Implantable Biomedical Devices Research Articles

Recent Advances in Energy Harvesting from the Human Body for Biomedical Applications

Energy harvesters serve as continuous and long-lasting sources of energy that can be integrated into wearable and implantable sensors and biomedical devices. This review paper presents the current progress, the challenges, the advantages, the disadvantages and the future trends of energy harvesters which can harvest energy from various sources from the human body. The most used types of energy are chemical; thermal and biomechanical and each group is represented by several nano-generators. Chemical energy can be harvested with a help of microbial and enzymatic biofuel cells, thermal energy is collected via thermal and pyroelectric nano-generators, biomechanical energy can be scavenged with piezoelectric and triboelectric materials, electromagnetic and electrostatic generators and photovoltaic effect allows scavenging of light energy. Their operating principles, power ratings, features, materials, and designs are presented. There are different ways of extracting the maximum energy and current trends and approaches in nanogenerator designs are discussed. The ever-growing interest in this field is linked to a larger role of wearable electronics in the future. Possible directions of future development are outlined; and practical biomedical applications of energy harvesters for glucose sensors, oximeters and pacemakers are presented. Based on the increasingly accumulated literature, there are continuous promising improvements which are anticipated to lead to portable and implantable devices without the requirement for batteries.

Resistance switching characteristics of Ag/ZnO/graphene resistive random access memory

In this work, an Ag/ZnO/Graphene structure resistive random access memory (RRAM) is prepared through RF magnetron sputtering. Compared to the Ag/ZnO/Au structure device, the endurance of the device using a graphene electrode up to 3 × 103 cycles. It has a self-current compliance function of 2 × 10−4 A and 30 times switching resistance ratio and characteristics without electroforming. The density of states (DOS) of ZnO supercells with different space groups are calculated by using the first-principles, and it is analyzed that the contributions of different supercells to the conductivity and contact type of the RRAM. Combined with the I–V curve of the RRAM, it illustrated that the conduction path is created by the space-charge-limited conduction (SCLC) of electrons captured by oxygen vacancy traps. The biocompatibility of the device is tested by a cell toxicity test. It proves that the Ag/ZnO/Graphene RRAM has high biocompatibility and broad applicability in implantable biomedical devices.

Actuators for Implantable Devices: A Broad View.

The choice of actuators dictates how an implantable biomedical device moves. Specifically, the concept of implantable robots consists of the three pillars: actuators, sensors, and powering. Robotic devices that require active motion are driven by a biocompatible actuator. Depending on the actuating mechanism, different types of actuators vary remarkably in strain/stress output, frequency, power consumption, and durability. Most reviews to date focus on specific type of actuating mechanism (electric, photonic, electrothermal, etc.) for biomedical applications. With a rapidly expanding library of novel actuators, however, the granular boundaries between subcategories turns the selection of actuators a laborious task, which can be particularly time-consuming to those unfamiliar with actuation. To offer a broad view, this study (1) showcases the recent advances in various types of actuating technologies that can be potentially implemented in vivo, (2) outlines technical advantages and the limitations of each type, and (3) provides use-specific suggestions on actuator choice for applications such as drug delivery, cardiovascular, and endoscopy implants.

Development of an Integrated Salt Cartridge-Reverse Electrodialysis (Red) Device to Increase Electrolyte Concentrations to Biomedical Devices.

Emerging technologies in nanotechnology and biomedical engineering have led to an increase in the use of implantable biomedical devices. These devices are currently battery powered which often means they must be surgically replaced during a patient’s lifetime. Therefore, there is an important need for a power source that could provide continuous, stable power over a prolonged time. Reverse electrodialysis (RED) based biopower cells have been previously used to generate continuous power from physiologically relevant fluids; however, the low salinity gradient that exists within the body limited the performance of the biopower cell. In this study, a miniaturized RED biopower cell design coupled with a salt cartridge was evaluated for boosting the salt concentration gradient supplied to RED in situ. For the salt cartridge, polysulfone (PSf) hollow fibers were prepared in-house and saturated with NaCl solutions to deliver salt and thereby enhance the concentration gradient. The effect of operational parameters including solution flow rate and cartridge salt concentration on salt transport performance was evaluated. The results demonstrated that the use of the salt cartridge was able to increase the salt concentration of the RED inlet stream by 74% which in turn generated a 3-fold increase in the open circuit voltage (OCV) of the biopower cell. This innovative adaptation of the membrane-based approach into portable power generation could help open new pathways in various biomedical applications.

