Implantable Neural Probes for Brain-Machine Interfaces - Current Developments and Future Prospects

A Brain-Machine interface (BMI) allows for direct communication between the brain and machines. Neural probes for recording neural signals are among the essential components of a BMI system. In this report, we review research regarding implantable neural probes and their applications to BMIs. We first discuss conventional neural probes such as the tetrode, Utah array, Michigan probe, and electroencephalography (ECoG), following which we cover advancements in next-generation neural probes. These next-generation probes are associated with improvements in electrical properties, mechanical durability, biocompatibility, and offer a high degree of freedom in practical settings. Specifically, we focus on three key topics: (1) novel implantable neural probes that decrease the level of invasiveness without sacrificing performance, (2) multi-modal neural probes that measure both electrical and optical signals, (3) and neural probes developed using advanced materials. Because safety and precision are critical for practical applications of BMI systems, future studies should aim to enhance these properties when developing next-generation neural probes

Direct growth of carbon nanotubes on new high-density 3D pyramid-shaped microelectrode arrays for brain-machine interfaces

Silicon micromachined, high-density, pyramid-shaped neural microelectrode arrays (MEAs) have been designed and fabricated for intracortical 3D recording and stimulation. The novel architecture of this MEA has made it unique among the currently available micromachined electrode arrays, as it has provided higher density contacts between the electrodes and targeted neural tissue facilitating recording from different depths of the brain. Our novel masking technique enhances uniform tip-exposure for variable-height electrodes and improves process time and cost significantly. The tips of the electrodes have been coated with platinum (Pt). We have reported for the first time a selective direct growth of carbon nanotubes (CNTs) on the tips of 3D MEAs using the Pt coating as a catalyzer. The average impedance of the CNT-coated electrodes at 1 kHz is 14 k. The CNT coating led to a 5-fold decrease of the impedance and a 600-fold increase in charge transfer compared with the Pt electrode

In Vivo Imaging to Characterize Dynamic Tissue Responses after Neural Electrode Implantation

Implantable neural electrodes are promising technologies to restore motor, sensory, and cognitive function in many neural pathologies through brain-computer interfacing (BCI). Many BCI applications require electrode implantation within neural tissue to resolve and/or modulate the physiological activity of individual neurons via electrical recording and stimulation. This invasive implantation leads to acute and long-term deterioration of both the electrode device as well as the neurons surrounding the device. Ultimately, damage to the electrode and neural tissue results in electrode recording failure within the first years after implantation. Many strategies to improve BCI longevity focus on mitigating tissue damage through improving neuronal survival or reducing inflammatory activity around implants. Despite incremental improvements, electrode failure persists as an obstacle to wide-spread clinical deployment of BCIs. This can be partly attributed to an incomplete understanding of the biological correlates of recording performance. These correlates have largely been identified through post-mortem histological staining, which cannot capture dynamic changes in cellular physiology and morphology. In the following dissertation, we use longitudinal two-photon in vivo imaging to quantify how neurons, microglia, and meningeal immune cells are affected by an intracortical electrode during and after implantation in mouse cortex. We go beyond conventional histological techniques to show the time-course of neuronal injury and microglial recruitment after implantation. Neuronal injury occurs instantaneously, with prolonged, high calcium levels evident in neurons within 100 µm of implants. Microglial activation occurs within minutes of implantation and subsequent microglial encapsulation of electrodes can be modulated by bioactive surface coatings. Within the first day post-implant, there is high trafficking of peripheral immune cells through venules at the surface of the brain as well as along the electrode’s shank at the surface of the brain. Over the next month, calcium activity in neurons increases while the collagenous meningeal tissues at the surface of the brain thicken. We further show that meningeal thickening can have profound implications for devices implanted into non-human primates as well. In sum, these results define new potential therapeutic targets and windows that could improve the longevity of implantable neural electrodes

A Wireless, High-Voltage Compliant, and Energy-Efficient Visual Intracortical Microstimulator

