. With this background, herein we present a comprehensive overview of the structural and functional biodegradable materials that have been used for various biodegradable or bioresorbable electronic devices. The discussion focuses on the dissolution rates and degradation mechanisms of materials such as natural and synthetic polymers, organic or inorganic semiconductors, and hydrolyzable metals. The recent trend and examples of biodegradable or bioresorbable materials-based sensors for body monitoring, diagnostic, and medical therapeutic applications are also presented. Lastly, key technological challenges are discussed for clinical application of biodegradable sensors, particularly for implantable devices with wireless data and power transfer. Promising perspectives for the advancement of future generation of biodegradable sensor systems are also presented.

A Flexible Transient Biomemristor Based on Hybrid Structure HfO2/BSA:Au Double Layers

AbstractBiomemristors have attracted increasing attention in neuromorphic computing as artificial biosynapses for wearable and implantable electronic systems. So far, biomemristors have achieved a series of neural outstanding functions, such as long‐term enhancement and long‐term inhibition, spiking‐time‐dependent plasticity, and paired impulse promotion, which has further developed memristors in the field of neurobionics. However, there is a problem in conventional memristors regarding the growth position and nucleation dynamics of the conductive filaments since they cause unstable switching parameters. In this study, a new hybrid structure with HfO2/BSA:Au (bovine serum doped with nanogold) is designed to improve biomemristor performance. The Ag/HfO2/BSA:Au/Pt stacked devices show a reversible and excellent bipolar resistive switching behavior. Moreover, the device can faithfully emulate the apoptotic process of biological synapses. Also, the same structure is constructed on a polydimethylsiloxane flexible substrate to examine the biosynapse's functional performance under bending conditions. Finally, the memristor cell can be completely dissolved in deionized water. The hybrid biomemristor can open up a new route to improve the reliability of the biomemristor based on the overall device performance of the BSA:Au, which could significantly accelerate hybrid biomemristor practical applications in wearable, degradable, or implantable electronic systems.

Wearable and Implantable Electronics: Moving toward Precision Therapy.

Soft wearable and implantable electronic systems have attracted tremendous attention due to their flexibility, conformability, and biocompatibility. Such favorable features are critical for reliably monitoring key biomedical and physiological information (including both biophysical and biochemical signals) and effective treatment and management of specific chronic diseases. Miniaturized, fully integrated self-powered bioelectronic devices that can harvest energy from the human body represent promising and emerging solutions for long-term, intimate, and personalized therapies. In this Perspective, we offer a brief overview of recent advances in wearable/implantable soft electronic devices and their therapeutic applications ranging from drug delivery to tissue regeneration. We also discuss the key opportunities, challenges, and future directions in this important area needed to fulfill the vision of personalized medicine.

Characteristic investigation of a flexible resistive memory based on a tunneling junction of Pd/BTO/LSMO on mica substrate

Recently, resistive memory devices based on flexible plastic substrates have attracted increasing attention due to their potential deployment in wearable or implantable circuits and systems. Most resistive memories on plastic substrates cannot grow well or function properly at high temperatures. In this study, in order to mitigate the challenges of high temperature and flexibility, mica is selected as the substrate for resistive memories. Specifically, resistive memories with a tunneling junction structure of Pd/BTO/LSMO are fabricated on a 10 μm-thick mica substrate. This innovation not only achieves a bending radius of 15 mm, but also exhibits excellent electrical characteristics even after bending 104 times. In addition to stable switching characteristics and multi-value storage demonstration at room temperature, excellent retention characteristics and robust state conversions between HRS and LRS are observed at high temperatures up to 200 °C. These measurement results indicate that the excellent flexibility and thermal stability of mica-based transparent resistive memories make the proposed device very promising in wearable or implantable electronic systems.

Palliation and Nonextraction Approaches.

Although definitive therapy for infected cardiac implantable electronic device systems requires removal of all hardware in the infected areas with extraction of intravascular components as well, there are situations where extraction is not available or appropriate. Palliative procedures and chronic suppressive antibiotics may be used in these cases. There are also options that may in some cases result in long-term freedom from infection.

Constructing Flexible and Binder-Free NaTi2(PO4)3 Film Electrode with a Sandwich Structure by a Two-Step Graphene Hybridizing Strategy as an Ultrastable Anode for Long-Life Sodium-Ion Batteries

Flexible energy storage devices show promising advantages in next-generation bendable, wearable, and implantable electronic systems, and therefore, they attract considerable interest for researchers to fulfill requirements of future energy storage devices. Here, we report a facile two-step strategy to construct flexible and binder-free NaTi2(PO4)3/graphene film with a sandwich structure (GN/NaTi2(PO4)3/GN). Such a design makes the resulting film with an excellent flexibility, which can be used for a binder-free anode for flexible sodium-ion batteries (SIBs). GN nanosheet supported NaTi2(PO4)3 nanocrystals (NaTi2(PO4)3/GN) are first prepared by a facile hydrothermal route. Then, the resultant NaTi2(PO4)3/GN hybrid is embedded homogeneously in interconnected GN nanosheet framework to form three-dimensional flexible GN/NaTi2(PO4)3/GN film. The flexible film exhibits excellent cycling stability (91% capacity retention over 1000 cycles at 500 mA g–1) for sodium half cells. Furthermore, it can be assembled into...

