Implantable Medical Electronics Research Articles

Minimally invasive power sources for implantable electronics

AbstractAs implantable medical electronics (IMEs) developed for healthcare monitoring and biomedical therapy are extensively explored and deployed clinically, the demand for non‐invasive implantable biomedical electronics is rapidly surging. Current rigid and bulky implantable microelectronic power sources are prone to immune rejection and incision, or cannot provide enough energy for long‐term use, which greatly limits the development of miniaturized implantable medical devices. Herein, a comprehensive review of the historical development of IMEs and the applicable miniaturized power sources along with their advantages and limitations is given. Despite recent advances in microfabrication techniques, biocompatible materials have facilitated the development of IMEs system toward non‐invasive, ultra‐flexible, bioresorbable, wireless and multifunctional, progress in the development of minimally invasive power sources in implantable systems has remained limited. Here three promising minimally invasive power sources summarized, including energy storage devices (biodegradable primary batteries, rechargeable batteries and supercapacitors), human body energy harvesters (nanogenerators and biofuel cells) and wireless power transfer (far‐field radiofrequency radiation, near‐field wireless power transfer, ultrasonic and photovoltaic power transfer). The energy storage and energy harvesting mechanism, configurational design, material selection, output power and in vivo applications are also discussed. It is expected to give a comprehensive understanding of the minimally invasive power sources driven IMEs system for painless health monitoring and biomedical therapy with long‐term stable functions.

Nature-derived, biocompatible silibinin based bioresorbable neuromorphic device for implantable medical electronics

Implantable medical electronics require strict standards distinct that are from conventional electronics, such as high data throughput of various signals from a living body and anti-inflammatory responses after a surgical operation. In addition, there is a major concern that the implanted medical device should be removed through additional surgery when its lifespan expires, or duty is terminated. Here, a nature-derived biomaterial silibinin (SLB)-based neuromorphic device that satisfies the requirements of implantable medical electronics is presented. SLB is a biocompatible and bioresorbable material extracted from milk thistle seeds and is mainly used as a pharmaceutical drug for fatty liver disease or cancer. The SLB-based neuromorphic device shows synaptic behaviors, such as a 130 % of paired-pulse facilitation index, potentiation-depression property, and short term-to-long term memory transition behavior of biological synapses. The synaptic behavior of the device is attributed to the MgOx formed by the redox reaction between the Mg electrode and the SLB layer with oxygen functional groups. Furthermore, SLB-based neuromorphic device fabricated on the biopolymer is fully biodegraded within 8 h. It is confirmed to have excellent biocompatibility by performing a cytotoxicity test for 120 h. These results suggest that SLB-based neuromorphic devices are a potential solution for implantable medical electronics.

New Era of Electroceuticals: Clinically Driven Smart Implantable Electronic Devices Moving towards Precision Therapy.

In the name of electroceuticals, bioelectronic devices have transformed and become essential for dealing with all physiological responses. This significant advancement is attributable to its interdisciplinary nature from engineering and sciences and also the progress in micro and nanotechnologies. Undoubtedly, in the future, bioelectronics would lead in such a way that diagnosing and treating patients’ diseases is more efficient. In this context, we have reviewed the current advancement of implantable medical electronics (electroceuticals) with their immense potential advantages. Specifically, the article discusses pacemakers, neural stimulation, artificial retinae, and vagus nerve stimulation, their micro/nanoscale features, and material aspects as value addition. Over the past years, most researchers have only focused on the electroceuticals metamorphically transforming from a concept to a device stage to positively impact the therapeutic outcomes. Herein, the article discusses the smart implants’ development challenges and opportunities, electromagnetic field effects, and their potential consequences, which will be useful for developing a reliable and qualified smart electroceutical implant for targeted clinical use. Finally, this review article highlights the importance of wirelessly supplying the necessary power and wirelessly triggering functional electronic circuits with ultra-low power consumption and multi-functional advantages such as monitoring and treating the disease in real-time.

