Implantable Biomedical Sensors Research Articles

Implantable and Semi-Implantable Biosensors for Minimally Invasive Disease Diagnosis

Implantable and semi-implantable biosensors fabricated with biodegradable materials and nanomaterials have gained interest in the past few decades. Functionalized biodegradable materials and nanomaterials are usually employed to satisfy clinical and research requirements because of their advanced properties. Novel fabrication techniques were developed to improve the efficiency and accuracy. Different working mechanisms were facilitated to design different types of sensors. This review discusses the recent developments of implantable and semi-implantable biosensors. The materials and fabrications are browsed, and different types of biomedical sensors for different variables are discussed as a focused topic. The biomedical sensors are discussed according to the targets and working mechanisms, followed by a focus on the nervous system sensing to provide an inspiration that different variables can be studied simultaneously on the single system. In the end, challenges and prospects will be discussed. This review aims to provide information of materials, fabrication approaches, mechanisms, and the state of the art for inspiration in designing novel implantable and semi-implantable biomedical sensors for general diagnostic activities.

Self-Powered Hybrid Motion and Health Sensing System Based on Triboelectric Nanogenerators.

Triboelectric nanogenerator (TENG) represents an effective approach for the conversion of mechanical energy into electrical energy and has been explored to combine multiple technologies in past years. Self-powered sensors are not only free from the constraints of mechanical energy in the environment but also capable of efficiently harvesting ambient energy to sustain continuous operation. In this review, the remarkable development of TENG-based human body sensing achieved in recent years is presented, with a specific focus on human health sensing solutions, such as body motion and physiological signal detection. The movements originating from different parts of the body, such as body, touch, sound, and eyes, are systematically classified, and a thorough review of sensor structures and materials is conducted. Physiological signal sensors are categorized into non-implantable and implantable biomedical sensors for discussion. Suggestions for future applications of TENG-based biomedical sensors are also indicated, highlighting the associated challenges.

Powering Implanted Devices Wirelessly Using Spider-Web Coil

Implantable biomedical (IBM) systems and biomedical sensors can improve life quality, identify sickness, monitor biological signs, and replace the function of malfunctioning organs. However, these devices compel continuous battery power, which can be limited by the battery's capacity and lifetime, reducing the device's effectiveness. The wireless power transfer (WPT) technique, specifically magnetic resonator coupling (MRC), was utilized to address the limited battery capacity of IBMs. By using WPT–MRC, the device can obtain power wirelessly, thereby reducing the need for frequent battery replacements and increasing the device's potential. In this research, spider-web coil (S-WC) based MRC–WPT was conceived and carried out experimentally to enhance low-power IBM's rechargeable battery usage time. The presented S-WC–MRC–WPT design uses series–parallel (S–P) configuration to power the IBM. Both transmitter and receiver coils exhibit an operating oscillation frequency of 6.78 MHz. The paper reports on experiments performed in the laboratory to assess the performance of the proposed design in terms of output DC at three different resistive loads and transmission distances with alignment conditions among the receiver and the transmitter coils. Various transfer distances ranging from 10 to 100 mm were investigated to analyze the DC output current (Idc). Specifically, under a 30 V voltage source (VS) and a transfer distance of 20 mm, the DC output current was observed to be 330, 321, and 313 mA at resistive loads of 50, 100, and 150 Ω, respectively.

Wireless Body Area Sensor Networks: Survey of MAC and Routing Protocols for Patient Monitoring under IEEE 802.15.4 and IEEE 802.15.6.

Wireless body area sensor networks (WBASNs) have received growing attention from industry and academia due to their exceptional potential for patient monitoring systems that are equipped with low-power wearable and implantable biomedical sensors under communications standards such as IEEE 802.15.4-2015 and IEEE 802.15.6-2012. The goal of WBASNs is to enhance the capabilities of wireless patient monitoring systems in terms of data accuracy, reliability, routing, channel access, and the data communication of sensors within, on and around the human body. The huge scope of challenges related to WBASNs has led to various research publications and industrial experiments. In this paper, a survey is conducted for the recent state-of-art in the context of medium access control (MAC) and routing protocols by considering the application requirements of patient monitoring systems. Moreover, we discuss the open issues, lessons learned, and challenges for these layers to provide a source of motivation for the upcoming design and development in the domain of WBASNs. This survey will be highly useful for the 6th generation (6G) networks; it is expected that 6G will provide efficient and ubiquitous connectivity to a huge number of IoT devices, and most of them will be sensor-based. This survey will further clarify the QoS requirement part of the 6G networks in terms of sensor-based IoT.