RÉSUMÉ L’objectif général de ce projet de recherche est la conception, la mise en oeuvre et la validation d’une interface sans fil intracorticale implantable en technologie CMOS avancée pour aider les personnes ayant une déficience visuelle. Les défis majeurs de cette recherche sont de répondre à la conformité à haute tension nécessaire à travers l’interface d’électrode-tissu (IET), augmenter la flexibilité dans la microstimulation et la surveillance multicanale, minimiser le budget de puissance pour un dispositif biomédical implantable, réduire la taille de l’implant et améliorer le taux de transmission sans fil des données. Par conséquent, nous présentons dans cette thèse un système de microstimulation intracorticale multi-puce basée sur une nouvelle architecture pour la transmission des données sans fil et le transfert de l’énergie se servant de couplages inductifs et capacitifs. Une première puce, un générateur de stimuli (SG) éconergétique, et une autre qui est un amplificateur de haute impédance se connectant au réseau de microélectrodes de l’étage de sortie. Les 4 canaux de générateurs de stimuli produisent des impulsions rectangulaires, demi-sinus (DS), plateau-sinus (PS) et autres types d’impulsions de courant à haut rendement énergétique. Le SG comporte un contrôleur de faible puissance, des convertisseurs numérique-analogiques (DAC) opérant en mode courant, générateurs multi-forme d’ondes et miroirs de courants alimentés sous 1.2 et 3.3V se servant pour l’interface entre les deux technologies utilisées. Le courant de stimulation du SG varie entre 2.32 et 220μA pour chaque canal. La deuxième puce (pilote de microélectrodes (MED)), une interface entre le SG et de l’arrangement de microélectrodes (MEA), fournit quatre niveaux différents de courant avec la valeur maximale de 400μA par entrée et 100μA par canal de sortie simultanément pour 8 à 16 sites de stimulation à travers les microélectrodes, connectés soit en configuration bipolaire ou monopolaire. Cette étage de sortie est hautement configurable et capable de délivrer une tension élevée pour satisfaire les conditions de l’interface à travers l’impédance de IET par rapport aux systèmes précédemment rapportés. Les valeurs nominales de plus grandes tensions d’alimentation sont de ±10V. La sortie de tension mesurée est conformément 10V/phase (anodique ou cathodique) pour les tensions d’alimentation spécifiées. L’incrémentation de tensions d’alimentation à ±13V permet de produire un courant de stimulation de 220μA par canal de sortie permettant d’élever la tension de sortie jusqu’au 20V par phase. Cet étage de sortie regroupe un commutateur haute tension pour interfacer une matrice des miroirs de courant (3.3V /20V), un registre à décalage de 32-bits à entrée sérielle, sortie parallèle, et un circuit dédié pour bloquer des états interdits.----------ABSTRACT The general objective of this research project is the design, implementation and validation of an implantable wireless intracortical interface in advanced CMOS technology to aid the visually impaired people. The major challenges in this research are to meet the required highvoltage compliance across electrode-tissue interface (ETI), increase lexibility in multichannel microstimulation and monitoring, minimize power budget for an implantable biomedical device, reduce the implant size, and enhance the data rate in wireless transmission. Therefore, we present in this thesis a multi-chip intracortical microstimulation system based on a novel architecture for wireless data and power transmission comprising inductive and capacitive couplings. The first chip is an energy-efficient stimuli generator (SG) and the second one is a highimpedance microelectrode array driver output-stage. The 4-channel stimuli-generator produces rectangular, half-sine (HS), plateau-sine (PS), and other types of energy-efficient current pulse. The SG is featured with low-power controller, current mode source- and sinkdigital- to-analog converters (DACs), multi-waveform generators, and 1.2V/3.3V interface current mirrors. The stimulation current per channel of the SG ranges from 2.32 to 220μA per channel. The second chip (microelectrode driver (MED)), an interface between the SG and the microelectrode array (MEA), supplies four different current levels with the maximum value of 400μA per input and 100μA per output channel. These currents can be delivered simultaneously to 8 to 16 stimulation sites through microelectrodes, connected either in bipolar or monopolar configuration. This output stage is highly-configurable and able to deliver higher compliance voltage across ETI impedance compared to previously reported designs. The nominal values of largest supply voltages are ±10V. The measured output compliance voltage is 10V/phase (anodic or cathodic) for the specified supply voltages. Increment of supply voltages to ±13V allows 220μA stimulation current per output channel enhancing the output compliance voltage up to 20V per phase. This output-stage is featured with a high-voltage switch-matrix, 3.3V/20V current mirrors, an on-chip 32-bit serial-in parallel-out shift register, and the forbidden state logic building blocks. The SG and MED chips have been designed and fabricated in IBM 0.13μm CMOS and Teledyne DALSA 0.8μm 5V/20V CMOS/DMOS technologies with silicon areas occupied by them 1.75 x 1.75mm2 and 4 x 4mm2 respectively. The measured DC power budgets consumed by low-and mid-voltage microchips are 2.56 and 2.1mW consecutively

Modulation of in Vivo Neural Network Activity with Electrochemically Controlled Delivery of Neuroactive Molecules

Neural interface technologies with implantable microelectrode arrays hold great promise for treating neural injuries or disorders. On neural electrode surfaces, conducting polymers can be electropolymerization with negatively charged molecules incorporated. When the polymer is reduced with negative current, dopant molecules are released from the polymer. This feature can be utilized to deliver neural transmitters and modulators from the electrodes to alter neural network activity. Previously, release of CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), an AMPA (2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl)propanoic acid) receptor antagonist in hippocampal neuron culture effectively suppressed local neural activity in a transient manner. In this study, we further advance this technology by characterizing the drug loading and release capacity from microelectrodes, expanding the range of candidate dopants, and demonstrating in vivo effectiveness in rat somatosensory (S1) barrel cortex. Firstly, to quantify the concentration of released drug, fluorescent model molecule was used and quantitatively assessed in a real time imaging system. Stimulation amplitude was varied to determine the amount of released drug from microelectrodes. Secondly, only negatively charged drugs have been effectively released in the past. In this study, zwitterionic transmitter γ-Aminobutyric acid (GABA) was successfully delivered with the technique, greatly expanding the applicable range for the technique. Finally, we used evoked response from barrel cortex to evaluate the release of DNQX (6,7-dinitroquinoxaline-2,3-dione), an analog of CNQX. The neural activity of barrel cortex reliably represents sensory stimuli from whiskers, hence provides an excellent in vivo network model for evaluating our neurochemical release system. Neural activity from multi-whisker stimulation was immediately and locally suppressed by released DNQX for one to six seconds, demonstrating the high spatial-temporal resolution of the technique. Furthermore, weaker activities were nearly abolished by released DNQX whilst stronger activities were less influenced, because the strong over-saturated neural input can only be partially antagonized. The system demonstrates successful modulation of neural network activity in a highly controllable manner. With the ease of being incorporated in existing neural implants without increasing the volume or complexity, this technology may find use in a wide range of neuroscience studies and potentially therapeutic devices