Low-Temperature Sealing of Titanium for Hermetic Implant Packages

Implantable medical electronics are almost exclusively packaged in titanium shells to ensure reliability and longevity. Additional silicone rubber encapsulation improves structural biocompatibility and limits the diffusion of ion from the body to package materials. These capsules must be hermetically sealed and provide electrical feedthroughs that are insulated against each other by connecting ceramic parts. In this study, a novel RoHS compliant low temperature soldering process is presented, allowing the required assembly. Tungsten/titanium as adhesion material and platinum as wetting layer were deposited by physical vapor deposition as thin-films and were structured by a rapid prototyping laser process. Different devices were soldered with a tin-silver alloy below 300 °C resulting in low thermal stress. The platinum acts as an excellent solder pad. A 50 nm tungsten/titanium adhesion promoter efficiently strengthens the bond to the titanium substrate. The results show that the platinum layer must be thicker than 300 nm to guarantee high bonding strength. Analyses of cross-sections of the joint show occurrence of diffusion of platinum and silver during the soldering process. At soldering times above 30 seconds, a large intermetallic layer forms at the soldering contact, which is prone to crack formation. Likewise, intermixing of tungsten and platinum were observed but without detrimental effects. Limitations in solder times are therefore advisable, for example by introduction of automatic processes. Soaking tests were performed with sealed capsules in water at 60 °C for one year without measurable increase of humidity inside the package. In the used accelerated aging model, this would correspond to a hermetic sealing of about 5 years at 37 °C.

Active photonic wireless power transfer into live tissues

Recent advances in soft materials and mechanics activate development of many new types of electrical medical implants. Electronic implants that provide exceptional functions, however, usually require more electrical power, resulting in shorter period of usages although many approaches have been suggested to harvest electrical power in human bodies by resolving the issues related to power density, biocompatibility, tissue damage, and others. Here, we report an active photonic power transfer approach at the level of a full system to secure sustainable electrical power in human bodies. The active photonic power transfer system consists of a pair of the skin-attachable photon source patch and the photovoltaic device array integrated in a flexible medical implant. The skin-attachable patch actively emits photons that can penetrate through live tissues to be captured by the photovoltaic devices in a medical implant. The wireless power transfer system is very simple, e.g., active power transfer in direct current (DC) to DC without extra circuits, and can be used for implantable medical electronics regardless of weather, covering by clothes, in indoor or outdoor at day and night. We demonstrate feasibility of the approach by presenting thermal and mechanical compatibility with soft live tissues while generating enough electrical power in live bodies through in vivo animal experiments. We expect that the results enable long-term use of currently available implants in addition to accelerating emerging types of electrical implants that require higher power to provide diverse convenient diagnostic and therapeutic functions in human bodies.

Emerging Implantable Energy Harvesters and Self-Powered Implantable Medical Electronics.

Implantable energy harvesters (IEHs) are the crucial component for self-powered devices. By harvesting energy from organisms such as heartbeat, respiration, and chemical energy from the redox reaction of glucose, IEHs are utilized as the power source of implantable medical electronics. In this review, we summarize the IEHs and self-powered implantable medical electronics (SIMEs). The typical IEHs are nanogenerators, biofuel cells, electromagnetic generators, and transcutaneous energy harvesting devices that are based on ultrasonic or optical energy. A benefit from these technologies of energy harvesting in vivo, SIMEs emerged, including cardiac pacemakers, nerve/muscle stimulators, and physiological sensors. We provide perspectives on the challenges and potential solutions associated with IEHs and SIMEs. Beyond the energy issue, we highlight the implanted devices that show the therapeutic function in vivo.