UV-Enhanced Electrical Performances of ZnO:Ga Nanostructure Nanogenerators by Using Ultrasonic Waves

In this work, nanogenerator (NG) devices based on gallium-doped zinc oxide (ZnO) nanorods (NRs) (Ga-doped ZnO NRs) were triumphantly developed and explored by a simple fabrication process. All one-dimensional (1-D) nanostructures were hydrothermally grown on an indium-tin-oxide (ITO) substrate at a low temperature of 90 °C for 6 h. After field-emission scanning electron microscope (FE-SEM), X-ray diffractometer (XRD), and high-resolution transmission electron microscope (HR-TEM) measurement, a hexagonal wurtzite structure with good single crystallinity was exhibited, and a preferential growth with <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${c}$ </tex-math></inline-formula> -axis direction was revealed. The optical properties of all samples were annealed at high temperature and explored through photoluminescence (PL) spectroscopy, displaying two different emission peaks, including ultraviolet (UV) and green emissions. The compositions of the NRs were also examined by an X-ray photoelectron spectroscopy (XPS) and an energy-dispersive X-ray (EDX) spectroscopy. As a result, the performance of ZnO NGs with Ga elements exhibits an outstanding improvement in electrical measurements compared with ZnO NGs. Furthermore, the output voltage and current of Ga-doped ZnO NG under UV irradiation were approximately 0.053 V and <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$4.86\times10$ </tex-math></inline-formula> −6 A, respectively. It is attributed to produce numerous electrons by UV light and Ga dopant. The designed NG in this article may collect electrical energy in the people’s surroundings and has potential Internet of Thing applications (e.g., portable electronics, wireless devices, and implantable biomedical sensors).

Giant magnetoelastic effect in soft systems for bioelectronics

The magnetoelastic effect-the variation of the magnetic properties of a material under mechanical stress-is usually observed in rigid alloys, whose mechanical modulus is significantly different from that of human tissues, thus limiting their use in bioelectronics applications. Here, we observed a giant magnetoelastic effect in a soft system based on micromagnets dispersed in a silicone matrix, reaching a magnetomechanical coupling factor indicating up to four times more enhancement than in rigid counterparts. The results are interpreted using a wavy chain model, showing how mechanical stress changes the micromagnets' spacing and dipole alignment, thus altering the magnetic field generated by the composite. Combined with liquid-metal coils patterned on polydimethylsiloxane working as a magnetic induction layer, the soft magnetoelastic composite is used for stretchable and water-resistant magnetoelastic generators adhering conformably to human skin. Such devices can be used as wearable or implantable power generators and biomedical sensors, opening alternative avenues for human-body-centred applications.

