Ultrasound data communication system for bioelectronic medicines

PhD ThesisThe coming years may see the advent of distributed implantable devices to support bioelectronic medicinal treatments. Such treatments could be complementary and, in some cases, may even prove superior to pharmaceutical treatments for certain chronic disease conditions. Therefore, a significant research effort is being undertaken in the bioelectronics domain. Target conditions include diabetes, inflammatory bowel disease, lupus, and arthritis. Modern active medical implantable devices require communications to transmit information to the outside world or other implantable sub-systems. This can include physiological data, diagnostics, and parameters to optimise the therapeutic protocol. However, the communication scheme can be very challenging especially for deeper devices. Challenges include absorption and scattering by tissue, and the need to ensure there are no undesirable heating effects. Wired connectivity is undesirable and tissue absorption of traditional radio frequency and optical methods mean that ultrasound communications have significant potential in this niche. In this thesis, a reliable and efficient ultrasonic communication telemetry is presented. An omnidirectional transducer has been employed to implement intra body communication inside a model of the human body. A prototype has been implemented to evaluate the system performance in saline and up to 30 distance between the transmitter and receiver. Short pulses sequences with guard intervals have been employed to minimise the multipath effect that leads to an increase in the bit and thus packet error rates with distance. Error detection and correction code have been employed to improve communication at a low signal to noise ratio. The data rate is limited to 0.6 due to the necessary guard intervals. Energy per bit and current consumption for the transmitter and receiver main parts are presented and discussed in terms of battery life. Transmission can be achieved at an energy cost of 642 per bit data packet using on/off power cycling in the electronics

Bioelectronic Sensor Nodes for Internet of Bodies

Energy-efficient sensing with Physically-secure communication for bio-sensors on, around and within the Human Body is a major area of research today for development of low-cost healthcare, enabling continuous monitoring and/or secure, perpetual operation. These devices, when used as a network of nodes form the Internet of Bodies (IoB), which poses certain challenges including stringent resource constraints (power/area/computation/memory), simultaneous sensing and communication, and security vulnerabilities as evidenced by the DHS and FDA advisories. One other major challenge is to find an efficient on-body energy harvesting method to support the sensing, communication, and security sub-modules. Due to the limitations in the harvested amount of energy, we require reduction of energy consumed per unit information, making the use of in-sensor analytics/processing imperative. In this paper, we review the challenges and opportunities in low-power sensing, processing and communication, with possible powering modalities for future bio-sensor nodes. Specifically, we analyze, compare and contrast (a) different sensing mechanisms such as voltage/current domain vs time-domain, (b) low-power, secure communication modalities including wireless techniques and human-body communication, and (c) different powering techniques for both wearable devices and implants.Comment: 30 pages, 5 Figures. This is a pre-print version of the article which has been accepted for Publication in Volume 25 of the Annual Review of Biomedical Engineering (2023). Only Personal Use is Permitte

Conformable transistors for bioelectronics

The diversity of network disruptions that occur in patients with neuropsychiatric disorders creates a strong demand for personalized medicine. Such approaches often take the form of implantable bioelectronic devices that are capable of monitoring pathophysiological activity for identifying biomarkers to allow for local and responsive delivery of intervention. They are also required to transmit this data outside of the body for evaluation of the treatment’s efficacy. However, the ability to perform these demanding electronic functions in the complex physiological environment with minimum disruption to the biological tissue remains a big challenge. An optimal fully implantable bioelectronic device would require each component from the front-end to the data transmission to be conformable and biocompatible. For this reason, organic material-based conformable electronics are ideal candidates for components of bioelectronic circuits due to their inherent flexibility, and soft nature. In this work, first an organic mixed-conducting particulate composite material (MCP) able to form functional electronic components and non-invasively acquire high–spatiotemporal resolution electrophysiological signals by directly interfacing human skin is presented. Secondly, we introduce organic electrochemical internal ion-gated transistors (IGTs) as a high-density, high-amplification sensing component as well as a low leakage, high-speed processing unit. Finally, a novel wireless, battery-free strategy for electrophysiological signal acquisition, processing, and transmission that employs IGTs and an ionic communication circuit (IC) is introduced. We show that the wirelessly-powered IGTs are able to acquire and modulate neurophysiological data in-vivo and transmit them transdermally, eliminating the need for any hard Si-based electronics in the implant

Bioelectronic Medicine: a multidisciplinary roadmap from biophysics to precision therapies

