Evolution of optogenetic microdevices

Implementation of optogenetic techniques is a recent addition to the neuroscientists\u27 preclinical research arsenal, helping to expose the intricate connectivity of the brain and allowing for on-demand direct modulation of specific neural pathways. Developing an optogenetic system requires thorough investigation of the optogenetic technique and of previously fabricated devices, which this review accommodates. Many experiments utilize bench-top systems that are bulky, expensive, and necessitate tethering to the animal. However, these bench-top systems can make use of power-demanding technologies, such as concurrent electrical recording. Newer portable microdevices and implantable systems carried by freely moving animals are being fabricated that take advantage of wireless energy harvesting to power a system and allow for natural movements that are vital for behavioral testing and analysis. An investigation of the evolution of tethered, portable, and implantable optogenetic microdevices is presented, and an analysis of benefits and detriments of each system, including optical power output, device dimensions, electrode width, and weight is given. Opsins, light sources, and optical fiber coupling are also discussed to optimize device parameters and maximize efficiency from the light source to the fiber, respectively. These attributes are important considerations when designing and developing improved optogenetic microdevices

Wireless power transfer for combined sensing and stimulation in implantable biomedical devices

Actuellement, il existe une forte demande de Headstage et de microsystèmes intégrés implantables pour étudier l’activité cérébrale de souris de laboratoire en mouvement libre. De tels dispositifs peuvent s’interfacer avec le système nerveux central dans les paradigmes électriques et optiques pour stimuler et surveiller les circuits neuronaux, ce qui est essentiel pour découvrir de nouveaux médicaments et thérapies contre des troubles neurologiques comme l’épilepsie, la dépression et la maladie de Parkinson. Puisque les systèmes implantables ne peuvent pas utiliser une batterie ayant une grande capacité en tant que source d’énergie primaire dans des expériences à long terme, la consommation d’énergie du dispositif implantable est l’un des principaux défis de ces conceptions. La première partie de cette recherche comprend notre proposition de la solution pour diminuer la consommation d’énergie des microcircuits implantables. Nous proposons un nouveau circuit de décalage de niveau qui convertit les niveaux de signaux sub-seuils en niveaux ultra-bas à haute vitesse en utilisant une très faible puissance et une petite zone de silicium, ce qui le rend idéal pour les applications de faible puissance. Le circuit proposé introduit une nouvelle topologie de décaleur de niveau de tension utilisant un condensateur de décalage de niveau pour augmenter la plage de tensions de conversion, tout en réduisant considérablement le retard de conversion. Le circuit proposé atteint un délai de propagation plus court et une zone de silicium plus petite pour une fréquence de fonctionnement et une consommation d’énergie donnée par rapport à d’autres solutions de circuit. Les résultats de mesure sont présentés pour le circuit proposé fabriqué dans un processus CMOS TSMC de 0,18- mm. Le circuit présenté peut convertir une large gamme de tensions d’entrée de 330 mV à 1,8 V et fonctionner sur une plage de fréquence de 100 Hz à 100 MHz. Il a un délai de propagation de 29 ns et une consommation d’énergie de 61,5 nW pour les signaux d’entrée de 0,4 V, à une fréquence de 500 kHz, surpassant les conceptions précédentes. La deuxième partie de cette recherche comprend nos systèmes de transfert d’énergie sans fil proposé pour les applications optogénétiques. L’optogénétique est la combinaison de la méthode génétique et optique d’excitation, d’enregistrement et de contrôle des neurones biologiques. Ce système combine plusieurs technologies telles que les MEMS et la microélectronique pour collecter et transmettre les signaux neuronaux et activer un stimulateur optique via une liaison sans fil. Puisque les stimulateurs optiques consomment plus de puissance que les stimulateurs électriques, l’interface utilise la transmission de puissance par induction en utilisant des moyens innovants au lieu de la batterie avec la petite capacité comme source d’énergie.Notre première contribution dans la deuxième partie fournit un système de cage domestique intelligent basé sur des barrettes multi-bobines superposées à travers un récepteur multicellulaire implantable mince de taille 1×1 cm2, implanté sous le cuir chevelu d’une souris de laboratoire, et unité de gestion de l’alimentation intégrée. Ce système inductif est conçu pour fournir jusqu’à 35,5 mW de puissance délivrée à un émetteur-récepteur full duplex de faible puissance entièrement intégré pour prendre en charge des implants neuronaux à haute densité et bidirectionnels. L’émetteur (TX) utilise une bande ultra-large à impulsions radio basée sur des approches de combinaison, et le récepteur (RX) utilise une topologie à bande étroite