SiNAPS: An implantable active pixel sensor CMOS-probe for simultaneous large-scale neural recordings

Abstract Large-scale neural recordings with high spatial and temporal accuracy are instrumental to understand how the brain works. To this end, it is of key importance to develop probes that can be conveniently scaled up to a high number of recording channels. Despite recent achievements in complementary metal-oxide semiconductor (CMOS) multi-electrode arrays probes, in current circuit architectures an increase in the number of simultaneously recording channels would significantly increase the total chip area. A promising approach for overcoming this scaling issue consists in the use of the modular Active Pixel Sensor (APS) concept, in which a small front-end circuit is located beneath each electrode. However, this approach imposes challenging constraints on the area of the in-pixel circuit, power consumption and noise. Here, we present an APS CMOS-probe technology for Simultaneous Neural recording that successfully addresses all these issues for whole-array read-outs at 25 kHz/channel from up to 1024 electrode-pixels. To assess the circuit performances, we realized in a 0.18  μ m CMOS technology an implantable single-shaft probe with a regular array of 512 electrode-pixels with a pitch of 28  μ m. Extensive bench tests showed an in-pixel gain of 45.4 ± 0.4 dB (low pass, F-3 dB = 4 kHz), an input referred noise of 7.5 ± 0.67 μVRMS (300 Hz to 7.5 kHz) and a power consumptio

Conception et caractérisation de microélectrodes flexibles pour le développement de neuroprothèses implantables

Brain-Computer Interfaces ensure a bidirectional connection between a patient and his environment. Using an implant in his brain, a patient suffering from severe motor deficiency can control external devices through the sole action of his cerebral activity. One of the major requirements for such application is to conceive an implant, also called neuroprosthesis, that is able to be implanted for long periods of time.Micro-nano-technology enable the fabrication of a neuroprosthesis that gives in the demands of such item: efficient, reliable and limiting body rejection mechanisms. To that aim, the implant is designed on a flexible substrate provided by a biocompatible polymer. Implant flexibility allows for better compliance with the brain tissues and insures a more intimate contact with the neurons while maintaining minimal inflammation. This implant is inserted in the brain using a bioresorbable support made of silk fibroin. First tests in vitro on culture cells, and in vivo on mice showed promising results in terms of biocompatibility and biostability in the short and medium term.Les Interfaces Cerveau-Machine assurent une connexion bidirectionnelle entre un patient et son environnement. Un patient atteint de déficience motrice lourde peut, au moyen d'un dispositif implanté dans son cerveau, commander des objets connectés par la seule action de son activité cérébrale. Une des premières exigences que cela requiert est de concevoir un implant, dit neuroprothèse, susceptible de rester implanté de façon chronique. L’utilisation des micro-nano-technologies permet de fabriquer une neuroprothèse qui réponde aux exigences d’un tel dispositif : performant, fiable et limitant la réaction de rejet par l’organisme. Pour cela, l’implant est conçu sur un substrat flexible à base de polymère biocompatible. La souplesse de l’implant lui permet de mieux s’adapter aux tissus cérébraux et d’assurer un contact intime avec les neurones en diminuant la réaction inflammatoire. Cet implant est inséré au moyen d’un support rigide biodégradable issu de la fibroïne de soie. Des premiers tests sur culture in vitro et sur petit animal (souris) ont montré des résultats prometteurs en termes de biocompatibilité et biostabilité sur le court et moyen terme

In vitro and in vivo biostability assessment of chronically-implanted Parylene C neural sensors

International audienceParylene C has rapidly gained attention as a exible biomaterial for a new generation of chronic neural probes. However, polymeric material failure in the form of delamination, swelling or tearing, often compromises device biostability in the long term. This work constitutes a rst step towards lifetime assessment of Parylene C implanted devices. We have conceived a Parylene C-based neural probe with PEDOT-nanostructured gold electrodes for the recording of brain activity. The material response to its biological environment was studied through in vitro soaking tests and in vivo wireless recordings in mice brain, both carried out for up to 6 months. Impedance monitoring and SEM images indicate that over the length of this trial, none of the implants presented with apparent signs of material degradation. Packaging reliability was a predominant factor in device failure, with a certain number of faulty connection appearing over time. This parameter aside, all soaked devices were stable in Articial Cerebro-Spinal Fluid, with impedances within 10% of their initial value after 6 months at 37°C. Besides, at least 70% of the implanted device were able to accurately record wirelessly high amplitude hippocampal Local Field Potentials from freely-moving mice, with steady Signal-to-Noise Ratio. In other terms, Parylene C implantable sensors responded minimally to articial and actual physiological conditions during a period of 6 months, which makes them promising candidates for reliable, chronically implanted sensors in the biomedical eld

Biostability Assessment of Flexible Parylene C-based Implantable Sensor in Wireless Chronic Neural Recording

International audienceThe stability of polymer-based sensors in a biological environment remains a challenge, as delamination and swelling often compromise mechanical and electrical capability. We have developed a neural implant based on Parylene C, a biocompatible flexible polymer, with PEDOT-nanostructured gold patterns to record the brain electrical activity. Here, we show first evidence of device biostability through in vitro soaking tests in artificial brain environment and in vivo recording in mice. Our results indicate that after over the six months trial, more than 75% of the in vitro electrodes have stable impedance, and the implanted sensors in mice were able to accurately record signals from mice hippocampi. None of the implants presented with signs of Parylene degradation or metal corrosion. Overall, the devices are promising candidates for reliable, chronically implanted sensors in the biomedical field