Research Highlights in the Beijing Institute of Nanoenergy and Nanosystems

The Beijing Institute of Nanoenergy and Nanosystems (BINN), Chinese Academy of Sciences, was founded in 2012 by Wang. The mission of BINN is to carry out fundamental research related to nanoenergy and nanosensors as well as train future scientists. The two major areas of BINN's research are nanogenerators for self-powered systems and blue energy and piezotronics and piezo-phototronics for third-generation semiconductors. After 7 years of development starting from scratch, BINN now has about 400 members including graduate students. This special issue published in Advanced Functional Materials showcases a group of selected papers submitted by colleagues at the BINN to represent some of the on-going research in the institute. Based on piezoelectric and triboelectric effects, nanogenerators represent a new approach that converts tiny mechanical energy into electric power, which now has attracted worldwide attention, particularly in the era of Internet-of-things, sensor networks, artificial intelligence, and robotics. Piezoelectric nanogenerators (PENGs) were first invented in 2006 using the piezoelectric effect obtained from nanowire materials. The triboelectric nanogenerator (TENG) was first invented in Wang's group in 2012 by using a conjunction of contact-electrification and electrostatic induction effects. TENGs have quickly gained worldwide attention and now comprise a new field of research that involves fundamental physics, chemistry, materials, electric engineering, and mechanical engineering. Nanogenerators have shown very broad applications in different fields. Firstly, they serve as the micro-power source for wireless distributed mobile/wearable electronics, Internet-of-things, sensor networks, and implantable medical electronics, which require a tremendous amount of mobile power sources, and in many cases, the batteries could not completely satisfy the practical requirements in terms of size, capacity, flexibility, or non-replaceable in vivo. Secondly, nanogenerators can serve as a self-powered sensor (or active sensor) for detecting mechanical triggering, pressure fluctuation, and environmental stimulation without requiring external power being supplied to the sensor tip, which thus possesses great potential for human-machine interfacing, security systems, physiological characterization, and infrastructure monitoring. They also have applications in smart skin, robotics, MEMS, and biomedical science among other fields. Lastly, nanogenerators can be a possible approach for harvesting large-scale energy from ocean waves. By constructing units that are the size of a baseball, inside which the TENGs are installed, millions or even billions of such units can be interconnected into a “fishing net,” which can float on the water surface for harvesting the kinetic energy. This technology has the merits of low cost, light weight, high efficiency, high output power density, and easy scaling, leading towards the dream of “blue energy”, the energy from the ocean. Piezotronics is a term coined by Wang in 2007, which involves using the piezoelectric effect to control electronics via mechanical stimuli. For wurtzite structures that have non-central symmetry, such as ZnO, GaN, and InN, piezoelectric polarization charges are created at the interface/surface by applying a strain. The strain created inner-crystal piezopotential can serve as a “gate voltage” that can effectively tune/control the charge transport across an interface/junction. This mechanism is termed the piezotronic effect and the electronics fabricated based on such a mechanism is coined as piezotronics, with applications in force controlled electronic devices, sensors, logic units, memories, and catalysts. Analogically, new electronic components can be fabricated as well by using the electric potential created by contact-electrification as a gating voltage, which is called tribotronics. The presence of polarization charges at a p-n junction can effectively distort the local band structure and consequently affect carrier transport, separation, or recombination. Applying either a compressive or tensile strain depending on the polarization of the piezoelectric material, the efficiency for charge carrier separation or recombination can be effectively enhanced. The combination of photon excitation, coupling among semiconductors, photon excitation, and piezoelectricity represents a new field of research called piezo-phototronics. The piezo-phototronic effect is the tuning and controlling of charge carrier generation, separation or recombination at a heterojunction by the strain induced piezoelectric polarization charge. This effect could lead to tremendous performance gain in LEDs, laser diodes, photodetectors, photovoltatic devices, and catalysis by applying static or quasi-static mechanical strains. The fields of research conducted at BINN can be summarized using a “science tree” (Figure 1) to project its main “trunk”, major fields, and applications. The main trunk is based on functional materials and fundamental physics effects, which leads to new and innovative fields. The major fields of research are self-powered systems, triboelectric nanogenerators, hybridized nanogenerators, blue energy, tribotronics, piezotronics, and piezo-phototronics, which are in the middle of the tree. The small branches are the potential applications, as well as future perspectives. We anticipate this tree will grow fast and expand quickly with abundant fruits in the near future.