à incrémentation de 2,4 GHz. L’émetteur-récepteur proposé fournit un débit de données de liaison montante TX à 500 Mbits/s double et un débit de données de liaison descendante RX à 100 Mbits/s, et est entièrement intégré dans un processus CMOS TSMC de 0,18-mm d’une taille totale de 0,8 mm2 . La puissance peut être délivrée à partir d’un signal de porteuse de 13,56-MHz avec une efficacité globale de transfert de puissance supérieure à 5% sur une distance de séparation allant de 3 cm à 5 cm. Notre deuxième contribution dans les systèmes de collecte d’énergie porte sur la conception et la mise en oeuvre d’une cage domestique de transmission de puissance sans fil (WPT) pour une plate-forme de neurosciences entièrement sans fil afin de permettre des expériences optogénétiques ininterrompues avec des rongeurs de laboratoire vivants. La cage domestique WPT utilise un nouveau réseau hybride de transmetteurs de puissance (TX) et des résonateurs multi-bobines segmentés pour atteindre une efficacité de transmission de puissance élevée (PTE) et délivrer une puissance élevée sur des distances aussi élevées que 20 cm. Le récepteur de puissance à bobines multiples (RX) utilise une bobine RX d’un diamètre de 1 cm et une bobine de résonateur d’un diamètre de 1,5 cm. L’efficacité moyenne du transfert de puissance WPT est de 29, 4%, à une distance nominale de 7 cm, pour une fréquence porteuse de 13,56 MHz. Il a des PTE maximum et minimum de 50% et 12% le long de l’axe Z et peut délivrer une puissance constante de 74 mW pour alimenter le headstage neuronal miniature. En outre, un dispositif implantable intégré dans un processus CMOS TSMC de 0,18-mm a été conçu et introduit qui comprend 64 canaux d’enregistrement, 16 canaux de stimulation optique, capteur de température, émetteur-récepteur et unité de gestion de l’alimentation (PMU). Ce circuit est alimenté à l’intérieur de la cage du WPT à l’aide d’une bobine réceptrice d’un diamètre de 1,5 cm pour montrer les performances du circuit PMU. Deux tensions régulées de 1,8 V et 1 V fournissent 79 mW de puissance pour tout le système sur une puce. Notre dernière contribution est un système WPT insensible aux désalignements angulaires pour alimenter un headstage pour des applications optogénétiques qui a été précédemment proposé par le Laboratoire de Microsystèmes Biomédicaux (BioML-UL) à ULAVAL. Ce système est la version étendue de notre deuxième contribution aux systèmes de collecte d’énergie.Dans la version mise à jour, un récepteur de puissance multi-bobines utilise une bobine RX d’un diamètre de 1,0 cm et une nouvelle bobine de résonateur fendu d’un diamètre de 1,5 cm, qui résiste aux défauts d’alignement angulaires. Dans cette version qui utilise une cage d’animal plus petite que la dernière version, 4 résonateurs sont utilisés côté TX. De plus, grâce à la forme et à la position de la bobine de répéteur L3 du côté du récepteur, la liaison résonnante hybride présentée peut correctement alimenter la tête sans interruption causée par le désalignement angulaire dans toute la cage de la maison. Chaque 3 tours du répéteur RX a été enveloppé avec un diamètre de 1,5 cm, sous différents angles par rapport à la bobine réceptrice. Les résultats de mesure montrent un PTE maximum et minimum de 53 % et 15 %. La méthode proposée peut fournir une puissance constante de 82 mW pour alimenter le petit headstage neural pour les applications optogénétiques. De plus, dans cette version, la performance du système est démontrée dans une expérience in-vivo avec une souris ChR2 en mouvement libre qui est la première expérience optogénétique sans fil et sans batterie rapportée avec enregistrement électrophysiologique simultané et stimulation optogénétique. L’activité électrophysiologique a été enregistrée après une stimulation optogénétique dans le Cortex Cingulaire Antérieur (CAC) de la souris.Our first contribution in the second part provides a smart home-cage system based on overlapped multi-coil arrays through a thin implantable multi-coil receiver of 1×1 cm2 of size, implantable bellow the scalp of a laboratory mouse, and integrated power management circuits. This inductive system is designed to deliver up to 35.5 mW of power delivered to a fully-integrated, low-power full-duplex transceiver to support high-density and bidirectional neural implants. The transmitter (TX) uses impulse radio ultra-wideband based on an edge combining approach, and the receiver (RX) uses a 2.4- GHz on-off keying narrow band topology. The proposed transceiver provides dual-band 500-Mbps TX uplink data rate and 100-Mbps RX downlink data rate, and it is fully integrated into 0.18-mm TSMC CMOS process within a total size of 0.8 mm2. The power can be delivered from a 13.56-MHz carrier signal with an overall power transfer efficiency above 5% across a separation distance ranging from 3 cm to 5 cm. Our second contribution in power-harvesting systems deals with designing and implementation of a WPT home-cage for a fully wireless neuroscience platform for enabling uninterrupted optogenetic experiments with live laboratory rodents. The WPT home-cage uses a new hybrid parallel power transmitter (TX) coil array