Bioelectronic Medicine stands as an emerging field that rapidly evolves and offers distinctive clinical benefits, alongside unique challenges. It consists of the modulation of the nervous system by precise delivery of electrical current for the treatment of clinical conditions, such as post-stroke movement recovery or drug-resistant disorders. The unquestionable clinical impact of Bioelectronic Medicine is underscored by the successful translation to humans in the last decades, and the long list of preclinical studies. Given the emergency of accelerating the progress in new neuromodulation treatments (i.e., drug-resistant hypertension, autoimmune and degenerative diseases), collaboration between multiple fields is imperative. This work intends to foster multidisciplinary work and bring together different fields to provide the fundamental basis underlying Bioelectronic Medicine. In this review we will go from the biophysics of the cell membrane, which we consider the inner core of neuromodulation, to patient care. We will discuss the recently discovered mechanism of neurotransmission switching and how it will impact neuromodulation design, and we will provide an update on neuronal and glial basis in health and disease. The advances in biomedical technology have facilitated the collection of large amounts of data, thereby introducing new challenges in data analysis. We will discuss the current approaches and challenges in high throughput data analysis, encompassing big data, networks, artificial intelligence, and internet of things. Emphasis will be placed on understanding the electrochemical properties of neural interfaces, along with the integration of biocompatible and reliable materials and compliance with biomedical regulations for translational applications. Preclinical validation is foundational to the translational process, and we will discuss the critical aspects of such animal studies. Finally, we will focus on the patient point-of-care and challenges in neuromodulation as the ultimate goal of bioelectronic medicine. This review is a call to scientists from different fields to work together with a common endeavor: accelerate the decoding and modulation of the nervous system in a new era of therapeutic possibilities

Comparative analysis of energy transfer mechanisms for neural implants

As neural implant technologies advance rapidly, a nuanced understanding of their powering mechanisms becomes indispensable, especially given the long-term biocompatibility risks like oxidative stress and inflammation, which can be aggravated by recurrent surgeries, including battery replacements. This review delves into a comprehensive analysis, starting with biocompatibility considerations for both energy storage units and transfer methods. The review focuses on four main mechanisms for powering neural implants: Electromagnetic, Acoustic, Optical, and Direct Connection to the Body. Among these, Electromagnetic Methods include techniques such as Near-Field Communication (RF). Acoustic methods using high-frequency ultrasound offer advantages in power transmission efficiency and multi-node interrogation capabilities. Optical methods, although still in early development, show promising energy transmission efficiencies using Near-Infrared (NIR) light while avoiding electromagnetic interference. Direct connections, while efficient, pose substantial safety risks, including infection and micromotion disturbances within neural tissue. The review employs key metrics such as specific absorption rate (SAR) and energy transfer efficiency for a nuanced evaluation of these methods. It also discusses recent innovations like the Sectored-Multi Ring Ultrasonic Transducer (S-MRUT), Stentrode, and Neural Dust. Ultimately, this review aims to help researchers, clinicians, and engineers better understand the challenges of and potentially create new solutions for powering neural implants

Modeling and measurement of an ultrasound power delivery system for charging implantable devices using an AlN-based pMUT as receiver

Ultrasound power delivery can be considered a convenient technique for charging implantable medical devices. In this work, an intra-body system has been modeled to characterize the phenomenon of ultrasound power transmission. The proposed system comprises a Langevin transducer as transmitter and an AlN-based square piezoelectric micro-machined ultrasonic transducer as receiver. The medium layers, in which elastic waves propagate, were made by polydimethylsiloxane to mimic human tissue and stainless steel to replace the case of the implantable device. To characterize the behavior of the transducers, measurements of impedance and phase, velocity and displacement, and acoustic pressure field were carried out in the experimental activity. Then, voltage and power output were measured to analyze the performance of the ultrasound power delivery system. For a root mean square voltage input of approximately 35 V, the power density resulted in 21.6 mu W cm(-2). Such a result corresponds to the data obtained with simulation through a one-dimensional lumped parameter transmission line model. The methodology proposed to develop the ultrasound power delivery (UPD) system, as well as the use of non-toxic materials for the fabrication of the intra-body elements, are a valid design approach to raise awareness of using wireless power transfer techniques for charging implantable devices.Web of Science1312art. no. 212

Theory, Design and Implementation of Energy-Efficient Biotelemetry using Ultrasound Imaging