A High-Accuracy Ultra-Low-Power Offset-Cancelation On-Off Bandgap Reference for Implantable Medical Electronics

An ultra-low-power and high-accuracy on-off bandgap reference (BGR) is demonstrated in this paper for implantable medical electronics. The proposed BGR shows an average current consumption of 78 nA under 2.8 V supply and an output voltage of 1.17 V with an untrimmed accuracy of 0.69%. The on-off bandgap combined with sample-and-hold switched-RC filter is developed to reduce power consumption and noise. The on-off mechanism allows a relatively higher current in the sample phase to alleviate the process variation of bipolar transistors. To compensate the error caused by operational amplifier offset, the correlated double sampling strategy is adopted in the BGR. The proposed BGR is implemented in 0.35 μm standard CMOS process and occupies a total area of 0.063 mm2. Measurement results show that the circuit works properly in the supply voltage range of 1.8–3.2 V and achieves a line regulation of 0.59 mV/V. When the temperature varies from −20 to 80 °C, an average temperature coefficient of 19.6 ppm/°C is achieved.

Fabrication and performance test of biodegradable supercapacitor

ABSTRACTPower source plays an important role in keeping normal functions of biodegradable electronic devices. In this paper, we proposed a fabrication method of biodegradable supercapacitor (BSC), which can provide energy for portable and implantable medical electronics. The BSC has a sandwich-like symmetric structure, which was assembled layer by layer. The electrochemical performances of BSC were measured, including the cyclic voltammetry test, galvanostatic charge-discharge and electrochemical impedance spectroscopy. Titanium foil was used as a template to generate microstructure for polylactic acid (PLA) supporting substrate. The microstructure provided strong adhesion force for iron film in sputtering process. The nanoporous zinc oxide layer was prepared by evaporation-driven self-assembly technology on iron film. The nanoporous structure was in favour of ionic storage in charging-discharging process. About 60% of capacitance retention was achieved after 3000 times of cycling test. After connecting three BSC in series, a green LED pattern was lighted up immediately, indicating that the energy was stored in BSC device successfully. After immersing the BSC in DMEM, the BSC can be totally degraded gradually. This work provided a feasible scheme for developing biodegradable energy storage device, it also gave a possible avenue for powering biodegradable electronic devices.

Micro/Nano Technologies for High-Density Retinal Implant.

During the past decades, there have been leaps in the development of micro/nano retinal implant technologies, which is one of the emerging applications in neural interfaces to restore vision. However, higher feedthroughs within a limited space are needed for more complex electronic systems and precise neural modulations. Active implantable medical electronics are required to have good electrical and mechanical properties, such as being small, light, and biocompatible, and with low power consumption and minimal immunological reactions during long-term implantation. For this purpose, high-density implantable packaging and flexible microelectrode arrays (fMEAs) as well as high-performance coating materials for retinal stimulation are crucial to achieve high resolution. In this review, we mainly focus on the considerations of the high-feedthrough encapsulation of implantable biomedical components to prolong working life, and fMEAs for different implant sites to deliver electrical stimulation to targeted retinal neuron cells. In addition, the functional electrode materials to achieve superior stimulation efficiency are also reviewed. The existing challenge and future research directions of micro/nano technologies for retinal implant are briefly discussed at the end of the review.