and segmented multi-coil resonators to achieve high power transmission efficiency (PTE) and deliver high power across distances as high as 20 cm. The multi-coil power receiver (RX) uses an RX coil with a diameter of 1 cm and a resonator coil with a diameter of 1.5 cm. The WPT home-cage average power transfer efficiency is 29.4%, at a nominal distance of 7 cm, for a power carrier frequency of 13.56-MHz. It has maximum and minimum PTE of 50% and 12% along the Z axis and can deliver a constant power of 74 mW to supply the miniature neural headstage. Also, an implantable device integrated into a 0.18-mm TSMC CMOS process has been designed and introduced which includes 64 recording channels, 16 optical stimulation channels, temperature sensor, transceiver, and power management unit (PMU). This circuit powered up inside the WPT home-cage using receiver coil with a diameter of 1.5 cm to show the performance of the PMU circuit. Two regulated voltages of 1.8 V and 1 V provide 79 mW of power for all the system on a chip. Our last contribution is an angular misalignment insensitive WPT system to power up a headstage which has been previously proposed by the Biomedical Microsystems Laboratory (BioML-UL) at ULAVAL for optogenetic applications. This system is the extended version of our second contribution in power-harvesting systems. In the updated version a multi-coil power receiver uses an RX coil with a diameter of 1.0 cm and a new split resonator coil with a diameter of 1.5 cm, which is robust against angular misalignment. In this version which is using a smaller animal home-cage than the last version, 4 resonators are used on the TX side. Also, thanks to the shape and position of the repeater coil of L3 on the receiver side, the presented hybrid resonant link can properly power up the headstage without interruption caused by the angular misalignment all over the home-cage. Each 3 turns of the RX repeater has been wrapped up with a diameter of 1.5 cm, in different angles compared to the receiver coil. Measurement results show a maximum and minimum PTE of 53 % and 15 %. The proposed method can deliver a constant power of 82 mW to supply the small neural headstage for the optogenetic applications. Additionally, in this version, the performance of the system is demonstrated within an in-vivo experiment with a freely moving ChR2 mouse which is the first fully wireless and batteryless optogenetic experiment reported with simultaneous electrophysiological recording and optogenetic stimulation. Electrophysiological activity was recorded after delivering optogenetic stimulation in the Anterior Cingulate Cortex (ACC) of the mouse.Currently, there is a high demand for Headstage and implantable integrated microsystems to study the brain activity of freely moving laboratory mice. Such devices can interface with the central nervous system in both electrical and optical paradigms for stimulating and monitoring neural circuits, which is critical to discover new drugs and therapies against neurological disorders like epilepsy, depression, and Parkinson’s disease. Since the implantable systems cannot use a battery with a large capacity as a primary source of energy in long-term experiments, the power consumption of the implantable device is one of the leading challenges of these designs. The first part of this research includes our proposed solution for decreasing the power consumption of the implantable microcircuits. We propose a novel level shifter circuit which converting subthreshold signal levels to super-threshold signal levels at high-speed using ultra low power and a small silicon area, making it well-suited for low-power applications such as wireless sensor networks and implantable medical devices. The proposed circuit introduces a new voltage level shifter topology employing a level-shifting capacitor to increase the range of conversion voltages, while significantly reducing the conversion delay. The proposed circuit achieves a shorter propagation delay and a smaller silicon area for a given operating frequency and power consumption compared to other circuit solutions. Measurement results are presented for the proposed circuit fabricated in a 0.18-mm TSMC CMOS process. The presented circuit can convert a wide range of the input voltages from 330 mV to 1.8 V, and operate over a frequency range of 100-Hz to 100-MHz. It has a propagation delay of 29 ns, and power consumption of 61.5 nW for input signals 0.4 V, at a frequency of 500-kHz, outperforming previous designs. The second part of this research includes our proposed wireless power transfer systems for optogenetic applications. Optogenetics is the combination of the genetic and optical method of excitation, recording, and control of the biological neurons. This system combines multiple technologies such as MEMS and microelectronics to collect and transmit the neuronal signals and to activate an optical stimulator through a wireless link. Since optical stimulators consume more power than electrical stimulators, the interface employs induction power transmission using innovative means instead of the battery with the small capacity as a power source