WIDEBAND ENERGY HARVESTING FOR IMPLANTABLE BIOMEDICAL APPLICATIONS

In this paper, a nonresonant electromagnetic micro-generator is proposed. The proposed device is capable of converting nonresonant environmental vibrations to electrical power. The energy harvester could generate output power from heartbeat, human leg and arm motion. The proposed energy harvester uses Frequency up CONVersion technique (FCONV) to improve the bandwidth of the device. The results approve the high bandwidth of the proposed method. The micro-generator is designed by micro-electro-mechanical systems (MEMS) methods. Consequently, the volume of the power harvester is minimized and power density is maximized. The new configuration of energy harvester with imposed motion trigger is proposed. Output power, bandwidth and performance of the designed micro-power harvester are discussed. The proposed micro-generator exhibits higher bandwidth in comparison with resonant, multi-resonant and tunable bandwidth structures. The nonresonant device is designed using FCONV to convert 1–3[Formula: see text]Hz heartbeat mechanical vibrations to output electrical power. The optimum upconverted mechanical vibration frequency is 60[Formula: see text]Hz and the output voltage frequency is 120[Formula: see text]Hz. The peak output electrical power of FCONV is 17.75[Formula: see text][Formula: see text]W. For 1[Formula: see text]Hz, 2[Formula: see text]Hz and 3[Formula: see text]Hz mechanical vibration with imposed motion trigger, average output powers are 1.60[Formula: see text][Formula: see text]W, 3.81[Formula: see text][Formula: see text]W and 5.19[Formula: see text][Formula: see text]W, respectively. The achieved results illustrate that the proposed FCONV method exhibits better and wider frequency response in comparison with different methods. The designed device can be utilized to supply implantable biomedical sensors. Also, the heat generation of the device is studied. The results illustrate that the temperature rise of the micro-generator remains in the normal human body temperature range. Hence, the proposed power harvester is biocompatible.

Emerging aluminium nitride nanoparticles: chemical synthesis and exploration of their biocompatibility and anticancer activity against cervical cancer cells

Objective(s): Aluminium nitride (AlN) could be used in implantable biomedical sensor devices, for which cytotoxicity analysis is of utmost importance. Materials and Methods: AlN nanoparticles were synthesized using a simple and effective solvothermal method. The X-ray diffraction results revealed the cubic phase of AlN, and the field emission scanning electron microscopy analysis demonstrated the structural morphology of the synthesized materials. In addition, the cytotoxicity of the AlN nanoparticles was assessed against healthy (HEK-293, HUVEC, and MCF10A) and cancerous cell line (HeLa). The intensity of the reactive oxygen species was also measured to determine the induced oxidative stress in the treated cells. Results: The cytotoxicity analysis indicated that the AlN nanoparticles were nontoxic against the cancerous and normal cell lines. No significant changes were observed between the low doses of the AlN nanoparticles in the treated and control cells. However, morphological changes were detected by a phase contrast microscope, while insignificant changes were observed similar to the control cells. Conclusion: The findings of this study could lay the groundwork for the development of AlN nanoparticles for further biomedical applications.

Highly Uniform, Flexible Microelectrodes Based on the Clean Single-Walled Carbon Nanotube Thin Film with High Electrochemical Activity

Electrochemical sensors based on carbon nanotubes (CNTs) have great potential for use in wearable or implantable biomedical sensor applications because of their excellent mechanical flexibility and biocompatibility. However, the main challenge associated with CNT-based sensors is their uniform and reproducible fabrication on the flexible plastic film. Here, we introduce and demonstrate a highly reliable technique to fabricate flexible CNT microelectrodes on a plastic film. The technique involves a process whereby the CNT film is formed by the dry transfer process based on the floating-catalyst chemical vapor deposition. An oxide protection layer, which is used to cover the CNT thin film during the fabrication process, minimizes contamination of the surface. The fabricated flexible CNT microelectrodes show almost ideal electrochemical characteristics for microelectrodes with the average value of the quartile potentials, Δ E = | E3/4 - E1/4|, being 60.4 ± 2.9 mV for the 28 electrodes, while the ideal value of Δ E = 56.4 mV. The CNT microelectrodes also showed enhanced resistance to surface fouling during dopamine oxidation in comparison to carbon fiber and gold microelectrodes; the degradation of the oxidation current after 10 consecutive cycles were 1.8, 8.3, and 13.9% for CNT, carbon fiber, and gold microelectrodes, respectively. The high-sensitivity detection of dopamine is also demonstrated with differential-pulse voltammetry, with a resulting limit of detection of ∼50 nM. The reliability, uniformity, and sensitivity of the present CNT microelectrodes provide a platform for flexible electrochemical sensors.