Proposed algorithm for the design of planar inductors in implantable biomedical devices

The AISI 316L steel is a material used to manufacture prostheses and medical instruments due to its high corrosion resistance. However, its wear resistance is low, but it can be improved by synthesizing thin films of titanium nitride (TiN) on the surface. This compound is a hard material that improves its tribological and corrosive properties, in addition to presenting good adhesion to the substrate. In this work, a Ti/TiN thin film was obtained using the Physical Vapor Deposition (PVD) technique. This coating was characterized by scanning electron microscopy, energy dispersion spectroscopy (EDS), and light microscopy; additionally, tribological tests under wet conditions and adhesion tests were conducted. The coating showed good adhesion to the substrate according to the VDI standard. In tribological tests, a low coefficient of friction vs. a polyethylene pin in a wet environment (bovine serum) was obtained. The EDS showed a high concentration of Ti and N on the substrate even after wear tests.

Enzymatic Biofuel Cells Embedded Polymer-Based Soft Actuators

Enzymatic biofuel cells are presented as an untethered alternative energy source that could power small implantable or wearable medical devices. However, most of these catalytic processes do not provide with enough energy to power common small electronic-mechanical devices. On the other hand, conducting polymer-based actuators are of great interest for their biocompatibility, flexibility, processability, possibility to be miniaturized and low power consumption. So far, these artificial muscles have been driven by external power sources that prevent them for being completely autonomous. There is a need for a novel power source to elaborate actuators that could use physiological processes as a driving force. These soft actuators’ low power consumption matches the electrical power generated by the biocatalysis of some enzymes, such as glucose oxidase and laccase in presence of glucose and oxygen in aqueous media. Here, we present the latest results in the development of polypyrrole-based soft actuators powered by enzymatic biofuel cells. The actuator consists of a tri-layer conductive substrate on which the polypyrrole is electrodeposited in both sides. The polypyrrole layers act as the active part, expanding and contracting upon a redox reaction, resulting in a bending movement. Tetrathiofulvlene-7,7,8,8-tetracyanoquinodimethane (TTF-TCNQ) and 2,2′-azino-di-(3-ethylbenzthiazoline sulfonic acid) (ABTS) electron transfer mediators are cast on the surface of the polypyrrole to help the electron transmission. The glucose oxidase and laccase enzymes are immobilized in the modified-conducting polymer surface, integrating the electrode to the actuator. The bio-catalysis of enzymes in presence of glucose and oxygen in aqueous solution provides the actuator with the electrons needed for the redox reaction, converting the chemical energy into mechanical energy, i.e., movement. The glucose-self-powered soft actuator may contribute to the development of more complex implantable, ingestible, or wearable biomedical devices such as cardio-stimulators, insulin pumps, or muscle implants.

Disposable sensors based on biodegradable polylactic acid piezoelectret films and their application in wearable electronics