Thin, Transferred Layers of Silicon Dioxide and Silicon Nitride as Water and Ion Barriers for Implantable Flexible Electronic Systems

Thin, physically transferred layers of silicon dioxide (SiO2) thermally grown on the surfaces of silicon wafers offer excellent properties as long‐lived, hermetic biofluid barriers in flexible electronic implants. This paper explores materials and physics aspects of the transport of ions through the SiO2 and the resultant effects on device performance and reliability. Accelerated soak tests of devices under electrical bias stress relative to a surrounding phosphate buffered saline (PBS) solution at a pH of 7.4 reveal the field dependence of these processes. Similar experimental protocols establish that coatings of SiNx on the SiO2 can block the passage of ions. Systematic experimental and theoretical investigations reveal the details associated with transport though this bilayer structure, and they serve as the basis for lifetime projections corresponding to more than a decade of immersion in PBS solution at 37 °C for the case of 100/200 nm of SiO2/SiNx. Temperature‐dependent simulations offer further understanding of two competing failure mechanisms—dissolution and ion diffusion—on device lifetime. These findings establish a basic physical understanding of effects that are essential to the stable operation of flexible electronics as chronic implants.

P1524Extractions of cardiac implantable electronic systems: a single centre experience

P1524Extractions of cardiac implantable electronic systems: a single centre experience

Lead insulation failure, a serious complication: risk factors and management

“OUTSIDE-IN” ABRASIONS: A NEW PHENOMENA — MORE QUESTIONS THAN ANSWERS We may divide abrasions according to mechanism into “outside-in” and “inside-out” abrasions. The “outside-in” abrasions are well known in the pocket as the result of friction between leads or between the lead and the device, as well as in the venous system, with tearing surfaces among leads, first rib, and clavicle. However, “outside-in” abrasions most frequently appear in the intracardiac part of the lead and are associated with infective endocarditis (IE) [2]. The outer insulation abrasion remains electrically signless unless concomitant inner insulation failure occurs and in the device control both oversensing and undersensing may be observed [3]. The Banacha classification was established to morphologically describe abrasions analysed with an optical microscope, and to facilitate comparison and analysis. The classification distinguishes three levels of silicone in vivo damage: mild, moderate, and severe, all in two subtypes: a and b [2]. A severe abrasion with conductor exposure may be assessed clinically (Fig. 1A) [4]. Insulation abrasion more often concerned patients with sub-pectorally or abdominally implanted devices. Risk factors of intracardiac abrasions are implantation of two or more leads in the heart cavities, and in the case of atrial leads: passive fixation, longer mean dwell time (time from implantation), and three or more procedures proceeding lead extraction [2]. Severe abrasions with conductor exposure were associated with the number of extracted leads, dwell time, location of the lead in the coronary sinus, and excessive lead length in the cardiac chambers [4]. The most important observation was that, irrespective of the abrasion level of degradation in the intracardiac part of the lead, they were associated with IE development [2]. The process of outside-in abrasion may be INTRODUCTION Endocardial leads are the most important parts of cardiovascular implantable electronic device systems. The endocardial lead parts are located in the tissue of the pocket, in the venous system, and finally in the right heart cavities. The three different microenvironments present different impacts on lead body parts, especially the outermost insulation. Lead design also concerns the outer insulation, which has been evaluated since implantation of the first pacemaker. In the current paper we present the different mechanisms of insulation failure of the leads available on the market, and of leads that have been withdrawn from the market but still exist in living patients. The outer lead insulation may dictate the lead reliability. Silicone, polyurethane, fluoropolymers (PTFE, ETFE), and co-polymer silicone-polyurethane (Optim) are materials widely used as insulation of endocardial leads. Insulation breach and abrasions may occur anywhere along the lead. The lead parameters: abnormal sensing amplitudes, abnormal and variant pacing thresholds, and lead impedance abnormalities may be indicators of lead failure. The insulation characteristics of typical damage, lead failure symptoms, and lead management are crucial for patients, theirs doctors, scientists, and manufacturers.

Flexible and Binder-Free Electrodes of Sb/rGO and Na3V2(PO4)3/rGO Nanocomposites for Sodium-Ion Batteries.

Flexible power sources have shown great promise in next-generation bendable, implantable, and wearable electronic systems. Here, flexible and binder-free electrodes of Na3V2(PO4)3/reduced graphene oxide (NVP/rGO) and Sb/rGO nanocomposites for sodium-ion batteries are reported. The Sb/rGO and NVP/rGO paper electrodes with high flexibility and tailorability can be easily fabricated. Sb and NVP nanoparticles are embedded homogenously in the interconnected framework of rGO nanosheets, which provides structurally stable hosts for Na-ion intercalation and deintercalation. The NVP/rGO paper-like cathode delivers a reversible capacity of 113 mAh g(-1) at 100 mA g(-1) and high capacity retention of ≈96.6% after 120 cycles. The Sb/rGO paper-like anode gives a highly reversible capacity of 612 mAh g(-1) at 100 mA g(-1) , an excellent rate capacity up to 30 C, and a good cycle performance. Moreover, the sodium-ion full cell of NVP/rGO//Sb/rGO has been fabricated, delivering a highly reversible capacity of ≈400 mAh g(-1) at a current density of 100 mA g(-1) after 100 charge/discharge cycles. This work may provide promising electrode candidates for developing next-generation energy-storage devices with high capacity and long cycle life.