IoT-Enabled Home Cage With Three-Dimensional Resonant Wireless Power and Data Transfer Scheme for Freely Moving Animal

The preclinical studies are conducted using small rodents for analysis on different functions of central neural system, cardiovascular functions, and neuropathological disorders. The implantable biomedical sensors used for sensing the behavior of test subject requires a continuous wireless power supply. Recently, many findings project that the inductive resonant power transfer method is a suitable choice for wireless power and data transfer to an implants. However, for the freely moving animal misalignment between the transmitting (Tx) and receiving (Rx) section reduce the power and data transfer efficiency. This paper proposes a new approach for the combined power and data transfer using 3-D Tx coils. The designed Tx coil itself is utilized for the data and power transfer at different orientation of the Rx unit. The mathematical modeling, circuit simulation, finite-element study, and experimental analysis are performed at different orientation of the Rx coil. The integration of the digital pressure sensor and the ESP-12E sensor node to the Rx and Tx coil section is examined. In addition, for the continuous data logging system and remote monitoring of test subject, an Internet of Things module is integrated with the demodulation unit. The obtained results from the measurement show that for the long-term continuous monitoring of the testing animal, the proposed 3-D wireless power and data transfer will be a better choice.

A Magnetic-Balanced Inductive Link for the Simultaneous Uplink Data and Power Telemetry.

When using the conventional two-coil inductive link for the simultaneous wireless power and data transmissions in implantable biomedical sensor devices, the strong power carrier could overwhelm the uplink data signal and even saturate the external uplink receiver. To address this problem, we propose a new magnetic-balanced inductive link for our implantable glaucoma treatment device. In this inductive link, an extra coil is specially added for the uplink receiving. The strong power carrier interference is minimized to approach zero by balanced canceling of the magnetic field of the external power coil. The implant coil is shared by the wireless power harvesting and the uplink data transmitting. Two carriers (i.e., 2-MHz power carrier and 500-kHz uplink carrier) are used for the wireless power transmission and the uplink data transmission separately. In the experiments, the prototype of this link achieves as high as 65.72 dB improvement of the signal-to-interference ratio (SIR) compared with the conventional two-coil inductive link. Benefiting from the significant improvement of SIR, the implant transmitter costs only 0.2 mW of power carrying 50 kbps of binary phase shift keying data and gets a bit error rate of 1 × 10, even though the coupling coefficient is as low as 0.005. At the same time, 5 mW is delivered to the load with maximum power transfer efficiency of 58.8%. This magnetic-balanced inductive link is useful for small-sized biomedical sensor devices, which require transmitting data and power simultaneously under ultra-weak coupling.

An NFC on Two-Coil WPT Link for Implantable Biomedical Sensors under Ultra-Weak Coupling.

The inductive link is widely used in implantable biomedical sensor systems to achieve near-field communication (NFC) and wireless power transfer (WPT). However, it is tough to achieve reliable NFC on an inductive WPT link when the coupling coefficient is ultra-low (0.01 typically), since the NFC signal (especially for the uplink from the in-body part to the out-body part) could be too weak to be detected. Traditional load shift keying (LSK) requires strong coupling to pass the load modulation information to the power source. Instead of using LSK, we propose a dual-carrier NFC scheme for the weak-coupled inductive link; using binary phase shift keying (BPSK) modulation, its downlink data are modulated on the power carrier (2 MHz), while its uplink data are modulated on another carrier (125 kHz). The two carriers are transferred through the same coil pair. To overcome the strong interference of the power carrier, dedicated circuits are introduced. In addition, to minimize the power transfer efficiency decrease caused by adding NFC, we optimize the inductive link circuit parameters and approach the receiver sensitivity limit. In the prototype experiments, even though the coupling coefficient is as low as 0.008, the in-body transmitter costs only 0.61 mW power carrying 10 kbps of data, and achieves a 1 × 10 bit error rate under the strong interference of WPT. This dual-carrier NFC scheme could be useful for small-sized implantable biomedical sensor applications.

Localization and Tracking of Implantable Biomedical Sensors.