The alarming rise of electronic waste has promoted increasing attention to modernizing sensing materials and devices. Especially, sensing devices featuring biodegradability and bioabsorbability are greatly desired. We therefore herein present a disposable sensor based on biodegradable flexible polylactic acid piezoelectret film (DS-PLA), which achieves significant longitudinal compressive and transverse tensile sensitivities and thus can act either as a pressure sensor or as a tensile sensor, extending its potential applications in wearable and implantable electronics. The core material-PLA piezoelectret film can be degraded in deionized water with a temperature of 170 ℃ in 11 h, which is of great significance for green and sustainable development. For longitudinal compressive sensing performance, a high quasi-static compressive sensitivity up to 1000 pC/N and a wide pressure detecting range of 0.03–62 kPa were obtained simultaneously. Most importantly, the compressive sensitivity does not show obvious deterioration after 1.08 million operation cycles at a pressure of 4.3 kPa, demonstrating good mechanical robustness. Transverse tensile sensitivities of S 31 = 24 pC/N and S 32 = 47 pC/N indicate that the short-circuit charge outputs upon stretching are significantly higher than that of the sensors based on traditional cellular polypropylene piezoelectret (~2 pC/N). Wearable DS-PLAs can be conformally attached to the surface of human skin to monitor human motions. We envision the sensor holds significant superiority in the next-generation wearable biosensors and implantable biomedical devices without maintenance and environmental damage. ● A novel disposable sensor based on biodegradable flexible polylactic acid piezoelectret film (DS-PLA) is developed. ● The sensor achieves significant longitudinal compressive and transverse tensile sensitivities, simultaneously. ● The core material-PLA film can be degraded completely in deionized water with a temperature of 170 ℃ in 11 h. ● The DS-PLA enabled accurate monitoring of finger bending, tactile and foot movement for evaluating its actual application.

An ultrasound-induced wireless power supply based on AlN piezoelectric micromachined ultrasonic transducers

Wireless power transfer is one of the enabling technologies for powering implantable biomedical devices. Biocompatibility and CMOS compatibility of wireless power transfer devices are highly desired due to safety and footprint concerns. Toward implantable applications, this paper presents an ultrasound-induced wireless power supply based on AlN piezoelectric micromachined ultrasonic transducer (PMUT). The wireless power supply integrates wireless power transfer, power management and energy storage functions. The PMUT array is used as a passive wireless power receiver, followed by electrical impedance matching networks and a voltage multiplier for efficient power transmission and rectification. The output power intensity of the wireless receiver reaches 7.36 μW/mm2 with an incident ultrasound power below the FDA safety limit. The output power of the wireless power supply reaches 18.8 μW and a 100-μF capacitor is fully charged to 3.19 V after power management, which are sufficient to power many low-power implantable biomedical devices such as for neural electrical stimulation, biosensors and intrabody communication applications. The wireless power supply is implemented in a PCB with a diameter of 1 cm. With biocompatibility and CMOS compatibility of AlN thin film compared to commonly used PZT, the proposed solution paves the way for safer and ultraminiaturized wireless power supplies with further development incorporating all the functions on a monolithic chip in the future.

DEA-based on optimization of inductive coupling for powering implantable biomedical devices

Inductive coupling wireless power transfer (WPT) is one of the best technologies for powering implantable microelectronic devices (IMD). A wireless power transfer system’s important elements (indicators) are power transfer efficiency (PTE) and power delivered to load (PDL). The key characteristics of WPT are the size of the transmitting (Tx) and receiving (Rx) coils, the operating frequency, and the separation distance between the two parts of the system. The main goal of this research is to use the differential evolution algorithm (DEA) to optimize a wireless energy transfer system in order to maximize the PTE and PDL. By comparing the results acquired by the proposed technique to those obtained by other methodologies, we were able to validate the results obtained by the suggested method. With the aim of raising the PTE and PDL. Using this metaheuristic approach, we were able to improve WPT’s critical parameters. For is, a PTE of 95% and 136 mW of power delivered to the load for a 13 cm separation distance.

Magnetostrictive biomechanical energy harvester with a hybrid force amplifier

Vibrating energy harvesters, capable of converting mechanical energy into electrical energy, have attracted unprecedented interest in both academia and industry because of their great potential for harvesting energy induced by human activity and energy around the body, and to drive low-power wearable biosensors and electronics, micro-robots, and implantable biomedical devices. In this paper, based on the magnetostrictive inverse effect, we propose a magnetostrictive vibration harvester using Terfenol-D, which generates electrical energy when subjected to human movement. A hybrid force amplification frame is integrated in this harvester to amplify weak biological movements. The detailed mathematical model of the multi-stage force amplification process is established, the hybrid force amplifier is also designed in detail, and its structural dimensions are optimized. The position and form of the bias magnetic field arrangement based on the Terfenol-D harvester is systematically analyzed. The experiment shows that 4.13 V peak voltage and 426.4 mW peak power are generated when the harvester is fully compressed. The output power is 213.16 mW and 371.43 mW at an average acceleration of 2.5 g for slow walking and 4 g for jogging, respectively. The results of this study suggest that the combination of rod Terfenol-D and force amplification mechanisms can be used to design bio-vibrational energy harvester with excellent performance, which is especially suitable for self-powered wearable electronic devices.