Fully Bioabsorbable Capacitor As an Energy Storage Unit for Implantable Medical Electronics

Implantable medical electronic devices are usually powered by batteries or capacitors, which have to be removed from the body after completing their function due to their non-biodegradable property. Here, a fully bioabsorbable capacitor (BC) is developed for life-time implantation. The BC has a symmetrical layer-by-layer structure, including PLA supporting substrate, PLA nanopillar arrays, self-assembled zinc oxide nanoporous layer and PVA/PBS hydrogel. The as-fabricated BC can not only work normally in air but also in a watery environment, including PBS and animal body. Long-term normal work time was achieved to 30 days in PBS and 50 days in SD rats. The work time of BC in the watery environment was tunable from days to weeks by adopting different encapsulations along BC edges. The operation voltage of BC reached up to 1.5 V. Capacitance retention of 70 % was achieved after 3000 cycles. Three BCs in series can light up fifteen green LEDs in vivo. Additionally, after completing its mission, the BC can be fully degraded in vivo and rebsorbed by a Sprague Dawley (SD) rat. Considering these performance, the developed BC has a great potential as a fully bioabsorbable power source for transient electronics and implantable medical devices.

EYE ON CHINA

Over 2,000 Belt and Road Scientists to conduct research in China. China to amend healthcare laws. Smart hospital program upgraded with 5G technology. First “one-minute clinic” in China university. Studies reveal “death switch” in plant immune systems. Faster and cheaper manufacturing of CAR-T production. Immunotherapy trials show positive results against blood disease. Gene-editing tool uses light to kill cancer cells. 3D printed bone tissue for implant surgery. Bioabsorbable power source for implantable medical electronics. New stomach check system developed to reduce diagnosis blind spots. Mapping of protein complex to help patients with osteoporosis.

Bioabsorbable Capacitors: Fully Bioabsorbable Capacitor as an Energy Storage Unit for Implantable Medical Electronics (Adv. Sci. 6/2019)

Bioabsorbable Capacitors: Fully Bioabsorbable Capacitor as an Energy Storage Unit for Implantable Medical Electronics (Adv. Sci. 6/2019)

Fully Bioabsorbable Capacitor as an Energy Storage Unit for Implantable Medical Electronics.

Implantable medical electronic devices are usually powered by batteries or capacitors, which have to be removed from the body after completing their function due to their non‐biodegradable property. Here, a fully bioabsorbable capacitor (BC) is developed for life‐time implantation. The BC has a symmetrical layer‐by‐layer structure, including polylactic acid (PLA) supporting substrate, PLA nanopillar arrays, self‐assembled zinc oxide nanoporous layer, and polyvinyl alcohol/phosphate buffer solution (PVA/PBS) hydrogel. The as‐fabricated BC can not only work normally in air but also in a liquid environment, including PBS and the animal body. Long‐term normal work time is achieved to 30 days in PBS and 50 days in Sprague–Dawley (SD) rats. The work time of BC in the liquid environment is tunable from days to weeks by adopting different encapsulations along BC edges. Capacitance retention of 70% is achieved after 3000 cycles. Three BCs in series can light up 15 green light‐emitting diodes (LEDs) in vivo. Additionally, after completing its mission, the BC can be fully degraded in vivo and reabsorbed by a SD rat. Considering its performance, the developed BC has a great potential as a fully bioabsorbable power source for transient electronics and implantable medical devices.

Implantable Energy-Harvesting Devices.

The sustainable operation of implanted medical devices is essential for healthcare applications. However, limited battery capacity is a key challenge for most implantable medical electronics (IMEs). The human body abounds with mechanical and chemical energy, such as the heartbeat, breathing, blood circulation, and the oxidation-reduction of glucose. Harvesting energy from the human body is a possible approach for powering IMEs. Many new methods for developing in vivo energy harvesters (IVEHs) have been proposed for powering IMEs. In this context energy harvesters based on the piezoelectric effect, triboelectric effect, automatic wristwatch devices, biofuel cells, endocochlear potential, and light, with an emphasis on fabrication, energy output, power management, durability, animal experiments, evaluation criteria, and typical applications are discussed. Importantly, the IVEHs that are discussed, are actually implanted into living things. Future challenges and perspectives are also highlighted.