Implantable sensor systems are effective tools for biomedical diagnosis, visualization and treatment of various health conditions, attracting the interest of researchers, as well as healthcare practitioners. These systems efficiently and conveniently provide essential data of the body part being diagnosed, such as gastrointestinal (temperature, pH, pressure) parameter values, blood glucose and pressure levels and electrocardiogram data. Such data are first transmitted from the implantable sensor units to an external receiver node or network and then to a central monitoring and control (computer) unit for analysis, diagnosis and/or treatment. Implantable sensor units are typically in the form of mobile microrobotic capsules or implanted stationary (body-fixed) units. In particular, capsule-based systems have attracted significant research interest recently, with a variety of applications, including endoscopy, microsurgery, drug delivery and biopsy. In such implantable sensor systems, one of the most challenging problems is the accurate localization and tracking of the microrobotic sensor unit (e.g., robotic capsule) inside the human body. This article presents a literature review of the existing localization and tracking techniques for robotic implantable sensor systems with their merits and limitations and possible solutions of the proposed localization methods. The article also provides a brief discussion on the connection and cooperation of such techniques with wearable biomedical sensor systems.

Implantable micro‐sized image sensor for data transmission with intra‐vital optical communication

Interest in implantable microchips for medical sensors is increasing. To reduce the invasiveness of implantation, wireless data transmission in a living body is an important issue shared by all such sensors. Here, the authors report on a light-based wireless data transmission method for implantable biomedical sensor chips. An implantable micro-sized image sensor (400 × 1200 μm2) that was designed to modulate a small light-emitting diode (λ = 855 nm) with pulse-width modulation for intra-vital optical communication (IOC) was developed. Both a transmitter device and a receiver device for IOC were prepared, and optical image data transmission through biological tissue (a mouse skull bone) was successfully demonstrated.

Wireless image-data transmission from an implanted image sensor through a living mouse brain by intra body communication

Intra body communication technology allows the fabrication of compact implantable biomedical sensors compared with RF wireless technology. In this paper, we report the fabrication of an implantable image sensor of 625 µm width and 830 µm length and the demonstration of wireless image-data transmission through a brain tissue of a living mouse. The sensor was designed to transmit output signals of pixel values by pulse width modulation (PWM). The PWM signals from the sensor transmitted through a brain tissue were detected by a receiver electrode. Wireless data transmission of a two-dimensional image was successfully demonstrated in a living mouse brain. The technique reported here is expected to provide useful methods of data transmission using micro sized implantable biomedical sensors.

Geometry Optimization Approaches of Inductively Coupled Printed Spiral Coils for Remote Powering of Implantable Biomedical Sensors

Electronic biomedical implantable sensors need power to perform. Among the main reported approaches, inductive link is the most commonly used method for remote powering of such devices. Power efficiency is the most important characteristic to be considered when designing inductive links to transfer energy to implantable biomedical sensors. The maximum power efficiency is obtained for maximum coupling and quality factors of the coils and is generally limited as the coupling between the inductors is usually very small. This paper is dealing with geometry optimization of inductively coupled printed spiral coils for powering a given implantable sensor system. For this aim, Iterative Procedure (IP) and Genetic Algorithm (GA) analytic based optimization approaches are proposed. Both of these approaches implement simple mathematical models that approximate the coil parameters and the link efficiency values. Using numerical simulations based on Finite Element Method (FEM) and with experimental validation, the proposed analytic approaches are shown to have improved accurate performance results in comparison with the obtained performance of a reference design case. The analytical GA and IP optimization methods are also compared to a purely Finite Element Method based on numerical optimization approach (GA-FEM). Numerical and experimental validations confirmed the accuracy and the effectiveness of the analytical optimization approaches to design the optimal coil geometries for the best values of efficiency.

Experimental UWB frequency analysis for implant communications.

Implantable biomedical sensors with the ability to transmit wirelessly real-time physiological data to an external unit can enable better management of chronic diseases. The IEEE Standard 802.15.6-2012 specifies the implementation of implant communications within 402-405 MHz, which unfortunately allows low data transmission rates only. Ultra wideband (UWB) interfaces within 3.1-10.6 GHz offer a number of advantages at the expense of higher path losses. Efforts to characterize the implant UWB channel have been undertaken via computer simulations, but these may not capture completely the effects on the implant radio channel of multiple physiological functions. To overcome these limitations we provide insight into the frequency-domain behavior of the UWB implant channel within 3.1-8.5 GHz based on propagation measurements in a liquid phantom and a living swine. A thorough comparison of the relative received power in phantom-based and in vivo measurements for the in-body to on-body (IB2OB) and in-body to off-body (IB2OFF) channel scenarios are presented.