Wireless power transfer system for deep-implanted biomedical devices

In this paper, a dual-band implantable rectenna is proposed for recharging and operating biomedical implantable devices at 0.915 and 2.45 GHz. The rectenna system consists of a compact dual-band antenna based on a meandered-resonator as well as efficient dual-band rectifier circuit. Both components (antenna and rectifier) are integrated inside a capsule device to simulate and experimentally validate the rectenna. The antenna occupies lower volume (5 times 5.25 times 0.25 hbox {mm}^{3}), where compactness is achieved using meandered geometry and a slotted ground plane. It maintains quasi-omnidirectional radiation patterns and peak realized gains of −22.1 dBi (915 MHz) and −19.6 dBi (2.45 GHz); thus, its capability is enhanced to harvest the ambient energy from multiple directions. Moreover, a dual-band rectifier is designed using a dual-branch matching network (an L-matching network and open-circuited stub in each branch) with a radio frequency (RF) to direct current (DC) conversion efficiency of 79.9% for the input power of 1 dBm (lower band: 0.915 GHz) and 72.8% for the input power of 3 dBm (upper band: 2.45 GHz). To validate the concept of the rectenna, the implantable antenna and rectifier are fabricated and attached together inside a capsule device, with the measured results verifying the simulated responses. The proposed rectenna efficiently rectifies two RF signals and effectively superimposes on a single load, thus, providing a distinct advantage compared to single-band rectennas. To the best of the authors’ knowledge, this is the first-ever implantable rectenna to perform dual-band RF signal rectification.

Single-step fabrication of di-titanium nitride thin-film flexible and biocompatible supercapacitor

Functional biomedical electronic devices rely on the energy storage units such as batteries and capacitors as their sole power sources. These power sources are constrained by issues such as low performance, non-biocompatibility, and lack of flexibility. In this work, nanocluster di-titanium nitride (n-Ti2N) thin films were sputtered onto the surface of 304 stainless steel substrate (SS-304) for the fabrication of a highly efficient symmetric supercapacitor device. The electrochemical studies were performed in Phosphate Buffer Saline (PBS) at different current densities and scan rates. The n-Ti2N@SS electrode-based symmetric supercapacitor device shows high areal energy density of 1.614 μWhcm−2 with optimum areal power-density of 49.98 mWcm−2. The device evinces a broader voltage window of 1.0 V with good capacitance retention of 86% even after 5000 CV cycles at a scan rate of 50 mVs−1. The biocompatibility of the electrode was checked in-vitro and it reveals excellent cell viability of around 85%. The SS device also performs ideally in bending state. Owing to these appealing properties, the proposed SS device can be considered potentially suitable for powering the battery-operated implantable biomedical devices (such as pacemakers, Implantable Cardiovert Defibrillators ICD, Cardiac Resynchronization Therapy CRT, and cochlear implants) and wearable electronics.

Biguanide- and Oligo(Ethylene Glycol)-Functionalized Poly(3,4-Ethylenedioxythiophene): Electroactive, Antimicrobial, and Antifouling Surface Coatings.

The challenge of infectious diseases remains a critical concern to the global public health. Recently, it is common to encounter touch-screen electronic devices everywhere to access services. The surface of such devices may easily get contaminated by an infected person, which leads to transmission of infectious diseases between individuals. Moreover, the challenge is complicated by surgical infections from implantable biomedical devices. Such problems can be minimized by the use of long-term active antimicrobial surface coatings. We present herein the preparation of novel electroactive antimicrobial surface coatings through the covalent attachment of the biguanide moiety onto 3,4-ethylenedioxythiophene (EDOT). The biguanide-functionalized EDOT (EDOT-BG) was thus electropolymerized on different substrates to give the corresponding poly(EDOT-BG) polymer. The poly(EDOT-BG) polymer showed an excellent bactericidal efficiency (∼92% bacterial death) and excellent biocompatibility with mammalian cells. Furthermore, the antimicrobial EDOT-BG was electro-copolymerized with antifouling tetra ethylene glycol functionalized-EDOT (EDOT-EG4) to give a multifunctional poly(EDOT-EG4-co-EDOT-BG) copolymer. The poly(EDOT-EG4-co-EDOT-BG) copolymer showed excellent resistance to protein adsorption and mammalian/bacterial cell binding without losing its bactericidal efficiency. These novel materials can be applied to domestic and bioelectronic devices to minimize infectious diseases.