(Invited) Self-Powered, Wireless Medical Sensor and Devices

Implantable medical devices and integrated wireless healthcare sensors are attracting extensive attention, but the batteries used for powering these devices usually display a limited lifetime. Although battery technology has improved, sustainable power sources for cardiac pacemakers, neural stimulators and other implantable biomedical devices are required. Mechanical energy was considered as one of most abundant and accessible energy sources around the human body. When a small system can efficiently convert mechanical energy in our daily life, this system would be a suitable solution for electricity generation and significantly extend the lifetime of the electronic devices, especially in medical area. Recently, triboelectric nanogenerator (TENG) has attracted much attention and been considered as another potential solution for harvesting mechanical energy. With its high output performance, outstanding biocompatibility and low cost, TENG has been studied for powering implantable medical electronic devices. Here, we demonstrated an in vivo biomechanical-energy harvesting using a TENG. An implantable triboelectric nanogenerator (iTENG) in a living animal has been developed to harvest energy from its periodic breathing. We also developing an encapsulation method for protecting iTENG from the contamination or liquid infiltration of the surrounding environment. Another important consideration is the versatility of the energy harvesters, which can facilitate the integration between iTENG and the various implantable medical electronics and promote the development of self-powered implantable medical devices and wearable/portable electronics. We also designed viable inner connections and universal outlet connectors for the system. The power management elements and NG were integrated on a flexible substrate; therefore, the entire system could be a “Plug and Play” mobile power source. The system was also packaged by PDMS as a waterproof implantable full energy unit for implantable medical electronic devices. The energy generated from breathing and body moving was used to power a prototype pacemaker and a low-level laser cure (SPLC) system, respectively. It was found that the self-powered system could regulate the heart rate of a rat and significantly accelerated the mouse embryonic osteoblasts' proliferation and differentiation. This is a significant progress for fabricating self-powered implanted medical electronic devices using TENG as a power source. Figure 1

Modelling and Simulation of Implantable Medical Electronics Communication Devices

Modelling and Simulation of Implantable Medical Electronics Communication Devices

Silicon‐containing liquid polymer electrolytes for application in lithium ion batteries

AbstractSince the initial discovery of poly(ethylene glycol) (PEG) as a good lithium ion conductor at elevated temperatures, efforts have been made to find ways of incorporating this biocompatible polymer into lithium ion batteries. In areas of research involving implantable medical devices, consumer electronics and automotive power sources, there is a need to develop a ‘safe’ alternative to the solvent‐based, flammable and toxic electrolytes currently employed. However, PEG has been shown to be electrochemically unstable and crystalline at room temperature. In order to overcome these problems, polysiloxanes have been conjugated to PEG in order to improve its conductivity and physical properties. Over the last few years, the group at the University of Wisconsin‐Madison has been involved in collaborations with scientists at Argonne National Laboratories, Grinnell College and Quallion LLC to develop commercially viable silicon‐containing polymer electrolytes. This mini‐review discusses the electrochemical, thermal and physical properties of these electrolytes, and highlights the progress from high molecular weight polysiloxane‐based electrolytes to low‐viscosity, highly conducting oligosiloxane and silane electrolytes. Copyright © 2009 Society of Chemical Industry

Challenges and constraints in designing implantable medical ICs

Implantable medical electronics are differentiated from most of the other electronic-system implementations by their unique combination of extreme low-power and high-reliability requirements. Many implanted medical devices rely on a fixed nonrechargeable battery over their entire lifetime. These constraints elevate power management and budgeting within the integrated circuits (ICs) to key system-design parameters. So much so, in fact, that the requirements drive not only differences in circuit design, but also place a number of constraints on the design environment and design tools, manufacturing processes, and targets used to implement those designs, test methodologies, and the fundamental understanding into the physics of failure. These constraints often make standard offerings available from the wafer foundries, electronic-design-automation (EDA) suppliers, and commercial third-party IP providers unviable without some level of modification. A successful design often requires process changes and monitoring to ensure low-static-current drain, digital-cell-library optimization with synthesis tools for low-power power-efficient memory design, weak-inversion analog design, accurate low-power models, and test visibility. As system complexity and activity rise, without a proportional increase in available energy, these challenges grow more persistent.