In-Body to On-Body Ultrawideband Propagation Model Derived From Measurements in Living Animals.

Ultrawideband (UWB) radio technology for wireless implants has gained significant attention. UWB enables the fabrication of faster and smaller transceivers with ultralow power consumption, which may be integrated into more sophisticated implantable biomedical sensors and actuators. Nevertheless, the large path loss suffered by UWB signals propagating through inhomogeneous layers of biological tissues is a major hindering factor. For the optimal design of implantable transceivers, the accurate characterization of the UWB radio propagation in living biological tissues is indispensable. Channel measurements in phantoms and numerical simulations with digital anatomical models provide good initial insight into the expected path loss in complex propagation media like the human body, but they often fail to capture the effects of blood circulation, respiration, and temperature gradients of a living subject. Therefore, we performed UWB channel measurements within 1-6 GHz on two living porcine subjects because of the anatomical resemblance with an average human torso. We present for the first time, a path loss model derived from these in vivo measurements, which includes the frequency-dependent attenuation. The use of multiple on-body receiving antennas to combat the high propagation losses in implant radio channels was also investigated.

Matching layer for path loss reduction in ultra wideband implant communications.

Real-time monitoring of various physiological signals is of utmost importance for the treatment of chronic conditions. Radio technology can enable real-time sensing and collection of physiological data to facilitate timely medication and early pre-hospital management of patients. This can be realized with the aid of implantable biomedical sensors with the capability to transmit wirelessly the collected information to an external unit for display and analysis. Currently, commercial wireless medical implantable sensors operate in frequencies below 1 GHz with narrowband signals. Recently, it has been demonstrated that ultra wideband (UWB) signals could be also used for the radio interface of these devices. However, establishing an implant communication link in the allocated UWB spectrum of 3.1-10.6 GHz is challenging. The attenuation of UWB signals propagating through biological tissues at these frequencies is high. Part of these path losses are caused by the impedance mismatch between the two propagation environments (i.e., air and biological tissues) that constitute an implant communication link. This mismatch results in inefficient power transmission of the radio waves. In this paper we propose the use of a layer of dielectric material that can be applied on the patient's skin. The permittivity value of this matching layer has to be chosen such that wave coupling is maximized. Through numerical simulations we determined the appropriate permittivity value of a matching layer for UWB implant communication links in the human thorax for 1-6 GHz. Path loss reduction of up to 10 dB can be obtained in this frequency band. These results can help improve the use of UWB signals for other in-body biomedical devices like the wireless capsule endoscope (WCE).

A Low-Frequency Versatile Wireless Power Transfer Technology for Biomedical Implants

Implantable biomedical sensors and actuators are highly desired in modern medicine. In many cases, the implant's electrical power source profoundly determines its overall size and performance . The inductively coupled coil pair operating at the radio-frequency (RF) has been the primary method for wirelessly delivering electrical power to implants for the last three decades . Recent designs significantly improve the power delivery efficiency by optimizing the operating frequency, coil size and coil distance . However, RF radiation hazard and tissue absorption are the concerns in the RF wireless power transfer technology (RF-WPTT) , . Also, it requires an accurate impedance matching network that is sensitive to operating environments between the receiving coil and the load for efficient power delivery . In this paper, a novel low-frequency wireless power transfer technology (LF-WPTT) using rotating rare-earth permanent magnets is demonstrated. The LF-WPTT is able to deliver 2.967 W power at ∼180 Hz to an 117.1 Ω resistor over 1 cm distance with 50% overall efficiency. Because of the low operating frequency, RF radiation hazard and tissue absorption are largely avoided, and the power delivery efficiency from the receiving coil to the load is independent of the operating environment. Also, there is little power loss observed in the LF-WPTT when the receiving coil is enclosed by non-magnetic implant-grade stainless steel.