3D Printability Assessment of Poly(octamethylene maleate (anhydride) citrate) and Poly(ethylene glycol) Diacrylate Copolymers for Biomedical Applications.

Herein, we present the first example of 3D printing with poly(octamethylene maleate (anhydride) citrate) (POMaC), a bio-adhesive material which has shown particular promise for implantable biomedical devices. The current methods to fabricate such devices made from POMaC are hindered by the imposed constraints of designing complex molds. We demonstrate the feasibility of exploiting additive manufacturing to 3D print structural functional materials consisting of POMaC. We present 3D printing of biomaterial copolymers consisting of mixtures of poly(ethylene glycol) diacrylate (PEGDA) and POMaC at different ratios. The required parameters were optimized, and characterization of the printing fidelity and physical properties was performed. We have also demonstrated that a range of mechanical properties can be achieved by tuning the POMaC/PEGDA ratio. The biocompatibility of the copolymers was ascertained via a cell viability assay. Such tunable 3D printed biomaterials consisting of POMaC and PEGDA will have significant potential application in the development of functional biomaterial tissue scaffolds and biomedical devices for the future of personalized medicine.

Design Approaches of Ultra-Low Power SAR ADC for Biomedical Systems — A Review

In recent years, implantable biomedical devices like cardiac pacemaker, defibrillators, cochlear implants, visual prosthesis etc. have gained immense importance in the personal health monitoring system. Most of these devices are battery powered. The life span of a pacemaker is expected to be between 10 and 12 years. This shows the importance of having an ultra-low power design technique to improve the reliability and battery life of the system. To achieve this, power draws from the battery must be kept low. Analog-to-Digital Convertor (ADC) is a main block in the front-end sensing unit of an implant for measurements of various biophysiological signals. This is the most power consuming unit in the system. ADC alone consumes about 30%–35% of the total power. This work surveys various successive approximation ADC designs for biomedical signal acquisition, in terms of power consumption, signal to noise distortion ratio, sampling rate, resolution and Figure of Merit. The different switching schemes for capacitive DAC are also surveyed.

Advanced Implantable Biomedical Devices Enabled by Triboelectric Nanogenerators.

Implantable biomedical devices (IMDs) play essential roles in healthcare. Subject to the limited battery life, IMDs cannot achieve long-term in situ monitoring, diagnosis, and treatment. The proposal and rapid development of triboelectric nanogenerators free IMDs from the shackles of batteries and spawn a self-powered healthcare system. This review aims to overview the development of IMDs based on triboelectric nanogenerators, divided into self-powered biosensors, in vivo energy harvesting devices, and direct electrical stimulation therapy devices. Meanwhile, future challenges and opportunities are discussed according to the development requirements of current-level self-powered IMDs to enhance output performance, develop advanced triboelectric nanogenerators with multifunctional materials, and self-driven close-looped diagnosis and treatment systems.

Piezoelectric ultrasound energy-harvesting device for deep brain stimulation and analgesia applications.

Supplying wireless power is a challenging technical problem of great importance for implantable biomedical devices. Here, we introduce a novel implantable piezoelectric ultrasound energy–harvesting device based on Sm-doped Pb(Mg1/3Nb2/3)O3-PbTiO3 (Sm-PMN-PT) single crystal. The output power density of this device can reach up to 1.1 W/cm2 in vitro, which is 18 times higher than the previous record (60 mW/cm2). After being implanted in the rat brain, under 1-MHz ultrasound with a safe intensity of 212 mW/cm2, the as-developed device can produce an instantaneous effective output power of 280 μW, which can immediately activate the periaqueductal gray brain area. The rat electrophysiological experiments under anesthesia and behavioral experiments demonstrate that our wireless-powered device is well qualified for deep brain stimulation and analgesia applications. These encouraging results provide new insights into the development of implantable devices in the future.