This dissertation investigates the fundamental limits of energy dissipation in establishing a communication link with implantable medical devices using ultrasound imaging-based biotelemetry. Ultrasound imaging technology has undergone a revolution during the last decade due to two primary innovations: advances in ultrasonic transducers that can operate over a broad range of frequencies and progresses in high-speed, high-resolution analog-to-digital converters and signal processors. Existing clinical and FDA approved bench-top ultrasound systems cangenerate real-time high-resolution images at frame rates as high as 10000 frames per second. On the other end of the spectrum, portable and hand-held ultrasound systems can generate high-speed real-time scans, widely used for diagnostic imaging in non-clinical environments. This dissertation’s fundamental hypothesis is to leverage the massive data acquisition and computational bandwidth afforded on these devices to establish energy-efficient bio-telemetry links with multiple in-vivo implanted devices. In the first part of the dissertation, I investigate using a commercial off-the-shelf (COTS) diagnostic ultrasound reader to achieve reliable in-vivo wireless telemetry with millimeter-sized piezoelectric crystal transducers. I propose multi-access biotelemetry methods in which several of these crystals simultaneously transmit the data using conventional modulation and coding schemes. I validated the feasibility of in-vivo operation using two piezoelectric crystals tethered to the tricuspid valve and the skin’s surface in a live ovine model. I demonstrated data rates close to 800 Kbps while consuming microwatts of power even in the presence of respiratory and cardiac motion artifacts. In the second part of the dissertation, I investigate the feasibility of energy harvesting from cardiac valvular perturbations to self-power the wireless implantable device. In this study, I explored using piezoelectric sutures implanted in proximity to the valvular regions compared to the previous studies involving piezoelectric patches or encasings attached to the cardiac or aortic surface to exploit nonlinearity in the valvular dynamics and self-power the implanted device. My study shows that power harvested from different annular planes of the tricuspid valve could range from nano-watts to milli-watts. In the final part of this dissertation, I investigate beamforming in B-scan ultrasound imaging to further reduce the biotelemetry energy-budget. In this context, I will study variance-based informatics in which the signal representation takes a form of signal variance instead of the signal mean for encoding and decoding. Using a modeling study, I show that compared to the mean-based logic representation, the variance-based representation can theoretically achieve a superior performance trade-off (in terms of energy dissipation) when operating at fundamental limits imposed by thermal-noise. I will then discuss how to extend variance-based representation to higher signal dimensions. I show that when applying variance-based encoding/decoding to B-scan biotelemetry, the power-dissipation requirements can be reducedto 100 pW even while interrogating from depths greater than 10 cm in a water medium

Advance in Energy Harvesters/Nanogenerators and Self-Powered Sensors

This reprint is a collection of the Special Issue "Advance in Energy Harvesters/Nanogenerators and Self-Powered Sensors" published in Nanomaterials, which includes one editorial, six novel research articles and four review articles, showcasing the very recent advances in energy-harvesting and self-powered sensing technologies. With its broad coverage of innovations in transducing/sensing mechanisms, material and structural designs, system integration and applications, as well as the timely reviews of the progress in energy harvesting and self-powered sensing technologies, this reprint could give readers an excellent overview of the challenges, opportunities, advancements and development trends of this rapidly evolving field

Bipolar Electroactive Conducting Polymers for Wireless Cell Stimulation

Electrochemical stimulation (ES) promotes wound healing and tissue regeneration in biomedical applications and clinical studies and is central to the emerging field of electroceuticals. Traditional ES such as deep brain stimulation for Parkinson’s disease, utilises metal electrodes that are hard wired to a power supply to deliver the stimulation. Bipolar electrochemistry (BPE) introduces an innovative approach to cell stimulation that is wireless. Developing conducting polymers (CPs)-based stimulation platforms wireless powdered by BPE bipolar will provide an exciting new dimension to medical bionics. In this project, Chapter 2 deals with development of a bipolar electrochemical activity testing system and bipolar electrochemical stimulation (BPES) system. Then, bipolar electroactive and biocompatible CPs grown on FTO substrate are successfully synthesised, modified, and characterised in Chapter 3 and Chapter 4 using the above systems prior to using for wireless cell stimulation. Furthermore, free standing and soft CP templates are developed (Chapter 5). More importantly, all these bipolar electroactive CPs have been applied to wireless cell stimulation using BPE (all research Chapters). Significant increase in both cell number and neurite growth has been demonstated, suggesting that the BPES system is highly efficient for stimulation of animal PC 12 cell and human SH-SY5Y cell. More specific information is presented in each chapter as below. In Chapter 3, a CP-based bipolar electrochemical stimulation (BPES) system for cell stimulation was present. Polypyrrole (PPy) films with different dopants have demonstrated reversible and recoverable bipolar electrochemical activity under a low driving DC voltage

Molecular Imaging

The present book gives an exceptional overview of molecular imaging. Practical approach represents the red thread through the whole book, covering at the same time detailed background information that goes very deep into molecular as well as cellular level. Ideas how molecular imaging will develop in the near future present a special delicacy. This should be of special interest as the contributors are members of leading research groups from all over the world