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

Wireless neural/EMG telemetry system for freely moving insects

Journal ArticleWe have developed a miniature telemetry system that captures neural, EMG, and acceleration signals from a freely moving insect and transmits the data wirelessly to a remote digital receiver. The system is based on a custom low-power integrated circuit that amplifies and digitizes four biopotential signals as well as three acceleration signals from an off-chip MEMS accelerometer, and transmits this information over a wireless 920-MHz telemetry link. The unit weighs 0.79 g and runs for two hours on two small batteries. We have used this system to monitor neural and EMG signals in jumping and flying locusts

Improving the mechanistic study of neuromuscular diseases through the development of a fully wireless and implantable recording device

Neuromuscular diseases manifest by a handful of known phenotypes affecting the peripheral nerves, skeletal muscle fibers, and neuromuscular junction. Common signs of these diseases include demyelination, myasthenia, atrophy, and aberrant muscle activity—all of which may be tracked over time using one or more electrophysiological markers. Mice, which are the predominant mammalian model for most human diseases, have been used to study congenital neuromuscular diseases for decades. However, our understanding of the mechanisms underlying these pathologies is still incomplete. This is in part due to the lack of instrumentation available to easily collect longitudinal, in vivo electrophysiological activity from mice. There remains a need for a fully wireless, batteryless, and implantable recording system that can be adapted for a variety of electrophysiological measurements and also enable long-term, continuous data collection in very small animals. To meet this need a miniature, chronically implantable device has been developed that is capable of wirelessly coupling energy from electromagnetic fields while implanted within a body. This device can both record and trigger bioelectric events and may be chronically implanted in rodents as small as mice. This grants investigators the ability to continuously observe electrophysiological changes corresponding to disease progression in a single, freely behaving, untethered animal. The fully wireless closed-loop system is an adaptable solution for a range of long-term mechanistic and diagnostic studies in rodent disease models. Its high level of functionality, adjustable parameters, accessible building blocks, reprogrammable firmware, and modular electrode interface offer flexibility that is distinctive among fully implantable recording or stimulating devices. The key significance of this work is that it has generated novel instrumentation in the form of a fully implantable bioelectric recording device having a much higher level of functionality than any other fully wireless system available for mouse work. This has incidentally led to contributions in the areas of wireless power transfer and neural interfaces for upper-limb prosthesis control. Herein the solution space for wireless power transfer is examined including a close inspection of far-field power transfer to implanted bioelectric sensors. Methods of design and characterization for the iterative development of the device are detailed. Furthermore, its performance and utility in remote bioelectric sensing applications is demonstrated with humans, rats, healthy mice, and mouse models for degenerative neuromuscular and motoneuron diseases

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

Bidirectional Neural Interface Circuits with On-Chip Stimulation Artifact Reduction Schemes