“Smart” alginate hydrogels in biosensing, bioactuation and biocomputing: State-of-the-art and perspectives

In addressing the demand for biocompatible wearable, implantable and injectable biomedical devices, alginate hydrogels stand out as promising candidates. Alginate hydrogels have been used as matrix for immobilization of proteins, responsive polymers and nanomaterials that lead to a wide range of stimuli-responsive “smart” (bio)(nano)composite hydrogels. In this perspective, we analyzed the most recent applications of “smart” alginate composite hydrogels in biomedical applications, such as biosensing, drug delivery, wound healing and biocomputing. The design and key-responsive element of the composites were discussed as well as their practical application in biologically relevant conditions and in vivo. Finally, we provide our insights into the limitations, challenges and future directions of this exciting research field.

Inkjet-Printed Phospholipid Bilayers on Titanium Oxide Surfaces: Towards Functional Membrane Biointerfaces.

Functional biointerfaces hold broad significance for designing cell-responsive medical implants and sensor devices. Solid-supported phospholipid bilayers are a promising class of biological materials to build bioinspired thin-film coatings, as they can facilitate interactions with cell membranes. However, it remains challenging to fabricate lipid bilayers on medically relevant materials such as titanium oxide surfaces. There are also limitations in existing bilayer printing capabilities since most approaches are restricted to either deposition alone or to fixed microarray patterning. By combining advances in lipid surface chemistry and on-demand inkjet printing, we demonstrate the direct deposition and patterning of covalently tethered lipid bilayer membranes on titanium oxide surfaces, in ambient conditions and without any surface pretreatment process. The deposition conditions were evaluated by quartz crystal microbalance-dissipation (QCM-D) measurements, with corresponding resonance frequency (Δf) and energy dissipation (ΔD) shifts of around −25 Hz and <1 × 10−6, respectively, that indicated successful bilayer printing. The resulting printed phospholipid bilayers are stable in air and do not collapse following dehydration; through rehydration, the bilayers regain their functional properties, such as lateral mobility (>1 µm2/s diffusion coefficient), according to fluorescence recovery after photobleaching (FRAP) measurements. By taking advantage of the lipid bilayer patterned architectures and the unique features of titanium oxide’s photoactivity, we further show how patterned cell culture arrays can be fabricated. Looking forward, this work presents new capabilities to achieve stable lipid bilayer patterns that can potentially be translated into implantable biomedical devices.

A Wideband Bear-Shaped Compact Size Implantable Antenna for In-Body Communications

Biomedical implantable antennas play a vital role in medical telemetry applications. These types of biomedical implantable devices are very helpful in improving and monitoring patients’ living situations on a daily basis. In the present paper, a miniaturized footprint, thin-profile bear-shaped in-body antenna operational at 915 MHz in the industrial, scientific, and medical (ISM) band is proposed. The design is a straightforward bear-shaped truncated patch excited by a 50-Ω coaxial probe. The radiator is made up of two circular slots and one rectangular slot at the feet of the patch, and the ground plane is sotted to achieve a broadsided directional radiation pattern, imprinted on a Duroid RT5880 roger substrate with a typical 0.254-mm thickness ( ϵr = 2.2, tan δ = 0.0009). The stated antenna has a complete size of 7 mm × 7 mm × 0.254 mm and, in terms of guided wavelength, of 0.027λg × 0.027λg × 0.0011λg. When operating inside skin tissues, the antenna covers a measured bandwidth from 0.86 GHz to 1.08 GHz (220 MHz). The simulations and experimental outcomes of the stated design are in proper contract. The obtained results show that the calculated specific absorption rate (SAR) values inside skin of over 1 g of mass tissue is 8.22 W/kg. The stated SAR values are lower than the limitations of the federal communications commission (FCC). Thus, the proposed miniaturized antenna is an ultimate applicant for in-body communications.