An Implantable Peripheral Nerve Recording and Stimulation System for Experiments on Freely Moving Animal Subjects

A new study with rat sciatic nerve model for peripheral nerve interfacing is presented using a fully-implanted inductively-powered recording and stimulation system in a wirelessly-powered standard homecage that allows animal subjects move freely within the homecage. The Wireless Implantable Neural Recording and Stimulation (WINeRS) system offers 32-channel peripheral nerve recording and 4-channel current-controlled stimulation capabilities in a 3 × 1.5 × 0.5 cm3 package. A bi-directional data link is established by on-off keying pulse-position modulation (OOK-PPM) in near field for narrow-band downlink and 433 MHz OOK for wideband uplink. An external wideband receiver is designed by adopting a commercial software defined radio (SDR) for a robust wideband data acquisition on a PC. The WINeRS-8 prototypes in two forms of battery-powered headstage and wirelessly-powered implant are validated in vivo, and compared with a commercial system. In the animal study, evoked compound action potentials were recorded to verify the stimulation and recording capabilities of the WINeRS-8 system with 32-ch penetrating and 4-ch cuff electrodes on the sciatic nerve of awake freely-behaving rats. Compared to the conventional battery-powered system, WINeRS can be used in closed-loop recording and stimulation experiments over extended periods without adding the burden of carrying batteries on the animal subject or interrupting the experiment

SenseBack - An implantable system for bidirectional neural interfacing

Chronic in-vivo neurophysiology experiments require highly miniaturized, remotely powered multi-channel neural interfaces which are currently lacking in power or flexibility post implantation. In this article, to resolve this problem we present the SenseBack system, a post-implantation reprogrammable wireless 32-channel bidirectional neural interfacing that can enable chronic peripheral electrophysiology experiments in freely behaving small animals. The large number of channels for a peripheral neural interface, coupled with fully implantable hardware and complete software flexibility enable complex in-vivo studies where the system can adapt to evolving study needs as they arise. In complementary ex-vivo and in-vivo preparations, we demonstrate that this system can record neural signals and perform high-voltage, bipolar stimulation on any channel. In addition, we demonstrate transcutaneous power delivery and Bluetooth 5 data communication with a PC. The SenseBack system is capable of stimulation on any channel with ±20 V of compliance and up to 315 μA of current, and highly configurable recording with per-channel adjustable gain and filtering with 8 sets of 10-bit ADCs to sample data at 20 kHz for each channel. To the best of our knowledge this is the first such implantable research platform offering this level of performance and flexibility post-implantation (including complete reprogramming even after encapsulation) for small animal electrophysiology. Here we present initial acute trials, demonstrations and progress towards a system that we expect to enable a wide range of electrophysiology experiments in freely behaving animals

An implantable mixed-signal CMOS die for battery-powered in vivo blowfly neural recordings

© 2018 A mixed-signal die containing two differential input amplifiers, a multiplexer and a 50 KSPS, 10-bit SAR ADC, has been designed and fabricated in a 0.35 μm CMOS process for in vivo neural recording from freely moving blowflies where power supplied voltage drops quickly due to the space/weight limited insufficient capacity of the battery. The designed neural amplifier has a 66 + dB gain, 0.13 Hz-5.3 KHz bandwidth and 0.39% THD. A 20% power supply voltage drop causes only a 3% change in amplifier gain and 0.9-bit resolution degrading for SAR ADC while the on-chip data modulation reduces the chip size, rendering the designed chip suitable for battery-powered applications. The fabricated die occupies 1.1 mm2 while consuming 238 μW, being suitable for implantable neural recordings from insects as small as a blowfly for electrophysiological studies of their sensorimotor control mechanisms. The functionality of the die has been validated by recording the signals from identified interneurons in the blowfly visual system

High-performance wireless power and data transfer interface for implantable medical devices