Bidirectional neural interfaces are tools designed to “communicate” with the brain via recording and modulation of neuronal activity. The bidirectional interface systems have been adopted for many applications. Neuroscientists employ them to map neuronal circuits through precise stimulation and recording. Medical doctors deploy them as adaptable medical devices which control therapeutic stimulation parameters based on monitoring real-time neural activity. Brain-machine-interface (BMI) researchers use neural interfaces to bypass the nervous system and directly control neuroprosthetics or brain-computer-interface (BCI) spellers. In bidirectional interfaces, the implantable transducers as well as the corresponding electronic circuits and systems face several challenges. A high channel count, low power consumption, and reduced system size are desirable for potential chronic deployment and wider applicability. Moreover, a neural interface designed for robust closed-loop operation requires the mitigation of stimulation artifacts which corrupt the recorded signals. This dissertation introduces several techniques targeting low power consumption, small size, and reduction of stimulation artifacts. These techniques are implemented for extracellular electrophysiological recording and two stimulation modalities: direct current stimulation for closed-loop control of seizure detection/quench and optical stimulation for optogenetic studies. While the two modalities differ in their mechanisms, hardware implementation, and applications, they share many crucial system-level challenges. The first method aims at solving the critical issue of stimulation artifacts saturating the preamplifier in the recording front-end. To prevent saturation, a novel mixed-signal stimulation artifact cancellation circuit is devised to subtract the artifact before amplification and maintain the standard input range of a power-hungry preamplifier. Additional novel techniques have been also implemented to lower the noise and power consumption. A common average referencing (CAR) front-end circuit eliminates the cross-channel common mode noise by averaging and subtracting it in analog domain. A range-adapting SAR ADC saves additional power by eliminating unnecessary conversion cycles when the input signal is small. Measurements of an integrated circuit (IC) prototype demonstrate the attenuation of stimulation artifacts by up to 42 dB and cross-channel noise suppression by up to 39.8 dB. The power consumption per channel is maintained at 330 nW, while the area per channel is only 0.17 mm2. The second system implements a compact headstage for closed-loop optogenetic stimulation and electrophysiological recording. This design targets a miniaturized form factor, high channel count, and high-precision stimulation control suitable for rodent in-vivo optogenetic studies. Monolithically integrated optoelectrodes (which include 12 µLEDs for optical stimulation and 12 electrical recording sites) are combined with an off-the-shelf recording IC and a custom-designed high-precision LED driver. 32 recording and 12 stimulation channels can be individually accessed and controlled on a small headstage with dimensions of 2.16 x 2.38 x 0.35 cm and mass of 1.9 g. A third system prototype improves the optogenetic headstage prototype by furthering system integration and improving power efficiency facilitating wireless operation. The custom application-specific integrated circuit (ASIC) combines recording and stimulation channels with a power management unit, allowing the system to be powered by an ultra-light Li-ion battery. Additionally, the µLED drivers include a high-resolution arbitrary waveform generation mode for shaping of µLED current pulses to preemptively reduce artifacts. A prototype IC occupies 7.66 mm2, consumes 3.04 mW under typical operating conditions, and the optical pulse shaping scheme can attenuate stimulation artifacts by up to 3x with a Gaussian-rise pulse rise time under 1 ms.PHDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147674/1/mendrela_1.pd

Design and Implementation of a Passive Neurostimulator with Wireless Resonance-Coupled Power Delivery and Demonstration on Frog Sciatic Nerve and Gastrocnemius Muscle

The thesis presented has four goals: to perform a comprehensive literature review on current neurostimulator technology; to outline the current issues with the state-of-the-art; to provide a neurostimulator design that solves these issues, and to characterize the design and demonstrate its neurostimulation features. The literature review describes the physiology of a neuron, and then proceeds to outline neural interfaces and neurostimulators. The neurostimulator design process is then outlined and current requirements in the field are described. The novel neurostimulator circuit that implements a solution that has wireless capability, passive control, and small size is outlined and characterized. The circuit is demonstrated to operate wirelessly with a resonance-coupled multi-channel implementation, and is shown powering LEDs. The circuit was then fabricated in a miniature implementation which utilized a 10 x 20 x 3 mm&179 antenna, and occupied a volume approximating 1 cm&179. This miniature circuit is used to stimulate frog sciatic nerve and gastrocnemius muscle in vitro. These demonstrations and characterization show the device is capable of neurostimulation, can operate wirelessly, is controlled passively, and can be implemented in a small size, thus solving the aforementioned neurostimulator requirements. Further work in this area is focused on developing an extensive characterization of the device and the wireless power delivery system, optimizing the circuit design, and performing in vivo experiments with restoration of motor control in injured animals. This device shows promise to provide a comprehensive solution to many application-specific problems in neurostimulation, and be a modular addition to larger neural interface systems