Plasma etching of thick Parylene C for fabrication of biocompatible electrodes

International audienceHere we report on the plasma etching of thick parylene C in order to define flexible implantable probes for neural applications. To reduce the foreign body response and to ensure a good stability for chronic in vivo recordings, the chosen substrate for the neural probes is Parylene C, a polymer known for its high biocompatibility, flexibility and chemical inertness. In the manufacturing process, highly defined structuration steps of Parylene C are essential. Techniques based on laser, scalpel and wet etching have shown to be unsuitable for properly cut structures, i.e. with good dimensions control and without residues. As an alternative, plasma etching has shown great promise in this area. However, because of the highly crystalline structure of this polymer, fast etching rate, lack of residues and high aspect ratios remain hard to achieve, especially for deep etching of thick layers

Plasma etching of thick Parylene C for fabrication of biocompatible electrodes

International audienceHere we report on the plasma etching of thick parylene C in order to define flexible implantable probes for neural applications. To reduce the foreign body response and to ensure a good stability for chronic in vivo recordings, the chosen substrate for the neural probes is Parylene C, a polymer known for its high biocompatibility, flexibility and chemical inertness. In the manufacturing process, highly defined structuration steps of Parylene C are essential. Techniques based on laser, scalpel and wet etching have shown to be unsuitable for properly cut structures, i.e. with good dimensions control and without residues. As an alternative, plasma etching has shown great promise in this area. However, because of the highly crystalline structure of this polymer, fast etching rate, lack of residues and high aspect ratios remain hard to achieve, especially for deep etching of thick layers

Deep plasma etching of Parylene C patterns for biomedical applications

We report on the plasma etching of thick Parylene C (~25 µm) in order to define flexible implantable probes for neural applications. Parylene C is a transparent polymer that presents with high biocompatibility, flexibility and chemical inertness, and has gained increased attention over the years in the biomedical field. In the manufacturing process, highly defined structuration steps of Parylene C are essential, but techniques based on laser, scalpel and wet etching have shown to be unsuitable for properly cut structures, i.e. with good dimensions control and without residues. Here, for the first time, negative resist (BPN) coating followed by RIE-ICP are used in order to pattern Parylene C-based structures, with a clean cut, vertical profile, fast etching rate (~0.8 µm/min) and conservation of device biocompatibility

Deep plasma etching of Parylene C patterns for biomedical applications

International audienceWe report on the plasma etching of thick (~23µm) Parylene C structures. Parylene C is a transparent polymer that benefits from high biocompatibility, flexibility and chemical inertness, and has gained increased attention over the years in the biomedical field. In the manufacturing process, highly defined structuration steps of Parylene C are essential, but techniques based on laser, scalpel and wet etching have shown to be unsuitable for properly cut structures. Plasma etching remains nowadays the most widespread option, though fast etching rate, lack of residues and high aspect ratios are still hard to achieve. To overcome these issues, the selection of both mask material and plasma conditions is crucial. Here, three masks-metal, positive and negative photoresists-are tested as stencils, and several plasma parameters are briefly studied in order to obtain the highest etching rate while maintaining good coverage. We showed that increasing the RF power up to a considerable 2800W while maintaining a moderate physical contribution (bias power, pressure, temperature), is optimal in the achievement of fast PaC etching without inducing thermal stress. Besides, the addition of a short fluorinated plasma in the midst of the process is shown to alleviate residues. For the first time, negative photoresist Intervia Bump Plating (BPN) coating followed by ICP 1-RIE 2 are used in order to pattern Parylene C-based structures, with a clean cut, vertical profile and fast etching rate (~0.87±0.06 µm/min) and a selectivity of 0.5. This solution was carried out to release unitary Parylene-based neural probes from a silicon wafer. Finally, cytotoxicity assays on these neural implants were performed to make sure that no trace of mask or stripper residues would jeopardize device biocompatibility

A review on mechanical considerations for chronically-implanted neural probes

International audienceThis review intends to present a comprehensive analysis of the mechanical considerations for chronically-implanted neural probes. Failure of neural electrical recordings or stimulation over time has shown to arise from foreign body reaction and device material stability. It seems that devices that match most closely with the mechanical properties of the brain would be more likely to reduce the mechanical stress at the probe/tissue interface, thus improving body acceptance. The use of low Young's modulus polymers instead of hard substrates is one way to enhance this mechanical mimetism, though compliance can be achieved through a variety of means. The reduction of probe width and thickness in comparison to a designated length, the use of soft hydrogel coatings and the release in device tethering to the skull, can also improve device compliance. Paradoxically, the more compliant the device, the more likely it will fail during the insertion process in the brain. Strategies have multiplied this past decade to offer partial or temporary stiffness to the device to overcome this buckling effect. A detailed description of the probe insertion mechanisms is provided to analyze potential sources of implantation failure and the need for a mechanically-enhancing structure. This leads us to present an overview of the strategies that have been put in place over the last ten years to overcome buckling issues. Particularly, great emphasis is put on bioresorbable polymers and their assessment for neural applications. Finally, a discussion is provided on some of the key features for the design of mechanically-reliable, polymer-based next generation of chronic neuroprosthetic devices