D’importants progès ont été réalisés dans le développement des systèmes biomédicaux implantables grâce aux dernières avancées de la microélectronique et des technologies sans fil. Néanmoins, ces appareils restent difficiles à commercialier. Cette situation est due particulièrement à un manque de stratégies de design capable supporter les fonctionnalités exigées, aux limites de miniaturisation, ainsi qu’au manque d’interface sans fil à haut débit fiable et faible puissance capable de connecter les implants et les périphériques externes. Le nombre de sites de stimulation et/ou d’électrodes d’enregistrement retrouvés dans les dernières interfaces cerveau-ordinateur (IMC) ne cesse de croître afin d’augmenter la précision de contrôle, et d’améliorer notre compréhension des fonctions cérébrales. Ce nombre est appelé à atteindre un millier de site à court terme, ce qui exige des débits de données atteingnant facilement les 500 Mbps. Ceci étant dit, ces travaux visent à élaborer de nouvelles stratégies innovantes de conception de dispositifs biomédicaux implantables afin de repousser les limites mentionnées ci-dessus. On présente de nouvelles techniques faible puissance beaucoup plus performantes pour le transfert d’énergie et de données sans fil à haut débit ainsi que l’analyse et la réalisation de ces dernières grâce à des prototypes microélectroniques CMOS. Dans un premier temps, ces travaux exposent notre nouvelle structure multibobine inductive à résonance présentant une puissance sans fil distribuée uniformément pour alimenter des systèmes miniatures d’étude du cerveaux avec des models animaux en ilberté ainsi que des dispositifs médicaux implantbles sans fil qui se caractérisent par une capacité de positionnement libre. La structure propose un lien de résonance multibobines inductive, dont le résonateur principal est constitué d’une multitude de résonateurs identiques disposés dans une matrice de bobines carrées. Ces dernières sont connectées en parallèle afin de réaliser des surfaces de puissance (2D) ainsi qu’une chambre d’alimentation (3D). La chambre proposée utilise deux matrices de résonateurs de base, mises face à face et connectés en parallèle afin d’obtenir une distribution d’énergie uniforme en 3D. Chaque surface comprend neuf bobines superposées, connectées en parallèle et réailsées sur une carte de circuit imprimé deux couches FR4. La chambre dispose d’un mécanisme naturel de localisation de puissance qui facilite sa mise en oeuvre et son fonctionnement. En procédant ainsi, nous évitons la nécessité d’une détection active de l’emplacement de la charge et le contrôle d’alimentation. Notre approche permet à cette surface d’alimentation unique de fournir une efficacité de transfert de puissance (PTE) de 69% et une puissance délivrée à la charge (PDL) de 120 mW, pour une distance de séparation de 4 cm, tandis que le prototype de chambre complet fournit un PTE uniforme de 59% et un PDL de 100 mW en 3D, partout à l’intérieur de la chambre avec un volume de chambre de 27 × 27 × 16 cm3. Une étape critique avant d’utiliser un dispositif implantable chez les humains consiste à vérifier ses fonctionnalités sur des sujets animaux. Par conséquent, la chambre d’énergie sans fil conçue sera utilisée afin de caractériser les performances d’ une interface sans fil de transmisison de données dans un environnement réaliste in vivo avec positionement libre. Un émetteur-récepteur full-duplex (FDT) entièrement intégré qui se caractérise par sa faible puissance est conçu pour réaliser une interfaces bi-directionnelles (stimulation et enregistrement) avec des débits asymétriques: des taux de tramnsmission plus élevés sont nécessaires pour l’enregistrement électrophysiologique multicanal (signaux de liaison montante) alors que les taux moins élevés sont utilisés pour la stimulation (les signaux de liaison descendante). L’émetteur (TX) et le récepteur (RX) se partagent une seule antenne afin de réduire la taille de l’implant. L’émetteur utilise la radio ultra-large bande par impulsions (IR-UWB) basée sur l’approche edge combining et le RX utilise la bande ISM (Industrielle, Scientifique et Médicale) de fréquence central 2.4 GHz et la modulation on-off-keying (OOK). Une bonne isolation (> 20 dB) est obtenue entre le TX et le RX grâce à 1) la mise en forme les impulsions émises dans le spectre UWB non réglementée (3.1-7 GHz), et 2) le filtrage espace-efficace (évitant l’utilisation d’un circulateur ou d’un diplexeur) du spectre du lien de communication descendant directement au niveau de l’ amplificateur à faible bruit (LNA). L’émetteur UWB 3.1-7 GHz utilise un e modultion OOK ainsi qu’une modulation par déplacement de phase (BPSK) à seulement 10.8 pJ / bits. Le FDT proposé permet d’atteindre 500 Mbps de débit de données en lien montant et 100 Mbps de débit de données de lien descendant. Il est entièrement intégré dans un procédé TSMC CMOS 0.18 um standard et possède une taille totale de 0.8 mm2. La consommation totale d’énergie mesurée est de 10.4 mW (5 mW pour RX et 5.4 mW pour TX au taux de 500 Mbps).In recent years, there has been major progress on implantable biomedical systems that support most of the functionalities of wireless implantable devices. Nevertheless, these devices remain mostly restricted to be commercialized, in part due to weakness of a straightforward design to support the required functionalities, limitation on miniaturization, and lack of a reliable low-power high data rate interface between implants and external devices. This research provides novel strategies on the design of implantable biomedical devices that addresses these limitations by presenting analysis and techniques for wireless power transfer and efficient data transfer. The first part of this research includes our proposed novel resonance-based multicoil inductive power link structure with uniform power distribution to wirelessly power up smart animal research systems and implanted medical devices with high power efficiency and free positioning capability. The proposed structure consists of a multicoil resonance inductive link, which primary resonator array is made of several identical resonators enclosed in a scalable array of overlapping square coils that are connected in parallel and arranged in power surface (2D) and power chamber (3D) configurations. The proposed chamber uses two arrays of primary resonators, facing each other, and connected in parallel to achieve uniform power distribution in 3D. Each surface includes 9 overlapped coils connected in parallel and implemented into two layers of FR4 printed circuit board. The chamber features a natural power localization mechanism, which simplifies its implementation and eases its operation by avoiding the need for active detection of the load location and power control mechanisms. A single power surface based on the proposed approach can provide a power transfer efficiency (PTE) of 69% and a power delivered to the load (PDL) of 120 mW, for a separation distance of 4 cm, whereas the complete chamber prototype provides a uniform PTE of 59% and a PDL of 100 mW in 3D, everywhere inside the chamber with a chamber size of 27×27×16 cm3. The second part of this research includes our proposed novel, fully-integrated, low-power fullduplex transceiver (FDT) to support bi-directional neural interfacing applications (stimulating and recording) with asymmetric data rates: higher rates are required for recording (uplink signals) than stimulation (downlink signals). The transmitter (TX) and receiver (RX) share a single antenna to reduce implant size. The TX uses impulse radio ultra-wide band (IR-UWB) based on an edge combining approach, and the RX uses a novel 2.4-GHz on-off keying (OOK) receiver. Proper isolation (> 20 dB) between the TX and RX path is implemented 1) by shaping the transmitted pulses to fall within the unregulated UWB spectrum (3.1-7 GHz), and 2) by space-efficient filtering (avoiding a circulator or diplexer) of the downlink OOK spectrum in the RX low-noise amplifier (LNA). The UWB 3.1-7 GHz transmitter using OOK and binary phase shift keying (BPSK) modulations at only 10.8 pJ/bit. The proposed FDT provides dual band 500 Mbps TX uplink data rate and 100 Mbps RX downlink data rate. It is fully integrated on standard TSMC 0.18 nm CMOS within a total size of 0.8 mm2. The total power consumption measured 10.4 mW (5 mW for RX and 5.4 mW for TX at the rate of 500 Mbps)