Clinical use of antibacterial mesh envelopes in cardiovascular electronic device implantations.

Cardiovascular implantable electronic device system infection is a serious complication of cardiac device implantation and carries with it a risk of significant morbidity and mortality. In the last 15 years, expansions of indications for cardiac devices have resulted in much higher volumes of much sicker patients being implanted, carrying significant risk of infection. Coagulase (−) Staphylococcus and Staphylococcus aureus are responsible for the majority of these infections, and these organisms are increasingly resistant to methicillin. The Aigis™ envelop is a Food and Drug Administration–approved implantable mesh that is impregnated with antibiotics that can be placed in the surgical incision prior to closure. The antibiotics elute off the mesh for 7–10 days, providing in vivo surgical site coverage with rifampin and minocyclin. This paper reviews the three retrospective clinical trials published in peer-reviewed journals and the interim analysis of the two ongoing prospective trials that have been presented at international conferences. Overall consensus is that the Aigis™ offers significant risk reduction for cardiovascular implantable electronic device infection. We then give a comprehensive discussion of how to use the Aigis™ envelop in the clinical setting, comparing the manufacturer’s recommendations with our extensive clinical experience.

A 65nm CMOS low-power MedRadio-band integer-N cascaded phase-locked loop for implantable medical systems.

This paper presents a low-power MedRadio-band integer-N phase-locked Loop (PLL) system which is composed of two charge-pump PLLs cascade connected. The PLL provides the operation clock and local carrier signals for an implantable medical electronic system. In addition, to avoid the off-chip crystal oscillator, the 13.56 MHz Industrial, Scientific and Medical (ISM) band signal from the wireless power transmission system is adopted as the input reference signal for the PLL. Ring-based voltage controlled oscillators (VCOs) with current control units are adopted to reduce chip area and power dissipation. The proposed cascaded PLL system is designed and implemented in TSMC 65-nm CMOS technology. The measured jitter for 216.96 MHz signal is 12.23 ps and the phase noise is -65.9 dBc/Hz at 100 kHz frequency offset under 402.926 MHz carrier frequency. The measured power dissipations are 66 μW in the first PLL and 195 μW in the whole system under 1-V supply voltage. The chip area is 0.1088 mm(2) and no off-chip component is required which is suitable for the integration of the implantable medical electronic system.

Novel Planar-Structure Electrochemical Devices for Highly Flexible Semitransparent Power Generation/Storage Sources

Flexible and transparent power sources are highly desirable in realizing next-generation all-in-one bendable, implantable, and wearable electronic systems. The developed power sources are either flexible but opaque or semitransparent but lack of flexibility. Therefore, there is increasing recognition of the need for a new concept of electrochemical device structure design that allows both high flexibility and transparency. In this paper, we present a new concept for electrochemical device design--a two-dimensional planar comb-teeth architecture on PET substrate--to achieve both high mechanical flexibility and light transparency. Two types of prototypes--dye-sensitized solar cells and supercapacitors--have been fabricated as planar devices and demonstrated excellent device performance, such as good light transparency, excellent flexibility, outstanding multiple large bending tolerance, light weight, effective prevention of short circuits during bending, and high device integration with up-date microelectronics, compared to conventional sandwich structure devices. Our planar design provides an attractive strategy toward the development of flexible, semitransparent electrochemical devices for fully all-in-one elegant and wearable energy management.

Plasma-assisted atomic layer deposition of Al2O3 and parylene C bi-layer encapsulation for chronic implantable electronics

Encapsulation of biomedical implants with complex three dimensional geometries is one of the greatest challenges achieving long-term functionality and stability. This report presents an encapsulation scheme that combines Al(2)O(3) by atomic layer deposition with parylene C for implantable electronic systems. The Al(2)O(3)-parylene C bi-layer was used to encapsulate interdigitated electrodes, which were tested invitro by soak testing in phosphate buffered saline solution at body temperature (37 °C) and elevated temperatures (57 °C and 67 °C) for accelerated lifetime testing up to 5 months. Leakage current and electrochemical impedance spectroscopy were measured for evaluating the integrity and insulation performance of the coating. Leakage current was stably about 15 pA at 5 V dc, and impedance was constantly about 3.5 MΩ at 1 kHz by using electrochemical impedance spectroscopy for samples under 67 °C about 5 months (approximately equivalent to 40 months at 37 °C). Alumina and parylene coating lasted at least 3 times longer than parylene coated samples tested at 80 °C. The excellent insulation performance of the encapsulation shows its potential usefulness for chronic implants.