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

Biointegrated and wirelessly powered implantable brain devices: a review

Implantable neural interfacing devices have added significantly to neural engineering by introducing the low-frequency oscillations of small populations of neurons known as local field potential as well as high-frequency action potentials of individual neurons. Regardless of the astounding progression as of late, conventional neural modulating system is still incapable to achieve the desired chronic in vivo implantation. The real constraint emerges from mechanical and physical diffierences between implants and brain tissue that initiates an inflammatory reaction and glial scar formation that reduces the recording and stimulation quality. Furthermore, traditional strategies consisting of rigid and tethered neural devices cause substantial tissue damage and impede the natural behaviour of an animal, thus hindering chronic in vivo measurements. Therefore, enabling fully implantable neural devices, requires biocompatibility, wireless power/data capability, biointegration using thin and flexible electronics, and chronic recording properties. This paper reviews biocompatibility and design approaches for developing biointegrated and wirelessly powered implantable neural devices in animals aimed at long-term neural interfacing and outlines current challenges toward developing the next generation of implantable neural devices

Roadmap on semiconductor-cell biointerfaces.

This roadmap outlines the role semiconductor-based materials play in understanding the complex biophysical dynamics at multiple length scales, as well as the design and implementation of next-generation electronic, optoelectronic, and mechanical devices for biointerfaces. The roadmap emphasizes the advantages of semiconductor building blocks in interfacing, monitoring, and manipulating the activity of biological components, and discusses the possibility of using active semiconductor-cell interfaces for discovering new signaling processes in the biological world

Carbon-based transparent microelectrodes for optical investigation and electrophysiology

The goal of this work was to develop carbon based transparent electrodes for advancement of microelectrode array (MEA) technology by allowing the possibility of combining optical methods with classical electrophysiology. Recent years have seen a surge of interest in novel methods such as optogenetics and calcium imaging with the focus on understanding the complex neuronal networks. The conventional microelectrode materials obstruct the optical access, which is from the substrate side with an inverted microscope, and this limitation is overcome by using carbon materials. This work was focused on three main materials - carbon nanostructures, graphene and graphene/PEDOT:PSS (poly(3,4- ethylenedioxythiophene)). The transparency often comes at the cost of high electrochemical impedance. This challenge was tackled by using a novel combination of chemical vapour deposited (CVD) graphene and PEDOT:PSS. Carbon nanostructures were grown at 550 °C by CVD with acetylene as the carbon source. The morphology was studied by scanning electron microscope (SEM) and the presence of nanostructures mixed with amorphous carbon confirmed by Raman spectroscopy. The semitransparent nature was revealed by UV-Vis measurements. The electrochemical impedance was in the acceptable range for electrophysiological recordings. The functionality of the carbon nanostructure microelectrodes was confirmed by recording electrogenic signals from cardiomyocytes where the optical inspection of the cells through the semitransparent microelectrodes was possible. The mechanical robustness and biocompatibility was revealed by studying the electrode-cell ultrastructure. Graphene was grown by CVD with methane as the carbon source and integrated in the MEA fabrication process. The largely single layer graphene was investigated with SEM and Raman spectroscopy. The excellent transparency over the entire microelectrode was revealed by optical transmittance measurements. The graphene microelectrodes displayed high electrochemical impedance which led to high noise during electrophysiology. The functionality of the transparent graphene mircoelectrodes was checked with cardiomyocytes where high amplitude signals were detected similar to recording with standard electrodes, however, the smaller amplitude signals went unrecorded owing to the high noise. Graphene/PEDOT:PSS microelectrodes were fabricated by electrodeposition of the conducting polymer PEDOT:PSS on graphene microelectrodes. Optical microscopy revealed that PEDOT:PSS followed the graphene surface and the continuous coverage of the latter by the former reduced to sparse coverage with decreasing amount of PEDOT:PSS. Raman spectroscopy, especially in the case of lower PEDOT:PSS amounts, revealed the presence of PEDOT:PSS on regions which appeared transparent optically. This information was crucial in understanding the electrodeposition mechanism. The electrochemical impedance was found to be comparable with the commercially available TiN microelectrodes and the applicability was tested with cardiomyocytes. Optical imaging was possible through the transparent microelectrodes. An optimum balance between the optical transparency and electrochemical impedance was obtained which allows flexibility in producing microelectrodes for a wide range of applications. This work presents a comprehensive view on carbon based transparent microelectrodes for novel applications employing combinations of electro- and opto-physiology. The electrodes fabricated in this work are expected to go a long way in assistance with decoding the complex biological systems and provide insights on the single cell level

Technological challenges in the development of optogenetic closed-loop therapy approaches in epilepsy and related network disorders of the brain

Epilepsy is a chronic, neurological disorder affecting millions of people every year. The current available pharmacological and surgical treatments are lacking in overall efficacy and cause side-effects like cognitive impairment, depression, tremor, abnormal liver and kidney function. In recent years, the application of optogenetic implants have shown promise to target aberrant neuronal circuits in epilepsy with the advantage of both high spatial and temporal resolution and high cell-specificity, a feature that could tackle both the efficacy and side-effect problems in epilepsy treatment. Optrodes consist of electrodes to record local field potentials and an optical component to modulate neurons via activation of opsin expressed by these neurons. The goal of optogenetics in epilepsy is to interrupt seizure activity in its earliest state, providing a so-called closed-loop therapeutic intervention. The chronic implantation in vivo poses specific demands for the engineering of therapeutic optrodes. Enzymatic degradation and glial encapsulation of implants may compromise long-term recording and sufficient illumination of the opsin-expressing neural tissue. Engineering efforts for optimal optrode design have to be directed towards limitation of the foreign body reaction by reducing the implant’s elastic modulus and overall size, while still providing stable long-term recording and large-area illumination, and guaranteeing successful intracerebral implantation. This paper presents an overview of the challenges and recent advances in the field of electrode design, neural-tissue illumination, and neural-probe implantation, with the goal of identifying a suitable candidate to be incorporated in a therapeutic approach for long-term treatment of epilepsy patients

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