Coupled resonator based wireless power transfer for bioelectronics

Implantable and wearable bioelectronics provide the ability to monitor and modulate physiological processes. They represent a promising set of technologies that can provide new treatment for patients or new tools for scientific discovery, such as in long-term studies involving small animals. As these technologies advance, two trends are clear, miniaturization and increased sophistication i.e. multiple channels, wireless bi-directional communication, and responsiveness (closed-loop devices). One primary challenge in realizing miniaturized and sophisticated bioelectronics is powering. Integration and development of wireless power transfer (WPT) technology, however, can overcome this challenge. In this dissertation, I propose the use of coupled resonator WPT for bioelectronics and present a new generalized analysis and optimization methodology, derived from complex microwave bandpass filter synthesis, for maximizing and controlling coupled resonator based WPT performance. This newly developed set of analysis and optimization methods enables system miniaturization while simultaneously achieving the necessary performance to safely power sophisticated bioelectronics. As an application example, a novel coil to coil based coupled resonator arrangement to wirelessly operate eight surface electromyography sensing devices wrapped circumferentially around an able-bodied arm is developed and demonstrated. In addition to standard coil to coil based systems, this dissertation also presents a new form of coupled resonator WPT system built of a large hollow metallic cavity resonator. By leveraging the analysis and optimization methods developed here, I present a new cavity resonator WPT system for long-term experiments involving small rodents for the first time. The cavity resonator based WPT arena exhibits a volume of 60.96 x 60.96 x 30.0 cm3. In comparison to prior state of the art, this cavity resonator system enables nearly continuous wireless operation of a miniature sophisticated device implanted in a freely behaving rodent within the largest space. Finally, I present preliminary work, providing the foundation for future studies, to demonstrate the feasibility of treating segments of the human body as a dielectric waveguide resonator. This creates another form of a coupled resonator system. Preliminary experiments demonstrated optimized coupled resonator wireless energy transfer into human tissue. The WPT performance achieved to an ultra-miniature sized receive coil (2 mm diameter) is presented. Indeed, optimized coupled resonator systems, broadened to include cavity resonator structures and human formed dielectric resonators, can enable the effective use of coupled resonator based WPT technology to power miniaturized and sophisticated bioelectronics

Flexible Near-Field Wireless Optoelectronics as Subdermal Implants for Broad Applications in Optogenetics

In vivo optogenetics provides unique, powerful capabilities in the dissection of neural circuits implicated in neuropsychiatric disorders. Conventional hardware for such studies, however, physically tethers the experimental animal to an external light source, limiting the range of possible experiments. Emerging wireless options offer important capabilities that avoid some of these limitations, but the current size, bulk, weight, and wireless area of coverage is often disadvantageous. Here, we present a simple but powerful setup based on wireless, near-field power transfer and miniaturized, thin, flexible optoelectronic implants, for complete optical control in a variety of behavioral paradigms. The devices combine subdermal magnetic coil antennas connected to microscale, injectable light-emitting diodes (LEDs), with the ability to operate at wavelengths ranging from UV to blue, green-yellow, and red. An external loop antenna allows robust, straightforward application in a multitude of behavioral apparatuses. The result is a readily mass-producible, user-friendly technology with broad potential for optogenetics applications.114419Ysciescopu

Dissection of Affective Catecholamine Circuits Using Traditional and Wireless Optogenetics

Parsing the complexity of the mammalian brain has challenged neuroscientists for thousands of years. In the early 21st century, advances in materials science and neuroscience have enabled unprecedented control of neural circuitry. In particular, cell-type selective manipulations, such as those with optogenetics and chemogenetics, routinely provide answers to previously intractable neurobiological questions in the intact, behaving animal. In this two-part dissertation, I first introduce new minimally invasive, wireless technology to perturb neural activity in the ventral tegmental area dopaminergic system of freely moving animals. I report a series of novel devices for studying and perturbing intact neural systems through optogenetics, microfluidic pharmacology, and electrophysiology. Unlike optogenetic approaches that rely on rigid, glass fiber optics coupled to external light sources, these novel devices utilize flexible substrates to carry microscale, inorganic light emitting diodes (μ-ILEDs), multimodal sensors, and/or microfluidic channels into the brain. Each class of device can be wirelessly controlled, enabling studies in freely behaving mice and achieving previously untenable control of catecholamine neural circuitry. In the second part of this dissertation, I apply existing cell-type selective approaches to dissect the role of the locus coeruleus noradrenergic (LC-NE) system in anxiety-like and aversive behaviors. The LC-NE system is one of the first systems engaged following a stressful event. While LC-NE neurons are known to be activated by many different stressors, the underlying neural circuitry and the role of this activity in generating stress-induced anxiety has not been elucidated until now. I demonstrate that increased tonic activity of LC-NE neurons is both necessary and sufficient for stress-induced anxiety; a behavior which is driven by LC projections to the basolateral amygdala. Furthermore, this activity and behavior is elicited by corticotropin releasing hormone-containing afferent inputs into the LC from the central amygdala. These studies position the LC-NE system as a critical mediator of acute stress-induced anxiety and offer a potential intervention for preventing stress-related affective disorders. Together these two objectives provide a rich technological toolbox for neuroscientists and yield important knowledge of how small catecholamine structures with widespread forebrain innervation can selectively mediate higher order behaviors

Microscale Inorganic LED Based Wireless Neural Systems for Chronic in vivo Optogenetics

Billions of neurons in the brain coordinate together to control trillions of highly convoluted synaptic pathways for neural signal processing. Optogenetics is an emerging technique that can dissect such complex neural circuitry with high spatiotemporal precision using light. However, conventional approaches relying on rigid and tethered optical probes cause significant tissue damage as well as disturbance with natural behavior of animals, thus preventing chronic in vivo optogenetics. A microscale inorganic LED (μ-ILED) is an enabling optical component that can solve these problems by facilitating direct discrete spatial targeting of neural tissue, integration with soft, ultrathin probes as well as low power wireless operation. Here we review recent state-of-the art μ-ILED integrated soft wireless optogenetic tools suitable for use in freely moving animals and discuss opportunities for future developments

Wireless tools for neuromodulation

Epilepsy is a spectrum of diseases characterized by recurrent seizures. It is estimated that 50 million individuals worldwide are affected and 30% of cases are medically refractory or drug resistant. Vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are the only FDA approved device based therapies. Neither therapy offers complete seizure freedom in a majority of users. Novel methodologies are needed to better understand mechanisms and chronic nature of epilepsy. Most tools for neuromodulation in rodents are tethered. The few wireless devices use batteries or are inductively powered. The tether restricts movement, limits behavioral tests, and increases the risk of infection. Batteries are large and heavy with a limited lifetime. Inductive powering suffers from rapid efficiency drops due to alignment mismatches and increased distances. Miniature wireless tools that offer behavioral freedom, data acquisition, and stimulation are needed. This dissertation presents a platform of electrical, optical and radiofrequency (RF) technologies for device based neuromodulation. The platform can be configured with features including: two channels differential recording, one channel electrical stimulation, and one channel optical stimulation. Typical device operation consumes less than 4 mW. The analog front end has a bandwidth of 0.7 Hz - 1 kHz and a gain of 60 dB, and the constant current driver provides biphasic electrical stimulation. For use with optogenetics, the deep brain optical stimulation module provides 27 mW/mm2 of blue light (473 nm) with 21.01 mA. Pairing of stimulating and recording technologies allows closed-loop operation. A wireless powering cage is designed using the resonantly coupled filter energy transfer (RCFET) methodology. RF energy is coupled through magnetic resonance. The cage has a PTE ranging from 1.8-6.28% for a volume of 11 x 11 x 11 in3. This is sufficient to chronically house subjects. The technologies are validated through various in vivo preparations. The tools are designed to study epilepsy, SUDEP, and urinary incontinence but can be configured for other studies. The broad application of these technologies can enable the scientific community to better study chronic diseases and closed-loop therapies

Highly Efficient Smart 3-Coil Wireless Power Transfer System with Automatic Tracking

This paper presents the design of a highly efficient smart wireless powering platform based on object detection algorithm. Power transfer efficiency (PTE) and power-delivered-to-the-load (PDL) are two key parameters used to evaluate the performance of the proposed design. A 3-coil inductive link is used to achieve higher PTE than a 2-coil link when coupled at a considerable distance. The simple design methodology employed enables an optimised geometry for the 3-coil link. The optimised 3-coil link achieves a PTE of 62.1% in measurements. A wireless power transfer system is constructed with a Class-E primary coil driver with 60.6% efficiency. A camera-based tracking system is implemented to maintain the transfer link robustness under changing coupling conditions. The You Only Look Once version.4 (YOLO4) algorithm is used to detect the moving receiver with 71% accuracy and 0.2s response time, and stepper motors controlled by an Arduino process drive the transmitter coil to track the moving receiver coil